Term
| what characterizes multiple sclerosis (MS)? |
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Definition
| this autoimmune disorder is characterizes by distinct episodes of neurologic deficits, separated in time and white matter lesions separated in space. women are affected more than men (1 in 1000 in US/europe). MS generally follows a relapsing, remitting course. risk is greater if 1st degree relatives are afflicted. |
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Term
| what characterizes the pathogenesis of MS? |
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Definition
| an immune response is directed against the myelin sheath according to genetic and environmental factors. MS is initiated by CD4+ Th1 cells which react against self antigen and secrete cytokines such as IFN gamma (activates macrophages). pathogenesis is associated w/the MHC complex and plaques (periventricular sclerosis) consisting of T cells and macrophages form. |
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Term
| what is the morphology of MS? |
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Definition
| white and gray matter is involved, either on the surface of the brainstem and/or along the spinal cord. the plaques are irregularly shaped, softened and depressed lesions. foci may be microscopic or large and are frequent in the **optic nerves/chiasm (optic neuritis)**, brainstem, cerebellum and spinal cord. |
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Term
| what characterizes an active MS plaque? |
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Definition
| ongoing myelin breakdown, abundant macrophages w/lipid rich debris containing lymphocytes and macrophages. |
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Term
| what characterizes a quiescent MS plaque? |
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Definition
| decreased inflammatory cell infiltrate and macrophages |
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Term
| what characterizes an inactive MS plaque? |
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Definition
| little myelin, decreased oligodendrocyte nuclei and gliosis astrocyte proliferation |
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Term
| what characterizes a shadow MS plaques? |
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Definition
| poorly demarcated lesions w/thinned out myelin sheaths (hard to visualize grossly/or on imaging) |
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Term
| what are other white matter diseases (MS ddx)? |
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Definition
| viral infectious (PML, SSPE), post viral immune (G-B, variola, varicella), post vaccinal immune (rabies, smallpox), idiopathic MS, degenerative (central pontine myelinolysis, marchiafava-bignami disease), ischemic (binswanger's disease), and radiation/drugs (methotrexate) |
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Term
| what are the etiologic-epidemiologic considerations for MS? |
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Definition
| peak age 20-40 years, F:M::2:1, more northern latitudes, human herpes virus-6, chlamydia pneumoniae, epstein-barr virus, **HLA-DR2-DR15 (boards)**, and unusual in african americans |
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Term
| what are the autoimmune characteristics of MS? |
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Definition
| 22.5% +ANA, CSF may show oligoclonal gammopathy and antiphospholipid antibodies are present (possible confusion between APLS+MS) |
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Term
| what are often the targets of the immune system in MS? |
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Definition
| myelin basic proteins (MBPs) |
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Term
| what is pathogenesis of MS in the relapsing-remitting clinical variant? |
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Definition
| Th1 and T cell inflammatory rxn, demyelination following inflammation, microglial cells act as antigen presenting cells and release IL-1 and other cytokines and phagocytize myelin debris, oligodendroglial cells undergo apoptosis, axonal degeneration end point of inflammation associated astrogliosis, antibodies to MBP, and TH2 follows w/oligodendrocyte recovery and remyelination (remitting portion). |
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Term
| what are the 5 general stages of MS? |
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Definition
| 1) initiation: age 13-15, auto-reactive lymphocytes activate. 2) latency: age 15-30, intrathecal lymphocytes appear. 3) onset: age 30, inflammatory demyelination, triggered by systemic infection. stage 4) inflammation/transition: age 30-55, recurrent demyelination w/later axonal injury. stage 5) neurodegeneration, age 45-75, ongoing cortical disease w/axonal degeneration. |
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Term
| what characterizes the presence of oligodendrocytes in MS lesions? |
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Definition
| variable number (dependent on phase of injury) - low in areas of active demyelination and normal to increased w/remyelination. |
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Term
| what characterizes **optic neuritis** as a syndrome associated w/MS? |
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Definition
| unilateral, painful, loss of acuity and decreased color perception |
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Term
| what characterizes myelitis as a syndrome associated w/MS? |
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Definition
| sensory (more common) & motor signs, lhermitte's sign (tingling of arms/trunk when neck is flexed) |
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Term
| what characterizes bladder/bowel dysfunction as a syndrome associated w/MS? |
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Definition
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Term
| what characterizes cerebellar signs as a syndrome associated w/MS? |
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Definition
| nystagmus, intention tremor, gait ataxia, and dysarthria |
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Term
| what characterizes cerebral signs as a syndrome associated w/MS? |
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Definition
| sensory, motor deficits w/spasticity, and cognitive deficits (later) |
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Term
| what characterizes midbrain-brainstem signs as a syndrome associated w/MS? |
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Definition
| ocular muscle (CN III, IV, VI) palsies, trigeminal neuralgia, CN VII paralysis, internuclear ophthalmoplegia, and vertigo. |
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Term
| what characterizes the uhthoff sign as a syndrome associated w/MS? |
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Definition
| visual blurring during exercise-intensification of s/s in hot tubs |
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Term
| what clinical characteristics point to a likely MS dx? |
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Definition
| young middle-aged adult with clinically isolated syndromes (optic neuritis, myelitis, brainstem-cerebrum, cerebellar) and 3 or more T2 MRI lesions (especially if one is periventricular) has an 80% or greater likelihood of the subsequent development of MS with in 7-10 years. |
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Term
| what are the clinical features of MS? |
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Definition
| mean age of onset: 30 y/o. # of attacks in the 1st year: 1.6. total attacks: 3.5. time to progressive disease: 18 yrs. |
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Term
| what characterizes the relapsing-remitting type of MS? |
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Definition
| symptoms appear, then pt goes back to baseline. this baseline may start slowly rising. |
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Term
| what characterizes the secondary progressive non relapsing type of MS? |
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Definition
| symptoms, then back to baseline, then symptoms and a slightly higher baseline. the baseline then slowly progresses higher. |
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Term
| what characterizes the secondary progressive relapsing type of MS? |
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Definition
| a few relapsing-remitting episodes, after which the baseline continues to rise |
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Term
| what characterizes the primary progressive non relapsing type of MS? |
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Definition
| gradual onset of symptoms w/no big exacerbations |
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Term
| what are the more common/less common clinical MS courses? |
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Definition
| 84% relapsing-remitting (symptoms last 6-8weeks separated by 15 month intervals), 13% are chronically progressive, and 2% are relapsing progressive. |
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Term
| what are some clinical predictors of a more rapidly progressive course in MS? |
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Definition
| older pt (> 40 yrs), cerebellar signs (ataxia etc), short first attack interval, and high # of attacks in the first year. |
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Term
| what pyramidal function impairment occurs in MS? |
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Definition
| degrees of paraparesis, hemiparesis, monoparesis, and quadriplegia |
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Term
| what cerebellar function impairment occurs in MS? |
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Definition
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Term
| what brainstem function impairment occurs in MS? |
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Definition
| degrees of nystagmus, dysarthria, dysphagia, extraocular weakness/paralysis |
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Term
| what sensory function impairment occurs in MS? |
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Definition
| degrees of loss of touch, pain, vibration and proprioception |
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Term
| what bowel/bladder function impairment occurs in MS? |
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Definition
| degrees of hesitancy, urgency, retention, and incontinence |
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Term
| what visual function impairment occurs in MS? |
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Definition
| scotoma, loss of visual fields and acuity |
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Term
| what cerebral function impairment occurs in MS? |
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Definition
| degrees of mood alteration and dementia |
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Term
| what characterizes cerebral atrophy seen in MS? |
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Definition
| there is a decrease in cortical thickness over several years or so |
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Term
| what characterizes the effects of MS histologically? grossly? |
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Definition
| histologically: perivascular Th1 CD4 T cell infiltration (acute phase of demyelination), prominent lymphocyte cuff/collar surrounding the blood vessels, reactive astrogliosis, axon degeneration, and perivascular demyelination (can be stained for). grossly: depressed softened areas in the perivascular areas, optic chiasm/optic nerve, brain stem and cerebellum which slowly progress. |
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Term
| where are MS plaques located? (*know these*) |
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Definition
| in the periventricular white matter (can extend into the grey matter since conneted), optic nerves/chiasm, brainstem, ascending and descending fiber tracts, cerebellum, and spinal cord. |
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Term
| what characterizes the plaques associated w/MS? |
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Definition
| vary in size, often have sharply defined borders, depressed gray-tan, irregular shape and may be firmer than the surrounding white matter due to sclerosis. |
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Term
| what are the 3 basic distribution patterns of demyelination lesions in MS? |
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Definition
| disseminated perivascular demyelination, irregular patchy demyelination, and diffuse continuous demyelination |
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Term
| what is marburg's disease? |
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Definition
| malignant monophasic multiple sclerosis, which is characterized by *one affected area (depending on who you talk to, some think it’s a variation of MS others think it’s own disorder) |
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Term
| what is acute disseminated encephalomyelitis? |
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Definition
| a monophasic illness, often seen in children following 3-21 days after **measles/mumps/rubella/varicella vax. viral disease usually only affects gray matter, but acute disseminated encephalomyelitis is more of a white matter disease. pts present with h/a, vomiting, fever, stupor, meningismus, paraplegia, and incontinence. on MRI: periventricular, symmetrical and asymmetrical lesions. |
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Term
| what is acute hemorrhagic leukoencephalitis? |
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Definition
| this occurs most commonly in adults post respiratory tract infection w/a fulminant clinical course. **CSF: PMNs, RBCs (not lymphocytes or oligoclonal bands). pathology: vasculitis w/hemorrhage and demyelination |
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Term
| what is central pontine myelinolysis? |
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Definition
| paraparesis, quadriparesis, dysarthria, disorder of conjugate eye movement, and "locked in" syndrome associated w/rapid correction of hyponatremia/alcohol abuse. |
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Term
| what is toxic leukoencephalopathy? |
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Definition
| leukoencephalopathy due to methotrexate, carmustine, cisplatin, levamisole, 5FU, IL-2, TNF, irradiation, cyclosporine, amphotericin B, alcohol, toluene, MDMA, cocaine, CO, carbon tet, and arsenic. |
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Term
| what are the different types of neurotoxicity due to alcohol? |
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Definition
| **wernicke's encephalopathy: demyelination/hemorrhage around the *3rd ventricle, atrophy of the *mammillary bodies (thiamine deficiency), ataxia, confusion opthalmoplegia (III, VI), **korsakoff (short term memory loss). marchiafava-bignami: demyelination of the corpus callosum = dementia, spasticity, and dysarthria. central pontine myelinolysis. polyneuropathy: weakness, paresthesias. atrophy of gray/white matter (T2 MRI bilateral periventricular attenuation similar to that in MS and increased subdural space [easier to tear bridging veins]). |
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Term
| what is X-linked adrenal leukodystrophy? |
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Definition
| deficiency of peroxisomal enzymes, which impair oxidation of VLCFA w/accumulation in the adrenal glands and CNS white matter. 30%: onset 4-8 y/o w/ADD and rapid regression of cognitive function. 40% adrenomyeloneuropathy: progressive paraparesis and sphincter disturbance, cerebral involvement in almost 1/2. 30% addisons w/o neurologic disease. (face: blank, cognitive problems, facial nerve palsy) |
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