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Multiple Sclerosis: Early Diagnosis And Optimal Treatment May Prevent Disability

Multiple sclerosis (MS) is a potential disabling disease of the brain and central nervous system. Read here to know about the treat, diagnosis and prevention of this condition.

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Symptoms of Multiple sclerosis include vision loss, pain, fatigue and impaired coordination

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The estimated risk of developing multiple sclerosis(MS) is quite low (approximately 0.1%) in the general population, however, the chronic nature of the illness makes this disorder highly prevalent. As per the Multiple Sclerosis International Federation (MSIF) global study of 2014, around 2.5 million people are affected with MS worldwide, though with a geographical heterogeneity. The Indian prevalence has been estimated in the distant past, using the then available tools, to be quite low i.e., 1.3 percent. But MS is second only to trauma as a cause of neurologic disability beginning in early to middle adulthood (20 to 40 years of age) and the onset is rare before 10 and beyond 50 years of age; involving females thrice as commonly as males.This implies that it hits an individual during her/his most productive phase of life.

There exists a complex interplay of environment and genetics in the genesis of MS as highlighted by the twin-studies and the migration-studies. No specific Mendelian gene or infective agent has been found to be causal for MS, however the risk is increased by 2-5 percent with an affected first-degree relative and furthermore with an affected monozygotic twin, up 30-50% concordance risk. The latitude gradient is evident from the MS prevalence graphs but it is interesting to note that an individual acquires the local geographical risk of MS if she or he migrates before puberty. Presence of antibodies against Epstein Barre Virus (EBV), vitamin D deficiency, smoking and obesity have been found to be highly prevalent in people with MS (pwMS).

MS manifests most commonly, in upto 85 percent of the cases, as clinical attacks or relapses resulting from an idiopathic or primary (i.e., not secondary to infectious, toxic, vascular or genetic developmental cause) immune-mediated inflammatory damage to the outer insulation of the central nervous system (CNS - brain, spinal cord, and optic nerve) neurons i.e., 'myelin'. The source and structure of CNS myelin is different from the myelin of the neurons of the peripheral nervous tissue, making MS a CNS-specific disorder and requiring differentiation as discussed further.

Loss of myelin (demyelination) causes diminished conductions across the affected neurons to produce variable signs and symptoms as per the site and the extent of CNS involvement that can be solitary, multifocal, or diffuse and can happen simultaneously or sequentially. This dissemination of time and space, either established clinically or radiologically using a magnetic resonance imaging (MRI) with Gadolinium-based contrast, is the basis of the diagnosis of MS after exclusion of other secondary causes of the demyelination, as described above, using blood investigations and cerebrospinal fluid (CSF) examination. This constitutes the most important and crucial step towards the optimal management of MS as any error may lead to undesired and unwarranted treatment and/or its effects.

The typical albeit non-specific manifestations are visual loss from one eye with pain on movement of the eye (optic neuritis - swelling of optic nerve, a common presenting symptom); double vision; sensory loss, abnormal sensation, or weakness of one or one-sided limbs; imbalance while walking; incoordination of upper or lower extremities, urinary urgency or incontinence; and/or stiffness of both the lower limbs. Fatigue (that is out of proportion to the activity), mental fogging or diminished speed of processing the information, and/or an electric shock like sensation travelling down the back on forward neck bending (the Lhermitte's sign) are some other important disabling symptoms. Many pwMS observe worsening of their complaints with rise in body temperature due to ambient heat, fever, or exercise (heat sensitivity or the Uhthoff's phenomenon) and may be mistaken as an attack (pseudo-relapse).

So, by definition, MS is a chronic primary CNS demyelinating disease with two predominant forms - the commoner relapsing remitting or the RRMS (85%) and the progressive MS. In RRMS, a typical attack, consisting of any individual or combination of the above-mentioned presentations, develops over hours and lasts for at least 24 hours with a gradual spontaneous complete or incomplete resolution. This may be followed by a variable inter-attack interval with or without residual disability. This unpredictability and the variability of the attack frequency and severity contribute to the heterogeneity of the MS and is a significant management challenge.

The progressive MS is characterised by the disability progression independent of the attacks. If this disability progression happens from the outset of the disease course, it is called as primary progressive (PPMS). On the other hand, if this happens after one or two decades into the course of RRMS, it is labelled as secondary progressive (SPMS). Restoration of the myelin sheath of the CNS neurons (remyelination) is possible with control of the inflammation and contributes to the recovery from a MS attack. However, the damage to the inside structure (axonal loss) due the demyelination or inflammatory attack is irreversible and causes disability. So, the key to prevent disability is early diagnosis and effectivecontrol of inflammation with the use of disease modifying therapies (DMTs).

Three aspects of the standard treatment are:

a) Treatment of acute attack or relapse with intravenous pulse steroids for a speedy recovery

b) Prevention of a relapse with use of DMTs that include oral, subcutaneous, intramuscular and intravenous agents to be administered using various regimens and each has a unique set of efficacies (annual relapse rate (ARR) reduction), cost and side-effect profile

c) Treatment of symptoms for example, neuralgic pain management. Literature supports the adoption of healthy lifestyle including vegan diet, cessation of smoking, adequate vitamin D levels, and regular exercise in prevention of relapses and improving the overall quality of life of pwMS.

(Dr. Manish Mahajan is a Senior Consultant Neurology & Head of Neuroimmunology at Artemis Agrim Institute of Neurosciences, Artemis Hospital Gurgaon)

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