MS And Other Inflammatory Demyelinating Diseases Flashcards
Pathologic criteria of a demyelinating disease
- Destruction of myelin sheaths of nerve fibers with relative sparing of other elements of nervous tissue
- Infiltration of inflammatory cells
- Lesions primarily in the white matter
Topography of lesions in MS
Periventricular (where subependymal veins line the ventricles)
Optic nerves and chiasm
Spinal cord (where pial veins lie next to or w/in white matter)
Gross Pathologic findings in MS
Numerous scattered patches sl depressed from cut surface
Pink-gray color
Pathology of relatively recent MS lesions
Partial or complete destruction and loss of myelin throughout zone of confluence of perivenous foci
Slight degeneration of oligodendroglia
Astrocytic reaction
Perivascular and para-adventitial infiltration w mononuclear cells and lymphocytes
Axons relatively spared or less affected
Histopathology of long-standing MS lesions
Thickly matted
relatively acellular glial tissue
Only occasional perivascular lymphocytes and macrophages
Few intact axons or descending and ascending Wallerian degeneration
“Shadow patches” - from partial remyelination or incompletely demyelinated axons
Critical age of immigration after which risk of MS becomes similar to that of person’s birthplace
15years
Histocompatibility locus antigen with strongest association to MS is located at
DR locus chromosome 6
HLA-DR2, to a lesser extent, -DR3, -B7, and -A3 are thought to be markers for an MS “susceptibility gene”. The presence of one of these increases risk for developing MS by what factor?
Any one would inc risk by a factor of 3-5
Heritable risk factors for MS
HLA-DR2 HLA-DR3 HLA-B7 HLA-A3 IL-2Ralpha IL7Ralpha
In optic neuritis, what color reduces in intensity?
Red
Uhthoff phenomenon
Temporary induction, by heat or exercise, of sx such as unilateral blurring of vision.
Syndromes typical of MS and may be initial manifestations
Optic neuritis
Transverse myelitis
Cerebellar ataxia
Brainstem syndromes (vertigo, facial pain or numbness, dysarthria, diplopia)
Lhermitte sign
Flexion of the neck induces a tingling electric-like feeling down the shoulders and back and, less commonly, down the anterior thighs
- also occurs in other conditions such ad cervical spondylosis
Pulfrich effect
An object swinging perpendicular to patient’s line of sight, appears to be moving in a 3D circular motion
Charcot triad of MS (often seen in advanced stages of the disease)
Nystagmus
Scanning speech
Intention tremor
Finding in a young adult that is virtually diagnostic of MS
Bilateral Internuclear Ophthalmoplegia
Occurrence of this in a young adult should always suggest the diagnosis of MS
Transient facial hypesthesia or anesthesia or of trigeminal neuralgia
(Intramedullary fibers of CNV)
Characteristics of cognitive impairment seen in about 1/2 of patients with long-standing MS
Reduced attention
Diminished processing speed and executive skills
Memory decline
(Language and other intellectual functions preserved)
la belle indifférence
Euphoria, a pathologic cheerfulness or elation that seems inappropriate in the face of obvious neurologic deficit
Also stupid indifference or morbid optimism
What drug/s is/are used in symptomatic management of these manifestations of MS
- Paroxysmal attacks of neuro deficit
- Painful tonic spasms
- Fatigue
- Depression
- Paroxysmal attacks of neuro deficit - CBZ
- Painful tonic spasms - acetazolamide
- Fatigue - modafinil 200-400mg/d, amantadine 100mg am&nn, pemoline 20-75mg OD AM
- Depression - antidepressants
Marburg variant
Rapidly progressive highly malignant form of MS rendering pt stuporous comatose or decerebrate with prominent CN and corticospinal abnormalities.
Death may end illness within few weeks or months
Lesions have a series of concentric rings that represent alternating areas of myelin loss and preservation. High incidence in the Philippines
Concentric sclerosis of Balo
Oligoclonal bands seen in more than 90% of MS cases and used to confirm dx is also appear in CSF of patients with what other conditions?
Syphilis, Lyme, SSPE
A positive test of IgG index
Greater than 12% of the total protein
Why is MBP not useful as a diagnostic test for MS
Other lesions that destroy myelin can also increase level of MBP in the CSF.
It only reflects destruction of central myelin
Usual BAER findings in MS
Prolonged interwave latency
Decreased amplitude of wave5
Feature most predictive of long-term disability
Degree of disability at 5y from the first symptom
MS associated with little change over time in MRI findings, negligible response to therapy, and poor outcome
Primary Progressive MS
In whom of the following is a higher rate of exacerbation and of MS expected
A. 28yo woman with MS in her first trimester of pregnancy
B. 30yo man diagnosed with MS who had loc after a vehicular crash while driving his motorcycle
C. 30yo woman with MS who gave birth 2 weeks ago
D. A 20yo woman who underwent a lumbar puncture for the 1st episode of optic neuritis
C. There appears to be an increased risk of exacerbations, up to 2-fold in the first few months postpartum
Dosing regimen of methylprednisolone for acute or subacute exacerbation of MS or optic neuritis
IV Methylprednisolone 500-1000mg daily x 3-5days
Followed by
Prednisone 60-80mg daily tapering over 12-20days
If IV cannot be given
Methylprednisolone 48mg OD x 1wk then 24mg OD x 1wk then 12mg OD x 1wk or equivalent doses of prednisone
This monoclonal antibody has been shown to be two times more efficacious in the treatment of relapsing-remitting MS but the complication of Progressive Multifocal Leukoencephalopathy hs precluded its use
Natalizumab
Directed against alpha-integrin in order to block lymphocyte and monocyte adhesion to endothelial cells and their migration through the vessel wall.
Distinctive clinical and pathologic features of NMO from MS
- Failure to develop Cerebral demyelinating lesions even years after
- Absence of oligoclonal bands in CSF
- Tendency to CSF pleocytosis
- Necrotizing and cavitary nature of spinal cord lesion (affects white and gray matter alike w prominent thickening of vessels and minimal inflammatory infiltrates
- Tendency to involve several contiguous longitudinal segments of the spinal cord
Typical rash of acute graft vs host disease
Tender erythematous macular rash
Pathologic findings of Acute Necrotizing Hemorrhagic Leukoencephalitis of Weston Hurst
Gross: white matter destroyed to almost liquefaction, pink or yellow-gray flecked with multiple petechial hemorrhages
Histo: widespread necrosis of small blood vessels and brain tissue around vessels, intense cellular infiltration, multiple small hemorrhages and inflammatory reaction in meninges
(Resembles adem save for more widespread necrosis and large foci)
A variant of post-infectious encephalomyelitis that involves solely or predominantly the cerebellum is particularly associated with this virus among others.
Varicella
Treatment for Hurst Syndrome
High dose intravenous corticosteroids
T/F
Recovery from ADEM is good among adult patients
T
Postexanthem encephalomyelitis symptoms generally begin ___ days after the appearance of the rash
2-4days
This drug may be used as symptomatic treatment for postural tremor in MS, albeit mechanism for its beneficial effects is unknown
Isoniazid
300mg initial daily inc by weekly increments of 300mg to a dose of 1200mg daily
To be given with Pyridoxine 100mg daily
T/F vaccinations are prohibited in patients with MS
F
Distribution of the NMO antibody
Located in astrocytic end feet adjacent to capillaries, pia, and Virchow-Robin spaces all in the periventricular region and surrounding central canal of spinal cord
Sn and Sp of the presence of NMO antibody
76% sensitive
94% specific
Treatment for PML complicating Natalizumab treatment
Stop Natalizumab
Plasma exchange
This oral therapy for MS that interferes with egress of lymphocytes from lymph nodes has a short term effect on MRI lesion burden and relapse rate
Fingolimod
Progressive Multifocal Leukoencephalopathy is associated with which virus
JC virus
T/F
All protein components of the respiratory chain are encoded in mitochondrial DNA.
F
About 83% of respiratory chain proteins are encoded in nuclear DNA.
Which complex of the respiratory chain is most often disordered leading to lactic acidosis
Complex IV (cytochrome-c oxidase)
First definite indication of disordered nervous system function in neonates with metabolic disease
Seizures
