OVERVIEW
• Multiple sclerosis (MS) is a disease of the nervous system where the protective myelin covering the nerve fibers in the brain and spinal cord is destroyed
• Breakdown of myelin sheath affects impulse transmission along these nerve fibers
• It is the most common disease of the CNS that affects young adults
• The condition is typically diagnosed between 20-40 years and women are more likely to be diagnosed compared to men (2:1)
• The incidence of MS is more in Europe and North America although the reasons are unclear
• It is a progressive disease but marked by periods of remissions and exacerbations or flare-up of symptoms
• Currently there is no cure for MS and treatment aims at symptomatic relief
• It is neither hereditary nor infectious and doesn’t affect survival except in the most severe cases

ETIOLOGY OF MULTIPLE SCLEROSIS
• It’s believed to be an autoimmune disease in which the body’s immune system attacks its own tissues. In MS, the dysfunctional immune system malfunction attacks and destroys the protective fatty substance (myelin) that surrounds nerve fibers in the brain and spinal cord (myelin)
• Some experts believe that there is a genetic susceptibility to MS but the responsible gene has not been identified still.
• Others believe that MS may be triggered by a viral infection eg measles or varicella zoster (chicken pox)

PATHOGENESIS:
The affected nerve fibers have several foci of thickening or scarring (sclerosis) along their length. This slows down or prevents the transmission of impulses to and from the brain and spinal cord. As a result, there is impaired sensation and movement.

RISK FACTORS
• Age between 20 – 50 years
• Female sex
• Family history
• Smoking
• Caucasians have the highest risk while Asians, Africans and native Americans have the lowest risk
• Presence of other autoimmune diseases eg diabetes, thyroid disease or inflammatory bowel disease
• Temperate regions such as North America, Europe, New Zealand have a higher incidence
• Low vitamin D levels increases risk of MS
• Viral infections such as measles, chicken pox and EBV (Epstein Barr virus)

PATTERNS OF MS
• Relapsing-remitting MS: Periods of normal health or remission are followed by sudden increase in symptoms or relapses (80% of people at onset).
• Secondary progressive MS: This develops in patients who are initially diagnosed with relapsing-remitting MS. This occurs within 10 years of diagnosis. Symptoms gradually worsen with fewer periods of remission.
• Primary progressive MS: Symptoms gradually develop and worsen over time right from the diagnosis(10-15% )

SIGNS & SYMPTOMS OF MS
Symptoms and signs of MS vary greatly depending on the nerve fibers affected and severity of disease such as
• Weakness and tingling of one or more limbs
• Lack of coordination and unsteady gait
• Tremor
• Electric-shock sensations associated with movements such as bending the neck forwards (Lhermitte sign)
• Slurred speech
• Tiredness and fatigue
• Bladder, bowel and sexual problems
• Dizziness
• Blurred vision
• Double vision
• Partial or complete visual loss affecting one eye at a time
• Horizontal nystagmus
• Disturbances in smell and taste

COMPLICATIONS OF MS
• Muscle stiffness or spasms
• Paralysis, especially lower limbs
• Bladder, bowel issues or sexual dysfunction
• Mental changes, such as memory problems or mood swings
• Depression
• Epilepsy

DIAGNOSIS OF MS
There are no specific diagnostic tests for MS. Diagnosis is made after a detailed physical examination and ruling out other conditions that can result in a similar clinical picture

BLOOD TESTS – Can help to rule out other conditions with similar presentation. Specific biomarkers for MS are under development and may help in the diagnosis in the future
LUMBAR PUNCTURE – A sample of cerebrospinal fluid is obtained. This sample may reveal abnormalities in antibodies that are associated with MS and to rule out infections and other conditions similar to MS
MRI –can demonstrate areas of MS in the brain and spinal cord. Injection of intravenous contrast material may be used to highlight lesions which indicate that the disease is in the active phase.
EVOKED POTENTIAL TESTS – record the electrical signals produced within the brain in response to stimuli. Electrodes measure how quickly the electrical signals travel down the nerve fibers.

TREATMENT OF MS
ACUTE ATTACKS
Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are advised to decrease nerve inflammation. Side effects may high blood pressure, impaired glucose tolerance, sleeplessness, weight gain and, mood swings.
Plasma exchange (plasmapheresis) – The liquid portion of the patient’s blood (plasma) is removed and separated from the blood cells. The blood cells are then mixed with a protein solution (albumin) and injected back into the body. Plasma exchange may be used if symptoms are severe, new onset and don’t respond to steroids

DISEASE MODIFYING DRUGS
Primary progressive MS
Ocrelizumab (Ocrevus) is a disease-modifying therapy (DMT) approved by the FDA for primary-progressive MS. Patients receiving this treatment have less likelihood of progression compared to those who have not

Relapsing and remitting MS
• Injectable treatments such as beta interferon and Glatiramer acetate are available
• Infusion treatments include natalizumab, ocrelizumab, alemtuzumab and mitoxantrone
• Oral medications include fingolimod, teriflunomide, Dimethyl fumarate, and siponimod

SYMPTOMATIC TREATMENT
• Muscle relaxations to relieve painful muscle spasms such as Baclofen and tizanidine
• Physiotherapy to improve muscle weakness and improve gait
• Medications to reduce fatigue such as amantidine, modafinil
• Antidepressants such as SSRIs
• Medications to help with bladder and bowel dysfunction and sexual problems