MS And Other Inflammatory Demyelinating Diseases

Question 1

Pathologic criteria of a demyelinating disease

Answer 1

1. Destruction of myelin sheaths of nerve fibers with relative sparing of other elements of nervous tissue
2. Infiltration of inflammatory cells
3. Lesions primarily in the white matter

Question 2

Topography of lesions in MS

Answer 2

Periventricular (where subependymal veins line the ventricles)
Optic nerves and chiasm
Spinal cord (where pial veins lie next to or w/in white matter)

Question 3

Gross Pathologic findings in MS

Answer 3

Numerous scattered patches sl depressed from cut surface

Pink-gray color

Question 4

Pathology of relatively recent MS lesions

Answer 4

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

Question 5

Histopathology of long-standing MS lesions

Answer 5

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

Question 6

Critical age of immigration after which risk of MS becomes similar to that of person’s birthplace

Answer 6

15years

Question 7

Histocompatibility locus antigen with strongest association to MS is located at

Answer 7

DR locus chromosome 6

Question 8

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?

Answer 8

Any one would inc risk by a factor of 3-5

Question 9

Heritable risk factors for MS

Answer 9

HLA-DR2
HLA-DR3
HLA-B7
HLA-A3
IL-2Ralpha
IL7Ralpha

Question 10

In optic neuritis, what color reduces in intensity?

Answer 10

Red

Question 11

Uhthoff phenomenon

Answer 11

Temporary induction, by heat or exercise, of sx such as unilateral blurring of vision.

Question 12

Syndromes typical of MS and may be initial manifestations

Answer 12

Optic neuritis
Transverse myelitis
Cerebellar ataxia
Brainstem syndromes (vertigo, facial pain or numbness, dysarthria, diplopia)

Question 13

Lhermitte sign

Answer 13

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

Question 14

Pulfrich effect

Answer 14

An object swinging perpendicular to patient’s line of sight, appears to be moving in a 3D circular motion

Question 15

Charcot triad of MS (often seen in advanced stages of the disease)

Answer 15

Nystagmus
Scanning speech
Intention tremor

Question 16

Finding in a young adult that is virtually diagnostic of MS

Answer 16

Bilateral Internuclear Ophthalmoplegia

Question 17

Occurrence of this in a young adult should always suggest the diagnosis of MS

Answer 17

Transient facial hypesthesia or anesthesia or of trigeminal neuralgia
(Intramedullary fibers of CNV)

Question 18

Characteristics of cognitive impairment seen in about 1/2 of patients with long-standing MS

Answer 18

Reduced attention
Diminished processing speed and executive skills
Memory decline

(Language and other intellectual functions preserved)

Question 19

la belle indifférence

Answer 19

Euphoria, a pathologic cheerfulness or elation that seems inappropriate in the face of obvious neurologic deficit
Also stupid indifference or morbid optimism

Question 20

What drug/s is/are used in symptomatic management of these manifestations of MS

1. Paroxysmal attacks of neuro deficit
2. Painful tonic spasms
3. Fatigue
4. Depression

Answer 20

1. Paroxysmal attacks of neuro deficit - CBZ
2. Painful tonic spasms - acetazolamide
3. Fatigue - modafinil 200-400mg/d, amantadine 100mg am&nn, pemoline 20-75mg OD AM
4. Depression - antidepressants

Question 21

Marburg variant

Answer 21

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

Question 22

Lesions have a series of concentric rings that represent alternating areas of myelin loss and preservation. High incidence in the Philippines

Answer 22

Concentric sclerosis of Balo

Question 23

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?

Answer 23

Syphilis, Lyme, SSPE

Question 24

A positive test of IgG index

Answer 24

Greater than 12% of the total protein

Question 25

Why is MBP not useful as a diagnostic test for MS

Answer 25

Other lesions that destroy myelin can also increase level of MBP in the CSF. It only reflects destruction of central myelin

Question 26

Usual BAER findings in MS

Answer 26

Prolonged interwave latency | Decreased amplitude of wave5

Question 27

Feature most predictive of long-term disability

Answer 27

Degree of disability at 5y from the first symptom

Question 28

MS associated with little change over time in MRI findings, negligible response to therapy, and poor outcome

Answer 28

Primary Progressive MS

Question 29

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

Answer 29

C. There appears to be an increased risk of exacerbations, up to 2-fold in the first few months postpartum

Question 30

Dosing regimen of methylprednisolone for acute or subacute exacerbation of MS or optic neuritis

Answer 30

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

Question 31

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

Answer 31

Natalizumab Directed against alpha-integrin in order to block lymphocyte and monocyte adhesion to endothelial cells and their migration through the vessel wall.

Question 32

Distinctive clinical and pathologic features of NMO from MS

Answer 32

1. Failure to develop Cerebral demyelinating lesions even years after 2. Absence of oligoclonal bands in CSF 3. Tendency to CSF pleocytosis 4. Necrotizing and cavitary nature of spinal cord lesion (affects white and gray matter alike w prominent thickening of vessels and minimal inflammatory infiltrates 5. Tendency to involve several contiguous longitudinal segments of the spinal cord

Question 33

Typical rash of acute graft vs host disease

Answer 33

Tender erythematous macular rash

Question 34

Pathologic findings of Acute Necrotizing Hemorrhagic Leukoencephalitis of Weston Hurst

Answer 34

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)

Question 35

A variant of post-infectious encephalomyelitis that involves solely or predominantly the cerebellum is particularly associated with this virus among others.

Answer 35

Varicella

Question 36

Treatment for Hurst Syndrome

Answer 36

High dose intravenous corticosteroids

Question 37

T/F | Recovery from ADEM is good among adult patients

Answer 37

T

Question 38

Postexanthem encephalomyelitis symptoms generally begin ___ days after the appearance of the rash

Answer 38

2-4days

Question 39

This drug may be used as symptomatic treatment for postural tremor in MS, albeit mechanism for its beneficial effects is unknown

Answer 39

Isoniazid 300mg initial daily inc by weekly increments of 300mg to a dose of 1200mg daily To be given with Pyridoxine 100mg daily

Question 40

T/F vaccinations are prohibited in patients with MS

Answer 40

F

Question 41

Distribution of the NMO antibody

Answer 41

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

Question 42

Sn and Sp of the presence of NMO antibody

Answer 42

76% sensitive | 94% specific

Question 43

Treatment for PML complicating Natalizumab treatment

Answer 43

Stop Natalizumab | Plasma exchange

Question 44

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

Answer 44

Fingolimod

Question 45

Progressive Multifocal Leukoencephalopathy is associated with which virus

Answer 45

JC virus

Question 46

T/F | All protein components of the respiratory chain are encoded in mitochondrial DNA.

Answer 46

F | About 83% of respiratory chain proteins are encoded in nuclear DNA.

Question 47

Which complex of the respiratory chain is most often disordered leading to lactic acidosis

Answer 47

Complex IV (cytochrome-c oxidase)

Question 48

First definite indication of disordered nervous system function in neonates with metabolic disease

Answer 48

Seizures