Demyelinating Diseases Flashcards
Generally accepted pathologic criteria for multiple sclerosis (3)
1 myelin sheath destruction with relative sparing of other elements
2 predominantly perivenous infiltration of inflammatory cells
3 primarily white matter lesions
Define MULTIPLE SCLEROSIS
Progessive chronic condition characterized clinically by episodes of focal disorders of the optic nerves, spinal cord, & brain, which remit & recur over many years
Pathologic findings in Multiple Sclerosis
sharply delineated periventricular white matter lesions in the brain & spinal cord that do not extend beyond the entry zones of cranial or spinal nerves
Histologic appearance of ACUTE lesions in MS (4)
- loss of myelin in the perivenous distribution
- slight oligodendroglial degeneration
- variable astrocytic reaction
- perivascular & para-adventitial mononuclear & lymphocytic infiltration
Histologic appearance of CHRONIC lesions in MS (4)
- thickly matted, acellular glial tissue
- occasional perivascular lympthocytes & macrophages
- walleraian degeneration of long fiber tracts
- shadow patches : partial remyelination of undamaged fibers
- cavitation : destruction of supporting tissues & vessels
4 Histologic subgroups or patterns of MS
1 inflammatory lesions made up of T cells & macrophages alone
2 an autoaAb lesion mediated by Ig & complement
3 characterized by apoptosis of oligodendrocytes
& no Ig, complement, & + partial remyelination
4 showing only oligodendrocyte dystrophy & no remyelination
*3-4 show a primary oligodendroglial degeneration
True or False.
MS has a bimodal age-specific onset curve
False
unimodal
Peak age of developing symptoms of MS
30-40 years of age
The strongest genetic factor thought to be associated to developing MS
DR locus on chromosome 6
Thought to be markers of MS susceptibility gene, and the presence of any of these increases the risk of developing MS by how much?
HLA-DR2 HLA-DR3 HLA-B7 HLA-A3 3-5x increased risk
Other than the HLA loci, thse too were said to increase the susceptibility to develop MS
IL2Ralpha
IL7Ralpha
Most immunologists believe that MS is medidated by
T-cell sensitization to some component of myelin
What is the Uhthoff phenomenon & what is its basis?
worsening of neurologic symptoms of MS patients upon exposure to heat.
Nerve conduction in demyelinated & remyelinated fibers are sensitive to subtle changes in metabolic & environmental changes
4 MS Syndromes
1 optic neuritis
2 transverse myelitis
3 cerebellar ataxia
4 brainstem syndromes
The pain in Lhermitte sign is most probably due to
increased sensitivity of demyelinated axons to the stretch or pressure on the spinal cord induced by neck flexion
Prognosis of optic neuritis
Good. half recover completely
treatment did not influence outcome
What is Pulfrich effect?
psychophysical percept wherein lateral motion of an object in the field of view is interpreted by the visual cortex as having a depth component, due to a relative difference in signal timings between the two eyes
What is Charcot triad?
1 scanning speech
2 nystagmus
3 intention tremor
True or False. the presence of bilateral internuclear ophthalmoplegia in a young adult is virtually diagnostic of MS.
True
True or False. the occurrence of transient facial hypesthesia or anesthesia or of trigeminal neuralgia in a young adult should always suggest the diagnosis of MS implicating the intramedullary fibers of the fifth cranial nerve
True
useful in controlling spontaneous attacks in MS
carbamazepine
blocks painful tonic spasms that are elicited by hyperventilation in MS
acetazolamide
True or False. Facial palsy along the lines of Bell’s palsy can be a sign of MS
false
Most common precipitating factors of MS
infection
trauma
pregnancy
Most common precipitating factors of MS (though not firmly established)
infection
trauma
pregnancy
Variant of MS that is rapidly progressive and highly malignant. A combination of cerebral, brainstem, and spinal manifestations evolves over a few weeks, rendering the patient stuporous, comatose, or decerebrate with prominent cranial nerve and corticospinal abnormalities
Marburg type or Tumefactive type
Variants of MS consisting of diffuse sclerosis
Balo & Schilder Disease
CSF oligoclonal bands is positive in what proportion of MS patients?
90%
Positive test of CSF IgG index in MS is?
> 12%
True or False. The finding of oligoclonal bands in a suspected MS patients connotes that the disease is already chronic
True
True or False. Oligoclonal bands in blood of MS patients is also diagnostic along with the clinical features consistent with MS
False
Most commonly used diagnostic test in MS
CSF oligoclonal bands
Most helpful diagnostic test in MS
MRI
In MS. T1 hypointensity is ___________ proportional to the degree of remyelination
inversely
filiform pattern in the corpus callosum in the MRI of MSI patients
Dawson’s fingers
Cranial MRI findings in MS
- T2 hyperintense, T1 hypointense
- multifocal, well-demarcated, oval or linear, radially oriented lesionsadjacent to the ventricular surface
- C-shaped partial or medially open ring of abnormal enhancement
___% of definite MS & ___% of probable or possible MS have abnormal VER.
70
60
___% of definite MS & ___% of probable or possible MS have abnormal SSEP
60
40
___% of definite MS & ___% of probable or possible MS have abnormal BAER
40
20
diagnostic study to dedmonstrate axonal loss or thinning of the retina
optical coherence tomography
4 typical locations of T2 hyperintesities in MS
1 periventricular
2 juxtacortical
3 infratentoria
4 spinal cord
The most predictive of long term disability in MS
degree of disability at 5 years from the onset of the first symptoms
True or False. IV methylprednisolone administered at 1 g/d for 5 days per month over 5 years, was shown to reduce disability and brain atrophy and total volume of hypodense lesions on Tl-weighted MRI
True
study by Zivadinov
MPPT dose for MS
1) 0.5-1g/day x 3-5days then oral prednisone 60-80mg/day x taper 12-20 days
2) oral methylprednisolone 48mg/day x 1 week
24mg/day x 1 week
12mg/day x 1 week
IV Ig dose for MS
0.2g/kg monthly x 2 years
The main problem in MS patients treated with interferon
development of antibodies against it
Monoclonal antibodies used in MS and their targets (4)
Natalizumab - anti alpha integrins to block lymphocyte, monocyte adhesion to endolium, migration
Alemtuzumab - anti CD52 antigen to reduce B, T cells
Rituximab - anti CD20 lymphocytes, depleting Bcell monoclonal Ab
Ocrelizumab - anti CD20
Monoclonal antibodies used in MS and their side effects (4)
Natalizumab - PML
Alemtuzumab -ITP, thyroiditis
Rituximab - infection, lymohoma
Ocrelizumab - infection, lymohoma
Mode of action of glatiramer acetate
mimics myelin basic protein
Side effects of fingolimod
lymphopenia, adenopathy, bradycardiam AV block, macular edema, herpes infection, increased LFTs
Medications that may be used to address fatigue in MS
amantadine modafinil permoline methylphenidate dextroamphetamine
Isoniazid can be used in MS to address what?
severe postural tremor
Distinctive characteristics of Devic’s Disease from MS (6)
1 failure to develop cerebral demyelinating lesions even after years of illness
2 absence of CSF oligoclonal bands
3 tendency to CSF pleocytosis more so than in MS
4 necrotizing cavitary nature of the spinal cord lesion, affecting white and gray matter alike with prominent thickening of vessels
5 but with minimal inflammatory infiltrates
6 involve several contiguous longitudinal segments of the spinal cord
Antibody specific to Devic’s Disease and its sensitivity and specificity?
NMO antibody
anti aquaporin 4
76% sensitive
94% specific
Criteria for the diagnosis of NMO which is 99% senstivie and 90% specific
2 of the following:
1 longitudinally extensive myelopathy
2 positive antibodies
3 nitial MRI that is not characteristic for MS
The only histopathologic characteristic of ADEM that distinguishes it from MS
multifocal meningeal infiltration
Most fulminant form of demyelinating disease
Weston Hurst Disease
acute hemorrhagic leukoencephalitis
Microorganism associated with Weston Hurst Disease
none. most cases has indeterminate cause.
Mycoplasma pneumoniae
Neuroimaging findings that distinguish Weston Hurst Disease from ADEM
1 size of the lesions
2 hemorrhagic character
3 extent of the surrounding edema
Neuroimaging findings in Weston Hurst Disease
bilateral asymmetrical large, confluent, edematous lesions white matter with a myriad of punctate
hemorrhages in gray and white matter
Distinctive pathologic characteristic of Weston Hurst Disease
destruction of white matter to the point of liquefaction
Mcdonald Criteria for MS
≥2 attack, ≥ 2 lesion ≥2 attack, 1 lesion = DIS 1 attack, ≥2 lesion = DIT 1 attack, 1 lesion = DITS 0 attack = 1 year of disease progression and 2 out of 3 criteria: DIS brain, DIS cord, +CSF
