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Paper Abstract

Multiple Sclerosis


Multiple sclerosis (MS) is the most common non-traumatic disabling disease that typically affects young adults. It is a chronic, autoimmune (a disease caused by antibodies or lymphocytes produced against substances naturally present in the body), inflammatory, neurodegenerative (causing destruction/degeneration of the nerves) disease of the central nervous system (CNS). MS presents with progressive demyelination (damage to the protective covering, called the myelin sheath, present around the nerve fibers; a nerve fiber and its myelin sheath are comparable to an electric wire and its outer protective covering, respectively) and subsequent axonal (the long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells) degeneration. Vitamin D deficiency, diet, obesity in early life, and cigarette smoking have been reported to trigger the development of MS; low Vitamin D levels and cigarette smoking have a strong association with MS. MS may also be triggered by certain infections, such as Epstein-Barr virus (EBV) infection.

Carriers of the HLA DRB1*15 allele (an allele that constitutes one of two or more versions of a gene, placed on the same chromosome) are 3 times more susceptible to MS than non-carriers. Additionally, IL2RA, IL7RA, CD58, TYK2, STAT3, and TNFRSF1A haven linked with MS. Although a few studies suggest that vaccination against yellow fever might increase the relapse rate of MS, the existing evidence is non-confirmatory of this association. This disease has a huge impact on the quality of life of the affected individuals, both functionally and financially.

Global perspective

The estimated number of people with MS worldwide has increased from 2.3 million in 2013 to 2.8 million in 2020. The pooled incidence rate across 75 reporting countries was 2.1 per 100,000 persons/year. Recognition of pediatric-onset MS has increased substantially with >/= 30,000 cases in individuals under the age of 18. Globally MS is twice more prevalent in females than males.

Indian perspective

Multiple Sclerosis was previously believed to be nonexistent in India. In recent years, with the advent of magnetic resonance imaging (MRI) and changes in the diagnostic criteria, it is now commonly diagnosed in clinical practice. The earlier belief that MS in India was vastly different from that seen in the western world has given way to the fact that they are more or less the same with minor differences. One of the earliest studies done by Wadia et al reported that 77.7% of the patients with MS had Class I HLA antigen association with HLA-B12 antigen (and notB7) as compared to 13.8% of the control group. Further studies of the class II HLA genes, DRB1, DQA1, and DQB1 were done in a limited number of patients and revealed the known association with the European susceptibility haplotype DRB1*1501—DQB1*0602. A recent study by Pandit et al has focused on evaluating the role of established non-MHC disease susceptibility loci in the Indian population. It was in turn found that a commonality exists in disease susceptibility genes in the Indian and the western population.


The diagnosis of MS is based on the presence of CNS lesions that are disseminated in time and space (i.e., occur in different regions of the CNS, at least 3 months apart), with no better explanation for the disease process. Clinical presentation remains the gold standard for diagnosing MS, which is supported by the findings of investigations comprising neuroimaging (mainly magnetic resonance imaging – MRI), sensory evoked potential testing, cerebrospinal fluid (CSF - clear fluid that surrounds the brain and spinal cord) analysis, and various serologic tests.

Clinical presentation

MS typically presents in adults in the age group of 20-45 years, and occasionally in childhood or late middle age. Women are affected two times more than men, and people of Northern European descent seem to be at a higher risk. MS can be considered a spectrum of diseases, ranging from relapsing (inflammatory dominant) to progressive (neurodegenerative dominant) forms. The onset of MS may be insidious and the symptoms of MS majorly depend on the anatomic location of the plaques along the neural axis.

  • Facial nerve involvement 

Facial paresis (weakened/impaired movement of the face muscles) in MS develops from demyelination of the facial nerve within the brainstem. Facial myokymia (twitching of face-muscle) is undulating, wave-like twitching that begins in the orbicularis oculi muscle (twitching of the muscle that supports the eyelid). Dysarthria (difficult/unclear speech), dysphagia (difficulty/discomfort in swallowing), and vertigo (sensation of spinning) are also common. 

  • Corticospinal tract involvement 

The involvement of the corticospinal tract manifests clinically as heaviness, stiffness, weakness, pain, or paralysis, leading to hemiparesis (weakness in one side of the body), paraparesis (partial inability to move one’s legs), or paraplegia (paralysis of the legs and/or lower body). The lower extremities are more frequently affected than the upper extremities. Fatigue is the most common complaint of patients with MS. Other manifestations include hyperactive deep tendon reflexes, and a positive Babinski’s sign (The Babinski reflex occurs after the sole of the foot has been firmly stroked – the big toe moves upward or toward the top surface of the foot, the other toes fan out). 

  • Sensory symptoms 

The sensory symptoms of MS include tingling or burning sensation, or complete loss of sensation.  Lhermitte’s sign (sudden transient electric-like shocks extending down the spine triggered by flexing the head forward) is a sensory manifestation in MS.

  • Neuralgia

MS is a potentially painful disease, presenting with trigeminal (cranial nerve V; innervates the eyes, face, mouth, tongue, and jaws) or glossopharyngeal (cranial nerve IX; innervates the tongue and middle ear) neuralgia (pain from an irritated or damaged nerve). The neuralgia is characterized by episodes of severe, short-lasting, lancinating pain, affecting the face or head-neck region. Headaches and migraines are more common in patients with MS than in normal healthy individuals. 

  • Cerebellar involvement 

Cerebellar involvement in MS clinically manifests as gait ataxia (uncontrolled gait), and dysmetria (inability to control/estimate the distance, speed, and range of motion necessary to perform smoothly coordinated movements) upon the performance of the finger-to-nose and heel-to-shin test. Limb ataxia and intention tremor (trembling of a body-part when attempting a precise movement) are found in 50% of the cases. Lower limb extremities are more commonly affected than the upper limb extremities. 

  • Neuropsychiatric symptoms

Neuropsychiatric symptoms are seen in around 65% of MS cases. A decline in language skills, memory, and intellectual function is common. Additionally, slowing of the thinking process, poor recent memory, word-finding difficulties, slow information processing, and difficulty with concentration are observed. 


  • Magnetic resonance imaging (MRI)

MRI has proven to be highly sensitive in the detection of clinically silent MS plaques. A brain MRI scan is the most useful investigation for confirming the diagnosis of MS. MS lesions appear as regions of high signal, predominantly in the cerebral white matter or spinal cord, on T2 weighted images. MRI also detects deep-seated MS plaques (those situated in the posterior fossa, or cranio-cervical junction or in the cervical cord) that are difficult to visualize in computed tomography (CT). A brain MRI scan performed with a high-field magnet (1.5 tesla or greater) is abnormal in almost all patients who have been clinically suspected to have MS.

  • Sensory evoked potential testing

Evoked potentials (visual, brainstem auditory, and somatosensory) are useful in identifying subclinical lesions in the sensory nerve pathways.  The visual evoked test can particularly provide objective evidence of an optic nerve lesion that may not be evident on MRI scan.

  • Cerebrospinal fluid (CSF) analysis

CSF immunoglobulin G (IgG) concentration is increased relative to other CSF proteins (e.g., albumin) in approximately 90% of patients with MS.  CSF analysis is most useful to rule out infectious or neoplastic conditions that mimic MS.

  • Serologic test

Peripheral blood tests may help exclude other diseases. Testing often includes estimating Vitamin B12 level, thyroid-stimulating hormone (TSH) level, erythrocyte sedimentation rate (ESR), and anti-nuclear antibody titers as well as test for Lyme disease and syphilis (rapid plasma regain test). Rarely, a more extensive evaluation may include tests for anti-neutrophil cytoplasmic antibodies, anti-phospholipid antibodies, Sjogren’s syndrome A and B, angiotensin-converting enzyme, human T-lymphotropic virus type 1, and very long chain fatty acids.

Quality of life

The factors that significantly impact the quality of life (QoL) in patients with MS include age, sex, socioeconomic status, disability status, depression, and fatigue. Comorbidities such as depression, and anxiety, physical conditions such as hypertension, hyperlipidemia, and chronic lung disease relate negatively to the QoL. Studies have established that physical disability is the most strongly related factor to QoL in MS, and that timely intervention with the help of psychotherapy, physiotherapy and support-groups is beneficial. Patients with MS and their caregivers may obtain information on MS and the various available support groups for MS from https://www.nationalmssociety.org/Resources-Support/Find-Support.


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