Neurology Firecracker

Ear Pathology next Organ Systems Neurology Pathology

12 questions

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The most common disorders of the ear are otitis media, otosclerosis, labrynthitis, andcarcinoma of external ear. Otitis media describes an inflammation of the middle ear, it is mainly a pediatric illness. less Otitis media typically begins as a viral infection which then is complicated by a bacterial super infection. The three most common species of bacteria implicated in otitis media are • Streptococcus pneumoniae • Haemophilus influenzae • Moraxella catarrhalis. Chronic otitis media results from repeated acute infections. Chronic infections often do not resolve completely. Cholesteatoma describes a cystic lesion of the middle ear that may result in perforation of the tympanic membrane. It is often a complication of chronic otitis media. Labyrinthitis describes an acute inflammation of the inner ear. It often occurs immediately after an upper respiratory tract infection. less Symptoms of labyrinthitis include: • tinnitus, vertigo • hearing loss • loss of balance • nausea and vomiting

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Treatment is usually conservative and symptomatic as the condition generally resolves on its own. Otosclerosis describes a fusion of the ossicles in the middle ear. It is a common form of conductive hearing loss in adults. Carcinoma of the external ear describes a malignant epithelial tumor which occurs most commonly on the pinna. It is often squamous cell carcinoma or a basal cell carcinoma and is linked to ultraviolet radiation. less Squamous cell carcinoma presents as a nodular, ulcerated lesion. Basal cell carcinoma may present as telangiectatic, pearly papules.

Disorders of Special Senses next Organ Systems Neurology Pathology

16 questions

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Deafness describes a loss of hearing. This can be further classified as either conductive deafness or sensorineural deafness, a differential which can be determined using specific auditory tests. See auditory system https://med.firecracker.me/topics/3442 less Conductive deafness describes a deficit in the mechanical conduction of sound. It is often a consequence of outer and middle ear pathology (seehttps://med.firecracker.me/topics/149). Otosclerosis describes a fusion of the middle ear ossicles. It is the most common cause of conductive deafness in the elderly.

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Otitis media describes an infection of them middle ear. It is the most common cause of conductive deafness in children. Sensorineural deafness describes a deficit in the neural perception and transmission of sound. It is often a consequence of inner ear pathology. Presbycusis describes a degeneration of cochlear hairs. It is the most common cause of sensorineural deafness in the elderly. Additionally, sensorineural deafness may result from compression of thevestibulocochlear nerve (Cranial Nerve VIII) at the cerebellopontine angle. This is often a consequence of mass effects of tumors such as Acoustic Neuromas (Schwannomas) and less commonly meningiomas. Therapeutic options for sensorineural deafness include cochlear implants and hearing aids. Anosmia describes a loss of the sense of smell, it may occur as a result of damage to any structure of the olfactory pathway. The olfactory tract is particularly vulnerable to traumatic less (skull fractures) or infectious (meningitis) damage or mass effects from tumors such as meningiomas. These deficits tend to be ipsilateral. Meningiomas arising in the anterior fossa can result in Kennedy Foster syndrome, which presents with clinical triad of ipsilateral anosmia, ipsilateral optic atrophy, and contralateral papilledema. Failure of the olfactory bulb to develop results in Kallmann Syndrome, which presents with both bilateral anosmia as well as hypogonadism, the latter being a consequence of the fact that Gonadotropin Releasing Hormone (GnRH) secreting neurons initially arise in the olfactory bulb before migrating to the medial preoptic nucleus of the hypothalamus. Lesions or seizures involving the parahippocampal uncus may result in olfactory hallucinations due to integration

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of the olfactory pathway with the limbic system. Special Senses https://med.firecracker.me/topics/2935 Ageusia describes a loss of taste. The most common cause is heavy smoking. less Ageusia may also result from damage to any of the neural structures involved in the gustatory pathway, including cranial nerves VII, IX, and X. Blindness describes a loss of vision. It may be a result of either eye pathology (https://med.firecracker.me/topics/934) or lesions of the optic pathway (https://med.firecracker.me/topics/3434). Night blindness may be a consequence of Vitamin A less deficiency.

Cerebrovascular Hemorrhages next Organ Systems Neurology Pathology

5 questions

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Intracerebral hemorrhage: bleeding into brain parenchyma less Intracerebral hemorrhage can result from: - Hypertension (acute hypertension=most common cause) - Tumor encroachment on vessels - Cerebral amyloid angiopathy Chronic hypertension → small vessel vasculopathy → predisposes to the formation of Charcot-Bouchard aneurysms, which may rupture due to the increased wall stress caused by hypertension → intracerebral hemorrhage Note: Charcot-Bouchard aneurysms = microaneurysms that occur in the small perforating arteries of the brain—for example:

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- Lenticulostriate vessels (most common site) - Thalamoperforator vessels - Paramedian branches of the basilar artery - Superior cerebellar arteries - Anterior inferior cerebellar arteries Most common sites of hypertensive bleeds in the CNS (in descending order of frequency): 1) Basal ganglia is most common site—50-60% of these basal ganglia bleeds originate in the putamen. Mechanism → Lenticulostriate vessels (branches of MCA) are susceptible to high pressure damage. 2) Thalamus 3) Pons 4) Cerebellum Cerebral amyloid angiopathy involves the same amyloid protein found in Alzheimers disease: - Deposition of β-amyloid protein in cortical vessels → weakening of vessel walls → ↑risk for lobar (eg, frontal, temporal, parietal, occipital cortex) intracerebral hemorrhage - Primary etiology of lobar hemorrhage is usually cerebral amyloid angiopathy, nothypertension Subarachnoid hemorrhage: bleeding into subarachnoid space less Xanthochromia (blonde color) of the CSF after a subarachnoid hemorrhage is caused by oxyhemoglobin and bilirubin Frequently caused by berry aneurysm (also known as a “saccular” aneurysm) of the circle of Willis (patients complain of a sudden worst headache)

Berry aneurysm rupture → subarachnoid hemorrhage

Much more common in the anterior segment of the circle of Willis

Highly predictable spatial distribution: - 40% at junction of anterior communicating artery and anterior cerebral artery - 34% at bifurcation of MCA - 20% at junction of ICA and posterior communicating artery - 4% at bifurcation of basilar artery

Commonly seen in: - Coarctation of the aorta - polycystic kidney disease - Marfan syndrome

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- Ehlers-Danlos syndrome Can be associated with arteriovenous malformations or trauma Potential complication: vasospasm. May be prevented by calcium channel blockers.

The presence of intracellular components of RBCs → ↑potential for vasospasm. General note: Any increase in intracranial pressure is initially compensated by shifting of cerebrospinal fluid into spinal subarachnoid space

Viral infections next Organ Systems Neurology Pathology

12 questions

339

Can be limited to meninges (meningitis), involve entire brain (encephalitis), or both (meningoencephalitis) Viral meningitis CSF profile: ↑ lymphocytes, moderate ↑protein, normal glucose Examples of viral infection: Arbovirus encephalitides (St. Louis, eastern equine, western equine): mosquito vector HSV (herpes simplex virus) encephalitis: seen in teenagers and young adults, localized to temporal region. Rabies: - Can be aborted by active immunization before the onset of clinical manifestations - Characterized by formation of Negri bodies, which are eosinophilic intracytoplasmic inclusions commonly found in the hippocampus and Purkinje cells of cerebellum. CMV (cytomegalovirus) encephalitis: - Common in immunosuppressed patients - Characterized by large intranuclear basophilic inclusions (surrounded by a clear halo, (offset)) and smaller intracytoplasmic basophilic inclusions.

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- Encephalomyelitis accompanied by kidney, liver, and/or lung lesions. In infants, periventricular calcifications with chorioretinitis, hepatosplenomegaly, and mental retardation are common. HIV encephalitis: characterized by diffuse myelin damage (spongy myelinopathy with gliosis), neuronal loss, vascular damage, lymphocytic infiltrates in white matter, and multinucleated giant cells (formed from fusing of membranes of infected macrophages). May manifest as AIDS dementia complex: personality less changes, depression, difficulty with balance Poliomyelitis: degeneration and necrosis of anterior horn cells of spinal cord Slow progression viral infections: two types of viral CNS infection that have a slow clinical progression less 1) Subacute sclerosing panencephalitis Persistent infection with an altered measles virus Infected during infancy but will not manifest with neurological symptoms until early teenage years, usually fatal Characteristic: CSF contains oligoclonal immunoglobulins against viral proteins 2) Progressive multifocal leukoencephalopathy Caused by JC polyoma type of papovavirus, which infects oligodendrocytes (inclusion bodies may be seen on microscopy) and astrocytes. Damaged oligodendrocytes → multifocal demyelination in brain Associated with leukemia, lymphoma, or HIV

Acute disseminated encephalomyelitis next Organ Systems Neurology Pathology

2 questions

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An acute inflammatory and demyelinating disease, ADEM is characterized by multiple foci of demyelination throughout the brain and spinal cord. Usually follows a viral illness, such as measles, mumps,less rubella, varicella zoster, Epstein Barr, herpes simplex or coxsackievirus (also known as postinfectious encephalitis) Rarely, ADEM may occur after vaccination or bacterial infection. (Though it can occur at any age, most cases are in children and adolescents.) Delayed hypersensitivity reaction. Symptoms include fever, headache, seizures and coma. These symptoms begin 1-3 weeks after infection or vaccination and may worsen rapidly. Full recovery is seen in most cases, but several patients may recover with minor residual disability. Average time to recovery is 1-6 months. Widespread demyelination, particularly in subcortical and central white matter. Treatment involves high dose intravenous corticosteroids and immunoglobulin.

Alzheimer disease next Organ Systems Neurology Pathology

22 questions

339

Alzheimer disease (AD): most common type of dementia (about 60% of all dementias), incidence increases with age less

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Clinical course : insidious onset with progressive deterioration characterized by gradual loss of memory and intellectual abilities with one (or more) of the following cognitive disturbances: 1. Aphasia (impaired language abilities) 2. Apraxia (impaired ability to execute voluntary motor activities despite intact ability to comprehend the task and intact sensorimotor function) 3. Agnosia (impaired ability to recognize or identify objects despite intact sensory function) 4. Disturbance in executive function (e.g. planning, organizing) Psychiatric manifestations are also common: personality changes, aggressive behavior, depression, sleep disturbances, paranoid thoughts and delusions In the late stages patients are often severely demented (sometimes even psychotic) with devastating memory loss → bedridden → eventual coma and death (commonly within 8-10 years of clinical diagnosis) Many factors are associated with increased frequency of AD, including age, female sex, history of head trauma, Down syndrome, and genetics Early-onset AD mutations: amyloid β precursor protein less (AβPP) gene on chromosome 21, presenilin-1 gene on chromosome 14, or presenilin-2 gene on chromosome 1 (presenillin part of a complex for gamma-secretase enzymes involved in degrading amyloid beta proteins) Down syndrome patients almost universally develop AD by 40 years of age (extra chromosome 21 → increased expression of AβPP gene)

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AβPP mutations → abnormal Aβ production with aggregation in neurons → metabolizing enzymes like alphasecretase unable to degrade proteins → neuritic “senile” plaques Gene for ApoE4 (on chromosome 19) shown to have an association with AD, while the gene for ApoE2 (also on chromsome 19) shown to have protective effect Major pathologic features of AD are cerebral and hippocampal atrophy with characteristic histological changes of neurofibrillary tangles and senile plaques less NFTs (neurofibrillary tangles): - Intracytoplasmic, basophilic inclusions which encircle or displace the nucleus of the host neuron - Composed predominantly of paired helical filaments containing abnormally hyperphosphorylated forms of tau protein. - NFTs are also found in other diseases (e.g., Pick disease) ∴ NFTs are not specific for Alzheimer disease! Note: tau is an axonal microtubule-associated protein that normally facilitates microtubule assembly; tau becomes insoluble “Senile” plaques : extracellular β amyloid core that may cause amyloid angiopathy Amyloid angiopathy: amyloid deposition around vessels leading to lobar intracranial hemorrhage Granulovacuolar degeneration: atrophy of hippocampus consisting of small vacuoles within cell body, each vacuole having small dense inclusion Hirano bodies: intracytoplasmic proximal dendritic eosinophilic inclusions of actin Degeneration of cholinergic cells that project to the cortex from the basal forebrain, especially the nucleus basalis of Meynert (main approach to enhancing cognition is to give acetylcholinesterase inhibitors to increase cholinergic function)

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Most effective initial interventions involve providing structured environment, specifically visual-orienting clues (labels over doors of rooms identifying their function, daily written activity of schedules, and practical safety measures like disconnecting the oven) Medications: Acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) and an NMDA antagonist (memantine) to slow progression of the disease For treatment and prognosis, important to make distinction between Alzheimer disease, pseudodementia and normal aging Alzheimer disease: insidious onset, severe memory loss,less cognitive problems, decrease in IQ, disruption of normal life Pseudodementia, a depression that mimics dementia: abrupt onset, moderate memory loss, cognitive problems, no decrease in IQ, previous psychiatric history (antidepressants or psychotherapy can help) Normal aging: minor forgetfullness, reduced ability to learn new things quickly, no decrease in IQ, no disruption of normal life (no intervention needed except practical and emotional support from physician)

her causes of Dementia next Organ Systems Neurology Pathology

22 questions

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Vascular dementia: second most common type of dementia, caused by cerebral atherosclerosis and vascular insult. less

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Three major mechanisms of vascular insult: multiple cortical infarcts, single and strategic infarct, and small vessel disease. Binswanger’s disease is a form of dementia caused by diffuse subcortical infarcts, usually resulting from chronic hypertension. Multi-infarct dementia: multiple, severe infarcts, causing a step-wise decline in cognitive function. Emphasis in treatment is on prevention of additional infarcts (anticoagulants like coumadin or aspirin). Infectious diseases: common in immunocompromised patients and the elderly. less Chronic infections: cryptococcus, neurosyphilis, and Lyme disease. HIV-associated neurocognitive disorder (HAND): improves with antiretroviral therapy. HIVassociated disorders, such as progressive multifocal leukoencephalopathy (PML), can also cause dementia. Prion diseases such a Creutzfeldt-Jakob: rapidly progressive dementia, culminating in death. Alcoholism: the etiology of dementia secondary to chronic alcoholism is multifactorial. However, of the possible etiologies, the most important is Wernicke dementia due to thiamine (vitamin B1) deficiency. less Wernicke dementia (sometimes called Wernicke encephalopathy or Wernicke-Korsakoff syndrome): Triad—“Eyes, lies capsize” 1. “Eyes”—ophthalmoplegia (e.g., nystagmus) 2. “Lies”—confusion with confabulation 3. “Capsize”—ataxia

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Severe atrophy of the brain—the most severe atrophy characteristically occurs in themammillary bodies. Tx for Wernicke syndrome: administer thiamine. Untreated, may result in rapid decline to death. Korsakoff psychosis, which is associated with alcoholism and Wernicke syndrome, is an irreversible chronic encephalopathy with antegrade and retrograde amnesia and confabulation. Nutritional deficiencies: thiamine (vitamin B1), niacin (vitamin B3), or cobalamin (vitamin B12). Improves with vitamin supplementation. Heavy metal toxicity: cognitive impairment, often with peripheral neuropathy. Often occurs in old homes or industrial jobs. Tx: Chelation therapy specific for heavy metal. Lead and copper (Wilson’s disease) are most common. less The only non-toxic heavy metal is gold. Traumatic brain injury can cause dementia. Dementia pugilistica is a form of delayed, head-trauma related dementia, seen mainly in boxers. less Can take decades for damage to become evident. Frontotemporal lobar degeneration (Pick disease): presents with alterations in personality, social behavior, and/or language → progressive deterioration of these faculties with eventual progression to global dementia. less Pronounced atrophy of the frontal and temporal lobes with sparing of the posterior 2/3rds of the superior temporal gyrus: 1. Frontal lobe degeneration → personality changes, abulia, and disinhibition. 2. Temporal lobe degeneration → impaired understanding of language. NFTs (neurofibrillary tangles): Alzheimer disease vs. Pick disease:

In both Alzheimer disease and Pick disease, NFTs begin as intracytoplasmic, basophilicinclusions which: 1. encircle or displace the nucleus of the host neuron 2. are composed predominantly of paired helical filaments containing aggregates ofabnormally hyperphosphorylated forms of tau protein. (Normally, tau is an axonal microtubule-associated protein that binds microtubules and facilitates their assembly; when damaged or distorted due to mutation or hyperphosphorylation, tau loses its ability to bind microtubules and instead tends to bind itself, forming aggregates). The NFTs in Alzheimer disease survive as "ghost"• or "tombstone"• tangles long after the demise of the host neuron∴ NFTs can be used as markers of disease severity. Indeed, in Alzheimer patients the number of NFTs correlates with the degree of dementia.

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The NFTs in Pick disease are called Pick bodies. Unlike the NFTs of Alzheimer disease, Pick bodies do not survive the death of their host neuron ∴ cannot serve as a marker indicating the presence or severity of Pick disease. DLB (dementia with Lewy bodies) — distinctive clinical features (in addition to dementia) include: 1. Fluctuating cognition 2. Visual hallucinations—recurrent and often quite detailed 3. Parkinsonism—“pill-rolling” tremor; rigidity (cogwheeling may be present); bradykinesia; stooped, unstable posture; festinating gait; mask-like facies (i.e., decreased range of facial expression) less DLB is associated with Alzheimer’s disease; DLB patients often have symptoms of both diseases. Lewy bodies—Parkinson disease vs. DLB:

In both Parkinson disease and DLB, Lewy bodies are intracytoplasmic, eosinophilic inclusions with a dense core (predominantly α-synuclein) surrounded by a pale halo. In Parkinson disease, Lewy bodies can only be found in a narrow range of locations including the substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, and the basal nucleus of Meynert. In other words, Lewy bodies do not typically occur in cerebral cortical locations in patients with Parkinson disease. On the other hand, Lewy bodies in patients with DLB can be found in a wide range of locations throughout the cerebral cortex in addition to the locations where they are characteristically found in Parkinson disease (e.g., substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, basal nucleus of Meynert)

Huntington disease next Organ Systems Neurology Pathology

9 questions

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Huntington disease: neurodegenerative trinucleotide expansion disorder that exhibitsanticipation — with each subsequent generation affected, age of onset ↓and disease severity ↑ less Huntington disease typically presents at age 30-40 → over the next 15-20 years, patients experience progressive clinical decline characterized by choreiform and athetoid movements, mental disturbances (e.g., depression, psychosis), and eventually dementia and death.

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Characteristics: “AC/DC” Autosomal dominant Choreiform (“dance-like”) movements Dementia, Depression, and other mental Disturbance (e.g., psychosis) Caudate atrophy is prominent on imaging and postmortem exam; atrophy of the putamen and frontal cortex also occurs but is less prominent than caudate atrophy. Additional clinical features: - Hypertonicity - Fecal/urine incontinence - Anorexia - Athetoid movements (hallmark of basal ganglia insult) = slow writhing hand movements Especially depletes cholinergic and GABA-ergic neurons: - ↑ Dopamine - ↓↓ GABA - ↓↓ ACh Atrophy of striatum (caudate nucleus and putamen) and frontal cortex. Because the caudate nucleus borders the lateral ventral ventricles, atrophy of the caudate nucleus can lead to hydrocephalus ex vacuo (i.e., the loss of brain matter bordering the ventricles makes the ventricles larger). Caused by a (CAG)n trinucleotide expansion in the Huntington gene located onchromosome 4 → “Hunt 4 an animal and put it in a CAGe” (Caudate loses ACh andGABA) less No other novel mutations are known to cause the disease 1/12,000 → 1/20,000 = incidence in high-prevalence areas Transcription of BDNF gene (neuronal pro-survival factor) is decreased

Treatment: - Reserpine + tetrabenazine: ↓excess dopamine → ↓dyskinesia - Haloperidol: dopamine receptor antagonist → ↓dyskinesia

Brain Tumors next Organ Systems Neurology Pathology

29 questions

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About one half to two-thirds of brain tumors are primary (from brain tissue) and the rest are metastatic. Glioblastoma Multiforme (grade 4 astrocytoma): Are GFAP positive Most common primary intracranial CNS neoplasm inless adults; very poor prognosis (highly aggressive, rapidly-growing) Located within white matter of cerebral hemispheres (often in the centrum semiovale)—can spread to the contralateral hemisphere via the corpus callosum, straddling the cerebral hemispheres to form the classic “butterfly glioma” Histopathology: 1. Marked anaplasia (nuclear atypia, pleomorphism) with florid vascular endothelial hyperplasia secondary to ↑ VEGF 2. Pseudopalisading necrosis—areas of necrosis and hemorrhage surrounded by rows of malignant cells CT with contrast or MRI with contrast: butterfly-shaped space-occupying lesion with central necrosis outlined by serpiginous, hetergenous contrast enhancement Meningioma: Most common benign intracranial neoplasm; 2nd most less common primary intracranial neoplasm in adults

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Meningiomas are benign slow-growing tumors that arise from meningothelial cells (most commonly the arachnoid mater) and are commonly located parasagitally (near the falx cerebri) or near the convexities of cerebral hemispheres. Although asymptomatic for years, meningiomas eventually become large enough to compress subjacent brain parenchyma → patients usually present with seizures Histology: whorled pattern of spindle cells with psammoma bodies (laminated calcifications) Medulloblastoma: less 75% are found in children (median age 9). Medulloblastoma accounts for 15-20% of all pediatric brain tumors

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Indeed, medulloblastomas are the most common malignant intracranial tumor in children. Most frequently arise in the posterior fossa (often in the cerebellum), where they may compress the 4th ventricle and impede CSF outflow via the midline foramen of Magendie and lateral foraminae of Luschka → hydrocephalus Histology: Hypercellular sheets of anaplastic cells. Medulloblastomas = PNET (primitive neuroectodermal tumor) ∴ highly malignant. However, despite being incredibly malignant, medulloblastomas are also radiosensitive. Neuroblastoma: less Occurs almost exclusively in children Primary CNS neuroblastomas are very rare and usually cerebral. Neuroblastomas are most often found in adrenal medulla but can be found anywhere along the sympathetic chain Most common extracranial solid cancer in infancy

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Associated with N-myc oncogene amplification. ↑ Amplification → poor prognosis. Systemic metastases, especially to bone, have been observed Retinoblastoma: Most common primary ocular malignancy of childhood less (generally found in children under age 6) Retina location, unilateral or bilateral Commonly discovered on fundoscopic exam, which reveals leukocoria: instead of seeing a red reflex, the examiner will see a white mass. Linked to homozygous deletion or inactivation of Rb gene (chromosome 13) Schwannoma: less Acoustic schwannoma: third most common primary intracranial neoplasm. Usually unilateral. Typically presents in middle-aged patients with progressive sensorineural hearing loss, tinnitus Occur on the vestibular division of CN VIII at the cerebellopontine angle Encapsulated tumor arising from Schwann cells Histology: Nuclei arranged in “palisades” Benign and resectable Bilateral acoustic neuromas (benign schwannomas usually occurring on the vestibular division of CN VIII) are diagnostic of neurofibromatosis type 2 Oligodendroglioma: less Typically affects middle-aged pts Cerebral location

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Histology: closely packed cells with large nuclei surrounded by clear halo of cytoplasm—“fried egg” appearance Slow growing and rare Astrocytoma (pilocytic): Are GFAP positive Affects young children.

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Low grade gliomas (including pilocytic astrocytomas) are the most common type of brain tumor in children. Posterior fossa location and circumscribed Histology: Rosenthal fibers—eosinophilic corkscrew fibers Benign, low grade, good prognosis Ependymomas are rare tumors of the ependymal cells, which line the ventricular system of the brain and the central canal of the spinal cord. less Ependymomas are more common in children than in adults. In children, ependymomas tend to occur in the fourth ventricle and cause hydrocephalus. In adults, ependymomas occur most often in the spinal cord and may cause syringomyelia. Craniopharyngiomas are rare tumors derived from Rathke’s pouch, the embryonic precursor of the anterior pituitary. less They are usually suprasellar in location and may compress the optic chiasm, causingbitemporal hemianopsia. These tumors occur most often in children, and on exams are often presented as a child with a visual field defect.

Seizures next Organ Systems Neurology Pathology

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Seizures may be partial (affects one area of the brain) or generalized (diffuse) However, partial seizures may progress to be generalized Epilepsy: used to describe condition of recurrent seizures Causes for epilepsy: genetic, infection, trauma, stroke, metabolic (hypo or hypernatremia) Simple partial seizures less Patient remains conscious Can manifest as motor, sensory, psychic, or autonomic changes Treatment: all anti-seizure drugs work effectively Complex partial seizures less Patient has impaired consciousness Treatment: all anti-seizure drugs work effectively Absence (Petit Mal) seizures less Usually in children, manifest as a blank stare Treatment: First line anti-seizures drug treatment is ethosuximide. Valproic acid is used as a second line agent Myoclonic seizures less Repetitive jerks of the body or extremities Treatment: First line agent is valproic acid. Tonic-Clonic (Grand Mal) seizures Patient is tonic (stiff) and then becomes clonic (jerking less movements) The 3 first line anti-epileptics for tonic-clonic seizures have a similar mechanism (↑ Na channel inactivation) and can be remembered by “PVC”: 1.

Phenytoin (also first line for prophylaxis of status epilepticus)

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Valproic acid (also used for myoclonic seizures) Carbamazepine (also first line for trigeminal neuralgia)

Status epilepticus Life threatening, persistent seizure activity in the brain less Treatment: First line anti-seizure drugs are benzodiazepines, such as diazepam. First line drug for prophylaxis is phenytoin to increase seizure threshold

Headaches next Organ Systems Neurology Pathology

12 questions

339

Migraines are POUNDing: Pounding (pulsatile), phonophobia, photophobia One-day duration Unilateral Nausea or vomiting Disabling due to excruciating pain (ie, so painful that it limits routine activities) Compare to: - Cluster headaches, which are also unilateral and disabling, but tend to be brief and are accompanied by autonomic Sx (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis) - Tension headaches, which are different from migraines in almost every respect: nonpulsating, bilateral, not disabling, not associated with nausea / vomiting less

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Migraines can be accompanied by "aura": constellation of neurological symptoms which can affect the auditory, visual or olfactory system. Treatment: - Migraines can be treated acutely with sumatriptan - β-blockers, TCAs or gabapentin are sometimes useful in migraine prophylaxis Tension headaches: less Most common type of recurring headache. Generally associated with either muscular or psychological stressors. Key clinical features: 1. Bilateral, non-pulsating headaches often described by patients as a “band-like” pressing / tightening / squeezing pain around the head. 2. Only mildly or moderately painful ∴ not disabling 3. Not associated with nausea or vomiting 4. Not aggravated by routine movement (eg, climbing stairs) Generally responds well to NSAIDs Cluster headaches: Unilateral, brief headaches characterized by periorbitalless / temporal pain as well asipsilateral autonomic symptoms in the face (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis) Occur in clusters — cluster headaches occur repeatedly within a “cluster” period of 3-6 weeks followed by month- or yearlong periods without cluster headaches. High flow O2 or sumatriptan can be used to arrest an acute episode. Key comparisons — Migraine vs. Tension vs. Cluster headaches: less

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Unilateral: - Migraine headaches - Cluster headaches Bilateral: - Tension headaches

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Excruciatingly painful ∴ disabling: - Migraine headaches - Cluster headaches Mildly / moderately painful ∴ not disabling: - Tension headaches Sinus headaches: less Worse when lying down Associated with nasal congestion, sinus tenderness, and maxillary tooth pain Headache due to intracranial mass: less Worse in morning on awakening May be aggravated by: 1. Exercise 2. Sexual activity 3. Changing position 4. Valsalva maneuvers (expiring forcefully against a closed glottis) such as coughing, sneezing, straining on the toilet Associated with abnormal neurologic exam Red-Flag signs of underlying pathology → require further work up less Sudden onset of severe persistent headache is suspicious of SAH (subarachnoid hemorrhage) from ruptured berry aneurysm. Headache associated with Valsalva maneuver, exercise or sexual activity may indicate increased ICP (i.e. from space occupying lesion).

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Headaches that awaken patients from sleep in the middle of the night. Fever accompanied by altered mental status suggests intracranial infection. Headache associated with neck stiffness or meningeal signs suggests meningitis or blood in the subarachnoid space. New onset headache in a patient < 5 years old or > 50 years old. New onset headache in a patient with a history of cancer.

Eye Pathology next Organ Systems Neurology Pathology

26 questions

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Cataracts describe painless, bilateral opacities of the lens of the eyes leading to a decrease in vision. They are the leading cause of blindness and have multiple etiologies. Advanced age is the most common cause of cataracts.less Lens proteins denature and degrade over time, clouding the lens. Cataracts can form as a result of osmotic damage from sugar alcohol deposition within the lens. Such disease processes include uncontrolled diabetes mellitus via sorbitoldeposits and classic galactosemia via galacticol deposits. Cataracts can be consequences of chromosomal abnormalities such as trisomy 21 (Down syndrome), trisomy 18 (Edward’s syndrome), trisomy 13 (Patau syndrome),5p deletion (Cri-du-chat syndrome), and Turner’s syndrome.

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Congenital infections such as rubella, cytomegalovirus (CMV), syphilis, and herpes simplex virus (HSV) can also induce cataract formation. Other risk factors include elements which may lead to increased oxidative stress or physical trauma, including cigarette smoking, steroid use, prolonged ultraviolet (UV) radiation exposure, trauma, and alcohol consumption. Glaucoma describes an increase in intraocular pressure (IOP) due to the disruption in the balance of aqueous humor production by the ciliary processes and drainage by the trabecular meshwork, leading to optic nerve damage. It is the second most common cause of blindness. Open (wide) angle glaucoma accounts for 90% of all less cases. It is characterized by an impaired outflow (e.g. Schlemm’s canal) of aqueous humor and an absence of symptoms, which may lead to a silent progression. Open angle glaucoma is most often idiopathic, but may also be due to mutations in the gene encoding the protein myocilin. Risk factors for open angle glaucoma include advanced age, African-American race,myopia, and diabetes mellitus. Treatments for open angle glaucoma include betablockers (Timolol), carbonic anhydrase inhibitors (acetazolamide), and prostaglandin analogues (latanoprost). Closed angle glaucoma is characterized by an occlusion of flow between the iris and lens, resulting in rapid increase in IOP. It may be chronic or acute. Risk factors for closed angle glaucoma include Asian or Inuit race, eye trauma, andintraocular infection. Acute closed angle glaucoma is an ophthalmologic emergency that leads to irreversible vision loss within hours if left untreated.

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Symptoms of closed angle glaucoma include a red and very painful eye, blurry vision or seeing “halos”, a rock-hard eye, a dilated and non-reactive pupil, and a severe frontal headache with nausea and vomiting. Treatments for closed angle glaucoma include immediate laser or surgical iridotomy, in which a hole is made in the iris to reestablish the flow of aqueous humor, thereby relieving intraocular pressure. Congenital glaucoma may be associated with a developmental defect in the structure of the anterior chamber, as sometimes is seen in syndromes such as SturgeWeber,neurofibromatosis type I (NF1), or Marfan’s. Age-related macular degeneration (ARMD) is characterized by a loss of central vision due to age-related degeneration of the macula. Nonexudative (“dry”) ARMD refers to an atrophy and less degeneration of central retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors. It is characterized by an accumulation of an extracellular material known as drusen. Exudative (“wet”) ARMD results in a sudden visual loss due to leakage of serous fluid into the retina as a result of abnormal vessel formation (neovascularization, hence “wet”) under retinal pigment epithelium. It is less common than dry ARMD. Risk factors for ARMD include: • advanced age • female gender • Caucasian race • smoking • hypertension. Familial ARMD is associated with mutations in complement factor H.

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Treatment options for wet ARMD include intraocular injections of anti-VEGF antibodies (ranibizumab and bevacizumab) in order to decrease the rate of neovascularization. Retinal detachment describes a separation of the neurosensory layer (part with rods and cones) of the retina from the pigment epithelium, leading to vision loss and blindness. Symptoms of retinal detachment include brief, painless less flashes of light in the periphery and dense shadows that start peripherally and moves centrally. Patients will claim a“curtain or veil is blocking my vision”. Risk factors for retinal detachment include: • myopia, as the retina in nearsighted people tends to be more thinly stretched and thus prone to detachment • proliferative retinopathy, as abnormal blood vessels in the vitreous can pull the retina away from the back wall of the eye • previous cataract surgeries • diabetes • trauma, as is sometimes seen in shaken baby syndrome.

Hydrocephalus next Organ Systems Neurology Pathology

9 questions

339

Hydrocephalus is the pathological condition resulting from an alteration of the normal flow of CSF, leading to compression of surrounding CNS tissue. less

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The expansion of the CSF compartment often leads to the radiographic finding of enlarged ventricles. There are 2 main classifications of hydrocephalus: communicating and non-communicating. Communicating hydrocephalus: Caused by decreased resorption of CSF by the arachnoid granulations. Unlike non-communicating, there is no blockage of CSF flow. Arachnoid granulations can be damaged by meningitis less or subarachnoid hemorrhage. The main type of communicating hydrocephalus is normal pressure hydrocephalus(NPH), the symptoms of which can be remembered with the mnemonic: “wacky, wobbly, wet.” less NPH is characterized by normal intracranial pressures. This is because the increase inCSF takes place over time, thus allowing the gradual increases in ICP to be offset by compression of the cerebral hemispheres. NPH presents with a clinical triad of dementia, gait disturbances and bladder incontinence, hence wacky, wobbly, wet. NPH should always be on the differential for a workup of dementia, because it’s one of the only treatable forms. Contrast NPH with an acutely occurring hydrocephalus caused from clogged arachnoid granulations after a subarachnoid hemorrhage. In the latter case, there is no shortterm cerebral compliance, thus life-threatening increases in ICP can rapidly occur. Non-communicating hydrocephalus takes place when there is a block at one of the narrow points in the CSF circulation. The etiology is chiefly mass effect caused by edema, less tumors, or congenital abnormalities (Dandy-Walker and Chiari malformations). Babies with hydrocephalus develop macroencephaly because the unfused fontanelles allow the head to expand. They

also develop the setting sun sign, where upward gaze palsy manifests as a predominant downward gaze. Another clinical entity, hydrocephalus ex vacuo is somewhat of a misnomer. Since it is caused from brain atrophy and resulting widening of ventricles, it is more of a descriptive term, and not true hydrocephalus.

Neurologic Pain Syndromes next Organ Systems Neurology Pathology

6 questions

339

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Trigeminal neuralgia (tic douloureux) causes brief but severe attacks of unilateral facial pain limited to the distribution of divisions of the trigeminal nerve. less Often triggered by simple stimuli (brushing teeth, shaving etc.). The cause is often unknown, but can be linked to an underlying disease process (MS, tumors, vascular disease). First-line treatment is with carbamazepine. Complex regional pain syndrome, CRPS presents with intense regional pain following trauma, the pain being excessive compared to the severity of trauma. Generally occurs in the extremities. CRPS type I, also called reflex sympathetic dystrophy, less has no definable nerve lesion, whereas CRPS type II does. Both types are often associated with edema, decreased mobility, and autonomic dysfunction → changes in skin temperature and color, sweating abnormalities. The pain is not limited to the area of the trauma, and frequently spreads to other areas.

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Patients with CRPS for over 2 months often require psychological assessment and treatment to help manage and cope with the symptoms. Post-stroke pain can occur because of a lesion at any level of the CNS, but most frequently occurs because of damage to the thalamus or brainstem. In thalamic syndrome (Dejerine-Roussy syndrome) less following thalamic insult, there is initially contralateral body sensory loss followed by a period of intense pain that may last for years.

Emotional distress, loud noises, and cutaneous stimuli can worsen the pain. Treatment for post-stroke pain is difficult, and may include antidepressants, analgesics, and anticonvulsants. Radicular pain is pain limited to the distribution of specific nerve roots, and is often named according to the roots and nerves affected (e.g. sciatica). Exacerbated by movements that stretch, compress, or less irritate the affected roots, or that increase intraspinal pressure. Peripheral neuropathy can cause many symptoms including pain.

Congenital Nervous System Disorders next Organ Systems Neurology Pathology

15 questions

339

Neural tube defects less

Associated with increased alpha fetoprotein in amniotic

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Associated with maternal folic acid deficiency Spina bifida – failure of posterior vertebral arches to close. Several forms which include: less 1) Meningocele – herniated membranes consisting of only meninges 2) Meningomyelocele – herniated meninges and spinal cord 3) Spinal bifida occulta – vertebral arches do not form in lumbar area but spinal cord is normal. No symptoms, may have a lumbar dimple, lipoma, or tuft of hair on exam. TORCHeS infections: less Toxoplasma Rubella CMV Herpes simplex, HIV

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Syphilis (Treponema pallidum) Associated symptoms include microcephaly, jaundice or hepatosplenomegaly. Arnold-Chiari malformation less Arnold-Chiari Type I: Low lying cerebellar tonsils herniate through the foramen magnum. Cervical syringomyelia (C8T1) may also be present. This can often be clinically silent. Arnold-Chiari Type II: Triad of - Small posterior fossa

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- Misshapen midline cerebellum - Downward extension of the cerebellar vermis through the foramen magnum. Results in obstruction of CSF (cerebrospinal fluid) outflow tract and causes hydrocephalus. May present with headaches, visual changes, seizures or confusion. Increased incidence of coexisting lumbosacral meningomyelocele. Fetal alcohol syndrome: most common cause of mental retardation (affecting 1 – 4.8 per 1000 children born in the US) — versus: - Down syndrome: most common genetic cause of mental retardation - Fragile X syndrome: most common inherited cause of mental retardation Mental retardation due to CNS (central nervous system)less damage: - prenatal alcohol exposure (especially during the first trimester) may disrupt crucial developmental pathways, including the retinoic acid and Hedgehog pathways Growth retardation → - small body size - microcephaly - midface hypoplasia Midface abnormalities: 1) short palpebral fissures 2) epicanthal folds 3) long philtrum 4) thin upper lip Heart defects: - VSD (ventricular septal defect) - ASD (atrial septal defect)

Trigeminal Neuralgia next Organ Systems Neurology Pathology

2 questions

339

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Trigeminal neuralgia (tic douloureux) causes brief but severe attacks of unilateral facial pain limited to the distribution of divisions of the trigeminal nerve. less Often triggered by simple stimuli (brushing teeth, shaving etc.). The cause is often unknown, but can be linked to an underlying disease process (MS, tumors, vascular disease). Not associated with any motor or sensory paralysis Dx: usually clinical. Can do an MRI to rule out cerebellopontoine angle tumor less pts with cerebellopontoine angle tumor often have loss of ipsilateral corneal reflex 2/2 mass effect from the tumor unlike patients with trigeminal neuralgia were no motor or sensory deficits are seen Treatment: • First line: Carbamazepine • Second line: Baclofen or Phenytoin. Can be used in conjunction with Carbamazepine • Surgical decompression if medical therapy fails

Epidural abscess next Organ Systems Neurology Pathology

5 questions

339

Life threatening infection that spreads in the epidural space and can compress the brain or the spinal cord leading to grave permanent complications. Risk Factors: IV drug abuse, HIV infection, bacteremia, surgical procedures, epidural catheters (for pain control) Most common culprit: S Aureus Presentation: classic triad of: • Spinal pain • Fever (sometimes) • Neural deficits

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DX: MRI > CT scan less Lumbar puncture should be done after imaging and lesion localization, since passing a needle through the abscess could seed the subarachnoid space. Treatment: Aspiration, drainage and antibiotics • Early surgical intervention, within 24 hrs, is crucial especially if the abscess has already produced neural deficits 2/2 mass effect • Antibiotics: Vancomycin + Metrondiazole (If pseudomonas is a concern, add Ceftazidime) • Drainage: can be achieved through burr holes or craniotomy

Brain abscess next Organ Systems Neurology Pathology

4 questions

339

Usually results from • Trauma to the cranial space e.g. neurosurgery • ENT infection spread • Dental infection Etiology: • Strep – Sinusitis • S. Aureus – trauma • Anaerobes – chronic otitis media •

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less Most brain abscesses are bacterial, however, in immunocompromised patients consider toxoplasmosis and fungal (Candida, Aspergillus) infections Pt usually presents with neural focal deficits secondary to mass effect. Can be accompanied by headache, seizure activity, vomiting, nuchal rigidity. less Fever and chills are NOT always present Dx: CT scan or MRI. Aspiration or surgical excision is both therapeutic and diagnostic. Tretament: • IV Antibiotic: Pen G + Chloramphenicol or Metrondizaole • If MSSA is suspected → Nafcillin • MRSA → Vancomycin • Surgical drainage: diagnostic and therapeutic • Glucocorticoids: if mass effect is present

Amyotrophic lateral sclerosis next Organ Systems Neurology Pathology

6 questions

339

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Etiology Degeneration of upper AND lower motor neurons Sensory neurons are not damaged Atrophy of lateral corticospinal tracts Atrophy of anterior motor neurons of spinal cord. Results in denervation atrophy of muscles Two forms of ALS:

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- Sporadic ALS (most common)

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- Familial ALS (5-10% of cases): occurs more than once in a family. Hereditary defects in superoxide dismutase 1 (autosomal dominant) are associated with 20% of familialALS cases. Clinical manifestations less Symmetric atrophy, fasciculation of muscles (lower motor neuron signs) Symmetric hyperreflexia, spasticity and pathological reflexes (upper motor neuron signs) Results in rapid course, ending in respiratory failure. Treatment: - Mostly supportive care (pain control, intubation by tracheostomy) - Riluzole (blocks glutamatergic neurotransmission by inhibiting glutamate release and inactivating voltage-gated Na channels) is an FDA-approved medication that extends survival and/or time to tracheostomy, but only by a couple months.

Herniation Syndromes next Organ Systems Neurology Pathology

9 questions

339

Herniation syndromes occur when the brain expands and displaces the contents of the intracranial cavity. Coma and death can result from compression of the brain stem by a herniation. The brain and spinal cord are protected by the rigid compartments comprised of the skull, vertebra, and dura mater.

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Brain swells → vein compression and CSF displacement → increased intracranial pressure → decreased perfusion of brain → increasing swelling Subfalcine (cingulated) herniation Herniation occurs when a cerebral hemisphere displacesless the cingulated gyrus under the falx cerebri. Herniation may compress branches of the anterior cerebral artery. This may result in paralysis, weakness, and sensory loss of the contralateral foot and leg. Transtentorial (uncinate, medial temporal) herniation less Herniation occurs when the medial aspect of the temporal lobe compresses the free margin of the tentorium. Herniation may cause the following: 1) Compress CN III → pupillary dilation and impairment of ocular movements on the side of the lesion 2) Compress Posterior cerebral artery → hypoperfusion of the primary visual cortex 3) Compression of crus cerebri (cerebral peduncle) → contralateral (to the crus cerebri) hemiparesis but ipsilateral to the lesion 4) Hemorrhagic lesions in the midbrain and pons

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Note that pontine hemorrhages are also known as duret hemorrhages. Tonsilar herniation less Herniation occurs when the cerebellar tonsils are displaced through the foramen magnum. Herniation is life-threatening because the brainstem compression affects respiratory and cardiac centers in the medulla oblongata. Tonsillar herniation can occur if an LP is performed on a patient with unrecognized hydrocephalus or a mass lesion leading to increased ICP.

LP should never be performed on a patient with ↑ ICP

Head injuries next Organ Systems Neurology Pathology

8 questions

339

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Can result from penetrating wounds or nonpenetrating injuries (contusions) In epidural hematomas, CT scan shows a highly attenuating convex ("lenticular") shaped mass overlying the brain. Epidural hematomas are also less likely to cross suture lines than subdural hematomas. less Associated with skull fracture Arterial hemorrhage from laceration of middle meningeal artery (branch of the maxillary artery) near the temporal bone Characterized by lucid interval (brief period of improvement) followed by rapid signs of cerebral compression

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Does not bleed into brain substance so amenable to emergent surgical evacuation to decrease intracranial pressure Subdural hematoma: less Associated with venous bleeding from torn bridging veins More common in victims of abuse (e.g., shaken baby syndrome, elderly abuse) and in patients with atrophic brains prone to falls (e.g., alcoholics, elderly) Characterized by gradual signs of cerebral compression that may manifest in hours to days. In this scenario, an elderly person can have progressive confusion which goes unnoticed until a coma occurs. CT scan shows a crescent shaped (concave) hematoma which is less dense than an epidural hematoma due to dilution of the blood by CSF. Subdural hematomas are also more likely to cross suture lines than epidural hematomas.

Parkinson disease next Organ Systems Neurology Pathology

15 questions

339

Parkinson disease: idiopathic degenerative CNS disorder associated with: 1. Abnormal eosinophilic intracellular inclusions of αsynuclein known as Lewy bodies 2. Loss of dopaminergic neurons in the SNc (substantia nigra pars compacta) → - ↓ dopamine - ↑ ACh less

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Mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBAgene on chromosome 1—GBA is the same gene which is deficient in patients withGaucher disease!) → ↑ risk of developing Parkinson disease Parkinson disease can sometimes be confused with progressive supranuclear palsy. Progressive supranuclear palsy usually presents as an isolated vertical gaze palsy, followed by paresis of other ocular movements, and signs and symptoms ofParkinsonism (ie, tremor, bradykinesia, rigidity, and postural instability). Normally, dopamine is released from the nigrostriatal neurons (i.e., neurons originating in the SNc → terminating in the striatum) to activate the direct pathway (D1 receptors) and inhibit the indirect pathway (D2 receptors). less DIRECT (excitatory) pathway: Dopaminergic neurons in the SNc send excitatory output to striatal neurons with D1receptors (i.e., DA binds D1 receptors → activation) → these striatal neurons send inhibitory (GABA) output to GPi/SNr → neurons in the GPi/SNr send inhibitory (GABA) output to VL nucleus of thalamus → neurons in VL nucleus of thalamus send excitatory (Glutamate) output to the motor cortex. Normally: Dopamine stimulates striatal neurons with D1 receptors → ↑ inhibition of GPi/SNr → disinhibition of thalamus → stimulation of motor cortex → ↑ in movement. Parkinson disease: Decreased striatal dopamine stimulation → ↓inhibition of GPi/SNr → ↑ inhibition of thalamus → ↓stimulation of motor cortex → ↓ in movement

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INDIRECT (inhibitory) pathway: Dopaminergic neurons in the SNc send inhibitory output to striatal neurons with D2receptors (i.e., DA binds D2 receptors → inhibition) → these striatal neurons send inhibitory (GABA) output to GPe (globus pallidus externa) → neurons in the GPe send inhibitory (GABA) output to STN (subthalamic nucleus) → neurons in the STN send excitatory (Glutamate) output to GPi/SNr → neurons in the GPi/SNr send inhibitory (GABA) output to VL nucleus of thalamus → neurons in VL nucleus of thalamus send excitatory (Glutamate) output to the motor cortex. Normally: Dopamine inhibits striatal neurons with D2 receptors → disinhibition of GPe → ↑inhibition of STN → ↓ stimulation of GPi/SNr → ↓ inhibition of thalamus → stimulation of motor cortex → ↑ in movement.

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Parkinson disease: Decreased dopamine inhibition → ↑inhibition of GPe → disinhibition of STN → stimulation of GPi/SNr → ↑ inhibition of thalamus → → ↓ stimulation of motor cortex → ↓ in movement Classic presentation: use the mnemonic “TRAPpED” - Tremor at rest (“pill-rolling”• tremor)→ illegible handwriting - cogwheel Rigidity - Akinesia - Postural instability (stooped “simian” posture) with shuffling (“festinating”) gait - Expressionless (mask-like) face - ↑ risk of Dementia (TRAPpED in your own body) Other Parkinson-like diseases: Postencephalitic parkinsonism: viral etiology → influenzaless pandemic

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Trauma: especially in professional fighters with brain injury secondary to repetitive brain trauma sustained over years—e.g., Muhammad Ali, arguably the greatest professional boxer of all time, developed Parkinson disease after years of taking punches to the head. Drugs and toxins, especially dopamine antagonists like MPTP (1-methyl-4-phenyl-1,2,3,6tetrahydropyridine, a contaminant in the illegal street drug MPPP) Treatment: use the mnemonic “BALSA”: less Bromocriptine: dopamine receptor agonist (ergot alkaloid) Note: Newer non-ergot dopamine receptor agonists such as pramipexole and ropinirole are now preferred for the treatment of Parkinson disease over bromocriptine, which is associated with a less favorable side effect profile. Amantadine: ↑dopamine secretion, NMDA receptor inhibition L-DOPA/carbidopa: converted to dopamine in CNS → LDOPA can cross blood-brain barrier; carbidopa is a peripheral decarboxylase inhibitor that increases the bioavailability of LDOPA to the brain Selegiline + COMT inhibitor (e.g. entacapone or tolcapone) : ↓dopamine breakdown Antimuscarinics like Benztropine can also be used to treat Parkinson disease → ↓ tremor and rigidity (mnemonic: Park your Mercedes-Benz)

Tension Headache next Organ Systems Neurology Pathology

2 questions

339

Most common type of recurring headache. Generally associated with either muscular or psychological stressors. Key clinical features: 1. Bilateral, non-pulsating headaches often described by patients as a “band-like” pressing / tightening / squeezing pain around the head. 2. Only mildly or moderately painful ∴ not disabling 3. Not associated with nausea or vomiting 4. Not aggravated by routine movement (eg, climbing stairs)

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Generally responds well to NSAIDs Key comparisons — Migraine vs. Tension vs. Cluster headaches: Excruciatingly painful ∴ disabling: • Migraine headaches • Cluster headaches

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Cluster headache next Organ Systems Neurology Pathology

4 questions

339

Key comparisons — Migraine vs. Tension vs. Cluster headaches: less

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Excruciatingly painful ∴ disabling: Migraine headaches Cluster headaches

Mildly / moderately painful ∴ not disabling: • Tension headaches Unilateral, brief headaches characterized by periorbital / temporal pain as well asipsilateral autonomic symptoms in the face (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis) Occur in clusters — cluster headaches occur repeatedly within a “cluster” period of 3-6 weeks followed by month- or year-long periods without cluster headaches. High flow O2 or sumatriptan can be used to arrest an acute episode. Prophylaxis: Most responsive of all headaches to ppx. • First line: Verapamil daily • Second line: Ergotamine, Li, prednisone

Vertigo next Organ Systems Neurology Pathology

8 questions

339

Vertigo describes an illusion of rotary movement caused by an acute asymmetry of neural impulses between left and right vestibular systems. Peripheral vertigo encompasses all etiologies of vertigo which involve the inner ear. It commonly presents with: • tinnitus • hearing loss • prominent nausea and vomiting •

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Positional testing in peripheral vertigo reveals delayedless horizontal nystagmus, which is inhibited by fixation of eyes onto object, and does not change direction with gaze to either side. The most common causes of peripheral vertigo are • benign paroxysmal positional vertigo • acute vestibular neuritis • Ménière’s disease Benign paroxysmal positional vertigo (BPPV) refers brief periods of vertigo which occur with change in position. It is due to freely moving crystals of calcium carbonate within the semicircular canals. Ménière’s disease describes an intermittent increase in endolymphatic volume of the inner ear. This results in episodic vertigo with nausea, vomiting, progressive hearing loss, and a sensation of fullness in the ear. Central vertigo results from cerebellar or brainstem lesions and is usually associated with cranial nerve signs (e.g. diplopia, dysarthria, dysphagia), weakness, ataxia, and other changes that may indicate a central process. Patients tend to suffer from a severe inability to stand still or walk. Positional testing in central vertigo reveals immediateless vertical, horizontal, or torsional (rotary) nystagmus, which is

not inhibited by fixation of eyes onto object, and can change direction with gaze towards the fast phase of the nystagmus.

Guillain-Barre syndrome next Organ Systems Neurology Pathology

6 questions

339

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Acute inflammatory demyelinating disease which primarily involves peripheral nerves, resulting in endoneurial inflammatory infiltrates Highest incidence in young adults Autoimmune etiology Associated with infections. Commonly present with muscle weakness preceded byCampylobacter jejuni infection. less In addition to C. jejuni, infections with an association with GBS include H. influenzae, herpes viruses (CMV, EBV, VZV), and M. pneumoniae. Clinical manifestation less Ascending muscle weakness and paralysis Begins in the lower part of extremities and ascends upwards Autonomic dysfunction, hypertension, orthostatic hypotension, EKG changes Most patients survive but severe cases can have respiratory failure with death Hallmark less Albumino-cytologic dissociation of CSF Increased CSF protein concentration with only modest increase in cell count. Treatment less

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Headache 2/2 Sinusitis next Organ Systems Neurology Pathology

3 questions

339

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Pt usually presents with purulent nasal discharge, stuffiness, facial pain over the sinuses that is worsened by bending down or applying pressure over the affected sinus. Maxillary sinuses are most commonly affected → can sometimes mimic the pain of dental caries. in cases of chronic sinusitis, pain and headache are mildless or absent Edema of the mucosal lining of the paranasal sinuses 2/2 inflammation leading to obstruction of the sinus opening and accumulation of sinus secretions Causes: URI, allergies (less common: polyps, foreign body, deviated septum) less Strep pneumo, H flu and common culprits in acute sinuisitis Diagnosis: Clinical diagnosis in most cases. In complicated cases, can consider CT scan of sinuses if surgery is considered Treatment: • Acute sinusitis: decongestants and saline nasal spray • Can use anti-histamines and nasal steroids if suspecting allergic sinusitis • Chronic sinusitis: abx: broad spectrum penicillinase-resistant antibiotic. May also need endoscopic drainage.

Phakomatoses (Neurocutaneous Syndromes) next Organ Systems Neurology Pathology

19 questions

339

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Phakomatosis incidence: NF (neurofibromatosis) > TS (tuberous sclerosis) > SWS (Sturge-Weber syndrome) less Inheritance: - NF: autosomal dominant with variable expression - TS: autosomal dominant - SWS: sometimes due to somatic mosaicism, other times due to sporadic mutation NF type 1: associated with mutation of a tumor suppressor gene called neurofibromin(which inhibits the p21 ras oncoprotein) on chromosome 17 ∴ overactivity of ras may cause some of the manifestations of NF type 1 NF type 2: associated with mutation in a tumor suppressor gene called merlin (a critical regulator of contact-dependent inhibition of proliferation) on chromosome 22 TS: associated with mutations of two genes: - TSC1 gene (chromosome 9) — codes for a protein called hamartin, which regulates the cell-cycle, neuronal synapse formation and axon development - TSC2 gene (chromosome 16) — codes for a protein called tuberin, which has GTPase-activating activity and regulates protein translation, growth and cell proliferation - hamartin and tuberin form heterodimers

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- Rapamycin has been shown to cause regression of giant cell astrocytomas and reduce seizure frequency. NF (neurofibromatosis) type 1: diagnosis is made if a patient has ≥2 of the “cannot fail to be first” criteria — “CA NN OT FAI L 2 B 1st”: less CA — ≥6 CAfé au lait (coffee-colored) macules (≥5mm in kids; ≥15mm in adults) NN — ≥2 Neurofibromas (flesh-colored skin nodules secondary to Schwann cell proliferation) or ≥1 plexiform neurofibroma OT — OpTic gliomas FAI — Freckling: Axillary or Inguinal L 2 — ≥2 Lisch nodules (pigmented iris hamartomas) B — Bone abnormality, for example: - kyphoscoliosis - tibial dysplasia → bowing of tibia - sphenoid dysplasia 1st — ≥1 1st degree relative with neurofibromatosis type 1 Malignancies associated with NF type 1 include: less pheochromocytoma Wilm’s tumor juvenile CML (chronic myelogenous leukemia) Note: pheochromocytoma and Wilm’s tumor are both associated with hypertension NF (neurofibromatosis) type 2: diagnosis is made if a patient has bilateral acoustic neuromas (benign schwannomas of vestibular division of CN8), which may present as sensorineural hearing loss, tinnitus, and vestibular disorientation. less Besides bilateral acoustic neuromas, other findings associated with neurofibromatosis type 2 include: - juvenile cataracts in ~80% of patients - schwannomas — e.g., unilateral acoustic neuromas, spinal schwannomas

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- meningiomas - gliomas Like NF type 1, patients with NF type 2 may have: - café au lait (coffee-colored) macules - cutaneous neurofibromas TS (tuberous sclerosis): use the mnemonic “AASS RRRASH”: less Ash Leaf Spots: Hypopigmented spots often found on the skin of TS patients Angiofibromas (adenoma sebaceum) of the face: reddish brown papules on the nose and cheeks in a butterfly distribution Shagreen patches: rough papules with orange-peel consistency usually on the trunk - best identified with a Wood’s lamp (UV-A light) Seizures (infantile spasms) Retardation (mental) Retinal lesions: - mulberry tumors - phakomas: round flat gray lesions located peripherally in the retina Rhabdomyomas in the heart → may cause CHF (congestive heart failure) - a cardiac rhabdomyoma in a young child is highly suspicious (nearly 100% specific) for tuberous sclerosis Angiomyolipomas of the kidney: hamartomatous lesions which can present with abdominal or flank pain and hematuria. Subependymal astrocyte proliferation in the brain: hamartomatous lesions that look like “candlestick dripping” in cerebral ventricles - multinucleated atypical astrocytes may also form tubers (small white nodules) in cerebral cortex and periventricular locations Hamartomas

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Sturge-Weber Syndrome (encephalotrigeminal angiomatosis): rare congenital syndrome characterized by: 1) Neurologic deterioration 2) Facial port-wine stain nevus flammeus “birthmark” in the trigeminal nerve distribution 3) Leptomeningeal hemangiomas 4) Buphthalmos (markedly enlarged eye) Children develop progressive neurologic deterioration:less - Seizures - Mental retardation - Hemiparesis - Hemisensory deficit Port-wine stain nevus flammeus “birthmark”: - Macular vascular lesion (congenital unilateral capillary or cavernous hemangioma) on the face in the dermatomal distribution of cranial nerve V — usually the V1 or V2dermatomal distribution - Does not blanch with pressure Some patients have an ipsilateral arteriovenous malformation of pia mater vessels (ipsilateral leptomeningeal angioma) overlying occipital and parietal lobes Skull X-ray of patients after 2 years of age: - Gyriform “tramline” intracranial calcifications Children often suffer from visual disturbances (eg, hemianopia) and often present withbuphthalmos (markedly enlarged eye): - Congenital glaucoma → retained aqueous humor → buphthalmos

Cerebrovascular Infarction next Organ Systems Neurology Pathology

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Cerebrovascular infarctions: vascular occlusion secondary to thrombosis or embolism. Can be long lasting and disabling, or transient. less Two types of stroke: ischemic and hemorrhagic. Two regions of an infarct: Core: receives blood only from the occluded artery. Most at risk for lasting damage. Penumbra: borders the core, perfused by other arteries,greater chance of surviving the infarction due to collateral blood flow. Watershed infarcts: occlusion of multiple arteries or decrease in cerebral perfusion results in "watershed infarcts" → areas at greatest risk of permanent injury are those at the border between major cerebral arteries Infarcted brain tissue is cleared by microglia, which are resident macrophages of theCNS and ultimately leads to liquefactive necrosis. CT is used to differentiate ischemic from hemorrhagic. First step in diagnosis of suspected stroke. less Non-contrast CT is best for identifying hemorrhagic strokes. Ischemic strokes are not usually visible on CT scans. MRI is required to diagnose ischemic strokes. Ischemic strokes: inadequate blood supply to a region of the brain, due to thrombosis or embolism. The vast majority of thromboses causing an ischemic less stroke are due toatherosclerosis.

The most common sites are: - Carotid bifurcation - Origin of MCA - Proximal or distal end of basilar artery

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Ischemic strokes can be caused by embolisms or thromboses. Most strokes are ischemic, rather than hemorrhagic. Tx: anticoagulants. In the emergency room setting, recombinant tissue plasminogen activator (rtPA or tPA) is the treatment of choice. Administration should be within 3 to 4.5 hours of onset of symptoms. Aspirin and/or clopidogrel can be used for secondary prevention of additional cerebrovascular events; however, antiplatelet therapy should not be initiated in the first 24 hours after delivery of tPA. Transient Ischemic Attacks (TIAs): occlusion of blood flow for only a short period of time. Usually caused by fragments of atherosclerotic plaques that embolize (often from carotids).

By definition, the deficits of TIAs last less than 24 hours, but TIAs can precede strokes causing permanent deficits. The most important determinant of severity of a stroke is the presence of collateral flow. Infarction of deep structures such as the thalamus and less basal ganglia are often more devastating because of the lack of collateral flow to these regions of the brain. Hemorrhagic strokes (intracerebral hemorrhages): rupture of cerebral blood vessel. less Hemorrhagic strokes are typically caused by embolisms rather than thromboses. Recall that embolism → ischemic stroke → converts to hemorrhagic stroke Most common causes: hypertension, amyloid angiopathy, and vascular malformations.

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Ischemic strokes can also transform into hemorrhagic strokes, due to disruption of the blood brain barrier and leakage of red blood cells into ischemic tissue, or leakage of capillaries during reperfusion of infarcted tissue. Mass effects are the most common cause of death following strokes. Cell death causes mass effects and edema, resulting less in herniation of brain tissue (since the skull cannot expand). Cardiogenic embolisms often result in strokes. Atrial fibrillation, myocardial infarction, and valvular disease predispose to cardiogenic embolisms by permitting blood stasis and increasing the risk of coagulation. Occlusions of one of the three major cerebral arteries produce a specific pattern of symptoms. less Anterior cerebral artery (ACA) infarcts: upper motor-neuron weakness and cortical-type sensory loss in the contralateral leg, gait apraxia, and urinary incontinence Posterior cerebral artery (PCA) infarcts: contralateral homonymous hemianopia.PCA infarcts can also affect the thalamus or posterior limbs of the internal capsule, resulting in contralateral hemiparesis or sensory loss. Middle cerebral artery (MCA) infarcts: aphasia (Broca’s or motor aphasia),hemineglect, hemianopia, and contralateral face-arm sensorimotor loss. There is sometimes gaze preference toward the same side as the lesion. MCA infarcts are common. Lacunar infarcts are often the result of small vessel disease caused by chronic hypertension. less Pure sensory strokes (thalamic lacune): infarcts of ventral posterior lateral nucleus of the thalamus result in sensory loss to the contralateral body and infarcts of ventral posterior medial nucleus result in sensory loss of the contralateral face.

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Pure motor strokes (hemiparesis with dysarthria and ataxic hemiparesis): infarcts of the posterior limb of the internal capsule and ventral pons. Lateral striate branches: supply internal capsule, caudate, putamen, globus pallidus. Infarct of the posterior limb of the internal capsule causes pure motor hemiparesis. Sensorimotor strokes (having both symptoms of pure sensory strokes and pure motor hemiparesis): infarcts of the internal capsule + regions of the thalamus. Strokes of the vertebrobasilar system: strokes in this region spare higher functioning, unlike cerebral artery strokes, but affect structures like the cerebellum and brainstem, resulting inipsilateral cranial nerve deficits and contralateral motor defects (lesion of lateral corticospinal tract). Locked-in syndrome: infarcts of the pons. It severs less corticobulbar, corticospinal, and corticopontine tracts, resulting in complete paralysis except for vertical eye movements, the nerves for which exit the brainstem above the level of the lesion. Lateral medullary syndrome (Wallenberg’s syndrome): infarcts of the vertebral artery or PICA, and causes ipsilateral ataxia, facial pain sense loss, temperature sense loss, Horner’s syndrome, and decreased taste, with contralateral decreased pain and temperature sense in the body, and hoarseness, dysphagia, vertigo, nystagmus, and nausea. Key diagnostic feature: involvement of autonomic nervous system (Horner’s syndrome and nausea) and cranial nerves (vertigo, nystagmus, dysphagia, hoarseness). Medial medullary syndrome: infarcts of the paramedian branches of vertebral and anterior spinal arteries. It results in contralateral arm or leg weakness, contralateral decreased position and vibration sense, and ipsilateral tongue weakness. Key diagnostic feature: involvement of hypoglossal

nucleus (tongue weakness) without other cranial nerve deficits.

Migraine Headache next Organ Systems Neurology Pathology

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339

Migraines are POUNDing: • Pounding (pulsatile), phonophobia, photophobia • One-day duration • Unilateral • Nausea or vomiting • Disabling due to excruciating pain (ie, so painful that it limits routine activities) Compare to: • Cluster headaches, which are also unilateral and disabling, but tend to be brief and are accompanied by autonomic Sx (eg, lacrimation, rhinorrhea, sweating, miosis, ptosis) • Tension headaches, which are different from migraines in almost every respect: nonpulsating, bilateral, not disabling, not associated with nausea/vomiting

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Migraines can be accompanied by “aura”: constellation of neurological symptoms which can affect the auditory, visual or olfactory system. Key comparisons — Migraine vs. Tension vs. Cluster headaches: less Excruciatingly painful ∴ disabling: • Migraine headaches

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Cluster headaches

Mildly / moderately painful ∴ not disabling: • Tension headaches Unilateral: • Migraine headaches • Cluster headaches Bilateral: •

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Tension headaches

Rebound analgesic headache: occur more frequently than migraines. Commonly misdiagnosed as chronic migraines. Do not respond to common treatments. Have to wean patient off analgesics > do not treat with narcotics! Treatment is abortive or prophylactic. Triptans such as sumatriptan are the first line agent forless migraine abortive therapy. They work by agonizing 5-HT serotonin receptors. Should only be taken 1-2x/week.

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Triptans are contraindicated in coronary artery disease, uncontrolled hypertension, prinzmetal angina, and hemiplegic migraines. Ergotamine derivatives such as dihydroergotamine also stimulate 5-HT receptors. Contraindications include pregnancy, coronary artery disease, transient ischemic attacks, peripheral vascular disease, and sepsis.

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Migraine prophylaxis is normally used in patients that have multiple migraines in a month. less β-blockers Tricyclic antidepressants Anticonvulsants Dihydroergotamine (DHE): 5HT agonist. Contraindications: CAD, pregnancy, TIA, PVD, sepsis less If patient is not responding to medications, consider alternative diagnoses.

Multiple Sclerosis next Organ Systems Neurology Pathology

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339

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Multiple Sclerosis (MS): chronic neurologic condition of white matter lesions separated by time (acute and past symptoms) and space (different parts of the CNS affected), marked by unpredictable relapses with long asymptomatic remissions less Optic neuritis (usually first sign, blurry vision or sudden painful loss of vision) Sensory dysfunction (paresthesias, loss of pain and temperature sensation, loss of vibratory sensation), upper motor neuron dysfunction, autonomic dysfunction (urge incontinence due to hyperactive detrusor muscle), cerebellar ataxia, flexion of the neck produces electrical sensation down spine Classic Charcot “triad” is a SIIIN: Scanning speech (sound drunk), Intention tremor, Incontinence,

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Internuclear ophthalmoplegia (bilateral demyelination of MLF), Nystagmus CSF: electrophoresis shows ↑proteins (IgG) often manifest as multiple oligoclonal bands, ↑leukocyte count, ↑protein, ↑ myelin basic protein, normal glucose Symptoms may worsen with heat (e.g., bath, warm weather) because heat slows rate of conduction of electrical activity through demyelinated nerves even more MRI is the gold standard for diagnosis because of ↑ sensitivity in detecting demyelinating plaques, shows periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with preservation of axons Begins most commonly in young adulthood, affecting women twice as often as men with peak incidence between 20 and 30 years of age Association with HLA haplotypes A3, B7, DR2, and DW2less More common in northern latitudes and those who move from a low-risk to a high-risk geographic region or vice versa before the age of 15, adopt the risk associated with their new home, while those who migrate after 15 retain risk of childhood home Pregnancy is associated with ↓relapse frequency, especially during the 3rd trimester. Autoimmune demyelination of oligodendrocytes in the CNS, histologically characterized by sharply defined area of myelin loss with relative preservation of axons less Peripheral nerves NOT affected, only CNS (Remember: the optic nerve is an extension of the CNS, not a true peripheral nerve) Environmental triggers → activate helper T cells whose receptors recognize CNS myelin basic protein and other antigens → multiple foci of demyelination plaques in the cortex, spinal cord, optic nerve, and paraventricular areas

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Treatment for MS falls into three categories: acute therapies for relapses (e.g. corticosteroids), chronic therapies that treat the underlying disease process (e.g. β Interferon), and symptomatic therapies (e.g. baclofen, an anti-spasmodic) β-Interferon: glycoprotein with anti-inflammatory propertyless that increases integrity of blood-brain-barrier, important to check a CBC and liver function test routinely because may cause leukopenia and reversible transaminitis Natalizumab: monoclonal antibody that binds α4-subunit of integrins on WBCs → disrupts interaction with VCAM-1 (vascular cell adhesion molecule-1) and MAdCAM-1 (mucosal addressin cell adhesion molecule-1) → prevents WBCs from exiting blood vessels to enter subjacent inflamed tissues Note that Natalizumab was removed from the market in 2005 after it was discovered to cause Progressive Multifocal Leukoencephalopathy (PML). It was then re-approved in 2006 because of its efficacy in treating MS.

Nonviral CNS Infections next Organ Systems Neurology Pathology

10 questions 339

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There are no lymphatics in the CNS The most common infection entry is through hematogenous spread Pyogenic meningitis can present with fever, headache, photophobia and nuchal rigidity CSF profile: numerous neutrophils, ↓glucose, ↑protein less Etiology is clued by patients age: neonates and infants – group B streptococcus, E. coli, Listeria

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Older infants – young adults : Streptococcus pneumoniae and Neisseria meningitidis Older adults – elderly: Streptococcus pneumoniae and gram negative rods Neisseria meningitidis can result in Waterhouse Friderichsen syndrome Cerebral abscess can result from: Direct extension from paranasal sinuses or middle ear less (most common) infection Infective endocarditis Bronchopulmonary infections Other nonviral CNS infections less 1) Tuberculosis with associated meningitis, hydrocephalus, vasculitis or infarction (>50% of patients). CT scan shows dilatation of ventricles with marked enhancement of basal cistern and meninges. 2) Fungal – Cryptococcus, Aspergillus, Histoplasma, and Coccidioides 3) Toxoplasmosis – Toxoplasma gondii parasitic infection is more common in HIV or immunocompromised patients. A. In neonates, transmitted transplacentally from mother. Results in periventricular calcifications and hydrocephalus B. In adults, ingestion of food contaminated by cat feces •

4) Prion disease (e.g. Creutzfeldt"“Jakob disease)

A. Infectious protein particles devoid of DNA or RNA B. Characterized by spongiform encephalopathy, which describes small cysts in CNS gray matter with striking absence of inflammatory response C. Long incubation period, but progresses rapidly once symptoms appear. Symptoms include subtle changes in memory and

behavior followed by dementia, confusion, and ataxia. D. Risk factors include ingestion of brain matter, corneal transplantation, and infection with mad cow disease

Opioid analgesics next Organ Systems Neurology Pharmacology

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Opioids interact with three major membrane receptor families throughout both the central and peripheral nervous system as well as in the gastrointestinal system. The opioid receptor families are designated mu (μ ), kappa (k), and delta (δ ) . The analgesic effects of opioids occur primarily through less μ receptors. Strong opioid agonists tend to have a high affinity for mu receptors. Morphine is the prototypical strong agonist. Morphine acts on μ receptors in the CNS and results inless a hyperpolarization of synaptic potentials and thus inhibits nerve fibers. It also acts at k receptors in the dorsal horn of the spinal chord to decrease the release of Substance P which mediates pain sensation. Morphine is indicated primarily for pain relief. It can also be used for diarrhea (due to decreased colonic smooth muscle tone), cough suppression (though weaker agonists are more often used for this condition), and acute pulmonary edema (due to vasodilatory effect). Morphine has several synthetic derivatives and analogs indicated for various situations. Make sure you recognize these drugs as belonging to the opioid class:

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Meperidine Methadone Fentanyl Heroin Oxycodone Codeine Dextromethorphan Diphenoxylate Loperamide Meperidine is a synthetic opioid with high affinity for μ less receptors, it is indicated for acute pain. Methadone is a synthetic, orally effective morphine derivative with less efficacy and a longer duration of action. It is indicated for withdrawal from opiate dependence. Fentanyl is one hundred times more potent than morphine and has a very short half-life and duration of action. It is highly lipophilic and indicated for anesthesia. Heroin is a semisynthetic opioid derived from morphine and is 3-5 times more potent. It has no medical use in the United States and is considered an illicit drug. Oxycodone is orally active and indicated in moderate to severe pain. Codeine is a weak naturally occurring opioid agonist which can be administered orally. It is indicated for moderate pain and cough suppression and has a far lower abuse potential than morphine. Buprenorphine is a partial agonist of the μ receptor and is approved for detoxification from opioid abuse. Opioid agonists are bio transformed in the liver by CYP450 enzymes. They often exhibit a strong first pass effect that tends to make parenteral administration necessary. less

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Strong opioids tend to be lipophilic and rapidly distribute to all body tissues. They are contraindicated in pregnancy. Morphine has a linear kinetic profile, allowing for predictable dosing regimens. Acute opioid overdose can result in respiratory arrest. Chronic use can result inconstipation,physical dependence, and infections associated with intravenous abuse. A high yield side effect to be aware of is miosis. less Tolerance develops to all drug effects except for constipation and miosis. Acute poisoning can be countered with opiate antagonists such as naloxone. Dependence can be managed with methadone treatment.

Sumatriptan next Organ Systems Neurology Pharmacology

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339

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5HT serotonin agonist that causes vasoconstriction Used to treat: acute migraines and cluster headaches less Toxicity: coronary vasospasm (contraindicated in patients with Prinzmetal’s angina)

Dantrolene next Organ Systems Neurology Pharmacology

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Muscle relaxant – prevents the calcium release from sarcoplasmic reticulum in skeletal muscle less Remember, actin = thin filaments, myosin = thick filaments Troponin = protein complex consisting of T (tropomyosin binding), I (inhibitory), and C (calcium binding) subunits. In resting muscle troponin I binds to actin. Tropomyosin = inhibitory protein that overlays the myosin binding sites on actin in resting muscle Calcium binds to troponin C, and this causes troponin I to release its hold on actin. Tropomyosin can then move away from the binding groove, and myosin heads can bind to actin filament. Dantrolene decreases the amount of available Ca and thus inhibits the excitation-contraction coupling. May act on the ryanodine receptor, has high lipid solubility Used to treat: 1) Malignant Hyperthermia: a genetically predisposed less hypermetabolic syndrome caused by exposure to inhalation anesthetics or succinylcholine 2) Neuroleptic Malignant Syndrome: a toxic hypermetabolic side effect in patients using combination antipsychotic drugs or associated with withdrawal of L-Dopa medication. Such side effects include rigidity, autonomic instability, fever, and coma. Unlike malignant hyperthermia, there is no genetic predisposition.

Anti-seizure drugs next Organ Systems Neurology Pharmacology

30 questions

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Anti-epileptic drugs are used in the management and prevention of both partial and generalized seizures. Drug choice is base on seizure classification, patient-specific variables, and drug interactions. In general, anti-epileptics act to decrease neural firing, less either by inhibiting depolarization or stimulating hyperpolarization of postsynaptic membranes. Benzodiazepines indirectly enhance the actions of GABA receptors, which increases inhibitory actions and reduces neuronal firing rates. less Lorazepam is indicated in the acute treatment of myoclonic, partial, and tonic-clonic seizures. Diazepam is indicated for prophylaxis or interruption of tonic-clonic seizures and status epilepticus. Benzodiazepines are also used as second line therapy to seizures that are secondary toeclampsia(see Pregnancy Complications). For more information, see Benzodiazepines and Barbiturates. Carbamazepine acts as a blocker of sodium channels. It is effective in the treatment of partial seizures. less Carbamazepine has been associated with StevenJohnson Syndrome and blood dyscrasias (angranulocytosis, aplastic anemia). Carbamazepine is an inducer of the CYP-450 enzyme system. Ethosuximide inhibits T-type calcium channels in the thalamus. It is indicated as for treatment of generalized absence seizures and has a very narrow therapeutic window. less Ethosuximide is associated with Stevens-Johnson syndrome, fatigue, GI distress, itching, and headache. Gabapentin is a GABA analog which curiously does not activate GABA receptors but instead may inhibit voltage gated

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calcium channels. It is approved as adjunct therapy for partial seizures and treatment of post-herpetic neuralgia. Gabapentin is well tolerated by elderly individuals due toless mild side effects (drowsiness, dizziness, weight gain, and diarrhea) and its limited drug interactions. Lamotrigine exhibits broad-spectrum antiseizure activity via the blocking of sodium channels as well as high voltage gated calcium channels. Lamotrigine is metabolized by the UGT system, and its less half-life will be significantly decreased when combined with drugs which induce these enzymes (carbamazepine and phenytoin). Lamotrigine is associated with Steven-Johnson Syndrome. Levetiracetam is approved for adjuvant therapy of partial onset seizures, myoclonic seizures, and primary generalized tonicclonic seizures. It has an unknown mechanism of action. more Phenobarbital acts by enhancing the inhibitory effects of GABA neurons. In the context of epilepsy, it is indicated in the treatment of all seizure types except absence, as well as in the second line treatment of status epilepticus. less Phenobarbital is associated with sedation, cardiorespiratory depression, tolerance and dependence. Phenobarbital is an inducer of the P450 system. Phenytoin blocks voltage gated sodium channels by prolonging their inactivated state. It is indicated in the treatment of partial seizures, generalized tonic-clonic seizures, and as a first line prophylaxis of status epilepticus. Along with ethanol and aspirin, phenytoin exhibits zeroless order kinetics, meaning it has a constant rate of elimination. Phenytoin is associated with many side effects, including: -Neurologic signs such as nystagmus, diplopia, ataxia, and peripheral neuropathy

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-Sedation -Megaloblastic anemia -Gingival hyperplasia -Drug-induced SLE -Stevens-Johnson syndrome -P-450 induction -Teratogenic Fosphenytoin is a prodrug which may be injected intramuscularly and is rapidly converted to phenytoin in the blood. Valproic acid acts to inhibit sodium channels, T-type calcium channels, and GABAtransaminase, the latter resulting in increased synaptic GABA concentrations. It is indicated as a first line therapy for generalized tonic-clonic seizures. less Valproic acid is a known teratogen, and is associated with neural tube defects and should thus be avoided in pregnancy. It may also cause hepatotoxicity. Topiramate has several mechanisms of action including the blockage of sodium channels and the enhancement of GABA activity. It is approved for the treatment of partial seizures and generalized tonic-clonic seizures. less Topiramate also inhibits carbonic anhydrase, and resultant glaucoma, oligohydrosis, and hyperthermia have been reported. It is also associated with nephrolithiasis. Topiramate is also indicated for migraine prevention. Tiagabine inhibits GABA reuptake into presynaptic neurons, thus increasing its synaptic concentration. It is effective at decreasing seizure numbers in patients with partial onset epilepsy. Vigabatrin is an irreversible inhibitor of GABA transaminase, thus increasing synaptic concentrations of GABA. It is indicated in the treatment of partial seizures. Vigabatrin is associated with mild to severe vision loss. less

Anesthetic Agents next Organ Systems Neurology Pharmacology

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The goal of anesthesia is to produce immobility, amnesia, and/or analgesia. Anesthetics can be divided into three general classifications. less Inhaled anesthetics: Nitrous oxide, isoflurane, desflurane, sevoflurane, and halothane. Non-volatile anesthetics: Ketamine, propofol, droperidol, etomidate, benzodiazepines, barbiturates, and opiates. Local anesthetics: Procaine, lidocaine, bupivacaine, tetracaine, mepivacaine, cocaine. Actions of CNS anesthetics are related to the solubility of an agent in lipids and in the blood. Agents with increased lipid solubility have an increased less potency → lower required dose. Agents with low blood solubility have a fast onset of action and fast recovery time. Conversely, ↑blood solubility → slower onset and slower recovery. General anesthesia, such as that used in surgery, is divided into 3 different stages: Induction, maintenance, and emergence. less Agents used for induction include propofol, etomidate, and ketamine. Agents used for maintenance include inhaled gases (see below) and IV general anesthetics drugs. During emergence there is excessive autonomic responsiveness → tachycardia, bronchospasm, hypertension.

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This is controlled with short acting narcotics, beta blockers, and lidocaine. There are many theories explaining the mechanism of action of inhaled anesthetics, including action on cortical centers and inhibition of excitatory transmission in the spinal cord. less Agents: Nitrous oxide, isoflurane, desflurane, sevoflurane, enflurane, and halothane Potency of inhaled agents is expressed as MAC → the Minimal Alveolar Concentration required to produce anesthesia in 50% of the population. Inhaled anesthetics produce the following systemic effects: Cerebral vasodilation and ↑cerebral blood flow → ↑intracranial pressure. ↓ Systemic blood pressure and ↓systemic vascular resistance. ↓ Tidal volume → ↑respiratory rate (most volatile anesthetics have a depressive effect on the respiratory system). Neuromuscular blockade.

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↓ Renal blood flow → ↓ glomerular filtration rate and ↓urine output. Toxicities: -Nitrous oxide: ↑ Pressure and/or volume of body cavities, Vit B~12~ deficiency -Halothane: Hepatotoxicity (Halothane hepatitis, which is exceedingly rare, but nevertheless a notable cause of postoperative hepatic dysfunction). -Sevoflurane: Nephrotoxicity -Enflurane: Proconvulsant

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-Inhaled anesthetics share the risk of inducing malignant hyperthermia in patients with a genetic predisposition. The majority of local anesthetics function by blocking voltage gated Na+ channels → disruption of impulse transmission in pain fibers. less Local anesthetics are used in epidurals, spinal anesthesia, peripheral nerve blocks, and painful skin procedures. Classified chemically as esters and amides: -Esters (those with one I): ProcaIne, cocaIne, tetracaIne -Amides (those with two I’s): LIdocaIne, mepIvacaIne, bupIvacaIne Often given with vasoconstrictors → increased local concentration while limiting systemic spread. Characteristics of the nerve fibers contribute to the efficacy of local anesthetics. -Size: Fibers with a smaller diameter are more easily blocked. -Myelination: Myelinated fibers are more easily blocked than unmyelinated fibers. The fibers of different sensory modalities possess different characteristics → loss of sensations in a specific order:

Pain (lost first) > temperature > touch > pressure (lost last) Toxicity of local anesthetics is related to concentration levels. The most common cause of toxic levels is accidental injection into a blood vessel, which can cause several systemic effects. less CNS: Tinnitus, disorientation, seizures. Cardiovascular: Hypotension, dysrhythmias, cardiac arrest. GI: Nausea and vomiting. Pulmonary: Respiratory arrest. Immunologic: Local allergic reaction and even anaphylaxis.

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Commonly used non-volatile anesthetics include ketamine, propofol, droperidol, andetomidate, benzodiazepines, barbiturates, and opiates. Ketamine increases cerebral metabolic rate and cerebralless blood volume. Thus, it is contraindicated in situations of increased ICP. Droperidol black box warning: can prolong QT interval (progressing to Torsades de pointes and ventricular fibrillation). Etomidate has a high incidence (30-60%) of myoclonus and long-term infusions can lead to adrenocortical suppression. More information on other drugs used in anesthesia can be found on these cards: less NMJ Blocking Agents (http://med.firecracker.me/topics/1670) Benzodiazepines and Barbiturates (http://med.firecracker.me/topics/1681) Opioids (http://med.firecracker.me/topics/748) Non-opioid Analgesics (http://med.firecracker.me/topics/2767) NSAIDs (http://med.firecracker.me/topics/337) COX-s Inhibitors (http://med.firecracker.me/topics/2807) Acetaminophen (http://med.firecracker.me/topics/774)

Benzodiazepines and Barbiturates next Organ Systems Neurology Pharmacology

7 questions

339

Benzodiazepines (e.g., diazepam, lorazepam, midazolam, chlordiazepoxide) work by potentiating the effect of GABA by increasing the frequency of chloride channel opening. Thus, these drugs are ineffective in the absence of GABA. less

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First line agents to treat alcohol withdrawal—known as Delirium Tremens (DTs) if the withdrawal is severe First line agents for status epilepticus Toxicity: sedation, respiratory depression, tolerance/dependence Treatment of toxicity: flumazenil, a competitive antagonist at GABA receptor. Flumazenil has a short half-life and has no effect in the absence of benzodiazepines. Short acting (MOAT): - Midazolam - Oxazepam - Alprazolam - Triazolam Long acting: Diazepam, Chlordiazepoxide, Flurazepam Barbiturates (e.g., phenobarbital, thiopental, secobarbital) Potentiates the effect of GABA by increasing the duration of chloride channel opening.

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the heme synthesis pathway, thereby exacerbating porphyrias (eg, acute intermittent porphyria, porphyria cutanea tarda) In addition to inducing the cytochrome P450 system, barbiturates also increase the metabolism of several drugs, which often decreases the pharmacological effect of these drugs Toxicity: sedation, respiratory depression, cardiovascular depression Treatment of toxicity: only supportive measures, there is no antagonist

Non-opioid analgesics next Organ Systems Neurology Pharmacology

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Non-opioid analgesics include acetaminophen, traditional NSAIDs and newer COX-2 inhibitors. Acetaminophen is used commonly as a first line pain reliever. less Unlike NSAIDs and COX-2 inhibitors, it does not have any anti-inflammatory properties. Mechanism of action is poorly understood. Most important toxicity is hepatotoxicity which results from prolonged use or acute overdose, as it causes free radical damage in the liver. Recall that the treatment for acetaminophen toxicity is Nacetylcysteine. NSAIDs are equally as effective as acetaminophen, although they are associated with more adverse effects. less Examples include: Diclofenac, Ketorolac, Ibuprofen, Indomethacin, Naproxen and Sulindac.

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Adverse Effects: - Platelets: Reversibly inhibit platelet activity → ↑risk for bleeding. - Stomach: Inhibition of prostaglandin synthesis → inhibition of synthesis of protective barrier (e.g. mucus) in stomach → ↑risk for ulcer. - Kidneys: ↑ risk for interstitial nephritis and ATN. Selective COX-2 inhibitors (celecoxib, valdecoxib, rofecoxib) do not affect COX-1, and therefore do not increase the risk for gastric ulcer formation. They selectively inhibit prostaglandin synthesis and thusless have anti-pyretic, anti-inflammatory and analgesic effects. COX-2 inhibitors have been associated with an increased risk for cardiovascular events.

Coronal section

A, B = Epidural haemorrhage, C = Acute, D = Subdural Haemorrhage

CNS/PNS cells next Organ Systems Neurology Physiology

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339

Astrocytes: star-shaped glial cells (in brain and spinal cord) which: 1. provide support and perform “housekeeping” functions — e.g.,

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buffer extracellular K, metabolize neurotransmitters (e.g., glutamate, GABA, serotonin) 2. help maintain the BBB (blood brain barrier), and 3. play a key role in repair/scarring following injury of the brain and spinal cord less Astrocytes express GFAP (glial fibrillary acidic protein), a type of intermediate filament.Note: ependymal cells also express GFAP. Ependymal cells: ciliated cells which form the inner epithelial lining of the choroid plexus, cerebral ventricles, and central canal of spinal cord less Involved in production of CSF Microglia: CNS phagocytes Origin is mesodermal — vs. all other CNS/PNS support less cell types which originate from ectoderm Current evidence suggests that chronic activation of microglia can accelerate the formation of neurofibrillary tangles Oligodendrocytes: form myelin around multiple CNS axons Oligodendrocytes are the major type of glial cell found inless the white matter of the CNS. Oligodendroglia are destroyed in multiple sclerosis, cerebral palsy, and progressive multifocal leukoencephalopathy (PML).

PML: - Demyelinating disease caused by JC virus (JCV), a type of human polyomavirus, in immunocompromised (e.g., AIDS) patients → limb weakness, problems with speech - JC virus: icosahedral capsid, nonenveloped, circular dsDNA

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Schwann cells: while one oligodendrocyte myelinates multiple axons in the CNS, one Schwann cell can only myelinate one axon in the peripheral nervous system. less Derived from neural crest cells Aid in axonal regeneration Clinical correlates: 1. Schwann cells can form acoustic neuromas (schwannomas), which are usually unilateral and located at the junction of the cerebellum and the pons ∴ mass effects of the tumor may cause cerebellopontine angle syndrome. 2. ~90% of bilateral schwannomas are associated with NF2 (neurofibromatosis type 2)

Location of Neurotransmitter Synthesis next Organ Systems Neurology Physiology

4 questions

339

DA (dopamine) – ventral tegmentum, substantia nigra, and hypothalamic arcuate nucleus 5HT (serotonin) – raphe nucleus NE (norepinephrine) – locus ceruleus ACh (acetylcholine) – basal nucleus of Meynert

Cerebral Cortex next Organ Systems Neurology Physiology

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The cerebral cortex is the largest component of the brain and is responsible for higher executive function and behavior. less Anatomically, the cortex can be divided into two hemispheres, separated longitudinally by the longitudinal fissure. In most people, one hemisphere is said to be dominant over the other. Dominance can be determined using the Wada test. The left hemisphere is responsible for propositional language, logic, and calculation. It is the dominant hemisphere in 100% of those who are right handed and 70% of those who are left handed. The right hemisphere is responsible for spatial and visual perception as well as abstract ideation. It is the dominant hemisphere in 30% of those who are left-handed. The dominant hemisphere contains the speech areas. The frontal lobe describes the area for cortex anterior to the central sulcus and superior to the Sylvian fissure (aka lateral sulcus) and contains the primary motor cortex and is responsible for executive function. less The primary motor cortex is located in the precentral gyrus. It is responsible for the initiation of voluntary motor movement. The premotor cortex is located anterior to the primary motor cortex. Both the primary and premotor cortices are organized somatotopically. The more medial portions of the primary and premotor cortices control the lower limb. As you move laterally, the areas of the body controlled by the motor cortices move superiorly: lower limb, trunk, upper limb, neck head, jaw and tongue. This can be illustrated with a motor homunculus.

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The frontal eye field is located anterior to the premotor cortex. It is involved in voluntary eye movement. Clinical Correlate: In lesions of the frontal eye fields, the eyes deviate towards the damaged side. The patient looks at the lesion. The prefrontal cortex is located at the most anterior portion of the cerebral cortex. It is responsible for executive decision making and functions. The parietal lobe is located on the superior portion of the cortex, posterior to the central sulcus and anterior to the parietooccipital sulcus, and contains the primary sensory cortex. less The primary sensory cortex is located in the post central gyrus. Like the motor cortex, the sensory cortex is organized somatotopically medial to lateral. More medially parts receive sensation from the lower limbs, lateral portions receive sensation from the head. The superior parietal lobule resides posterior to the post central gyrus. It is responsible for the integration and association of somatosensory information. Clinical Correlate: Lesions of the superior parietal lobule may result in contralateral sensory neglect. The temporal lobe is located inferior to the parietal lobe, posterior to the Sylvian fissure, and anterior to the pre-occipital notch. It contains centers of speech and language comprehension. Clinical Correlate: Unilateral destruction of the primary less auditory cortex has little if any clinical relevance, but bilateral destruction results in cortical deafness, in which the patient can physically receive auditory stimuli, but cannot recognize or acknowledge it. This is an example of sensorineural deafness.

The occipital lobe resides at the most posterior portion of the cortex and contains the visual cortex. Clinical Correlate: Unilateral destruction of the primary visual cortex results in contralateral hemianopia with macular sparing. Bilateral destruction results in cortical

The lateral surface of the brain showing the major sensory, motor, and association areas of cortex. The top left image shows Brodmann's map. The bottom right shows the loacation of the gustatory cortex. Noteworthy Brodmann areas: 3, 1, 2: Somatosensory cortex 4 = Primary motor cortex 6 = Premotor and Supplementary motor areas 17, 18, 19 = Visual cortex 22 = Wernicke's area (superior temporal gyrus) 41, 41 = Auditory cortex 43 = Gustatory cortex 44, 45 = Broca's area (inferior frontal gyrys)

Spinal Cord next Organ Systems Neurology Physiology

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Gray matter vs. White matter less Gray matter consists of neuronal cell bodies and is divided into dorsal horn, ventral horn, and lateral horn White matter consists of neuronal fibers Divisions of the spinal cord less Cervical level: C1-C8 (8 nerves) 1) C1-C7 nerves exit via intervertebral foramina at the level above the corresponding vertebra 2) C8 exits below vertebra C7. T1 through L5 exit at the level below the corresponding vertebra. Thoracic level: T1 – T12 (12 nerves) Lumbar level: L1 – L5 (5 nerves)

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Vertebral disk herniation is most common at the L5-S1 level Sacral level: S1 – S5 (5 nerves) Conus medullaris vs. Cauda equina Conus medullaris = end of the spinal cord. In adults, thisless is usually at the level of L1-L2 Cauda equina = spinal nerve roots (dorsal and ventral) of L2 through coccygeal 1. These nerves travel in the subarachnoid space, below the conus. Lumbar puncture less Usually performed L4-5 interspace, which corresponds to the level of the iliac crest. They can be performed at L3-4. CSF is obtained from the subarachnoid space. Pia is not pierced. The needle passes through the dura mater and arachnoid. Subarachnoid space extends to S2 level in adults

Thalamus next Organ Systems Neurology Physiology

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The thalamus is the largest subdivision of the diencephalon, whose primary function is to relay and integrate information. The only sensory pathway not mediated through the thalamus is that of smell. The anterior nucleus project to the anterior cingulate gyrus and themammillothalamic tract. It is an important part of the Papez circuit. less

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Clinical Correlate: Lesions of the anterior nucleus result in memory impairment. The ventral nuclei are divided into anterior and lateral, posteromedial, and posterolateral nuclei. The anterior and lateral nuclei are motor relays and the posterior nuclei are sensory relays. The ventral lateral nucleus relays information betweenless the primary motor cortex, thesupplementary motor cortex, the dentate nucleus of the cerebellum , the globus pallidus, and the substantia nigra. The ventral posteromedial (VPM) nucleus relays information from the trigeminal nerve, corresponding to sensory information from the head and face. Input: trigeminal and gustatory → Output: primary somatosensory and gustatory cortex. Mnemonic: (Makeup goes on the face, VPM) The ventral posterolateral (VPL) nucleus relays information from the spinothalamic tract and the medial lemniscus, to the somatosensory cortex and post-central gyrus. The pulvinar nucleus is the largest nucleus of the thalamus, it projects to the posterior Heteromodal Cortices (PTO Cortex) and is involved in the integration of sensory and spatial information. Clinical Correlate: Lesions of the pulvinar nuclei result less in visual-spatial, perceptual, and language disturbances, particularly sensory aphasia and hemispatial neglect. The metathalamus consists of the medial geniculate nucleus, the major relay center for auditory information, and the lateral geniculate nucleus, the major relay center for visual information. Mnemonic: Lateral=Light, Medial=Music. less

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The lateral geniculate nucleus is the major relay center for visual information, it receives input from the optic tract and projects to the primary visual cortex. The medial geniculate nucleus is the major relay center for auditory information, it receives information from the inferior colliculus and projects to the primary auditor cortex. The intralaminar nuclei are enclosed within the internal medullary lamina. Clinical Correlate: Lesions of the intralaminar nuclei result in disturbances in attention and arousal. The reticular nuclei are embedded on in the external medullary lamina on the lateral surface of the nuclei. The reticular nuclei receive input from and projects inhibitory output to other thalamic nuclei, It is the only circuit which is completely intra-thalamic.

Spinal Tract Anatomy and Functions next

Organ Systems Neurology Physiology

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Lateral CST (corticospinal tract): descending motor pathway controlling the voluntary movement of the extremities (not completely myelinated until the end of the 2nd year of life → Babinski’s sign present in infants) less 1st-order-neuron: UMN (upper motor neuron) with cell body in primary motor cortex → descends ipsilaterally in the posterior limb of the internal capsule → middle three-fifths of the crus cerebri in the midbrain → decussates at caudal medulla (i.e., pyramidal decussation) → descends contralaterally in dorsal quadrant of lateral funiculus → terminates on LMNs (lower motor neurons) 2nd-order-neuron: LMN with cell body in the anterior horn of the spinal cord → axons exit the spinal cord via ventral roots → synapse on muscles through neuromuscular junction Somatotopic organization: fibers in the spinal cord controlling the upper extremity are located medially to those controlling the lower extremity (since fibers are descending, those that need to synapse in gray matter should be closest to gray matter) DCML (Dorsal column medial lemniscus) pathway: ascending sensory pathway that mediates vibration sensation, tactile discrimination, and conscious proprioception (joint and muscle sensation) Receptors: Pacinian corpuscles (vibration and pressure less sensitivity), Meissner’s corpuscles (light touch sensitivity), joint receptors, muscle spindles and Golgi tendon organs (muscle proprioception)

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1st-order-neuron: cell bodies located in dorsal root ganglia at all levels of spinal cord → axons give rise to gracile ("thin"•) fasciculus (medially) for lower extremity sensation and cuneate (“wedge shaped”•) fasciculus (laterally) for upper extremity sensation → ascend ipsilaterally in the dorsal columns of the white matter to terminate in gracile and cuneate nuclei of caudal medulla 2nd-order-neuron: located in gracile (lower extremity) and cuneate (upper extremity) nuclei of caudal medulla → axons give rise to internal arcuate fibers that decussate in the medulla to form compact bundle called medial leminiscus → ascends and terminates in ventral posteriolateral (VPL) nucleus of thalamus 3rd-order-neuron: located in the VPL nucleus of thalamus → project to posterior limb of internal capsule → synapse in post-central gyrus, the primary somatosensory cortex Somatotopic organization: in the spinal cord feet are most medially represented and arms are most laterally represented (picture axons adding on laterally as the dorsal columns ascends in the spinal cord) Lateral spinothalamic tract (anterolateral pathway): ascending sensory pathway that mediates pain and temperature sensation Receptors: free nerve endings of fast (A-delta) and slowless C conducting pain fibers 1st-order-neuron: cell bodies located in dorsal root ganglia at all levels of spinal cord → axons enter the spinal cord in an area posterior to the dorsal horn, known as the dorsolateral fasiculus of Lissauer (lateral root entry zone) → ascend two levels before synapsing on second-order neurons (lateral cord lesion will affect contralateral pain and temperature sensation beginning a few segments below the level of the lesion)

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2nd-order-neuron: located in the dorsal horn, give rise to axons that decussate across the anterior comissure and ascend in the (now contralateral) ventral quadrant of the lateral funiculus → ascend through lateral brainstem as the spinal lemniscus until synapsing in the VPL nucleus of the thalamus 3rd-order-neuron: located in the VPL nucleus of thalamus → project to posterior limb of internal capsule → synapse in post-central gyrus, the primary somatosensory cortex Somatotopic organization: in the spinal cord feet are most laterally represented (opposite of dorsal columns, picture axons from anterior commisure adding on medially as the spinothalamic tract ascends in the spinal cord)

Motor Neuron Signs next Organ Systems Neurology Physiology

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Upper motor neurons (UMNs): constitutes the 1st-order-neuron of the lateral corticospinal tract that terminates on lower motor neurons (LMNs) in the spinal cord Damage of an UMN leads to: 1. Muscle weakness (weakness of the lower limb flexors and upper limb extensors, aka pyramidal weakness) 2. Hyperreflexia 3. Hypertonia 4. Spasticity (spastic paralysis and clasp knife spasticity) 5. Babinksi's sign 6. Pronator drift less

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Acute UMN lesions produce flaccid paralysis with ↓tone and ↓ reflexes but over time hyperreflexia and hypertonia develop (it is thought that the loss of UMN inhibitory influences may lead to increased excitability of LMNs, resulting in brisk reflexes and increased tone) Symptoms can be ipsilateral (if injured below pyramidal decussation) or contralateral to lesion (if injured above pyramidal decussation) Babinski's sign: scrape an object across sole of the foot from the heel, moving toward small toe, and then arcing towards the big toe. Normal response is downward contraction of big toe but if big toe is up-going and other toes fan outward, Babinski's sign is present Clasp-knife spasticity (similar to the sudden closing of a claspknife after enough pressure is applied): this occurs within the extensors of the upper limb and the flexors of the lower limb. There is asudden resistance to contraction while passively extending the elbow and passively flexing the knee. Pronator drift: patient holds arms extended, palms up, and eyes closed. Slight inward drifting rotation (pronation) of one forearm or a curling of fingertips is abnormal Lower motor neurons (LMNs): neurons that relay impulses from UMNs of the lateral corticospinal tract to skeletal muscles

Damage of a LMN leads to (symptoms always ipsilateral to lesion): 1. Muscle weakness (symptoms specific to muscles innervated by the damaged nerves) 2. Hyporeflexia 3. Hypotonia 4. Flaccid paralysis

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5. Denervation atrophy 6. Fasciculations less Muscle paresis/paralysis, hypotonia/atonia, and hyporeflexia/areflexia are usually seen immediately following injury but muscle wasting and atrophy are typically signs of endstage muscle denervation Fasciculations: involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers If a patient presents with signs of UMN disease along with a LMN sign like fasciculations → think Amyotrophic Lateral Sclerosis (ALS)!

Control of Eye Movement next Organ Systems Neurology Physiology

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The goal of different classes of eye movement is to keep the object of interest centered on the fovea, the area responsible for sharp/detailed vision. less Saccade: Fast eye movement that brings the object onto the fovea. Vestibular: Holds the static image on the fovea during short rotation of the head. Optokinetic: Allows sequential fixation on a series of stationary targets passing in front of a viewer’s eyes (such as looking at trees out of the window of a moving car). Smooth pursuit: Keeps a moving image on the fovea.

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Vergence: Moves eyes towards the center simultaneously to keep the image centered on both fovea. Divergence: Opposite of vergence → simultaneous movement of both eyes outwards to keep image centered on both fovea. Initiation of saccadic movement begins in cortical centers, control and coordination of saccadic movement originates in saccadic generators in the brainstem. Pathway for initiation of voluntary saccades, both verticalless and horizontal: Frontal lobe (frontal eye field area 8) → pass through basal ganglia → bilateral pretectal areas for vertical saccades, contralateral PPRF (paramedian pontine reticular formation) for horizontal movements. Lesions of the medial longitudinal fasciculus result in internuclear opthalmoplegia. In young persons, multiple sclerosis is the most common cause whereas stroke is the most common cause in the elderly. Pathway for initiation of involuntary saccadic movements: Visual cortex and retina → superior colliculus. Brainstem pathway for horizontal saccadic movements: PPRF (the location of horizontal saccadic generator) → ipsilateral abducens nucleus → two branches:

First branch: Ipsilateral abducens nerve → ipsilateral lateral rectus Second branch: Inter-neurons within abducens nucleus → motor neurons of contralateral medial rectus muscle (via medial longitudinal fasciculus).

This is why if you look laterally with your left eye, the right eye will follow by looking medially (and vice versa). The functionality

of this system depends on the integrity of theMLF (medial longitudinal fasciculus).

The Limbic System and Emotional Behavior next Organ Systems Neurology Physiology

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The limbic system consists of structures and pathways thought to be responsible for behavioral and emotional expression. The olfactory bulb is a mass of paleocortex above the cribriform plate that relays sensory information concerning smell via

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the olfactory tract as well as the olfactory stria to theorbitofrontal cortex and the amygdala. Lesion of the orbitofrontal cortex result in disinhibition,less emotional lability, and impulsive behavior. Clinical Correlate: Meningiomas and other mass lesions of the olfactory groove can push down on the olfactory tract and optic nerve, resulting in Foster Kennedy syndrome, which presents with ipsilateral anosmia and optic atrophy. The amygdala is a mass of corticoid grey matter within the temporal lobe that receives information from the olfactory cortex and tract, activation of which results in fear and an increase in sympathetic nervous system activity. Clinical Correlate: Bilateral destruction of the amygdalaless results in visual agnosia, hyperphagia, docile behavior, and hyper sexuality. Collectively, this is known as Kluver-Bucy Syndrome. The septal nuclei sit anterior to the lamina terminalis and are thought to function as a pleasure zone in humans, and may serve in positive reinforcement of behavior. less Clinical Correlate: Bilateral transection of the fornix results in acute amnestic syndrome, characterized by an inability to convert short-term memory to long-term memory. The circuit of Papez is the limbic pathway consisting of the hippocampal formation, themammillary nucleus of the hypothalamus, the anterior nucleus of the thalamus, thecingulate gyrus, and the entorhinal cortex. less The hippocampal formation lies within the parahippocampal gyrus that plays a major role in memory, learning, and recognition of novelty. Clinical Correlate: Bilateral lesions of the hippocampal formation result inconfabulatory syndrome, which is marked by anteroretrograde amnesia.

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The mamillary body is located in the inferior posterior nuclear group of the hypothalamus and are involved in the creation of memory. Clinical Correlate: Thiamin (vitamin B1) deficiency, often in the setting of chronic alcoholism, may result in Wernicke’s encephalopathy, which is characterized by gait ataxia, ocular disturbances, mental dysfunction, and memory loss. The cingulate gyrus is involved in drive and emotional responses. Lesion of the cingulate gyrus can cause akinesia, mutism, indifference to pain, apathy and overall diminished emotional response.

Arteries of the Brain and Spinal Cord next Organ Systems Neurology Physiology

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MCA (middle cerebral artery) Supplies lateral surface of brain Supplies Broca and Wernicke areas as well as motor/sensory cortex of the trunk-arm-face

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Occlusion of MCA (middle cerebral artery) may result in: 1. Paralysis/sensory loss of contralateral face and arm 2. Broca’s and Wernicke’s aphasia 3. Contralateral neglect syndrome ACA (anterior cerebral artery) less Supplies anteromedial surface of brain Olfactory bulb and tract Occlusion in ACA (anterior cerebral artery) may result in: 1. Paralysis/sensory loss of contralateral foot and leg 2. Gait apraxia 3. Urinary incontinence PCA (posterior cerebral artery) less Supplies posterior and inferior surface of brain (ex: occipital cortex) Macular sparing occurs because there is a small amount of collateral supply to the occipital cortex representing the macula from the MCA. Occlusion in PCA may result in: contralateral hemianopia with macular sparing Anterior communicating artery Most common location of berry aneurysms in the Circle less of Willis Aneurysm here may result in visual field defects such as bitemporal hemianopsia Posterior communicating artery: aneurysm may result in CN III palsy Basilar artery less Occlusion may result in: “locked-in” syndrome AICA (anterior inferior cerebellar artery) less Occlusion may result in lateral inferior pontine syndrome: 1. Ipsilateral facial paralysis

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2. Ipsilateral hearing loss due to ipsilateral cochlear nucleus damage 3. Vestibular signs (e.g., vertigo, nystagmus) due to ipsilateral vestibular nucleus damage 4. Ipsilateral loss of facial pain and temperature sensation 5. Ipsilateral ataxia PICA (posterior inferior cerebellar artery) Occlusion may result in Wallenberg’s syndrome (aka less lateral medullary syndrome): 1. Contralateral loss of body pain and temperature sensation 2. Ipsilateral loss of facial pain and temperature sensation 3. Ipsilateral dysphagia, hoarseness, decreased gag reflex 4. Vertigo, nystagmus 5. Diplopia 6. Ipsilateral Horner’s syndrome (ptosis, miosis, anhidrosis) 7. Ipsilateral ataxia Anterior spinal artery less Occlusion (at the level of the medulla) may result in medial medullary syndrome: 1. Contralateral hemiparesis (lower extremities) 2. Decreased contralateral proprioception 3. Ipsilateral paralysis of hypoglossal nerve

Aphasia next Organ Systems Neurology Physiology

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Aphasia: impairment of language ability ranging from difficulty comprehending to speaking, reading, or writing

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Broca’s (motor) aphasia: damage to the posterior part of the inferior frontal gyrus on the dominant side leading to expressive, non-fluent aphasia (meaning the patient understands written and spoken language but is unable to articulate or write) less Damage often extends into primary motor cortex and can be associated with contralateral facial or arm weakness Patients are quite aware of deficit and are inevitably frustrated because of lack of ability to express themselves Transcortical motor aphasia: damage near Broca’s area leads to similar symptoms except patients are able to repeat words after examiner Wernicke’s (sensory) aphasia: damage to posterior part of the superior temporal gyrus on the dominant side leading to receptive, fluent aphasia (meaning the patient cannot understand any form of language but is able to verbalize fluently, except the speech lacks any meaning) less In contrast to Broca’s aphasia, Wernicke’s aphasia patients are unaware of deficit and show no distress Transcortical sensory aphasia: damage near Wernicke’s area leads to similar symptoms except patients are able to repeat words after examiner Conduction aphasia damage to arcuate fasciculus (connection between Wernicke’s and Broca’s area) results in patient’s inability to repeat words but an intact ability to comprehend with fluent speech Global aphasia: damage to both Broca’s and Wernicke’s area resulting in a patient with poor comprehension, nonfluent speech, and poor repetition To differentiate the six different forms of aphasia, need to have three parameters identified: comprehension, speech, repetition less Broca’s (motor) aphasia: nonfluent, good comprehension, poor repetition vs.

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Transcortical motor aphasia: nonfluent, good comprehension, good repetition Wernicke’s (sensory) aphasia: fluent, poor comprehension, poor repetition vs. Transcortical sensory aphasia: fluent, poor comprehension, good repetition Conduction aphasia: fluent, good comprehension, poor repetition vs. Global aphasia: nonfluent, poor comprehension, poor repetition

Cerebellum next Organ Systems Neurology Physiology

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The cerebellum is a neural formation responsible for maintenance of posture, balance, and muscle tone, and coordination of voluntary motor activity. less Purkinje cells are GABAergic, inhibitory neurons that are the only cells that produce output from the cerebellum. Clinical Correlate: Purkinje cells are very vulnerable to hypoxia. There are four bilateral cerebellar and vestibular nuclei which relay all output from the cerebellum. From lateral to medial they are the dentate, emboliform, globose, andfastigial nuclei. Mnemonics: From lateral to medial, Don’t EMBrace GLOBal FASTIng

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Or alternatively, Don’t (Dendate) Eat (Emboliform) Greasy (Globose) Foods (Fastigial)! Proximal and trunk muscles and vestibulo-ocular circuits are controlled by the midline structures of the cerebellum, the vermis and the flocculonodular lobes. The intermediate and lateral portions of the cerebellar hemispheres control distal and appendicular muscles. The posterior lobe sits in the rostral end of the lateral hemispheres and receives input from the cerebral cortex to coordinate voluntary movement. Clinical Correlate: Lesions of the posterior lobe results less in a loss of coordinated voluntary movement. This is also known as posterior lobe syndrome and often occurs secondarily to cerebellar brain tumors in children (most commonly medulloblastomas or ependymomas). The anterior lobe sits in the caudal end of the lateral hemispheres and receives input from the limbs and spinal tracts to coordinate gait and lower limb coordination. Clinical Correlate: Lesions of the anterior lobe result inless a loss of lower limb coordination and “drunk” walking. This is also known as anterior lobe syndrome . Anterior lobe syndrome is classically associated with alcoholism. The three cerebellar peduncles transmit information to and from the cerebellum. less The superior cerebellar peduncle transmits all cerebellar output. The inferior and middle peduncles transmit cerebellar input. Clinical Correlate: Output from the cerebellum decussates twice. As a result, lesions cause ipsilateral symptoms.

Brain Lesions next Organ Systems Neurology Physiology

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Frontal lobe: involved in motor function, problem solving, spontaneity, memory, language, initiation, judgement, impulse control, and social and sexual behavior, extremely vulnerable to injury due to location and size less Pre-frontal cortex lesion: deficits in concentration, orientation, problem-solving ability, inappropriate social behavior, and sometimes reemergence of sucking and grasping reflexes Frontal eye field lesion: deviation of the eyes to the ipsilateral side (“right way eyes”), in contrast to a lesion of the paramedian pontine reticular formation (PPRF)

Compare this to seizure activity in the frontal eye field which causes contralateral gaze due to increased excitatory activation of the ipsilateral frontal eye field and thereforecontralateral PPRF. Inferior frontal gyrus in dominant hemisphere (Broca’s area): deficit in the ability to articulate speech but intact ability to understand language Parietal lobe: integrates sensory information from different modalities, symptoms depend on whether lesion is on dominant (language and mathematics) or non-dominant (imagery and spatial relationships) side less Dominant (usually left) parietal lobe lesion: Dysgraphia, Dyslexia, Dyscalculia,Disorientation Nondominant (usually right) parietal lobe lesion: contralateral sensory neglect of usually the left side and topographic memory loss Temporal lobe: involved in auditory perception (primary auditory cortex lesion leads to cortical deafness) and higher order auditory function (Wernicke’s speech area lesion leads to deficit in the ability to understand language but intact ability to speak)

Occipital lobe: involved in visual processing, unilateral destruction causes contralateral hemianopia or quadrantopia and bilateral lesions cause cortical blindness Mammillary bodies: bilateral destruction such as in thiamine deficiency (Wernicke-Korsakoff syndrome), leads to impaired formation of new memories or anterograde amnesia Reticular activating system: reticular (meaning net-like) formation of the brain responsible for alterations in arousal and sleep-wake transitions, extreme damage can cause coma Amygdala: bilateral lesions of amygdala → Kluver-Bucy syndrome. Mnemonic: “HIP HIP”: - Hypermetamorphosis (old visual stimuli approached as if they are new) - Increased oral exploratory behavior (putting everything in mouth) - Placidity (no aggression) - Hypersexuality and Hyperphagia - Impaired memory (Anterograde Amnesia) - Psychic Blindness (objects in visual field treated inappropriately)

Spinal Cord Lesions next Organ Systems Neurology Physiology

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Hemisection (Brown-Sequard syndrome):

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1. Ipsilateral UMN signs below lesion (lateral corticospinal tract) 2. Ipsilateral loss of vibration sensation, tactile discrimination, and proprioception (dorsal column) 3. Contralateral loss of pain and temperature sensation 2 dermatomal levels below lesion (lateral spinothalamic tract) 4. Loss of all sensation and LMN signs only at the level of the lesion 5. Ipsilateral Horner’s syndrome, only if hemisection is above T1 Complete transection: bilateral spastic paralysis, LMN signs (e.g. flaccid paralysis) at the level of the transection, no cutaneous sensation below transection, and if transection occurs above C3-C5 nerve roots (i.e. phrenic nerve) respiratory insufficiency may result Anterior spinal artery (ASA) syndrome (infarction of anterior two-thirds of spinal cord): bilateral loss of pain and temperature (spinothalamic tract), bilateral weakness (lateral corticospinal tract) with preservation of fine touch, proprioception, and vibration (dorsal column) less Anterior spinal artery syndrome results in the occlusion of the artery at the level of the spine; this is in contrast to medial medullary syndrome which results from the occlusion of the anterior spinal artery at the level of the medulla (thus, producing different symptoms). Superior portion of ASA supplied by branches of two vertebral arteries and inferior portion of ASA is supplied by the great anterior medullary artery of Adamkiewicz (originating from perforating arteries of the aorta at T10 to L1) → creates a watershed area vulnerable to hypoperfusion in upper thoracic ASA (T4 to T8) Central cord lesions (classically syringomyelia): fluid space in the center of the spinal cord over several levels resulting in bilateral loss of pain and temperature sensation (crossing

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spinothalamic tracts within anterior white commissure are affected with enlargement of the cavity) less Cavity usually starts in C8-T1 levels → numbness begins in hands in a cape-like distribution → loss of motor neurons as the cavity expands leads to wasting and weakness → spasticity is a later sign but dorsal column function usually preserved Half of syrinxes associated with posterior skull malformation (Arnold-Chiari malformations) and occasionally syrinx may extend into brainstem (syringobulbia) causing brainstem disfunction Tabes dorsalis: result of untreated tertiary syphilis, leading to a slow demyelination over many years of the dorsal (posterior) columns and dorsal roots Symptoms: high-stepping gait and consequent foot slapless due to patient’s loss of proprioception (locomotor ataxia), degeneration of joints (Charcot’s joints), and episodes of intense shooting pain Physical exam: Argyll Robertson pupils (accommodate but do not react to light), diminished or absent deep tendon reflexes (loss of sensory arc of reflex), positive Romberg test (loss of proprioception) Subacute combined degeneration (Vitamin B12 deficiency): demyelination of dorsal (posterior) columns and lateral corticospinal tract leading to loss of vibration sensation, tactile discrimination, proprioception and with time weakness, spasticity, and hyperreflexia Similar to vitamin E deficiency dorsal (posterior) column less and spinocerebellar tract demyelination) but vitamin B12 deficiency will present with macrocytic anemia while vitamin E deficiency will present with hEmolytic anemia Friedreich’s ataxia: presents with the corticospinal and dorsal column degeneration (similar to vitamin B12 and E deficiency) but has additional findings of cerebellar dysfunction (nystagmus,

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dysarthria, dysmetria), frontal balding, diabetes mellitus, high plantar arches (pes cavus), and cardiac involvement Lower motor neuron disease (e.g. poliomyelitis and WerdnigHoffman disease): destruction of anterior horns leads to muscle weakness, denervation atrophy, fasciculations, hyporeflexia, hypotonia → constellation of symptoms known as flaccid paralysis less Werdnig-Hoffman disease (infantile spinal muscular atrophy): autosomal recessive inheritance, infants presents with feeble movements of the arms and legs, swallowing and feeding difficulties, tongue fasciculations (LMN sign) → unable to sit or stand unassisted and require respiratory support to survive

Inner Ear next Organ Systems Neurology Physiology

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The inner ear (also called the labyrinth) is a system of passages that is dedicated to hearing and balance, which can be divided into layers (bony and membranous) or regions (cochlear and vestibular). less The bony (osseous) labyrinth is a network of passages within the petrous part of the temporal bone. It is filled with perilymphan extracellular fluid with ionic composition similar to plasma or cerebrospinal fluid, high in sodium and low in potassium. The cochlea is a region within the bony labyrinth of the auditory system and contains two channels, the scala vestibule and the scala tympani.

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The membranous labyrinth is a network of passages inside of the bony labyrinth that contains the neurosensory epithelium, important for vestibular and auditory function. It is filled with endolymph, a fluid which is high in potassium and low in sodium. The cochlear duct or the scala media is the membranous labyrinth of the auditory system that separates the scala vestibuli and scala tympani along most of their length. The vestibular membrane lies between the scala media and the scala vestibule. The basilar membrane lies between the scala media and the scala tympani. Sound waves transmitted from the outer ear by the tympanic membrane are amplified by the ossicles of the middle ear, the malleus (hammer), the incus (anvil), and the stapes (stirrups), before being transmitted into the in the perilymph of the scala vestibule via theoval window. less The basilar membrane is lined with specialized columnar hair cells, each of which is arranged with specialized stereocilia arranged from short to tall along the apical membrane. They serve as the sensory epithelium in what is known as the organ of corti. Low-frequency sounds cause maximum displacement in the basilar membrane at the apex. High-frequency sounds cause maximum displacement in the basilar membrane at the base. The inner ear also serves as a sensory component of the vestibular system, detecting linear and angular acceleration. less The otolith organs detect linear acceleration. They consist of the utricle and the saccule. The utricle detects horizontal acceleration. It may elicit eye movements as a response.

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The saccule detects vertical acceleration. It may elicit muscles that control posture. The semicircular canals consist of three perpendicular canals. The serve to detect angular acceleration.

CN8 - The three scalae of the cochlea. Viewed in cross section, the cochlea contains three small parallel chambers. These chambers, the scalae, are separated by Reissner's membrane and the basilar membrane. The organ of Corti contains the auditory receptors; it sits upon the basilar membrane and is covered by the tectorial membrane

CN8 - Depolarization of a hair cell. (a) Potassium channels at the tips of the stereocilia open when the tip links joining the stereocilia

are stretched. (b) The entry of potassium depolarizes the hair cell, which opens voltage-gated Ca2+ channels. Incoming calcium leads to the release of neurotransmitter from synaptic vesicles, which then diffuses to the postsynaptic spiral ganglion neurite.

CN8 - The basilar membrane in an uncoiled cochlea. Although the cochlea narrows from base to apex, the basilar membrane widens toward the apex. The helicotrema is a hole at the apex of the basilar membrane, which connects the scala vestibuli and scala tympani

CN8 - The response of the basilar membrane to sound. The cochlea is again shown uncoiled. (a) High-frequency sound produces a traveling wave, which dissipates near the narrow and stiff base of Low-frequency sound produces a wave that propagates all the way to the apex of the basilar membrane before dissipating. (The bending of the basilar membrane is greatly exaggerated for the purpose of illustration.) (c) There is a place code on the basilar membrane for the frequency that produces the maximum amplitude deflection

Hypothalamus next Organ Systems Neurology Physiology

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The hypothalamus is a cluster of nuclei located inferior to the thalamus whose primary function is to maintain homeostasis. less Functions of the hypothalmus—“TAN HATSS”: Thirst (and water balance) Adenohypophysis control (via release factors) Neurohypophysis control (via direct axon transport)

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Hunger and satiety Autonomic regulation Temperature regulation Sexual desires and emotions Sircadian (circadian) rhythm control via suprachiasmatic nucleus The hypothalamic nuclei can be anatomically divided into three groups; anterior, tuberal, and posterior. Additionally, these three groups are flanked on either side by two lateral nuclei. The lateral nucleus consists of neuropeptide Y (NPY) and Agouti related protein (AgRP) containing neurons, which trigger hunger and food intake. Clinical Correlate: Destruction of the lateral nucleus less results in starvation via hypophagia. The anterior group includes the paraventricular, anterior, preoptic, supraoptic, and suprachiasmaticnuclei. The preoptic nucleus has an endocrine function and less regulates the release of gonadotropic hormones. It has a testosterone dependent development The anterior nucleus is involved in both temperature regulation and autonomic activation. It receives input from heat sensory systems and serves to cool the body via heat dissipation. It is also and activator of the parasympathetic nervous system.

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Clinical Correlate: Destruction of the anterior nucleus results in hyperthermia. The paraventricular nucleus is involved in water homeostasis. Neurons of this nucleus produce antidiuretic hormone (ADH) (and oxytocin) in their soma which are transported along their axons to the neurohypophysis of the pituitary gland, where they are stored until triggered for release into systemic circulation. ADH is an important mediator of water conservation. Clinical Correlate: Destruction of the paraventricular nucleus results in central diabetes insipidus which is characterized by polydipsia and polyuria as a result of an inability to concentrate urine due to an absence ADH Clinical Correlate: Syndrome of inappropriate secretion of antidiuretic hormone (ADH), is characterized by severe water retention and urine concentration due to abnormally high plasma concentrations of ADH. It is generally a paraneoplastic syndromeassociated with small cell lung cancer. It can also be induced by certain drugs. For more information on SIADH and diabetes insipidus, see Posterior Pituitary. In addition to ADH, the paraventricular nucleus also synthesizes, stores, and secretesoxytocin and cotricotropin releasing hormone (CRH), the former which is released into system vasculature from the posterior pituitary and the latter from the median eminence. The supraoptic nucleus has functions similar to those of the paraventricular nucleus. It synthesizes and secretes both ADH and oxytocin. The suprachiasmatic nucleus is involved in the regulation of circadian rhythms. It receives input from the retina and secretes melatonin in the absence of light.

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The tuberal group includes the dorsomedial, ventromedial, and arcuate nuclei. The ventromedial nucleus is the major satiety center ofless the hypothalamus, it consists of proopiomelanocortin (POMC) expressing neurons which secrete alpha-melanocyte stimulating hormone in response to leptin in order to decrease appetite. See Leptin and Ghrelin. Clinical Correlate: Destruction of the ventromedial nucleus results in hyperphagia and savage behavior. The arcuate nucleus produces, stores, and secretes a number hypothalamic releasing factors which are released into the hypophysial portal veins via sinusoids in the median eminence of the infundibulum. The arcuate nucleus also synthesizes and secretes dopamine, which acts on cells of the anterior pituitary to inhibit prolactin release The posterior group includes the posterior nucleus and the mammillary body. The posterior nucleus is involved in both temperature less regulation and autonomic activation. It serves to warm the body via heat conservation. It is also and activator of thesympathetic nervous system. Clinical Correlate: Destruction of the posterior nucleus results in hypothermia. The mammillary body is an integral part of the circuit of Papez of the limbic system. It receives input from the hippocampal formation and projects to the anterior nucleus of the thalamus. Clinical Correlate: Wernicke’s encephalopathy, an irreversible demented and amnestic state as a consequence of thiamin deficiency generally seen in homeless populations and alcoholic, is often characterized by hemorrhagic lesions of the mammillary bodies in the hypothalamus. See The Limbic System.

Special Senses next Organ Systems Neurology Physiology

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In the context of anatomy and physiology, the special senses include olfaction, vision,gustation, and hearing and balance. The axons of the olfactory cells pass through the cribriform plate of the ethmoid bone of the skull, where they congregate to form the Olfactory nerve (Cranial Nerve I). •

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Fibers of the olfactory nerve travel along the olfactory less groove before they ultimately synapse on mitral cells of the olfactory bulb. The olfactory tract is vulnerable to mass effects and lesions as it travels along the olfactory groove, making it a common sight of pathology. From the olfactory bulb, olfactory information is relayed and further integrated in the amygdala, the hippocampus, and the orbito-frontal cortex. Olfaction is the only sensory modality without a thalamic relay to the cortex. Gustation is the sense of taste. It begins within taste buds of the oral mucosa. Gustatory cells are specialized chemoreceptors which less are located centrally within taste buds. They respond preferentially to a specific type of taste (salty, sweet, sour, bitter, or umami) and relay this information to primary neurons within the taste bud.

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Primary neurons relaying taste sensation travel along one of three cranial nerves depending on location: CN VII, CN IX, and CN X. Axons originating from the anterior two thirds of the tongue travel along the chorda tympani branch of the Facial nerve (Cranial Nerve VII). Cell bodies of these neurons are located within the geniculate ganglion. Axons originating from the posterior one third of the tongue travel along theGlossopharyngeal nerve (Cranial Nerve IX)/ Cell bodies of these neurons are located within the petrosal ganglion. Axons originating from the epiglottic area travel along the Vagus nerve (Cranial Nerve X). Cell bodies of these neurons are located in the nodose ganglion. Axons traveling from each cranial nerve then either synapse on cells the Solitary Nucleus of the medulla oblongata, or travel along the Nucleus Tractus Solitarius to various other non-specific sites within the medulla. From the medulla, taste fibers are projected are to the Ventral Posteromedial (VPM)nucleus of the thalamus. From the Thalamus, cells then project to the gustatory cortex of the insula. Vision begins with photoinhibitionof rod and cone receptor cells within the retina (light ultimately hyperpolarizes rod and cone cells which themselves inhibit the bipolar cells they synapse too). The cells further synapse on retinal ganglion cells by way of intervening bipolar cells. Photoactivation of retinal cells requires a derivative of less vitamin A. A vitamin A deficiency can thus result in blindness, particularly night blindness.

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Rod cells are evenly distributed throughout the retina, they respond uniformly to a single wavelength of light and are thus unable to detect differences in color.

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Multiple rod cells ultimately converge and synapse on a single ganglion cell, giving them two important properties; 1) Due to the summation of their collective action potential, rod cells have a low threshold to light and thus have a very high sensitivity and are therefore very important in night vision, where little light is available. 2) Because the visual fields received by a single ganglion cell by multiple rod cells is very large, rod cells have a very low acuity. This contributes to the sensation of peripheral vision, in which items are easily detected due to high sensitivity but rarely identified due to low acuity. Cones cells are concentrated in the fovea centralis, they come in three subtypes called S, M, and L which preferentially respond to wavelengths of blue, green, and redlight respectively and are thus able to detect differences in color Cone cells ultimately synapse on retinal ganglion cells in a one to one fashion, thus giving them both a low sensitivity to light while imparting a high acuity. Axons from retinal ganglion cells converge and exit the eye via the optic disk. less Because there are no photoreceptors present at the optic disk, it is an area of blindness and is also referred to as the physiological blind spot The blind spot is ultimately not perceived as the brain interpolates the missing visual field using surrounding information.

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After exiting the eye, the retinal ganglion axons collectively make up the Optic nerve (Cranial Nerve II). Axons originating in the nasal hemiretinas (and thus temporal visual fields) then decussate at the optic chiasm while those originating in the temporal hemiretinas (and thus nasal visual fields) continue ipsilaterally into the optic tracts. Therefore, each optic tract contains axons from both the ipsilateral temporal hemiretina as well as the contralateral nasal hemiretina. The axons of the optic tracts synapse on cells of the ipsilateral lateral geniculate body of the thalamus. Cells in the lateral geniculate body receiving input from superior retinal cells (and thus inferior visual fields) project along the dorsal optic radiation of the parietal lobe to cortical cells of the cuneus on the superior bank of the calcarine sulcus while those receiving input from inferior retinal cells (and thus superior visual fields) project along theventral optic radiation (Meyer’s Loop) of the temporal lobe to cortical cells of thelingual gyrus on the inferior bank of the calcarine sulcus. Together, the cuneus and the lingual gyrus make up the primary visual cortex. Lesions at any point along the visual pathway cause visual field defects corresponding to the origin of the affected fibers. See https://med.firecracker.me/topics/3434 The Vestibular system mediates the sense of balance and equilibrium. It begins within specialized structures of the inner ear (see http://med.firecracker.me/topics/1777) Bipolar cells of the vestibular ganglion relay positional less information from the ear along the vestibular nerve. These fibers then combine with fibers of the Cochlear nerve to for theVestibulocochlear nerve (Cranial

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Nerve VIII) and ultimately synapse on thevestibular nuclei of the medulla. From the vestibular nuclei, axons project to a variety of locations in an effort to coordinate appropriate responses to dynamic input. These interactions include: 1) Reciprocal communication with nuclei of the flocculonodular lobes of the cerebellum, allowing for coordinated muscular responses. 2) Projections via the medial longitudinal fasciculus to the nuclei of the cranial nerves innervating the extraocular muscles (CN III, IV, and VI), allowing for appropriate eye movements in response to changing positions. 3) Projections along the spinal chord via the lateral vestibulospinal tract, allowing a maintenance of posture. 4) Projections to the primary sensory cortex by way of the ventral posteromedialand ventral posterolateral nuclei of the thalamus, allowing for a conscious perception of position and equilibrium.

Cranial Nerves next Organ Systems Neurology Physiology

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CN I is the olfactory nerve. It relays the special sense of smell from sensory cells perforating the cribriform plate to the ipsilateral olfactory bulb via the olfactory tract. For more information, see Special Senses and Disorders of Special Senses.

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CN II is the optic nerve. It relays visual information from the retina and is unique in that it is not a true peripheral nerve, but rather an extension of brain matter from the diencephalon enveloped around a central retinal artery. more CN III is the Oculomotor nerve. It innervates four extraocular muscles which control eyeball movement: the medial rectus, the inferior rectus, the superior rectus, and theinferior oblique. Clinical Correlate: Lesions to motor components of theless oculomotor nerve result in CNIII palsy , which includes “down and out” pupil, external strabismus, and diplopia when looking toward the lesioned side. The pupil looks “down and out” due to the unopposed actions of the superior oblique and lateral rectus muscles. CN III also innervates the levator palpebrae superioris, which serves to elevate the upper eyelid. A lesion would thus result in ptosis (droopy upper eyelid). CN III has autonomic functions, which serve as the efferent limb of the pupillary light reflex and in accomodation. Parasympathetic fibers from CN III innervate the sphincter pupillae (circular muscles)and the ciliary muscles of the eye. Lesions of the parasympathetic pathway of CN III will result in mydriasis and lack of accommodation (blurry vision). Note: Peripheral fibers innervating the sphincter pupillae fibers are preferentially affected by: • Uncal (transtentorial) herniation • Aneurysms of the posterior communicating or carotid arteries In contrast, diabetic CN III palsy spares the sphincter pupillae and damages fibers located more centrally within the nerve (i.e. those innervating the extraocular muscles). CN IV is the trochlear nerve. It innerves the superior oblique muscle, which depresses, intorts, and abducts the eye. less

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Lesions of CN IV result in the eye being pointed superomedially (up and in), and vertical diplopia with downward gaze. CN IV is the only cranial nerve to emerge from the dorsal aspect of the brainstem. CN V is the Trigeminal nerve. It has three divisions, designated V1, V2, and V3 which relay sensory and motor information to specific territories of the face and oral/nasal mucosa. less For more information, see the related topics: https://med.firecracker.me/topics/858 https://med.firecracker.me/topics/859 https://med.firecracker.me/topics/2933 CN VI is the Abducens nerve. It innervates the lateral rectus muscle of the eye. less See related topics The orbit https://med.firecracker.me/topics/2699 Control of Eye Movement https://med.firecracker.me/topics/2699 Eye Pathology https://med.firecracker.me/topics/934 CN VII is the Facial nerve. It innervates the muscles of facial expression and the stapedius of the ear. less CN VII also carries taste information from the anterior two thirds of the tongue via theLingual nerve of V3. CN VII provides parasympathetic output to the lacrimal gland via the pterygopalatine ganglion and the submandibular and sublingual glands via the submandibular ganglion. CN VII exits the brainstem at the cerebellopontine angle and courses alongside CN VIIIinto the internal auditory meatus, exits skull through stylomastoid foramen. Extra cranial branches distal to the stylomastoid foramen pass through the parotid gland. Clinical Correlate: This is why surgeons need to locate and avoid the facial nerve when resecting the parotid gland.

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CN VII is vulnerable at the cerebellopontine angle from compression damage byacoustic neuromas (schwannomas of the vestibular division of CN VIII). Upper motor neurons (UMNs) involved in voluntary movement of the face originate in the primary motor cortex of the precentral gyrus, and project to the motor nucleus of CN VII. The motor nucleus of CN VII is subdivided into an upper face division which innervates muscles of the upper face and a lower face division which innervates muscles of the lower face. The upper face division receives input bilaterally from both precentral gyri. The lower face division receives unilateral input from the contralateral precentral gyrus. Therefore, Lower motor neuron (LMN) lesions of CN VII result in ipsilateral flaccid paralysis of upper and lower facial muscles of expression (Bell’s palsy—note: bilateral Bell’s palsy can be seen in second stage Lyme disease) and a loss of efferent limb of corneal blink reflex (afferent limb = V1). Upper motor neuron (UMN) lesions of CN VII (supranuclear facial palsy) result in contralateral paresis of lower facial muscles of expression only (upper face is spared, e.g., can wrinkle forehead). Paralysis of the stapedius muscle results in hyperacusis. CN VIII is the Vestibulocochlear. It exits the brain stem at the cerebellopontine angle and has two functional divisions involved in special sensation. less The Vestibular nerve maintains equilibrium and balance, and the Cochlear nervemediates hearing. See the following related topics The ear http://med.firecracker.me/topics/862 Inner ear http://med.firecracker.me/topics/1777 Auditory system http://med.firecracker.me/topics/3442

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Ear pathology http://med.firecracker.me/topics/149 Vertigo http://med.firecracker.me/topics/2835 CN IX is the Glossopharyngeal nerve. It exits the skull at the jugular foramen and mediates taste and general sensation of the posterior one third of the tongue and mucosa of the oropharynx, and monitors input from carotid body and sinus chemo-baroreceptors, and provides motor innervation for the stylopharyngeus muscle. less It also provides motor innervation for the stylopharyngeus muscle. CN IX provides parasympathetic output to the parotid gland via the Otic ganglion. Lesions of CN IX cause a loss of the afferent limb of the gag reflex and loss of taste and general sensation from posterior third of the tongue. See related topics The palate http://med.firecracker.me/topics/861 The oral cavity and tongue http://med.firecracker.me/topics/859 CN X is the Vagus nerve. It exits the skull at the jugular foramen and mediates speech, swallowing, elevation of the palate. less It also mediates taste from the epiglottic region, cutaneous sensation from the ear, and information from aortic arch and sinus chemo and baroreceptors. CN X also innervates the viscera of the neck, abdomen, and thorax and provides parasympathetic input to various organs as far as the left colic flexure via a variety of ganglia. CN X functions as the efferent limb of the gag reflex (CN IX is afferent). Lesions of CN X result in paralysis of the pharynx and larynx, and a deviation of the uvula to the opposite side of injured nerve. The is also a loss of the efferent limb of the gag reflex.

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CN XI is the Accessory nerve. It exits the skull via the jugular foramen and innervates the sternocleidomastoid (SCM) and trapezius muscles. less Unilateral lesions of CN XI result in a decreased ability to turn the head to the opposite side of injured nerve and a decreased ability to shrug the ipsilateral shoulder. Bilateral lesions of CN XI result in a decreased ability to look straight down by tilting chin toward chest and a decreased ability to shrug both shoulders. Related topic, see Back: Muscles – Superficial http://med.firecracker.me/topics/871 CN XII is the Hypoglossal nerve. It exists the skull through the hypoglossal canal and innervates the intrinsic and extrinsic tongue muscle (except for palatoglossus, which is innervated by CN X). Lesions of CN XII result in a deviation of the tongue to less the SAME side of the injured nerve. Related topic Oral cavity and tongue http://med.firecracker.me/topics/859

Basal ganglia next Organ Systems Neurology Physiology

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The basal ganglia provide excitatory and inhibitory corticothalamic feedback loops that modulate motor activity. The connection between the striatum and the substantialess nigra (pars reticulata) usesGABA.

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The feedback from the substantia nigra (pars compacta) on the striatum uses dopamine. The basal ganglia produce effects on motor actions which are indirect, and thus termed “extrapyramidal” to distinguish them from cortical pathways which travel through the pyramids of the medulla. The direct pathway begins in the cortex and follows the less following pathway: Cortex → striatum (the putamen and caudate nucleus) → internal globus pallidus and the substancia nigra pars reticulate → thalamus → cortex. It is excitatory, which means it promotes movement. The indirect pathway also begins in the cortex and proceeds as follows: Cortex → striatum (caudate and putamen) → external globus pallidus → subthalamic nuclei → internal globus pallidus and the substancia nigra pars reticulata → thalamus → and back to the cortex. It is inhibitory, meaning it inhibits movement. It is thought that the direct pathway promotes voluntary movement in targeted muscles. The indirect pathway simultaneously inhibits movement in other muscles that do not contribute to the overall wanted movement. The result is a coordinated, smooth movement in which those muscles necessary for the desired movement are recruited, while other muscles that might “throw off” the desired movement are inhibited. The striatum is composed of the caudate nucleus and the putamen, the first of which is c-shaped and follows the contours of the lateral ventricles. Clinical Correlate: Destruction of the striatum results inless Huntington’s disease, characterized by random, jerky

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movements called chorea, due to the loss of inhibitory GABAergic neurons and consequent unopposed excitatory activity. See Huntington Disease. The striatum receives excitatory input from dopaminergic neurons of the pars compacta of the substancia nigra. The substancia nigra is a collection of neurons in the midbrain which are darkly pigmented with neuromelanin. less Clinical Correlate: Destruction of the dopaminergic neurons of the pars compacta of the substancia nigra results in Parkinson’s disease due to unopposed inhibitory activity. The disease is characterized by a festinating gait, cog wheeling, masked facies, and a resting tremor of the hands that resembles somebody rolling a pill between their fingers. See Parkinson Disease.

Direct pathway reduces thalamic inhibition -> excitatory effect on movement vs. Indirect pathway increases thalamic inhibition -> inhibitory effect.

Internal Capsule next Organ Systems Neurology Physiology

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The internal capsule is a tract of white matter that contains the corticospinal tract andsensory pathways. The internal capsule separates the caudate nucleus and the thalamus medially from thelentiform nucleus laterally. less The anterior limb runs between the caudate nucleus and the lentiform nucleus. The genu contains fibers of the corticonuclear tract. The posterior limb is located between the thalamus and the lentiform nucleus and contains the corticospinal tract and sensory pathways (pain, temperatire, touch, visual, and auditory pathways). Clinical Correlate: Lesions of the internal capsule result in contralateral hemiparesis and contralateral hemianopia. The internal capsule is a common location for strokes.

Visual Field Defects next Organ Systems Neurology Physiology

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Visual Defects are a consequence of lesions at any point along the visual pathway: Related topic: Special Senses https://med.firecracker.me/topics/2935 Light sensation begin in the retina, and a given region ofless retina detects light from theopposite visual field. Thus; 1. The superior retina receives light from the inferior visual fields. 2. The inferior retina receives light from the superior visual fields. 3. The nasal hemiretina receives light from the temporal visual fields. 4. The temporal hemiretina receives light from the nasal visual fields. The optic chiasm contains fibers decussating from the contralateral nasal retina. The optic tract (after the chiasm) contains fibers from the nasal hemiretina of the contralateral eye as well as the temporal hemiretina of the ipsilateral eye. Anopia describes a total loss of vision from a given eye. Neurologically, this may be due to lesions of the optic nerve (before the optic chiasm), which contains fibers from all parts of the retina of the ipsilateral eye. less Lesions to the optic nerve also result in a loss of the afferent limb of the pupillary light reflex: See Cranial Nerves (under CN II and III) https://med.firecracker.me/topics/2980 Central scotomas describe a blind spot in central vision. less Central scotomas are commonly the result of demyelinating diseases such as multiple sclerosis, age related or congenital macular degeneration, toxic substances such as methanol, ethambutol, and quinine, or vascular blockages within the retina or optic nerve. Bitemporal heteronymous hemianopia describes a loss of the temporal visual fields from both eyes. It is commonly a

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consequence of damage to the central optic chiasm, which contains fibers decussating from the nasal retinas. less Damage to the optic chiasm is generally a result of a mass effect from a parasellar tumor, commonly a pituitary adenoma, a craniopharyngioma, or a meningioma. Binasal heteronymous hemianopia describes a loss of nasal visual field from both eyes. It is commonly a consequence of bilateral peripheral compression of the optic chiasm, as this region contains fibers from the temporal hemiretinas. These lesions are commonly a consequence of mass less effects from calcified internal carotid arteries or aneurysms. Homonymous Hemianopia describes a loss of either the right of left visual fields from both eyes. It results from a transection of the contralateral optic tract (after the chiasm), which contains fibers from the nasal hemiretina of the contralateral eye as well as the temporal hemiretina of the ipsilateral eye. Upper quadrantic anopia describes a loss of half of the upper visual fields (either right or left) of both eyes. It is caused by damage to the contralateral ventral optic radiations (Meyer’s loop of the temporal lobe, which contain fibers from the inferior temporal retinal quadrant of the ipsilateral eye, and the inferior nasal retinal quadrant of the contralateral eye. less Clinical Correlate: Lesions or tumors of the temporal lobe have the potential to damage Meyer’s Loop, resulting in upper quadrantic anopia. Lower quadrantic anopia describes a loss of half of the lower visual fields (either right or left) of both eyes. It is caused by damage to the contralateral dorsal optic radiations of the parietal lobe, which contain fibers from the superior temporal retinal quadrant of the ipsilateral eye, and the superior nasal retinal quadrant of the contralateral eye. Homonymous hemianopia with macular sparing describes a loss of either the right of left visual fields from both eyes with

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exception of the macula region. It is commonly a result of occlusion of the Posterior Cerebral Artery (PCA) is the resulting ischemic damage to the primary visual cortex. An occlusion of the PCA will spare the macula as the less macula receives collateral blood supply from the Middle Cerebral Artery (MCA).