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.
Diagnosis
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