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.
Unknown
Genetic Factors: HLA DR2, DW2 in Danish patients with relapsing-remitting multiple sclerosis (MS), DR4 in Mediterranean patients
Environmental Factors
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
Symptom | % Affected Patients |
|---|---|
Weakness | 26 |
Sensory change | 25 |
Optic neuritis | 21 |
Ataxia | 14 |
Urinary function change | 14 |
Other | 10 |
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
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
Schumacher Criteria (old criteria)
Two separate CNS lesions
Two separate attacks or 6 months progression
Objective findings on examination
White matter disease
Age 10 to 50 years (usually)
No other disease that explains the constellation of signs and symptoms
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.
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