Multiple Sclerosis (MS)

Multiple sclerosis (MS) is an immune mediated inflammatory demyelinating disease. It affects the myelinated axons of the central nerve system, destroying the myelin, an insulativecovering of the axons of brain and spinal cord. The hallmark sign of MS is the occurrence of symptoms separated in time and space, which means symptomatic episodes, lasting for more than 24 hours, occurring months or years apart and affecting different anatomic locations. In many cases, the first symptom appears between the ages of 20 and 40, though it can appear before or after this age range in minority of patients. Each episode results in a variety of symptoms and signs depending on the location of MS lesion in the brain and spinal cord. Common symptoms and signs of MS are as follows:

• Sensory loss: abnormal sensory feelings such as numbness, tingling or pins-needles sensation. Lhermitte’s sign, an electrical sensation running down the back on bending the neck, can be present.
• Optic Neuritis: presenting as double vision, red-green color distortion or complete blindness in one eye
• Motor: due to lesions in spinal cord presenting as muscular weakness or spasms.
• Autonomic: due to lesion in spinal cord causing bladder, bowel or sexual dysfunction
• Ataxia: difficulty in coordination and balance
• Trigeminal neuralgia
• Depression and unstable mood
• Heat intolerance
• Cognitive impairment such as difficulties with concentration, attention, memory, and poor judgment.
• Loss or difficulty in speech

Based on the clinical criteria, MS is categorized into following four categories:

1) Relapsing-remitting MS (RRMS):
Most common form of MS, presenting with temporary flare ups followed by complete resolution

2) Secondary-progressive MS (SPMS):
In this category, there is continuous decline of neurological deficits. There could be periods of remissions and relapses. Around 65% of cases who were initially diagnosed with RRMS will be transition in to this category at some point.

3) Primary-progressive MS (PPSMS):
It is characterized by slow progression of symptoms without any remissions or relapses.

4) Progressive-relapsing MS (PRMS):
In PRMS, there is steadily progression of symptoms with superimposed acute episodes of relapses with no recovery. It is a rare form occurring in less than 5% of cases.

The cause of MS is unknown. However there are several triggering factors described in the literature which can contribute in the occurrence of MS episode combined with genetic predisposition. Those contributing factors are viral infection affecting immune system and activating auto-reactive T cells, environmental factors such as low exposure to sunlight in regions farther from the equator, smoking and stress. There is reported connection between hepatitis B vaccination and MS but center for disease control (CDC) found lack of strong evidence to suggest such link.

The diagnosis of MS is typically based on the presenting signs and symptoms couples with evidence from imaging and cerebrospinal fluid (CSF) testing. MRI is the most sensitive imaging study which can detect areas of demyelination in brain and spinal cord. Testing of CSF entails the detection of oligoclonal IgG bands which can provide evidence of chronic inflammation in the brain and spinal cord.

Figure: MRI brain image showing hyperintense signals due to demyelination in the T2 (A) and FLAIR (B) images

There is no definite cure for MS but it is managed in 2 aspects:

Acute flare-ups are treated by intravenous steroids, and in some cases, intravenous immunoglobulins and plasmapheresis can be considered. There are several medications which are approved by US Food and Drug Administration (FDA) as disease modifying agents for relapsing MS. These include interferons, glatiramer, Mitoxantrone, Fingolimod, Teriflunomide, Dimethyl fumarate, and TNF inhibitor biologic agents.