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Prevalence of multiple sclerosis in a south London borough.

A survey of multiple sclerosis in the London Borough of Sutton, population 169,600, yielded 195 cases, giving an overall prevalence of 115/100,000. This is the third highest prevalence for a first survey of a geographical area in the United Kingdom, exceeded only by 127/100,000 in north east Scotland and 134/100,000 in Shetland. On the classification system of Allison and Millar, three quarters of the cases were classified as probable multiple sclerosis, 15% as early probable and latent multiple sclerosis, and 10% as possible multiple sclerosis. The mean age was 49 years, the mean age at onset was 34 years, and the mean duration of the disease was 15.4 years. The age standardised female to male ratio was 2:1. The prevalence found in this survey does not differ significantly from that recorded in the first north east Scotland survey. This study suggests that, firstly, the prevalence of multiple sclerosis in south east England is probably about 100/100,000 and, secondly, the latitudinal effect on the prevalence of multiple sclerosis in the United Kingdom is less appreciable than previously believed.

Adolescent↗

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study.

OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis.

Adolescent↗

Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review.

OBJECTIVE: To determine the accuracy of magnetic resonance imaging criteria for the early diagnosis of multiple sclerosis in patients with suspected disease. DESIGN: Systematic review. DATA SOURCES: 12 electronic databases, citation searches, and reference lists of included studies. Review methods Studies on accuracy of diagnosis that compared magnetic resonance imaging, or diagnostic criteria incorporating such imaging, to a reference standard for the diagnosis of multiple sclerosis. RESULTS: 29 studies (18 cohort studies, 11 other designs) were included. On average, studies of other designs (mainly diagnostic case-control studies) produced higher estimated diagnostic odds ratios than did cohort studies. Among 15 studies of higher methodological quality (cohort design, clinical follow-up as reference standard), those with longer follow-up produced higher estimates of specificity and lower estimates of sensitivity. Only two such studies followed patients for more than 10 years. Even in the presence of many lesions (> 10 or > 8), magnetic resonance imaging could not accurately rule multiple sclerosis in (likelihood ratio of a positive test result 3.0 and 2.0, respectively). Similarly, the absence of lesions was of limited utility in ruling out a diagnosis of multiple sclerosis (likelihood ratio of a negative test result 0.1 and 0.5). CONCLUSIONS: Many evaluations of the accuracy of magnetic resonance imaging for the early detection of multiple sclerosis have produced inflated estimates of test performance owing to methodological weaknesses. Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack of neurological dysfunction may lead to over-diagnosis and over-treatment.

Case-Control Studies↗

Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study.

BACKGROUND: Evoked potentials are used in the functional assessment of sensory and motor pathways. Their usefulness in monitoring the evolution of multiple sclerosis has not been fully clarified. OBJECTIVE: The aim of this longitudinal study was to examine the usefulness of multimodal evoked potential in predicting paraclinical outcomes of disease severity and as a prognostic marker in multiple sclerosis. METHODS: Eighty four patients with clinically definite multiple sclerosis underwent Expanded Disability Status Scale (EDSS) and functional system scoring at study entry and after a mean (standard deviation) follow-up of 30.5 (11.7) months. Sensory and motor evoked potentials were obtained in all patients at study entry and at follow-up in 64 of them, and quantified according to a conventional score. RESULTS: Cross-sectionally, the severity of each evoked potential score significantly correlated with the corresponding functional system (0.32 < R < 0.60, p < 0.01, for all but follow-up visual evoked potential) and with EDSS (0.34 < R < 0.61; p < 0.001 for all but brain stem evoked potential). EDSS significantly correlated with global evoked potential score severity (baseline R = 0.60, follow-up R = 0.46, p < 0.001). Using longitudinal analysis, only changes in somatosensory evoked potential scores were significantly correlated with changes of sensory functional system (R = 0.34, p = 0.006). However, patients with multiple sclerosis with disability progression at follow-up had more severe baseline evoked potential scores than patients who remained stable. Patients with severe baseline global evoked potential score (higher than the median value) had a risk of 72.5% to progress on disability at follow-up, whereas patients with multiple sclerosis with lower scores had a risk of only 36.3%. CONCLUSIONS: These results suggest that evoked potential is a good marker of the severity of nervous damage in multiple sclerosis and may have a predictive value regarding the evolution of disability.

Adult↗

A clinical comparative study of multiple sclerosis and neuro-Behçet's syndrome.

Clinical comparisons were made between Japanese patients with multiple sclerosis (66 cases) and neuro-Behçet's syndrome (23 cases). Those with neuro-Behçet showed marked male predominance, while those with multiple sclerosis showed slight female preponderance. Both showed encephalomyelopathy disseminated in time and space. Patients with multiple sclerosis, however, showed a more polyphasic course, whilst those with neuro-Behçet showed a more progressive one. In multiple sclerosis optic neuritis, acute transverse myelitis, painful tonic seizures, mental disturbance and internuclear ophthalmoplegia were common. On the other hand, in neuro-Behçet the main neurological manifestation was progressive pseudobulbar palsy. Serum and CSF showed more inflammatory changes in neuro-Behçet than in multiple sclerosis. Clinical estimation suggested that in multiple sclerosis the main lesions were in the optic nerve, tegmentum of the brain stem and spinal cord, whereas in neuro-Behçet they were in the basal parts of the brain stem.

Adolescent↗

On the role of sensitised T-lymphocytes in the pathogenesis of multiple sclerosis.

Peripheral blood lymphocytes from 24 out of 26 patients with clinically well-defined multiple sclerosis in remission showed sensitisation to multiple sclerosis brain extracts as assayed by enhancement of the early erythrocyte rosette test. Such an increase in the number of early rosettes was not found when the lymphocytes of multiple sclerosis patients were exposed to extracts of control brains. In contrast the sensitised cells were found in the circulation in only two of 11 patients with multiple sclerosis in acute relapse. The percentage of circulating T-lymphocytes which formed early rosettes was lower in the group of patients suffering a relapse than in patients in remission. A longitudinal study of one patient who was tested before, during and after a relapse revealed the disappearance from the blood of the sensitised T-cells during the relapse and their subsequent reappearance after recovery. Of 36 patients with other neurological diseases, two responded solely to multiple sclerosis brain, two responded to both multiple sclerosis and control brain, and three responded only to control brain. No healthy controls showed sensitisation to any brain extract.

Adult↗

Acute optic neuritis: a prospective study of risk factors for multiple sclerosis.

Eighty two patients with isolated optic neuritis were studied prospectively to determine the frequency with which multiple sclerosis developed and the factors which increased its risk. Patients were followed for 6 to 264 months (mean, 57 months). Twenty six patients (32%) developed clinically definite or probable multiple sclerosis during the period of follow-up. Actuarial analysis predicted that 42% would develop multiple sclerosis by 7 years. Of those patients who developed multiple sclerosis, 92% had symptoms within 4 years of the first attack of optic neuritis. The highest incidence of multiple sclerosis occurred in the 21-40 year age group. There was an increased risk of MS in patients with HLA-DR2 and HLA-B7 tissue types. The frequency of HLA-DR4 was increased in patients with optic neuritis alone compared to controls and to patients with multiple sclerosis, but further studies are required to confirm this finding.

Acute Disease↗

A study of oligoclonal band negative multiple sclerosis.

OBJECTIVES: To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis. METHODS: Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS: Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs. CONCLUSIONS: OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis.

Adult↗

Paradoxical puborectalis contraction is a feature of constipation in patients with multiple sclerosis.

OBJECTIVE: To study the disturbed anorectal physiology associated with constipation in multiple sclerosis. METHODS: Anorectal function in 10 patients with clinically definite multiple sclerosis and constipation has been compared with 10 normal persons and 11 patients with idiopathic constipation, without multiple sclerosis. RESULTS: All 10 constipated patients with multiple sclerosis had difficulty evacuating barium paste during defaecography. In four of these there was complete failure of puborectalis relaxation when straining to defaecate, and in another four there was incomplete puborectalis relaxation. There was no evidence of lower motor neuron involvement of pelvic floor muscles in the multiple sclerosis group. CONCLUSIONS: Paradoxical puborectalis contraction is common in patients with multiple sclerosis in whom constipation is a symptom. This may be a feature of the disturbed voluntary sphincter control mechanism, analogous to detrusor sphincter dyssnergia in the bladder.

Adult↗

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium.

OBJECTIVES: To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. METHODS: Lifetime risks were calculated using the maximum likelihood approach. RESULTS: Vital information was obtained on 674 probands with multiple sclerosis in Flanders and a total of their 26225 first, second, and third degree relatives. Full medical information to allow documentation of multiple sclerosis status was available for 21351 (81.4%) relatives. The age adjusted risk for parents was 1.61 (SEM 0.35)%, for siblings 2.10 (SE 0.36)%, and for children 1.71 (SEM 0.70)%. For aunts and uncles, the risk was 0.66 (SEM 0.13)%. CONCLUSIONS: The risk for first degree relatives of patients with multiple sclerosis in Flanders is increased 10-fold to 12-fold; for second degree relatives, it is increased threefold. This information can be used for risk counselling in families and provides additional support for the role of more than one locus contributing to the susceptibility of multiple sclerosis.

Adult↗

Assessment of olfaction in multiple sclerosis: evidence of dysfunction by olfactory evoked response and identification tests.

OBJECTIVE: To resolve whether the olfactory pathways are affected in multiple sclerosis. METHODS: Olfaction was assessed by: (1) The University of Pennsylvania smell identification test (UPSIT, which uses microencapsulated odours that are released when scratched with a pencil) in 72 patients with multiple sclerosis and 96 controls, (2) olfactory evoked potentials (OEP) to 20 ppm H2S by volume, and 50% CO2 in air for 45 patients with multiple sclerosis and 47 controls. The abnormality rate in patients with multiple sclerosis for both tests (1) and (2) was compared with that for visual evoked potentials measured using a standard checquerboard technique. RESULTS: By comparison with controls, patients exhibited significantly low scores on the smell identification test with 15% of patients scoring outside the 95% confidence intervals for controls. The UPSIT was occasionally abnormal when the visual evoked potential (VEP) was normal. In general UPSIT scores correlated well with the H2S-evoked response in controls and patients. For H2S, there was a statistically significant increase of latency and decrease of amplitude for patients compared with controls. Increased H2S latency and reduced UPSIT score correlated with greater disability on conventional rating scales. Overall, H2S responses were abnormal in about one quarter of patients with multiple sclerosis. The sensitivity of UPSIT and OEP was similar although disorder on one test did not necessarily indicate abnormality in the other. The visual evoked potential was found to be a more sensitive indicator of disease than OEP or UPSIT. CONCLUSION: These findings confirm the existence of olfactory dysfunction in multiple sclerosis and validate a new evoked potential technique.

Adult↗

Transitional progressive multiple sclerosis: a clinical and imaging study.

OBJECTIVE: To study the prevalence and the natural course of transitional progressive multiple sclerosis (TPMS). This clinical form is defined by a progressive course beginning many years after an isolated bout. METHODS: 214 consecutive outpatients with definite or probable multiple sclerosis were studied. The prevalence of TPMS was established. Patients with TPMS were compared with patients with other progressive forms of multiple sclerosis according to the clinical course. A prospective one year follow up study was performed in a subgroup of patients to compare progression of the disease using clinical indices and MRI. RESULTS: In this clinical population of 214 outpatients with multiple sclerosis, 55 had secondary progressive multiple sclerosis (SPMS), 38 primary progressive multiple sclerosis (PPMS), and 12 TPMS. Retrospective analysis of the clinical data of these patients shows that TPMS is very similar to SPMS at the beginning of the disease (age at onset, time before progression, clinical symptoms at onset, progression index). In addition a cohort of patients was prospectively followed up clinically and by MRI for one year. CONCLUSIONS: The results did not show any significant differences between the three forms during this follow up. However, all data showed a concordant trend suggesting that at this progressive stage, TPMS is closer to PPMS in terms of progression of disability and new MRI lesions.

Brain↗

Clinical and MRI study of brain stem and cerebellar involvement in Japanese patients with multiple sclerosis.

OBJECTIVES: To investigate the clinical and MRI features of brain stem and cerebellar lesions in Japanese patients with multiple sclerosis. METHODS: A retrospective study of 66 consecutive Japanese patients with multiple sclerosis (42 women and 24 men) was done by reviewing the medical records and MRI films. Forty nine patients were diagnosed as having clinically definite multiple sclerosis and 17 patients as having clinically probable multiple sclerosis according to Poser's criteria. Prevalence rates of each brain stem and cerebellar manifestation and frequency and distribution of MRI lesions in these patients were studied. RESULTS: Forty three patients (65%) had one or more infratentorial manifestations. Cranial nerves were clinically involved in 28 patients (42%), and most of the lesions were identified by MRI. Among them, manifestations of facial, trigeminal, and abducens nerves were relatively common. Cerebellar ataxia was found in 20 patients (30%). The MRI study showed that the lesions responsible for ataxia in these patients were mainly found in the cerebellar peduncles, but cerebellar hemispheric lesions were detected in only four patients (6.4%). CONCLUSION: The low frequency (6.4%) of the cerebellar MRI lesions in these patients is in sharp contrast with the figures reported for white patients with multiple sclerosis (50%-90%). Racial and genetic differences may have an influence on the susceptibility of each part of the CNS to demyelination in multiple sclerosis.

Asian People↗

Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study.

The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1beta and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines. The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient. Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0. 05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions. In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.

Adult↗

Gut focused behavioural treatment (biofeedback) for constipation and faecal incontinence in multiple sclerosis.

OBJECTIVES: To determine whether gut focused behavioural treatment (biofeedback) is a useful therapy in multiple sclerosis patients referred for constipation, incontinence, or a combination of these symptoms. Most patients with multiple sclerosis complain of constipation, faecal incontinence, or a combination of the two. Patients rate these bowel symptoms as having a major impact on their life. Until now the management of these problems has been empirical, with a lack of evaluated therapeutic regimes. METHODS: Thirteen patients (eight women, median age 38 years, median duration of multiple sclerosis 10 years) complaining of constipation, with or without faecal incontinence underwent a median of four sessions of behavioural treatment. Anorectal physiological tests were performed before therapy. Impairment and disability were rated with the Kurtzke score and the Cambridge multiple sclerosis basic score (CAMBS). Patients were contacted a median of 14 months after completion of treatment. RESULTS: A beneficial effect was attributed to biofeedback in five patients. Mild to moderate disability, quiescent and non-relapsing disease, and absence of progression of multiple sclerosis over the year before biofeedback were predictive of symptom improvement. No physiological test predicted the response to therapy. CONCLUSION: Biofeedback retraining is an effective treatment in some patients with multiple sclerosis complaining of constipation or faecal incontinence. A response is more likely in patients with limited disability and a non-progressive disease course.

Adult↗

Community services in multiple sclerosis: still a matter of chance.

OBJECTIVES: People with multiple sclerosis often have multiple complex needs that require input from a wide range of services. Many complain that services are inadequate and poorly coordinated. Few studies have been undertaken to support this contention and objective data are scarce. The level of services and home modifications received by people with multiple sclerosis across a broad range of disease severity has been investigated. METHODS: As part of a quality of life study, 150 adults with clinically definite multiple sclerosis were interviewed, using a structured questionnaire, to determine their current use of outpatient and community services and the home modifications in place. Disability, handicap, and emotional status were also measured. RESULTS: Forty five per cent of people did not receive any community services other than contact with their general practitioner. Thirty nine per cent of people with moderate and 12% with severe disability failed to receive community services. For the services received: 17% had contact with a community nurse; 33% with a care attendant or home help; 23% with a physiotherapist, 21% with an occupational therapist, and 10% with a social worker. Fifty eight per cent of people had modifications to their home as a direct result of multiple sclerosis. The relation between level of disability and number of services and adaptations received was moderate (r=0.58 and 0.54 respectively) and the relation between level of services and age (r=0.12), living alone (r=0.16), and emotional status (r=0.10) was negligible. CONCLUSIONS: Despite a shift of emphasis from hospital to community care, and the establishment of standards of care for multiple sclerosis, many people with moderate or severe disability fail to receive assistance. These results provide evidence to support the dissatisfaction felt by people with multiple sclerosis in relation to the services they receive. It raises questions about equitable allocation of resources and highlights the urgent need for a review of community services.

Adult↗

The range of multiple sclerosis associated with neurofibromatosis type 1.

Multiple sclerosis associated with neurofibromatosis type 1 (NF1) is a very rare event. Seven patients with multiple sclerosis and NF1 are described in the literature, and all were reported to have the primary progressive form of multiple sclerosis. Three new patients with NF1 that developed multiple sclerosis are described and it is shown that the range of multiple sclerosis associated with NF1 includes the relapsing forms of the disease. The risk of having both NF1 and multiple sclerosis in north east Italy is higher than would be expected based on the prevalence rates of the two diseases.

Adult↗

Using the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson's disease with normal population health profiles.

OBJECTIVE: To examine the relative impact of two chronic neurological disorders, multiple sclerosis and Parkinson's disease, by comparing patients' scores on the medical outcomes study 36-item short form health survey (SF-36) with the health profile of the United Kingdom population norms. METHODS: 638 people representing the full spectrum of multiple sclerosis and 227 patients with Parkinson's disease were studied. Health status was measured by the SF-36. Scores for the eight health domains were compared after controlling for age, sex, disease duration, mobility, social class, ethnicity, education, marital status, and employment status. RESULTS: People with multiple sclerosis and those with Parkinson's disease had significantly worse health than the general population on all eight domains measured by the SF-36. The relative impact of multiple sclerosis and Parkinson's disease were similar, but multiple sclerosis resulted in poorer scores on physical functioning and better scores in mental health. People with mild multiple sclerosis who walked without an aid also had significantly worse scores in all dimensions than the general UK population. CONCLUSIONS: The results highlight the need for further research into aspects of health measured by the SF-36. Nevertheless, generic measures that are applicable across multiple diseases may fail to address clinically important aspects of the impact of specific disorders.

Adult↗