Multiple Sclerosis Literature Review

FACTS
Most common disabling condition in young adults. MS is second only to trauma as a cause of neurologic disability in early to middle adulthood.

Most common demyelinating disorder

Chronic disease of the CNS

Progresses to disability in majority of cases Unpredictable course variety of signs and symptoms; sometimes mistaken
for psychiatric diagnosis

Definition
Multiple sclerosis (abbreviated MS) is an inflammatory disease in which the fatty myeliin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptomsThe peripheral nervous system (PNS) is spared, and most patients

 Multiple sclerosis (MS) is characterized by a triad of inflammation, demyelination, and gliosis (scarring); the course can be relapsingremitting or progressive. Lesions of MS are typically disseminated in time and location. Manifestations of MS vary from a benign illness to a rapidly evolvingand incapacitating disease requiring profound life-style adjustments.

History of MS
The French neurologist Jean-Martin Charcot (1825 1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868. A young woman called Halldora, who lived in Iceland around 1200, suddenly lost her vision and mobility, but after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (13801433) a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of 16 until her death at 53, she suffered intermittent pain, weakness of the legs, and vision losssymptoms typical of MS

 Augustus Frederick d'Este (17941848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George III of the United Kingdom, almost certainly suffered from MS. D'Este left a detailed diary describing his 22 years living with the disease

Epidemiology
In the UK the prevalence is 120 per 100 000 of the population, with an annual incidence of around 7 per 100 000. The lifetime risk of developing multiple sclerosis is about 1 in 800. The incidence is higher in temperate climates and in Northern Europeans. The highest known prevalence for MS (250 per 100,000) occurs in the Orkney islands, located north of Scotland The disease is about twice as common in women as men. Mainly young adults between and age of 20 to 40.

 Reports suggest that individuals who move from an area of high prevalence to one of low prevalence (or vice versa) before the age of 15 years adopt the risk of MS in their new environment. whereas if they move after this age, they retain the risk of their native land Caucasians are twice as likely to get MS than any other race. The risk of familial recurrence is 15%, with highest being for first-degree relatives (age-adjusted risk: 2-3%) and a monozygotic twin concordance of 35%

Aetiology
Not Known

Epidemiological and genetic evidence suggests that multiple

sclerosis is caused by an interplay of multiple genetic and environmental factors

Infection---raised titers of many common viruses(HSV) in

CSF and serum however no virus-induced animal MS model

An immune mechanism is suggested by increased levels of

activated T lymphocytes in the CSF, and increased immunoglobulin synthesis within the central nervous system

 Activated (myelin basic protein) MBP-reactive T cells are often found in the blood or cerebrospinal fluid (CSF) of MS patients and, occasionally also, in MS lesions. Autoantibodies, directed against myelin antigens such as myelin oligodendrocyte glycoprotein (MOG), probably act in concert with a pathogenic T cell response to cause the demyelinating lesions in many patients. Recent evidence suggests that the presence of anti MOG antibodies in the serum of patients with a clinically isolated syndrome (CIS) is highly predictive of the development of MS in the future.

Pathogenesis
An attack of central nervous system inflammation in multiple sclerosis starts with the entry of activated T lymphocytes through the blood-brain barrier. These recognise myelin-derived antigens on the surface of the nervous system's antigenpresenting cells, the microglia, and undergo clonal proliferation The resulting inflammatory cascade releases cytokines and initiates destruction of the oligodendrocyte-myelin unit by macrophages

PATHOLOGY
Perivascular inflammation and demyelination

Plaques occur anywhere in the CNS

Most frequent: Periventricular region of the brain Optic nerve Brainstem

Cerebellum
Spinal cord

 Degenerative changes in myelin

Infiltration with macrophages or microglia

Preservation of axons Degree of oligodendrocyte preservation
determines remyelination potential Slower conduction time along affected nerve

CLINICAL FEATURES
Inducement: infection, fatigue, delivery a baby Initial symptoms:

Impaired vision Disequilibrium Heat intolerance Problems with bladder control Sensory disturbance Motor weakness
Initial symptoms indicate the site of onset

SENSORY DISTURBANCES
Ascending numbness starting in feet Bilateral hand numbness Hemiparesthesia/dysesthesia Dorsal column signs Loss of
vibration/proprioception

Lhermittes sign

VISION DISTURBANCE
Unilateral or bilateral partial/complete internuclear ophthalmoplegia Optic neuritis

MOTOR DISTURBANCE
Weakness

(mono-, hemi- or quadriparesis)

Increased spasticity

Pathologic signs
(Babinski, Chaddock, Hoffman)

Dysarthria

Classification of MS
Several subtypes, or patterns of progression, have been described.

INVESTIGATIONS

CSF (Oligoclonal bands)

Evoked potentials

MRI
Blood and urine(non-specific)

MRI
Most useful tool in diagnosis MRI is abnormal in 90% of definite MS Gadolinium enhancement identifies active
lesions

Lesions abutting central ventricles, with

diameter of >0.6 cm, in the posterior fossa, help to diagnose MS

MRIcerebellum

MRIoptic nerve

MRIcerebral hemisphere

MRIspinal cord