Demyelinating Diseases

Multiple Sclerosis

I. Epidemiology

Onset: women aged 20 to 35 years; men aged 35 to 45 years
Female:male ratio is 2:1.
Age of onset of symptoms

<20 years old

5% to 10% of patients

20 to 40 years old

70% to 85 % of patients

>40 years old

15% to 25% of patients
Most common in Whites.
First-degree relatives have a 10- to 20-fold greater risk.
Residence for the first 15 years of life determines risk, most common in temperate regions.

II. Cause

Unknown
Genetic Factors: HLA DR2, DW2 in Danish patients with relapsing-remitting multiple sclerosis (MS), DR4 in Mediterranean patients
Environmental Factors

III. Pathologic Findings

Plaques—areas of demyelination
- Usually occur in deep white matter
- Usually near ventricles, corpus callosum, optic nerve
- May occur in spinal cord, grey matter, and brainstem
Acute
- Demyelination
- Sparing of axons
- Perivascular infiltrate with lymphocytes, macrophages, and plasma cells near the leading edge of demyelination
- Perivascular edema
- Activated astrocytes and hyperplastic oligodendroglia at border
Chronic
- Oligodendrocytes disappear
- Axonal degeneration
- Astrocytic hypertrophy and hyperplasia—sclerosis

IV. Presentation

V. Clinical Course

Relapsing-remitting: clearly defined relapses with no progression between relapses
Secondary progressive: initially relapsing-remitting, followed by progression of symptoms with or without plateaus
Primary progressive: progressive from the onset of symptoms with occasional plateaus and possible temporary improvement
Progressive-relapsing: progressive from the onset with relapses

Course

% Affected Patients

Benign

30

Neurologic dysfunction

60

Malignant

10

Relapsing remitting

35

Relapsing progressive

45

Chronic progressive

20

VI. Prognosis

Better prognosis for women, predominantly sensory disease, less residual after relapse
Worse prognosis for men, multifocal disease, progressive disease
Kurtzke Five-Year Rule: minimal dysfunction at 5 years correlates with minimal dysfunction at 15 years

VII. Diagnosis

Poser Committee for the Diagnosis of Multiple Sclerosis

*Category*	*Relapses*	*No. of Lesions(Clinical/Paraclinical)***	*CSF (OCB/IgG)*
Clinically definite	2	(1-2/0-1)	NA
Laboratory-supported definite	1-2	(1-2/0-1)	+
Clinically probable	1-2	(1-2/0-1)	−
Laboratory-supported probable	2	(0/0)	+
CSF, cerebrospinal fluid; OCB, oligoclonal bands.

New MS Diagnostic Criteria (McDonald et al.)

*Clinical Attacks*	*Objective Lesions*	*Additional Requirements to Make Diagnosis*
2 or more	2 or more	None, clinical evidence will suffice
2 or more	1	Dissemination in space by MRI or
		Positive CSF and 2 or more MRI lesions
1	2 or more	Dissemination in time by MRI or
		A second attack
1 (monophasic)	1	Dissemination in space by MRI or
		Positive CSF and 2 or more MRI lesions AND
		Dissemination in time by MRI or a second attack
0 (progressive)	1	Positive CSF and
		Dissemination in space by MRI with 9+ lesions or
		2 or more cord lesions or
		4-8 brain lesions and 1 cord lesion or
		Positive VEP with 4-8 MRI lesions or
		Positive VEP with <4 brain lesions, 1 cord lesion
		AND Dissemination in time by MRI or
		Continued progression for 1 year
CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; VEP, visual evoked potential. 1. McDonald WI, Compston A, Edan G, Goodkin D, Hartong HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van der Noort S, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul;50(1):121-7. 2. Polman CH, Reingold SC, Edan G, Filippi M, Hartong HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol. 2005 Nov 10;58(6):840-846.