Volume 4 - Issue 4
Consultant Neurologist and Neuroelectrophysiologist, Kauvery Hospital, Chennai, India
Multiple sclerosis (MS) is an inflammatory condition that causes demyelination and axonal loss in the central nervous system (brain and spinal cord).
The primary brain insult- Sclerosis, and its clinical sequelae are 'disseminated in space', affecting different anatomical sites, and 'disseminated in time', appearing episodically over time.
It could have an auto-immune basis but real aetiology is not clear. Environmental factors and genetics do play a role but there is still a lot of ambiguity on the interplay of these factors. Vitamin D deficiency seems to have an influence on the severity of the disease process and thus correction and supplementation is recommended for MS patients.
Multiple sclerosis has a predilection for young females, with a ratio of 3:1. It is usually seen between 20-40 years of age.
However late or early presentations can be encountered and almost 10% of cases have onset before 18 years.
MS in general demonstrates a prevalence based on latitude, with increased prevalence in northern latitudes of Europe and North America.
Various studies have noted that populations that migrate to areas of greater MS prevalence during childhood also acquire a higher risk of acquiring MS. Other studies have called this observation into question.
In India, visuo-spinal variant was more commonly reported initially and MS was considered rare. But we are now seeing more patients with various other manifestations including brain stem and cerebral involvement.
MS exists in India, although its prevalence is lower than among European and American populations. The phenotypic presentation of MS in India seems quite similar to the West, and it has also been observed that some of the genes in Indian patients are similar to those seen in the Western patient population. Large epidemiological studies are needed to study MS incidence and prevalence in India.
ICMR has recently launched a registry for MS patients in the country and hopefully this shall help us understand the Indian pattern better.
The sub-division of MS as relapsing and remitting type (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) is based more on clinical characteristics and not specific biologic pathophysiology. Nonetheless, they provide an organized framework for diagnosis and long-term management.
Relapsing and remitting type is the most common and represents clearly the spatial and temporal framework of MS presentation in general. Our available disease-modifying drugs are most effective against this type and helps prevent new lesion formation.
There are a few rare types of MS described such as:
(1) Marburg type: This type has a fulminant monophasic course in most cases, with poor response to treatment.
(2) Balo type: By definition shows a peculiar pattern of pathology in cerebral hemispheric white matter consisting of a concentric, mosaic, or floral configuration of alternating bands of white matter whose basis is relatively preserved myelination alternating with regions of demyelination.
(3) Schilder's disease: This is an acute MS that occurs in childhood with widespread white matter involvement. The clinical course is diverse.
(4) Tumefactive MS (TMS): Rarely the plaque size can be >= 2 cm with mass effect, edema, or ring enhancement on magnetic resonance, features pointing to a tumour-like space-occupying lesion.
The presentation of MS depends on the locations of the multifocal lesions in the CNS. The severity of symptoms is reflective of lesion burden, location, and degree of tissue injury. The common manifestations include
If spinal cord is involved then symptoms include
The RR course of MS is observed in a majority of patients and is characterized by exacerbation and relapses of neurological symptoms, with stability between episodes. The following features generally characterize the RR course of MS:
Symptoms from relapses frequently resolve. However, over time, residual symptoms relating to episodes of exacerbation occur.
The secondary-progressive (SP) course is often noted in patients with RR after a few years of onset and is characterized by a more gradual worsening of symptoms with continued progression with or without superimposed relapses in some patients.
A small proportion of patients demonstrate gradual worsening of disability from onset of disease, described as the primary progressive (PP) course of MS. Myelopathy, cognitive symptoms, and visual symptoms are most frequently the clinical manifestations in this clinical course.
No single pathognomonic test exists for the diagnosis of MS. There are no definitive bio-markers too.
Diagnosis is made by weighing the history and physical examination. In addition, laboratory tests are used such as
Clinically a diagnosis can be made with evidence of two or more relapses: this is possible through objective clinical evidence of two or more lesions or objective clinical evidence of one lesion with reliable historical evidence of a prior relapse. Dissemination in space (DIS) and dissemination in time (DIT) are two hallmarks of the accurate diagnosis of MS. DIS is assessed using information from the history and physical and understanding in determining the location of CNS involvement.
The 2010 McDonald's criteria, later revised in 2017, combines these factors and are used world-wide for the diagnosis of Multiple Sclerosis.
The chief characteristics of MS lesions on MRI can be summarized as the following:
The classic abnormal CSF findings in MS are as follows:
Specific blood studies to include CBC, TSH, vitamin B12, sedimentation rate, and ANA should also be obtained in all patients.
Blood Aquaporin (NMO) antibodies and Anti MOG ( myelin ) antibodies are also checked to rule out NMSOD as this inflammatory condition is slightly more common in the Indian population.
Fig. 1. Multiple typical demyelination lesions in brain and spine.
Fig. 2. Showing evidence for Tumefactive MS.
Table 1. 2017 Mc Donald 's criteria for Dissemination of time and Space
Acute attacks are always treated with high dose steroids, initially given intravenously and then changed to oral route, and tapered over time. This is common to treatment of the NMSOD group too.
For prevention of new lesions, disease-modifying therapies are the mainstay of treatment of relapsing-remitting MS. Early treatment should commence upon establishing a diagnosis of MS. Short term goal includes a reduction in MRI lesion activity. Long term goals include prevention of secondary progressive MS. The primary issues after initiating therapy include patient compliance, costs of treatment and monitoring for drug toxicity.
In India, considering the cost of treatment, compliance is a challenge and as physicians, we need to reiterate the importance of continuation of long-term treatment.
Oral drugs although taken every day are slightly cheaper in terms of monthly expense. Following are the commonly used medications.
In India, Beta interferon therapies and Natalizumab are easily available and most commonly used.
In India, Dimethyl Fumarate and Teriflunomide are mostly commonly used. In fact, oral drugs preferred by patients as they are most cost effective on long-term basis.
An increasing body of evidence supports the high efficacy and the low drug discontinuation rate of B-cell-depleting anti-CD20-antibody RTX for the treatment of MS.
Long-term observation of RTX therapy in RA and in NMOSD suggests that RTX is highly effective, safe and well tolerated. There is also some evidence for the use RTX in primary progressive type of MS.
There are many more drugs available outside this list but this paper includes only those most commonly used in India and with maximum evidence for efficacy.
Patients with either secondary progressive MS or primary progressive MS appear to represent primarily neurodegenerative processes. Disease-modifying therapies are, therefore, less effective, and treatment with these therapies has ranged from possible benefit to little effect on disease progression.
In March 2017, ocrelizumab was approved in the United States for the treatment of primary progressive multiple sclerosis in adults and active secondary progressive disease in adults.
Other demyelinating or inflammatory CNS syndromes: Examples include optic neuritis, Marburg disease, acute disseminated encephalomyelitis, Devic neuromyelitis optica, and partial transverse myelitis.
The prognosis and severity of the disease vary between patients. The condition is often mild early on in the disease and worsens as time progresses.
Factors that suggest a worse prognosis include:
The long-term disability of MS reflects an accumulation of symptoms from each successive incomplete recovery from relapse.
MS is a complex neurologic disorder that results in both neurologic and non-neurologic symptoms, disability, and complaints. Other specialities are also involved in the care.
A diagnosis of MS can be difficult for a patient, and the doctor plays a supportive role in counselling the patient about the diagnosis. Predicting disease course is difficult, and a provider should educate the patient on the wide range of possibilities in disease progression. Clinicians should emphasize that patients often do well and explain the role of effective medications on disease treatment. Patients should know to contact their provider if they experience new neurologic symptoms. There should be a lot of emphasis on lifestyle, exercise, habits, Vitamin D supplementation, a balanced diet. Patients should also be counselled on the importance of compliance with disease-modifying therapy, considering the side-effect profile of these medications. In India, as the cost of treatment is so high, when the patient is well for considerable duration, there is a general tendency to stop medication and follow up. As doctors, we need to keep counselling and checking on these patients to make sure that they do not end with severe complications or secondary progression on sudden with-drawl of treatment.
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Senior Consultant - Neurology & Neurophysiology