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154 Cards in this Set
- Front
- Back
Neuronal Structure
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-nucleus w/ prominent nucleolus
- nissel substance (RNA rich rough ER) -lipofuscin from unbroken down material |
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Glial Cells
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- Oligodendrocytes : make myelin sheath in CNS equivalent to Schwann cells in PNS; round regular dark nuclei surrounded by a pale halo histologically; one cell myelinates several axons
*Luxol Fast Blue stains myelin* - Astrocytes : star cells; stain with GFAP(glial fibrillary acidic protein) along with ependymal cells; induce blood brain barrier and surround blood vessels; support neuronal processes; act as sink for ions and NTs - Ependymal cells : lining of ventricular system |
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Microglial Cells
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- bone marrow derived histiocytic cells similar to Kupfer cells of liver
- cigar-shaped elongated nuclei - aggregate into clusters in viral infections - turn into foamy macrophages, indistinguishable from monocytes |
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Meninges
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- three layers (dura, arachnoid and pia)
- three spaces (epidural, subdural and subarachnoid) -CSF flows through subarachnoid space along with vessels supplying the brain -venous sinuses reabsorb CSF |
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Choroid Plexus
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- main function = production of CSF (~500ccs a day)
- found in the ventricles and may protrude through foramen of Luschka in cerebellopontine angle. - calcifications occur with aging |
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Stroke Terminology
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STROKE - acute, persisting focal neuro deficit due to vascular cause; either purely ischemic vs. hemorrhagic;
TRANSIENT ISCHEMIC ATTACK (TIA) - focal neuro deficit from ischemia lasting less than 24 hours w/ full recovery; usually several minutes representing transient blockade; warn of HIGH RISK for subsequent stroke REVERSIBLE ISCHEMIC NEUROLOGIC DEFICIT (RIND) - stoke syndome lasting more than 24 hours w/ full recovery; usually represent small infarctions |
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Key Brain Anatomy Features
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1)cerebral control is contralateral (motor - precentral gyrus, sensory - post central)
2)left hemisphere dominant for speech (90% rt. handers, 60% lft. handers) 3)cerebellar and brainstem control is IPSILATERAL 4) descending motor pathways cross in MEDULLA(pyramidal decussation) 5) Cerebral cortex = higher integrative function - language formation/processing and spatial conceptualization |
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Stroke Localization Implications
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1) CEREBRAL lesions have contralateral sydromes with motor and sensory components
2) BRAINSTEM lesions can cause "crossed patterns" *ie. ipsilateral face and CN deficits w/ contralateral arm and leg 3) APHASIAS suggest cortical involvement in left (dominant) hemisphere 4) SPATIAL CONSTRUCTION deficits suggest cortical involvement in right(non-dominant) side |
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Vascular Anatomy Review
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- four vessels supply brain 2 internal carotid (anterior circ.) and 2 vertebral merging into basilar(posterior circ.)
-internal bifurcates into ACA and MCA; basilar into PCA -small penetrating branches of ant. and post. circ. supply deep structures/cerebellum -penetrating aa. of basilar and PCA supply BRAINSTEM -OPTHALMIC A. is first major branch of internal carotid |
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Typical Stroke Syndromes:
Anterior Cerebral Artery (ACA) |
-CONTRALATERAL distal leg weakness and numbness; motor + sensory
-distal > proximal |
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Typical Stroke Syndromes:
Middle Cerebral Artery (MCA) |
-CONTRALATERAL face and arm greater than leg weakness; motor + sensory deficit
-w/ appropriate cortical signs (aphasia or constructional deficit) |
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Typical Stroke Syndromes:
Typical Lacunar Infarcts |
-pure motor hemiparesis
-pure hemisensory loss -clumsy hand (dysarthria) -risk factors are HTN and diabetes - mechanism - direct vessel wall damage and thickening, luminal narrowing - usually minor and rapidly improve |
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Typical Stroke Syndrome:
Posterior Cerebral Artery (PCA) Cerebellar Artery and Unilateral Brainstem Infarction |
-PCA: CONTRALATERAL visual field deficit (hemianopsia)
Cerrebellar A.: IPSILATERAL limb ataxia Brainstem: IPSILATERAL cranial nerve deficits + CONTRALATERAL motor and sensory deficits; vertigo, diplopia, ataxia and dysarthria are common *Watershed infactions = boundary zones, usually occurs in hypotensive episode or flow limiting stenosis of carotid a.* |
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What are the four intracranial hemorrhages?
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1)INTRAPARENCHYMAL - deep brain (basal ganglia, cerebellum, wht. matter); rapidly progressing; usually due to HTN also embolus, tumors, vasculitis, AV malformations, coagulopathies, drugs; large = increased ICP, herniation and frequent death
2)SUBARACHNOID - ruptured aneurysm or trauma (typically at junctions of major aa.); sudden onset with severe headache, neck stiffness, lethargy and coma; complications - hemorrhage, arterial spasm, brain swelling, herniation, DVTs; mortality rate is high 3)SUBDURAL - venous bleed; chronic mass effect with headache, hemiparesis, depressed mental state; common in alcoholics/elderly with minor head trauma 4)EPIDURAL - arterial bleed; usually following head trauma; rapid accumulation of localized hematoma with herniation and death |
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What are the mechanisms of vascular occlusion?
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1)ATHEROSCLEROSIS/THROMBOSIS - slow/stuttering stroke over a number of hours; limited to major neck and cerebral aa. and cirle of willis; HTN, diabetes and smoking are highest risk factors; occasional venous thrombosis
2)EMBOLIC - sudden onset stroke with early or late hemorrhage; wedge-shaped cortical infarct a)cardio - mural thrombus from calcified/mechanical/infected heart valve; can have AV septal defect (paradoxical emboli); repeated emboli are randomly distributed due to turbulent blood flow b)artery to artery - plaques in vessel walls that embolize to other distal vessels; steriotypical TIAs as blood flow is laminar (monocular blindness due to opthalmic a. occlusion is a good example) 3)VASCULOPATHIC - lacunar (HTN and diabetes), inflammatory conditions (vasculitis, neurosyphylis), arterial wall dissection (minor trauma like whiplash, chiropractic manipulation, athletic injury), and spasm |
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What are the physiologic consequences?
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1)ISCHEMIC CORE: cessation in membrane ionic gradient and electrical function of neurons; excessive Ca influx, cell swelling, activation of enzymes to damage proteins and structures; neurons die in 4 minutes and glial cells take hours
2)ISCHEMIC PERIPHERY ("penumbra") - nl brain tissue regulates blood flow; ischemic tissue loses reg. and diffusion is reliant on pressure; periphery has some collateral circulation and supplies some O2 and glucose; can persist for hours and areas of clinical deficit can be revived |
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How are stroke patients managed?
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HISTORY - onset, TIAs, cardiac problems, FH
EXAM and STUDIES - BP, auscultation, EKG, U/A, CXR BRAIN IMAGING - CT (fast and reliable to rule out hemorrhage), MRI (best resolution, high sensitivity to early stroke changes, DWI - recent infarcts, MRA - stenosis/occlusion of major aa.), carotid doppler, electrocardiograph, cerebral angiography BLOOD WORK - CBC, ESR, coag studies |
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What is the primary prevention of stroke?
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1)Risk factor modification: HTN treatment, smoking cessation, diabetes management, excercise, decrease cholesterol, etc.
2)Aspirin - better for women than men 3)Cardiac abnormalities - heart valves manage with warfarin 4)Carotid stenosis - endarterectomy used in high grade stenosis (>80%) |
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What is the treatment for acute stroke?
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1)Supportive - maximize profusion, maintain BP, maintain vascular volume, avoid hyperglycemia, fevers and watch for complications
2)Aspirin - given acutely results in less risk of recurrence/extension 3)Anticoagulation - full dose IV heparin NOT adivisable for most pts. (considered for cardioembolic pts.), also used in stroke in 'evolution', acute dissection, and thrombosis 4)IV tPA - beneficial in first 180 minutes of stroke onset, delayed delivery is harmful, 5)Intra-arterial thrombolytics (pro-urokinase) - effective in stroke of less than 6 hrs duration 6)Neuroprotection - glutamate receptor antagonists (NMDA and nonNMDA), antioxidants, mild hypothermia |
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What is secondary stroke prevention?
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-ASPIRIN is first antiplatelet drug used; combination with DIPYRIDAMOLE is more effective than aspirin alone (headache is common side effect)
-CLOPIDOGREL is slightly better than aspirin alone in patients with coronary, peripheral or cerebral vascular dz. -TICLOPIDINE stops ADP dependent aggregation and is more efficatious than asprin but not used due to SEs (diarrhea, neutropenia, thrombotic, and TTP) -STATINS and WARFARIN |
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What is the evolution of cerebral hemorrhage?
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-external capsule hemorrhage dissects anteriorly into the lateral ventricle
-blood enters aqueduct and 4th ventricle irritating autonomic control --> cardiorespiratory arrest -2/3 show spontaneous secondary hemorrhage into pons -clinical course is rapid and death in 1-2 days -pontine hemorrhage invariably fatal due to location to autonomic control -cerebellar hemorrhage have better prognosis |
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What are the most significant causes of subarachnoid bleeding?
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95% are from saccular or "berry" aneurysms (ballooning of arterial wall with thinning and fragmentation of media and elastica); always occur at branch points (anterior cerebral 37%, internal carotid 36%, MCA 21%, verterobasilar 5%, multiple 20%); congenital defects
4% are atherosclerotic aneurysms - more likely to be thrombosis |
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What is a germinal matrix hemorrhage?
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-disease of premature infant
-germinal matrix is zone of proliferation of neuronal and glial cells around the neural tube that will later be the ventricles -all neurons migrate to final place by 24 weeks -hemorrhage into periventricular germinal matrix is most common pathology of premature infants born btwn 24-35 weeks -most occur in thalamostriate groove near foramen of Monro |
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What is the pathogenesis of germinal matrix hemorrhage?
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-b/f 35 weeks bf to brain is shunted by recurrent aa. of Huebner bypassing the cortex, shunts stopped at 35 wks
- vessels are large and thinned walled (one layer of endothelial cells) destined to become major venous drainage -pulmonary parenchymal immaturity leads to hemodynamic fluctuations with both decreased flow and hypoxemia -changes in bf to germinal matrix causes damage to vessels leading to rupture and blood spreads readily through matrix and surrounding tissue |
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What can happen after germinal matrix hemorrhage?
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1 - acute ICP raised preventing bf to brain --> brain death
2 - infant survives prone to obstructive hydrocephalus 3 - hematoma into matrix destroys oligodendrocyte progenitors leading to decreased myelination later 4 - when reaching internal capsule may destroy long tracts |
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What are the epidemiological factors in MS?
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-most common disabling condition of young people
-highest prevalence in northern European descent and rare in native populations (Eskimos, Lapps, Aborigines) -concordance rate of 26% btwn monozygotic twins --> strong genetic component |
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What are the genetic factors in MS?
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-clinical expression of disease probably initiated by environment
-overrepresented in MHC Class II genes: HLA-DRB 1501 or DR2 halotype -in ppl w/o DR2 the IL-4 receptor genes are more prominent -APOE may cause an accelerated course, null CNTF shows an earlier development of disease |
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What is the pathology of MS?
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-inflammation, demyelination and axonal degeneration --> hallmark MS lesion is plaque that is sharply demarcated from the white matter
-activated monocytes and lymphocytes cross the the endothelial cells and enter brain parenchyma (interaction with integrins and cells surface adhesions facilitate migration) |
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How is MS diagnosed?
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-key criterion is to determine recurrence (no specific diagnostic test)
-classic criteria: relapses at different times and different CNS location "dissemination in space and time"; appearance of new lesion on follow up MRI 3-6 mo later CONFIRMS diagnosis -can also use "McDonald criteria" - evoked potentials and spinal fluid exam for increased IgG synthesis and oligoclonal bands |
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What would the differential diagnosis of MS be?
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-Sjogren syndrome (immune cells attack exocrine glands)
-Neuromyelitis Optica (immune cells attack optic nerve and spinal cord) -SLE and Sarcoidosis -Tumor and vitamin deficiencies (vitD) |
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What imaging studies should be performed in MS?
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-MRI vefore and after infustion with gadolinium - T1 and FLAIR
-FLAIR best shows white matter lesions: enhanced lesions indicate active MS -T1 shows low density lesions called "black holes" that indicate permanent damage |
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What are the acute treatments of MS?
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-prevention of inflammation with immunomodulatory drugs
-acute attacks are often self limited -use of IV methylprednisolone for significant flares of optic neuritis, brain stem dysfunction or progressive motor weakness (longterm use is not recommended) |
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What are the long term treatments of MS?
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-Interferon-beta and Glatiramer are first line in relapsing/remitting MS
-Interferon Beta: inhibits entry or activated cells into the CNS, decrease of interferon gamma, augmentation of non-specific suppressor function; given by subcutaneous injection; SE(s) flu-like symptoms -Glatiramer Acetate: mimcs myelin-basic protein (MBP) to induce tolerance to myelin products, induction of Th2 regulatory cells; given daily as subcutaneous injection; SE(s) injection site reactions, lipoatrophy, chest pain -other suppresive therapies including cyclophosphamide, azathioprine, methotrexate and mycophenolate mofetil -monoclonal antibodies: tysabri, campath, rituximab, |
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What can cause CNS demyelination?
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-immunologic attack on myelin membrane (MS and post-infections encephalomyelitis)
-viral infection of oligodendrocytes (PML) -toxic insult/metabolic derangement (CO poisoning, acute hypoxic episodes, methanol poisoning) -central pontine myelinolysis (CPM) -Machiafava-Bignami syndrome: rapid deterioration of corpus callosum and adjacent white matter associated with alcoholism |
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What is the pathology of acute and chronic plaques?
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-Acute: cellularity greater than in normal white matter due to infiltration of monocytes/macrophages with some lymphocytes and reactive astrocytes
-Chronic: cellularity is less than in normal white matter; most axons still present; oligodendrocytes, macrophages, lymphocytes are gone; fibrillary astrocytes remain and replace oligos -Shadow plaques: incomplete demyelination; most axons are myelinated and oligodendrocytes are still present |
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What is Devic's Neuromyelitis?
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-variant of MS with a different pathogenesis
-patients present with optic neuritis and transverse myelitis occuring w/in a few weeks of each other -lesions are more destructive than typical MS plaques --> axonal loss along with demyelination |
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What is Acute Disseminated Encephalomyelitis?
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-acute perivenous, post-infectious, post-vaccinal encephalomyelitis
-result of an aberrant immune response to an infectious agent in a perivascular distribution, circulating lymphocytes become sensitized to a central component of myelin -disease is monophasic and self limited -most virulent form shows marked edema and petechial hemorrhages (actue hemorrhagic leukoencephalitis) |
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What are the inherited diseases of myelin - leukodystrophies?
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-metabolic defect often shared by Schwann cells and oligos
-myelin is normally formed during early post-natal development but myelin turnover is blocked by specific enzyme defects resulting in an accumulation of breakdown products that are toxic to Schwann cells and oligos -Metachromatic leukodystrophy: defect in aryl sulfatase leading to sulfatide accumulation; "metachromatic with aniline dyes -Krabbe's (globoid cell) leukodystrophy: defect in galactocerebrosidase leading to accumulation of cerebroside causing syncytia to form in macrophages ingesting degenerated myelin -Adrenoleukodystrophy: X-linked abnormality resulting in accumulation of long-chain fatty acids in oligos, Schwann cells, and adrenal cortex |
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What is the primary pathology of cell body disorders?
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-Motor neuron disease: ALS (pure motor neuropathy w/o sensory symptomes
-sensory ganglionitis: paraneoplastic syndrome with circulating Ab(s), often associated with occult neoplastic dz; attack DRG cells resulting in pure sensory neuropathy -genetic degenerative disease: Friedreich's ataxia |
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What is the primary pathology of diseases of spinal nerve roots?
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-Radiculopathy: inflammatory infiltrates or neoplastic infiltrates in SAS and spine; frequently compresses spinal roots
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What is the primary pathology in diseases of peripheral nerve axons?
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-axonal neuropathy: etiology is mostly unknown; known etiologies are nutritional deficiency diseases(vitB12, thiamine) and toxins (vincristine, arsenic, uremia); all usually result in "axonal dying-back neuropathy" where most distal portions of longest axons degenerate before proximal portions resulting in symmetrical distal sensory and motor findings
-inflammation or ischemia w/in axon may destroy axons distal to the lesion, patchy, "mononeuritis multiplex, vascular diseases (SLE, PAN) and sarcoidosis -diabetes: progressive mixed sensory and motoraxonal degeneration not related to small vessel disease -autoimmune attack against epitopes of axolemma exposed at nodes of Ranvier (axonal variant of Guillain-Barre) -systemic amyloidosis |
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What is the primary pathology of diseases of myelin sheath?
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-aquired demyelinating neuropathy (Guillain-Barre): immune attack on peripheral myelin (peripheral equivalent of MS); most common cause of demyelinating neuropathy; myelin sheath stripped by macrophages, destruction of myelin is patchy resulting in segmental demylination, remyelination results in shorter and thinner myelin internodes --> increased nodes of Fanvier = slowed conduction velocities
-toxic demyelination: lead poisoning -genetic defects in leukodystrophies (metachromatic, adrenoleukodystrophy) |
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What is the primary pathology in the diseases of the NMJ?
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-pre-synaptic (Lambert-Eaton): ab binding to voltage gated Ca channels of axon terminus block Ca influx preventing release of acetylcholine(associated with occult cancer)
-post synaptic (myasthenia gravis): ab to acetylcholine receptor prevents Ach from binding and initiating ligand gated depolarization; Ab-ag complex causes focal destruction of post synaptic membrane (simplification) -animal venoms block synaptic transmission by binding Ach receptor, cholinesterase or channels -genetic defects of Ach receptor subunits or proteins involved in synaptic cell cycling |
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What is the primary pathology in diseases of the muscle cell?
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-denervation: NMJ is interrupted trophic input is lost and cell undergoes atrophy; weakness and atrophy affectdistal more than proximal because distal portions of longest axons are affected earlier
-myopathy: degenerating myocytes leak muscle proteins (creatinine kinase, myoglobin) into blood; weakness more frequently proximal than distal |
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Peripheral Neuropathy
Focal Axonal Injury (Wallerian degeneration) |
-due to inflammatory disease
-may directly involvenerve fascicles but usually involves blood supply to fascicles -random, patchy distribution w/in individual nerves -biopsy usually shows asymmetric loss |
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Peripheral Neuropathy
Diffuse Axonal "dying back" Degeneration |
-finding in most symmetric axonal distal neuropathies
-typically distal portions of long axons affected before proximal -"stocking-glove" distribution" -usually due to pathology affecting metabolism of nerve cell -toxins (vincristine, uremia), nutritional deficiency, idiopathic |
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Peripheral Neuropathy
Primary Demyelination |
-toxins affecting Schwann cells, but usually an autoimmune attack (Guillain-Barre) or genetic defect of myelin synthesis (CMT-1)
-segmental demyelination with rapid remyelination preceded by mitotic division of injured Schwann cells -"onion bulbing" --> thickened nerve fascicles |
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What is the mechanism of Myasthenia gravis?
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POST SYNAPTIC
-circulating anti-ACH receptor antibodies -Ab binds to receptor, complex becomes endocytosed by a lysosome, leading to decreased post-synaptic receptor density -Ab on receptor blocks ACH from attaching and having effects -Ab-ag complex attracts complement, activating macrophages to strip off large segments of the synaptic sarcolemma |
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What is the mechanism of Congenital cholinesterase deficiency?
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SYNAPTIC
-markedly reduced end-plate cholinesterase histochemical staining -presynaptic axon termini abnormally small |
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What is the mechanism of Lambert Eaton Myasthenic Syndrome?
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PRE-SYNAPTIC
-circulating Ab to voltage-gated Ca channel on PRE-SYNAPTIC membrane -reduced Ca inflow during depolarization --> reduced vesicles fusing with membrane --> reduced release of ACH |
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What are the neuropathic changes seen in muscle pathology?
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1) grouped atrophy - several overlapping motor units lose innervation (type 1 and 2 fibers)
2) fiber type grouping - loss of normal "checkerboard" ATPase pattern due to denervation followed by reinnervation 3)target fibers - loss of myosin filaments and mitochondria from center due to denervationa and reinnervation 4) "nuclear bags" - remote denervation; loss of all contractile elements shrinking to a collection of nuclei in a sarcolemmel sac |
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Inflammatory myopathies:
Polymyositis, Dermatomyositis, Collagen Vascular Disease and Vasculitis |
-POLYMYOSITIS: scattered myofibril necrosis and/or regeneration w/ diameter variation; variable amt of lymphocytic infiltrate; markedly elevated CPK; primary autoimmune attack against myocyte
-DERMATOMYOSITIS: focal atrophy of fibers at periphery of fascicles and loss of endomysial capillaries; "moth-eaten" myocytes; primary autoimmune attack agains endothelial cells -COLLAGEN VASCULAR DISEASE: SLE, mixed CT, RA; myofiber necrosis and inflammatory infiltrate (more prominent that seen in polymyositis) -VASCULITIS: often no necrosis of muscle because of adequate collateral circulation, occasional infarct |
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Inflammatory Myopathies:
Inclusion Body Myositis, Para-infectious (viral) Myositis, Sarcoid, Parasites |
-INCLUSION BODY MYOSITIS: focal degeneration "rimmed vacuoles" or inclusion bodies with autophagic vacuoles filled with membranous debris (containing filaments of hyperphosphorylated tau, beta amyloid, prion protein); slowly progressive; CPK is not usually high
-PARA-INFECTIOUS (VIRAL) MYOSITIS: acute rhabdomyolysis; no lymphocytic infiltrates occuring at end of flu-like illness; monophasic and self limited -SARCOID: typical granulomas -PARASITES: trichinella, toxo |
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What are the Sarcolemmal-ECM defects?
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-Dystrophinopathies(X-linked): Duchenne (severe) and Becker (less severe); dystrophin binds to dystroglycansarcoglycan complex stabilizing the sarcolemma during contraction; degeneration due to tearing of sarcolemma
-Sarcoglycanopathies (autosomal recessive): limb girdle muscle dystrophy histopath similar to dystrophinopathy -Laminin Deficiency: alpha 2-isofor of basal lamina protein (muscle dystrophy + brain development affected with white matter changes) -Dysferlinopathy (autosomal recessive): mild adult onset of proximal LGMD -Caveolinopathy (autosomal dominant LGMD): membrane protein involved in transmembrane transport and signal transduction with a mutation |
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What are the channelopathies?
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MYOTONIC DYSTROPHY (autosomal dominant): CTG repeat in DMPK gene, age of onset related to CTG expansion, worse through paternal inheritance; abnormality of membrane depolarization/repolarization (occurs in Chloride channel)
MYOTONIA CONGENITA: can be autosomal recessive loss of function or dominant negative - cholride channel MALIGNANT HYPERTHERMIA: autosomal dominant, exposure to inhalant anesthetic/depolarizing mm. relaxant resulting in tetany + fever + lactic acidosis + rhyabdomyolysis; mutation of voltage gated Ca channel on SR causing sustained activation of contractile mechanism |
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What are the congenital myopathies?
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MYOFIBRILLAR (cytoskeletal defects): nemaline myopathies (mutation in tropomyosin, troponin, alpha-actin), variable severity, accumulation of nemaline rods; central core disease (mutation in same Ca channel as in malignant hyperthermia) variable weakness
MYONUCLEAR: centronuclear (mild hypotonia/weakness) and myotubular (sever congenital myopathy leading to respiratory failure in infancy |
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What are the disorders of carbohydrate metabolism?
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MUSCLE SPECIFIC MYOPHOSPHORYLASE DEFICIENCY (McArdle's): excercised induced lactic accumulation, acute necrosis following exercise, absence of enzymatic activity in muscle biopsy
ACID MALTASE (Pompe's): severe glycogen accumulation in skeletal and cardiac mm. along with liver, weakness of respiratory muscles |
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What are the disorders of fatty acid metabolism?
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DEFICIENCY OF SERUM CARNITINE: usually associated with liver disease/ secondary deficiency of carnitine synthesis escess lipid in mm. fibers
DEFICIENCY OF CARNITINE TRANSPORTER: prevents serum carnitine from entering myofiber DEFICIENCY OF CARNITINE PALMITYL TRANSFERASE: needed to transport fatty acids across outer and inner mito membrane, rhabdomyolysis with stress |
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What are the defects of oxidative phosphorylation?
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-due to mutation of mitochondrial DNA
-"ragged red fibers" accumulation of ultrastructurally abnormal mitochondria, syndromes include MELAS, MERRF, KSS (Kearns-Sayre Syndrome) and PEO (Progressive external ophthalmoplegia |
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How do you diagnose a motor neuron disease?
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-"diseases of exclusion" need to eliminate other causes before arriving at diagnosis
-suspect ALS if there is upper + lower motorneuron weakness, also suspect post-polio or spinal muscular atrophy with just lower -EMG: will see diffuse spontaneous activity, fasciculation and large motor unit potentials firing rapidly -Biopsy: neurogenic abnormalities (angular fibers/group atrophy) |
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How do you diagnose a neuropathy?
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-sensory signs, absent reflexes, symptoms of tingling/numbness, distal weakness
-EMG distinguishes between axonal or demyelinating and localizes site of nerve entrapment -Biopsy: cause --> inflammatory, infiltrative (amyloid), demyelinating (G-B |
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How do you diagnose Neuromuscular Transmission Disease?
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-fluctuating weakness; easy fatigueability (MG), increased strength with effort (Lambert Eaton); "tensilon test" give AChE inhibitors, MGs get stronger
-Repetitive nerve stimulation: low frequency (fatigue in presynaptic and postsynaptic disorder) and high frequency (indcremental response in Ca dependent presynaptic disorder) -Biopsy: nothing without biopsy samples that contain end-plates |
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How do you diagnose myopathies?
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-usually proximal weakness, high CPK and small CMAP
-Biopsy: cause --> inflammatory (acute vs. subacute), dystrophies, mito disease, lipid or glycogen storage disease -MITO DISEASES: exercise intolerance, tachycardia and profuse sweating, lactic acidosis, neurologic affects, respiratory chain deficiency; PEO - eyelid ptosis, w/ involvement of other organ systems (KSS); MERRF - ragged red fibers, myoclonus/generalized seizures, ataxia, myopathy; MELAS - mitochondrial encephalomyopathywith lactic acidosis, early onset stroke, dementia, seizures, ragged red fibers |
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Tumors of the Nervous System: general findings
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-metastasis to sites like lungs, lymph nodes and liver are not a significant problem
-"benign" and "malignant" along with grades I to IV are used to classify tumors; benign tumors can still be fatal -there is high risk of spread along CSF pathways, treatment of the entire craniopinal axis must sometimes be used when there is spread |
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Pilocytic astrocytoma
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-primarily a pediatric tumor
-commonly located in cerebellum, chiasm hypothalamus, brainstem -usually no progression to more aggressive grades, usually well circumscribed with no infiltration -microscopically - bipolar fibrillary astrocytes |
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Infiltrating astrocytoma / Glioblastoma Multiforme
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-primarily in adults
-commonly located in the hemispheres/deep white matter -diffuse infiltration fo parenchyma, can't be completely resected; poorly circumscribed mass -microscopic: proliferation of atypical astrocytic cells into normal brain parenchyma -difference btwn primary GBMs and secondary GBMs: primary account for 90% and occur in somewhat older populations |
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Oligodendroglioma
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-primarily in adults, commonly located in the hemispheres
-diffusely infiltrating and cannot be resected -respond better to chemo than astrocytomas -microscopic: fried egg appearence, cells with regular round to ovoid nuclei -loss of chrom 1p or 19q: need to distinguish on a molecular level to distinguish from an astrocytoma |
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Ependymoma
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-infratentorial = kids, supratentorial = adults and kids, spinal ependymoma = adults
-commonly in and around the ventricles or in sc -can be resected based on location; pronosis better in adults than kids -tendency to spread along CSF space, low grade tumors are typically well circumscribed -microscopic: immunohistochemical staining is positive for GFAP |
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Pituitary Adenoma
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-primarily in adults
-can present with microadenoma with endo problems or as a macroadenoma w/ or w/o hormone production causing problems due to size -typically well circumscribed consisting of sheets, nests or ribbons |
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Ganglioma/Gangliocytoma
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-primarily seen in kids / young adults
-commonly seen in the temporal lobe --> associated with chronic epilepsy -can be cured by complete resection |
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Meningioma
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-primarily seen in adult females
-typically in the dura, vascular and well circumscribed -excellent prognosis with complete resection, but complete resection may not be possible due to location -porr prognositic factors include: high proliferation, brain invasion, loss of architecture, areas of tumor necrosis -can occur as manifestation of NF2 |
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Chordoma
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-primarily in adults
-notochord reminants in nucleus pulposus of spine most are in sacrum or clivus -microscopic: myxoid matrix and epithelioid cells, bubbly cytoplasm |
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Medulloblastoma
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-malignant pediatric tumor
-cerebellar mass, grossly well circumscribed -may present with blockage of CSF flow of the fourth ventricle -microscopic: small blue cell tumor that grow in sheets, also see focal rossette formation -primary prolem is aggressive local growth that can spread through the CSF -seen w/ increased frequency in familial syndromes (Gorlin's, Li-Fraumeni) |
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Pineoblastoma
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-malignant pediatric tumor
-penial region mass, small blue cell tumor with focal rossette formation, -familial retinoblastoma patients(due to mutation in the Rb gene) can develop pineoblastomas |
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Craniopharyngioma
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-occur most often in young adults
-suprasella/sella tumors -derived from Rathke's pouch, grossly lobulated, cystic tumors with oil like "cholesterol crystal" fluid and calcification COLLOID CYST/ RATHKE'S CLEFT CYST - incidental autopsy finding in pituitary/ pituitary stalk |
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Metastatic Disease in the Brain
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-sigle or multiple lesions
-well circumscribed nodules found anywhere (leptomeninges usually associated with tumor cells in the CSF) -can be hemmorhagic and affect neurologic function through compression |
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Lymphoma
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-can occur in two different settings 1) sproadic extranodal lymphoma or 2) in immunocompromised patients
-both are typically deep parenchymal lesions -tumors show temporary response to steroids but overall prognosis is poor |
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Schwannoma
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-primarily in adults
-arrise from cranial nerves (esp. 8th), also arise from spinal nerve roots or peripheral branches -microscopically: palisading of nuclei "school of fish", spindles nuclei with a wavy/buckled/bend shape and blunt tips -multiple schwannomas associated with NF2 |
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Neurofibroma
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-commonly occur in adults
-central large nerves, plexus or nerve roots or peripheral nerve branches -mixed cell population of fibroblasts, perineurial cells, mast cells and Schwann cells -there are different forms: small subcutaneous nodules not infrequently found as sporadic lesions; diffuse soft tissue large masses associated with NF1, can be large and disfiguring; plexiform neurofibromas expand in normal shell of perineurium, bag of worms gross appearance, always associated with NF1 |
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Malignant Peripheral Nerve Sheath Tumors (MPNST)
|
-primarily in adults, associated with nerve roots or plexus
-half occur in NF1 and half ar sporadic |
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Familial Tumor Syndromes
|
NF1 - autosomal dominant; gene on 17q; risk of neurofibromas, MPNSTs, optic gliomas, astrocytomas, learning disability and seizures; can see Lisch nodules, pheochromocytoma, cafe-au-lait spots
NF2 - autosomal dominant; gene on 22q; vestibular schwannomas, meningiomas and ependymomas (spinal) TUBEROUS SCLEROSIS (TSC): autosomal dominant; mutation on gene 9q or 16p encoding hamartin and tuberin; clinically seizures and learning delay VON HIPPEL LINDAU DISEASE (VHL): autosomal dominant; mutation on VHL gene on 3p to induce the transcription of hypoxia induced genes; at risk for hemagioblastomas in brain and retina, renal cysts, renal cell carcinoma, islet cell tumors and pheochromocytoma LI-FRAUMENI SYNDROME: autosomal dominant; p53 mutation on 17p; can get astrocytoma, medulloblastoma,osteosarcoma, breast cancer, leukemia adrenocortical carcinoma GORLIN'S SYNDROME: autosomal dominant; mutation on PTCH gene on 9q; medulloblastomas and others |
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What are the signs and symptoms os CNS infections?
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-fever, headache, meningismus, photophobia, n/v, neck pain and stiffness, seizures, change of mental status
-meningeal signs (nuchal rigidity, Kernig's sign (painful knee extension), Brudzinski's sign (lifting of legs when head is lifted), focal neurologic signs (hemiparesis, CN palsies), skin lesions |
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Subdural Empyema
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-infection between DURA and ARACHNOID
-crescent-shaped nypodense collection over cerebral convexity, can have interhemispheric region enhancement -intracranial subdural empyema is a complication of either sinusitis(frontal) or otitis media/mastoiditis. rare complication fo head trauma, neurosurgery, bacteremia or dental infection -pathogens: oral strep, bacteroides fragilis, S. aureus and H. influenza -surgical drainage required -pathogenesis: infection in frontal sinus veins spreads through emissary veins across the skull into subdural space in into the interhemispheric region |
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Intracranial Epidural Abscess
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-pus collection btwn dura mater and skull, associated with osteomyelitis, can cross dura along emissary veins and infect subdural space
-insidious onset with sinus/ear pain, local headache to generalized headache, leading to alteration of neurologic status and seizures -almost always associated with head trauma or a complication of sinusitis, otitis media, mastoiditis, craniotomy; always associated with osteomyelitis and septic thrombophlebitis -pathogens similar to subdural -surgical drainage required |
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Acute Bacterial vs. Aseptic Meningitis
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-bacterial is more severe; CSF: low glucose, high white count, lots of neutrophoils, positive gram stain and culture; may have positive blood culture
-aseptic: usually more benign; CSF: normal glucose, small wht cell increase, lymphocytes are predominant, CSF gram stain/blood cultures are negative |
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Treatment of Bacterial Meningitis
|
-vancomycin plus ceftriaxone for S. pneumo, N. meningitidis, S. agalactiae, E.Coli
-high dose ampicillian when Listeria is suspected |
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Causes of Actue Aseptic Meningitis
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-viral: enterovirus, arbovirus, herpes, mums, influenza, parainfluenza, HIV
-leptospirosis -syphillis -lyme disease -drugs (NSAIDS, TMP/SMX -SLE |
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When should you suspect encephalitis?
|
-meningitis symptoms
-change of mental status, forcal neuro exam, personality changes, temporal lobe syndromes (hallucinations, erratic behavior, short term memory loss), frontal lobe syndromes (loss of smell, motor weakness) |
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Etiology of Viral Encephalitis
|
-enteroviruses (echo, coxsackie, polio, hep A)
-arthropod-born -herpes (HSV1 and 2, VZV, EBV, CMV -measles, mumps, rubella -HIV, JC Virus (PML), Rabies (variable incubation period, multifocal areas of neuronal degeneration and perivascular cuffing, cytoplasmic inclusion(negri body) found in least devastated areas) |
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What is Reye's Syndrome?
|
Acute fatty liver degeneration, encephalopathy with cerebral edema and elevated intracerebral pressure
-no CSF pleocytosis, follows viral infection (usually H. flu or varicella) -epidemiologically associated with aspirin use |
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Acute Disseminated Encephalomyelitis
|
-previously called post-infectious encephalitis
-occurs 2-12 days after respiratory viral infection, measles, varicella, rubella or mumps -abrupt onset of symptoms with frequent seizures, lethargy and coma -treatment is with steroids, and IV immunoglobulins |
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Subacute and Chronic Meningitis
|
-TB, neurobrucellosis, fungal, syphilis, lyme disease, acanthamoeba
|
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Brain Abscesses
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-contiguous spread: sinusitis, otitis media, dental infections, bacteremia, inoculation
-in AIDS patients: toxo, nocardia, TB, listeriosis, crypto, aspergillosis |
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Epidural Infections
|
-usually bacterial and almost always secondary to head trauma
-more common in the spinal canal with a true epidural space; compression of the spinal cord can result leading to ischemic necrosis (a surgical emergency) -mycobacterial infection also a common source of compression |
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Subdural Infection
|
-usually bacterial pyrogenic that can be loculated with focal abcesses or a massive empyema
-usual route is through paranasal sinuses |
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What is the pathogenesis of acute bacterial meningitis?
|
Inflammatory response with neutrophil migration to the CSF --> meningeal inflammation compresses arterial blood flow through the subarachnoid space causing brain ischemia --> edema fluid escapes parenchymal vascular bed causing swelling of the brain and increased ICP --> CSF glucose levels fall causing increased anaerobic metabolism and CSF protein rises with breakdown in the blood-brain barrier
|
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Chronic Meningitis
|
-TB: granulomatous inflammation can be seen throughout the meninges, most severe at base of brain around the brainstem and sc; frequently obstructs CSF outflow from 4th ventricle
-SYPHILIS: lymphocytic infiltrate of CSF found in early infection; three froms of tertiary neurosyph 1) meningovascular (meninges) 2) paresis (parenchyma) 3) tabes dorsalis (long tracts of sc, dorsal roots) -LYME DISEASE: borrelia burgdorferi infection with cranial and spinal root involvement |
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Fungal CNS Infection
|
-cryptococcus is most common fungal infection producing chronic menigitis
-common with AIDS and immunosuppression patients -hematogenously spread from a primary lung focus (primary infection is asymptomatic, prevalent in pigeon poop) -can be found in CSF with "india-ink" test |
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Protozoal CNS Infections
|
-TOXOPLASMOSIS: most common opportunistic infection of brain in AIDS patients (also immunocompromised and neonates)
-present in animal feces and raw meat, reaches brain by blood stream - a lesion forms that looks grossly like an abscess with central necrotic tissue and little macrophage activity; toxo is toxic to small vessels and creates and expanding area of infarction -CONGENITAL TOXO: transplancental transmission during the 3rd - 7th month of gestation; causes widespread destruction of central grey and white matter with cystic degeneration and calcification -others (uncommon): Naeglaria, entameba histolytica, hartmannella-acanthameba (normal gut organism that affects immunocomprimised), trypanosomes |
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Multicellular Parasite CNS Infection
|
-CYSTICERCOSIS: larvae of pork tapeworm Taenia solium, common in Central and South America; larval lesions due to ingestion of ova in food contaminated by infected people or autoinfection in people with intestinal tapeworm infection; widespread lesions in meninges, parenchyma and ventricles
-ECHINOCOCCAL cysts: larval stage of dog tapeworm, common in areas where sheep are raised |
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Herpes Simplex Encephalitis
|
-most common viral encephalitis in immunocompromised hosts, acute focal presentation
-produces asymmetric hemorrhagic necrosis of inferior surface of temporal and/or frontal lobes leading to spread to underlying white matter -entry through to be through olfactory epithelium or CN 5 -patients die from massive swelling in contained frontal-temporal region |
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Arbovirus Encephalitis
|
-usually incidental human infections spread by mosquito or tick bites, endemic and seasonal, acute disseminated presentation
-autopsy shows swollen brains with widespread cell necrosis and microglial invation -RICKETTSIA: rocky mountain spotted fever, infection of endothelial cells causes brain edema and death due to swelling -ENTEROVIRUS: poliomyelitis, predilection for motor neuron infection in anterior horns and brainstem |
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HIV Encephalitis
|
-HIV can produce a chronic encephalitis or myelitis
-primarily confined to lymphocytes or monocytic cells -characteristic lesions are multiple foci of white matter degeneration with clusters of microglial nuclei -multinucleated giant cells have HIV identified in microglial cells -loss of cortical neurons and pruning of dendritic arborizations of cortical neurons may be responsible for dementia seen with infection - |
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Progressive Multifocal Leukoencephalopathy (PML)
|
-opportunistic infection in AIDS patients and immunosuppressed organ transplant patients
-confined to white matter where there are multiple centrifugally expanding areas of myelin degeneration -oligodendrocyte nuclei at expanding margins are swollen and filled with JC virus -astrocytes may be infected but do not replicate the virus - |
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Subacute Sclerosing Panencephalitis (SSPE)
|
-persistent viral infection which has almost disappeared with the invention of the measles vaccination
-found in kids with typical measles syndrome of pharyngitis who recovered and ultimately died due to progressive deterioration fo the CNS (atrophy and gliosis of cortex and white matter) -intranuclear inclusions were filled with paramyxovirus nucleocapsid in neurons, oligos and astrocytes -viral RNA is passed from cell to cell through adhesions by viral neuraminidase -encephalopathy not due to virus entering the brain rather due to an autoimmune demyelination (post-infectious encephalomyelitis |
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Prions
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-neurogenerative diseases that are both genetically inherited and transmissible
-CJD: sporadic form, rapidly progressive dementing illness lasting a few months; spongy degeneration of background neuropil with neuronal loss and some astrocytic proliferation; infectious agent can be transmitted (others are fatal insomnia, GSS and vCJD) -infectious protein encoded by a gene present in normal ppl; normal PrP is post-translationaly modified to PrPSc which is resistant to proteases; 10% is familial -see rapid dementia, ataxia and myoclonus |
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Demenitia in General
|
- age is most significant risk factor, 5-10% of population aged 65-75 has dementia, 10-15% from 75-85 and 50% over 85
- "an aquired persistent impaiment of intellectual function that involves memory and one other area of cognitive function (language, visuo-spatial skills, emotion/personality, abstration, judgement, etc.) that is severe enough to interfere with ADLs - presenile dementia<65 and senile>65 - vs. delirium: due to different etiologies; dementia = chronic progressive course of cognitive impairment; delerium = acute and affects global cognitive function and alertness |
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What are the causes of Dementias?
|
-Degenerative (Alzheimer's, Huntington's, Dem. with Lewy Bodies, Frontaltemporal, Prions)
-Endocrine (hypothyroid, hypo- hyperparathyroid, pit dz, adrenal dz) -Metabolic (ETOH, electrolyte disturbance, renal dz, B12/folate def.) -Exogenous (toxins, drugs) -Neoplasms (CNS tumos, paraneoplastic syndromes) -Trauma -Infection -Affective Disorder (depression) -Structural (vasculitis, normal pressure hydrocephalus) |
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How do you diagnose dementia?
|
HPI
-onset of disease (acute or gradual) -memory problems, use of language, psychiatric manifestations, ADLs PE -appearance and affect -mental status exam: MMSE has low sensitivity but is specific for cognitive impairment -Lab tests: BLOOD STUDIES - Dementia panel including CBC, B12, glucose, electrolytes, calcium, TSH, RPR, and HIV),LFTs, blood cultures, vasculitis screens; IMAGING STUDIES - evaluate for subdural hemorrhage, generally MRI or CT; EEG (rule out seizures); CSF; Functional imaging (PET and SPECT looking for regional decreases in brain activity); Genetic studies (generally not performed except for rare incidences familial forms of AD, FTD, Huntington's or Prions) |
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Alzheimer's Disease
|
-most common cause of dementia in the elderly (10% of people over age 65 and 50% over age 85)
- clinical features: short term memory loss followed by differing degrees of disorientation to "3 As"- agnosia (forgetting to use common items), apraxia (difficulty with learned motor movements), aphagia (difficulty with understanding or expression) -frontal release signs (snout, grasp, palmomental, rood and suck) can be observed early on -should not have focal weakness or numbness -in later stage of dz may show gegenhalten (increased mm. tone), myoclonus, and seizures; if in early stages may think of some other dz process -patients die from aspiration pneumonia or sepsis from bladder infection -Three major diagnostic catagories: 1) definite AD- pathologically confirmed with characteristic plaques and tangles 2) probable AD- clinical criteria suggest AD only cause of dementia 3) possible AD- AD present with other conditions contributing to the demented syndrome -genes associated: Presenilin1 (PS1), Presenilin2 (PS2), APP and ApoE |
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Dementia with Lewy Bodies
|
-main features: mild parkinsonism (rigidity, bradykinesia, hypophonia, reduced facial expression, tremor), hallucinations ("friendly type" that they are fully aware are hallucinations) and large fluctuations in level of alterness/conciousness
-parkinsonian features not as responsive to meds as in normal Parkinson's -brain path shows nuclear inclusions consisting primarily of alpha-synucelin scattered throughout the neurons rather than isolated to dopamine neurons |
|
Frontotemporal Dementia (FTD)
|
-compromise 10% of dementia patients and 20% of those patients under 60
-early appearance of behavior/personality changes (impulsivity, decrease in tact, public exposure, stealing, etc) -on exam will see "frontal release" symptoms (grasp, snout, and palmomental (scratching the palm causes the ipsilateral chin to itch -memory not affected early in the disease due to location along with visuospatial -some pts. have language function affected early, progression of the disease leads to a common feature of reduced speech output and mutism -called tauopathies as tau is the central protein |
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Vascular Dementia
|
-commonly thought of in two ways: 1)multi-infarct dementia (MID), patient has several subcortical strokes to global loss of cognition 2) Binswanger's disease, repeated small lacunar type strokes leading to white matter encephalopathy: difference between the two are determined by CT or MRI
-usually see a "step-wise" decline rather than a gradual one -characteristic features: hypertension, abrupt onset of symptoms after recovery, gait difficulty, inappropriate emotionalism -most probably coexist with AD |
|
Normal Pressure Hydrocephalus
|
-classice triad 1)gait disturbance 2)urinary incontinence and 3)dementia; may also show spasticity in lower extremities and decreased coordination in upper extremities
-less cortical pathology ("3 A's") than seen in AD -usually have a history of head trauma/subarachnoid hemorrhage, cause is scarring of arachnoid granulations preventing CSF resorption -treatment is usually placement of a shunt to divert CSF out of the brain into the peritoneum |
|
AIDS Dementia Complex/HIV Encephalopathy
|
-observed in 70% of patients with AIDS, common in late disease
-insidious onset with forgetfulness, apathy, social withdrawl, impaired balance, leg weakness,etc. -on exam will see cerebellar ataxia, upper motor neuron signs of weakness, hyperreflexia, extensor plantar responses -could see myoclonus, seizures, quadraparesis and psychosis -MRI shows diffuse atrophy of white matter involvement |
|
What is the therapy for dementia?
|
-best known treatment of AD is cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) that inhibit activity of acetylcholinesterase increasing ACh in the post-synaptic terminal --> better memory formation
-effect on the patient is subtle and tends to stabilize the disease rather than improve symptoms -also use NMDA partial antagonists (memantine) that protect from glutamate toxicity and stimulate memroy formation --> statistically significant affect when combined with anticholinesterase in late AD |
|
What happens in neurodegenerative diseases of the sc? cerebellum? hippocampal area? and frontal cortex?
|
-sc: muscle weakness
-cerebellum: ataxia -hippocampal area: memory deficits -frontal cortex: apathy, disinhibition, or depression |
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What are the diseases of the archicortex and neocortex and how do they present?
|
-AD, Dementia with Lewy Bodies, Pick's disease, FTDP-17, Corticobasal degeneration
-dementia with problems like impaired memory function or personality changes |
|
What are the diseases of the basal ganglia and how do they present?
|
-Parkinson's, Huntington's, Triatonigral pattern of multiple system atrophy
-movement disorders with abnormalities in muscle tone and speed of movement |
|
What are the diseases of the brain stem and/or cerebellum?
|
-Progressive supranuclear palsy (PSP), Spinocerebellar ataxias, Dentatorubropallidoluysian atrophy
-movement disorder with cerebellar features/ataxia (not PSP) |
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What are the diseases of the sc and how do they present?
|
-motor neuron disease, ALS, spinal muscular atrophy, Friedreich's ataxia
-variable presentation with mixed upper and lower neuron signs, weakness or ataxia |
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Pathology of AD
|
-prominent changes in medial temporal lobes grossly
-two main histologic changes are neurofibrillary tangles (hyperphosphorylated tau protein most seen in large pyramidal neurons)and senile plaques (extra-cellular accumulations of beta-amyloid; can distinguish diffuse, neuritic and burnt-out -also see hirano bodies in hippocampus with degeneration |
|
Parkinson's Disease (Lewy Body disease)
|
-presents with bradykinesia, rigidity and tremor
-primary feature is neuronal loss in pars compacta of substantia nigra, pigment-laden macrophages ("tomb-stones") can also be found; lewy bodies are a very helpful diagnostic feature (homogeneous red/eosinophillic core surrounded by a clear halo -accidental ingestion of toxin MPTP has been linked to parkinson-like dz in humans -has been linked to mutations in alpha-synuclein, parkin, DJ-1 and PTEN-induced kinase 1 which may cause mitichondrial and oxidative stress, also leading to accumulation of substrates |
|
Pick's Disease
|
-one of the more rarer forms of dementia
-atrophy in fronto-temporal distribution with thin atrophied cortical ribbons, caudate has significant atrophy mimicking Huntington's -see Pick bodies histologically that are prominent in the pyramidal cells of the hippocampus, look like "ballooned neurons" -characterized by accumulation of 3-repeat tau isoforms -80% are sporadic |
|
Corticobasal Degeneration (CBD)
|
-affects the neocortex and basal ganglia (atrophy with pigment loss of the nigra) clinically manifesting as akinetic rigid syndrome with dementia (movement and dementia)
-cells look like Pick cells "ballooned neurons" -is a tauopathy with 4-repeat tau |
|
Progressive Supranuclear Palsy (PSP)
|
-downward gaze is preserved as a reflex movement and patients loose their ability to voluntarily gaze downwards followed later by upward gaze
-can affect multiple nuclei leading to a diverse and variable presentation -grossly is not associated with alterations -hyperphosphorylated tau are 4-repeat tau along with CBD, can be hard to distinguish between the two |
|
Huntington's Disease
|
-dominant neurodegenerative movement disorder primarily affecting the basal ganglia, patients can develop dementia late
-see degeneration of normal function in striatum (caudate and putamen) manifesting as chorea and rigidity -histologically see neuronal loss (faster in small to medium sized GABAergic neurons) and gliosis -caused by an increased number of CAG repeats in huntington gene on chromosome 4 <29 not associated wtih disease state >40 typically means clinical disease, increase in number means increase in severity and degrease in age of onset |
|
Multisystem Atrophies (MSA)
|
-presentation depends on what nuclei are primarily affected
-striatonigral atrophy = parkinsonism; olivopontocerebellar atrophy = ataxia; Shy-Drager = degeneration of sympathetic preganglionic cells -see glial cytoplasmic inclusions -abnormal accumulations of MSA have a tubular morphology |
|
Cerebellar ataxias
|
-triplet repeat diseases causing protein accumulations that can be seen as nuclear inclusions, diseases are not associated with distinct pathologic changes
-group includes spinocerebellar ataxias and others like dentatorubruopallidoluysian atrophy |
|
Friedreich's Ataxia
|
-autosomal recessive disease linked to a GAA triplet repeat expansion in centromeric frataxin gene on 9q
-patients develop ataxia, sensory neuropathy, cardiomyopathy and diabetes mellitus -see degeneration of dorsal root ganglion cells, dorsal columns, and cerebellar tracts |
|
Motor Neuron Disease (ALS)
|
-primarily affects the primary motor neurons in sc (anterior horn cells or lower motor neurons), CN motor neurons and pyramidal neurons in primary cortex
-see a mixture of UMN and LMN degeneration -most cases are autosomal dominant and some have Cu/Zn superoxide dismutase gene mutations |
|
Spinal Muscular Atrophy (SMA)
|
-genetically determined degenerative diseases of LMN associated with anterior horns, the roots look shrunken
-SMA1 is most severe in acute infantile form also known as Werdnig's Hoffman disease, infants are "floppy" at birth and die of early due to respiratory failure |
|
What are seizures?
|
-acute onset of neurologic dysfunction symptoms
-paroxysmal episodes of brain dysfunction manifested by stereotypical alterations on behavior; symptoms (sensory, motor, autonomic w/ or w/o loss of conciousness -excessive or oversynchronized discharges of cortical neurons or ineffectice recruitment of inhibitory neurons together with excessive neuronal excitation, imbalance of GABA/NMDA -epilepsy = recurrent unprovoked seizures |
|
What is the pediatric vs. adult etiology of seizures?
|
PEDS: genetic, congenital malformations, infection, tumor, metabolic disorder, idiopathic
ADULTS: tumor, trauma, vascular, infection, occult cortical dysplasias, idiopathic |
|
What are the partial seizures?
|
SIMPLE PARTIAL SEIZURES: no impaired conciousness; motor symptoms - involves motor strip, abnormal movements of extremities, jacksonian March-spread over motor strip, Todd's paralysis post-ictal weakness of seizing limb; sotmatosensory - sensory strip involvement, temporal (hearing or smell) occip (visual); autonomic - temporal lobe (tachycardia, pallor, flushing, sweating); phychological - frontal or temporal (patients are aggitated)
COMPLEX PARTIAL: impaired conciousness, onset followed by loss of conciousness, can progress to a generalized seizure, frequently seen in adult onset epilepsy, usually found in temporal lobe |
|
What are the generalized seizures?
|
-always occur with a loss of conciousness
-can be convulsive or nonconvulsive movements -types: absence (starring spells), clonic (convulsive), tonic (stiffness), tonic-clonic, myoclonic (rapid jerks), atonic (drop attacks) |
|
What are Psuedoseizures/Psychogenic seizures?
|
-seizure-like episodes without abnl cerebral discharge
-may be psychiatric -movements are not tonic-clonic, video EEG can be helpful in dx |
|
How do you diagnose epilepsy?
|
-can be done on clinical history alone: H&P important in evaluating type and etiology of seizure/syndrome
-Lab and imaging: rule out metabolic disorders and structural lesions -EEG: aid in the diagnosis and characterization of seizure type/syndrome |
|
Electroencephalography (EEG)
|
- measure of electrical activity (post-synaptic currents, IPSP and EPSP) produced by brain and recorded by electrodes on the scalp
-determines level of alertness/encephalopathy and stage of sleep -EPILEPTIFORM DISCHARGES: abnormal wave forms (sharp waves, spikes, spike and wave, polyspike and wave); change must break from the background (change in frequency, sudden onset and termination, should last greater than 10 sec) |
|
What are febrile seizures?
|
-seen from 6 mo. to 6 y.o.
-brief tonic-clonic seizures not associated with infection or other cause -EEG abnl only during seizure -possibly related to too rapid of a rise in a fever -prognosis is good as most outgrow the seizures by 5, don't always treat with meds |
|
What are Infantile Spasms?
|
-onset < 6 mo., spasms are less than 5 sec.
-head drop, neck flexion, arm extension or a mix -EEG - hypsarrhythmia (disorganized chaotic background) -treat with depakote w/ ACTH possibly; also surgery if focal area is found |
|
What is Lennox Gastaut Syndrome?
|
-age of onset 6 mo. - 2 yrs, different types of seizures (complex partial, generalized, drop attacks, etc.)
-associated with mental retardation, EEG shows slow spike and wave -usually follows infantile spasms |
|
What are Absence Seizures?
|
-onset < 13yrs, conciousness impaired by "starring spell"
-very brief < 10 seconds, sensitive to hyperventilation -very responsive to Ethosuxide (dramatic improvement) and can be outgrown |
|
What is Myclonic Epilepsy?
|
-Juvenille Myoclonic Epilepsy is the most common with onset in the teen years
-usually generalized convulsive seizures, sensitive to sleep deprivation and photic stimulation -responds well to Valproic Acid (Depakote) |
|
What is temporal lobe epilepsy?
|
-onset in late tenns/early adult, mostly idiopathic
-complex partial seizures are mostly seen; EEG shows focal discharge from temporal lobes -can see hippocampal atrophy/sclerosis on imaging -doesn't respond to meds, can respond very well to surgery if an appropriate candidate |
|
Dilantin/Fosphenytoin
|
-good for focal and generalized seizures
-affects sodium channels -works through the P450 system -TOXICITY:ataxia, nystagmus, sleepiness -SEs: rash, tremor, hepatotoxicity, purple glove, increased fatial har, gum hypertrophy (avoid use in teens) -watch out fo rapid infusion bradycardia/heart block |
|
Phenobarbital
|
-good for focal and generalized seizures
-affects Na channels and GABA receptors -popular with babies, easy to get levels -watch for respiratory depression/hypotension with rapid IV infusion |
|
Valproic Acid/Depakote
|
-good for GENERALIZED seizures
-affects Na channels and GABA receptors -P450 enzyme inhibitor -can cause elevated LFTs and liver failure; also pancreatitis, thrombocytopenia, rash, tremor, sedation |
|
Carbamazepine/Tegretol
|
-good for focal onset seizures, could aggravate generalized epilepsies
-Na channels are affected -STRONG P450 INDUCER = DRUG DRUG INTERACTIONS -SEs: rash, elevated LFTs, hyponaturemia -TOXICITY: tremor, sedation, n/v, double vision |
|
Topiramate/Topamax
|
-good for focal and generalized
-Na channels, GABAa receptors and glutamate receptors affected -SEs: weight loss, sedation, kidney stones, inability to sweat -also used in chonic migranes |
|
Lamotrigine/Lamictal
|
-focal and generalized
-affects Na and glutamate -"stimulant" effect (insomnia) -NEVER USE WITH DEPAKOTE |
|
Levetiracetam/Keppra
|
-focal and generalized seizures
-unclear mechanism of action, renally excreted -associated with rare mood swings and ataxia |
|
Ethosuximide/Zarontin
|
-absence seizures only, affects Ca channels
-SEs: GI upset, rash, rare - SLE agranulocytosis, parkinsonian changes |
|
Status Epilepticus
|
- a NEUROLOGIC EMERGENCY
- a seizure that lasts greater than 30 minutes, greater than 2 seizures in a row without regaining conciousness in between -new onset seizures, infection, trauma, SAH, stroke Drugs, etc. -treatment: ABCD, Lorezepam, phenytoin, and do labs (CBC, LFTs, head CT, drug screen and possible LP) -second and third line treatments: phenobarbital and depakote; ICU admission, intubation, pentobarbitol and midazolam |