Clinical profile of multiple sclerosis in north-west India.
A total of 100 patients were enrolled in this study with the clinical diagnosis of multiple sclerosis (MS). This included prospective analysis of 35 patients and retrospective analysis of 65 patients from their medical records spanning a period from January 1986 to March 1998. They were divided into 3 groups (i) overall group (ii) MRI group (where MRI was available) (iii) No MRI group (where MRI was not available). Data in terms of clinical features and laboratory investigations were compared in the three groups. MS was found to constitute 2.54% of neurology admission between January 1993 to December 1997. It was higher as compared to previous data from our institute (1.58%). Cerebellar symptoms were higher in the MRI group as compared to the non MRI group. The clinical spectrum of MS in the MRI group was comparable to that in the west. Obviously the MRI helps in early diagnosis of milder and atypical cases. Oligoclonal bands were found in 30.5% of cases only.
Multiple sclerosis (MS) is a chronic disorder of the central nervous system, which usually begins in early adult life and pursues a variable course causing significant morbidity. The variation in prevalence of MS according to geographical location and the modification of clinical picture by ethnic factors are all well known features of the disease. MS is more prevalent in Caucasians and thus has been extensively studied and reported from the West. There have been relatively few studies from Asia and India in particular. Asian MS has traditionally been thought of as a distinct entity characterised by high incidence of visual involvement at onset, a more severe visual involvement during follow up, prevalence of recurrent acute transverse myelitis, high incidence of optico-spinal involvement (Devic's disease), severe involvement of spinal cord with greater functional disability and less frequent involvement of cerebellum.,,,,,
With gradually expanding neurological services in India and particularly with the advent of magnetic resonance imaging (MRI), the clinical spectrum of MS is changing. MRI not only helps in early diagnosis of mild cases, but also helps in the diagnosis of many atypical cases. Results of some of the recent Indian studies, done in the MRI era have found relatively few differences from the West lending support to the theory that the differences between MS in the West and our population are more apparent than real.
However, differences in Caucasian and Oriental patients with MS in terms of human leukocyte antigen (HLA) association and oligoclonal bands (OCB's) positivity continue to be reported.,, It was in this context that we undertook to conduct this study comparing patients with MS in the pre and post MRI era.
A total of 100 patients of multiple sclerosis fulfilling Poser's criteria for multiple sclerosis were studied., Out of these, 35 patients were studied prospectively which included patients admitted in Neurology ward and attending outpatient department (OPD) between October 1996 to March 1998. In addition, a retrospective analysis of medical records of 65 patients admitted since January 1986 was also undertaken. The following parameters were noted : i) age at onset of the disease, ii) sex, iii) symptoms and signs during the course of illness, and at the onset, iv) course of the disease i.e. remitting and relapsing or progressive, v) number of attacks during the course of illness, vi) family history of disease and vii) other rare manifestations of the disease. Devic's syndrome (acute spino-optic demyelination) which is one of the presentations of multiple sclerosis, is usually considered when bilateral visual impairment and transverse spinal cord lesions develop concomitantly or within several weeks of each other, with or without subsequent improvement.,
Patients were classified into the following categories based on Poser's criteria : 1) Clinically definite multiple sclerosis (CDMS), 2) Laboratory supported definite multiple sclerosis (LSDMS), 3) Clinically probable multiple sclerosis (CPMS), 4) Laboratory supported probable multiple sclerosis (LSPMS) [Table I.]
A full set of investigations was performed wherever possible to aid the diagnosis of multiple sclerosis and to exclude other diseases, particularly connective tissue disorder which is a common differential diagnosis. Blood tests comprised complete blood counts, ESR, Blood biochemistry and where required antinuclear factor and rheumatoid factor. CSF analysis for oligoclonal bands and evoked potentials (VEP, BAER) were performed to support the diagnosis of multiple sclerosis wherever possible. MRI was considered suggestive if it showed multiple white matter lesions in the brain or intramedullary plaques in the spinal cord.
For the sake of comparison, patients were divided into three groups : 1) overall group, 2) in whom MRI was available as part of investigation, 3) in whom MRI was not available as a part of investigations. The clinical features, both in the beginning and during the course of illness, were compared in these three groups and also with some of the major Oriental and Caucasian series. The positivity of various investigations like MRI, evoked potentials and CSF oligoclonal bands was noted in different groups.
The overall group comprised of 100 patients. `MRI group' (in whom MRI was available) had 61 patients, and `No MRI' group (in whom MRI was not available) had 39 patients.
Hospital Incidence : During the period between Jan'93 to March'98, which corresponded to the MRI era, patient with MS constituted 2.54% of neurology admissions in Postgraduate Institute of Medical Education and Research Chandigarh. Male : Female ratio was 1:1.32 (There were 57 females and 43 males) [Table I]. Mean age at onset was 28.49+9.54 years. 89% of these patients followed a remitting and relapsing course while 11% had a progressive course from the beginning. The average relapse rate was found to be 0.63 attacks per year.
Initial neurological symptoms and signs : The initial symptoms in the overall group showed a predominance of pyramidal involvement (46.4%). This was followed by optic involvement in 23.6% of patients, extraocular involvement in 11% and cerebellar involvement in 8.6% of patients. In the MRI group, cerebellar involvement as initial presentation rose to 11.6% as compared to 8.6% in the overall group while incidence of optic involvement as initial presentation fell to 15.5% as compared to 23.6% of the overall group. The rest of the symptoms remained comparable [Table II].
During the course of illness, the pyramidal involvement was the most common sign in 87% of patients followed by sensory involvement (65%). The optic nerve was involved in 57% of patients. Devic's type of presentation was found in 7% of cases. Sphincters were involved in 46% of cases. On comparing the two groups it was found that in the MRI group cerebellar involvement was higher (44.3%) as compared to no MRI group (17.9%). Internuclear ophthalmoplegia was observed in 3 patients. No familial occurrence was found in any Case Table II].
Laboratory data : MRI study was done in 69 patients. Abnormality in the form of multiple white matter lesions in the brain or intramedullary plaques in the spinal cord was seen in 53 cases (86.9%). CSF examination to look for oligoclonal bands (OCB) was available in 46 patients. It was positive for OCB's in 14 patients (30.4%). Increased gamma globulins were found in another 5 patients (10.9%). VEP's were studied in 79 patients. These were abnormal in 62 (78.5%). BAER's were studied in 74 patients and were abnormal in 30 (40.54%).
Until a few years back, the physicians in India were sceptical of making a diagnosis of MS. However, with increasing awareness of medical illnesses, availability of modern investigative facilities, particularly MRI and expanding neurological services in our country, more and more cases are being reported from all over India. Various Indian studies have shown that MS constitutes 0.32 to 1.58% of neurology admissions in hospitals.,,, Singhal et al estimated the prevalence of MS by using prevalence of another neurological disease (ALS) and reported it to be 1.33/100,000 general population.16 The series of 54 patients from our own institute spanning 10 years from 1968 to 1977 showed that MS constituted 1.58% of neurology admissions. In the present study MS cases were found to be 2.54% of total neurology admissions between January'93 to March'98. This striking increase in incidence of MS perhaps owes itself primarily to the availability of MRI and increasing awareness about the disease.
In the present study the age of onset was 28.49+9.54 yrs which is comparable to previous Indian studies.,, The female to male ratio was 1.32 : 1, which is in agreement with the accepted notion. Some of the Indian studies reported a higher male ratio., Increase in literary awareness of medical illnesses in our country are probably responsible for more females being diagnosed as MS. The remitting and relapsing type of MS is the commonest mode of presentation. The relapse rate has varied between 0.4 to 0.6 attacks/yr., In our study a relapse rate of 0.63/yr was found which is similar to the previous studies. The initial symptoms and signs in the present report show that pyramidal involvement is the most common (46.4%) followed by optic involvement (23.6%), extraocular involvement (11.1%) and cerebellar involvement (8.6%). Comparison between the patients in whom MRI was done and in those in whom MRI was not done shows that more cerebellar lesions were detected in the former group. The early diagnosis of these cases with pure cerebellar involvement was made possible solely because of availability of MRI.
In the symptoms/signs observed during the course of illness, pyramidal (87%) and sensory (65%) involvement predominated whereas optic nerve involvement was seen in 57% of cases. A close look at the clinical features between the groups with MRI and without MRI, reveals that the MRI group had lower incidence of optic nerve involvement and higher incidence of extraocular and cerebellar involvement. The incidence of Devic's syndrome too was higher in the `No MRI' group (12.8%) as compared to the MRI group (3.2%). The possible reason for the above findings may be that in the pre MRI era only very typical and severe cases were being diagnosed while now even milder cases are being picked up.
A major difference in Caucasians and Oriental series has been the incidence of cerebellar involvement which was found in over 80% in the former, and 30-58% in the latter.,,,,, In the present study, cerebellar involvement was 44.3% in the MRI group and 17.9% in the non MRI group. There was also a fall in the incidence of optic nerve involvement in the MRI group. The above findings suggest that in the MRI era, there is occurring a deviation of the clinical spectrum from the more classical Asian type of MS towards the Caucasian type and re-emphasizes the fact that clinical spectrum in the two races is essentially similar.
MRI has established itself as the best investigation for diagnosis of MS and in detecting asymptomatic dissemination of the disease. In a given case it may predict the progression of MS. The sensitivity of MRI in detecting MS is known to vary between 81 to 90% with use of different criteria. In the present series, out of 61 patients in whom MRI was done, it was suggestive of MS in 86.9% of cases. In previous Indian studies its positivity ranged from 87.8 to 92%., In the present study, BAER was abnormal in 40.54% of patients in whom it was done. It was higher than reported previously (16.4-21.2%)., Abnormalities in VEP's were found in 78.5% of patients in whom it was done and is comparable to other Indian studies (70-83%).,,
Oligoclonal bands represent abnormal synthesis of gamma globulins in the CSF and therefore strongly implicate an immuno-pathological process. It has been found that in Caucasians the CSF OCB's are found in a higher number of cases (90%) and tend to remain stable during the course of disease, whereas in Asian studies its incidence has been found to be ranging between 33 to 45%.,, Present study shows the positivity of OCB's in 30.5% of patients and rise in gamma globulins in 11% of patients, which is in agreement with other Asian studies. It has been suggested that the association of HLA-DR2 and occurrence of OCB's are related phenomena and the genes which determine production of OCB's may be related to genes which determine one or more variants of HLA-DR2. It may be inferred that there may be absence of DR2 association in Indian patients as is the case in other Asian countries. This along with absence of family history in our patients may reflect different genetic and disease triggering factors in our population.