Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study

The aim of the study was to estimate the rate of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS. Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospective study from December 2004 through June 2007. Conversion from CIS to MS according to both McDonald and Clinically Defined Multiple Sclerosis (CDMS) criteria was prospectively recorded until March 2010. The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS. Among 168 patients included in the analysis, 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria. The 2-year probability of conversion was 57 % for McDonald Criteria and 36 % for CDMS criteria. Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria, and according to Poser’s CDMS criteria, age, positivity for Barkhof criteria and no disease modifying therapy. In this large prospective cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of randomized trials. We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies.     

Long-term follow-up of multiple sclerosis studies and outcomes from early treatment of clinically isolated syndrome in the BENEFIT 11 study

Journal of Neurology - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a diverse disease course involving inflammation and degeneration of neurons and...     

Bladder dysfunction in multiple sclerosis: a 6-year follow-up study

Bladder dysfunction (BD) is the most common autonomic disturbance in multiple sclerosis, but often overlooked and undertreated. The purpose of this longitudinal study was to explore the changes in the frequency of BD symptoms in MS cohort after a period of 3 and 6 years of follow-up, as well as to investigate the correlations between the presence of BD symptoms and both clinical characteristics and the health-related quality of life (HRQoL) at each subsequent point of estimation. The study population comprises a cohort of 93 patients with MS (McDonald’s criteria, 2001). At each time point (baseline, and at the 3- and 6-year follow-up) of estimation, Expanded Disability Status Scale, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Szasz Sexual Functioning Scale and HRQoL (measured by MSQoL-54) were assessed. The proportion of patients with at least one symptom of BD significantly increased over time, for both men and women (from 48.1% at baseline to 51.9% after 3 years and to 71.4% after 6 years of follow-up for males and from 45.5% at baseline to 50.0% after 3 years and to 66.7% after 6 years of follow-up for females). The most common BD problem was urgency of urination. The presence of BD was statistically significantly associated with higher level of physical disability, sexual dysfunction and HRQoL at each point of follow-up, for both men and women. Our results suggested outstanding frequency of BD in patients with MS, with increasing tendency over time.     

Spinal cord axonal loss in multiple sclerosis: a post-mortem study

There is increasing interest in the contribution that axonal damage may make to clinical disability in multiple sclerosis (MS). The present study reports a post-mortem examination of the area occupied by the lateral white matter columns of the spinal cord and nerve fibre density in the corticospinal tracts at C3 and T2 in 23 males and 20 females with MS, who lacked plaques at these levels, and in 31 controls who, although most had had some neurological disease, showed no sign of cervical or spinal cord thoracic disease. The lateral column cross-sectional area, measured by low power image analysis of the outlined lateral columns, was reduced in MS by 17% at C3 and 21% at T2 in males and by 13% at C3 and 18% at T2 in females. These reductions were significant at both levels in males (P<0.004 at C3 and P<0.009 at T2 ) but only at T2 in females (P<0. 03). The nerve fibre density, measured by automatic image analysis of x200 microscopic fields in the region occupied by the crossed pyramidal tracts, was reduced by 41% at C3 and 42% at T2 in males and by 19% at both C3 and T2 in females. These reductions were likewise significant at both levels in males (P<0.003 and P<0.000 at C3 and T2, respectively) and T2 only in females (P<0.045). In MS, nerve fibre density was significantly lower at C3 (P<0.004) and T2 (P<0.000) in males than females. No differences were seen in these parameters between males and females in controls. The reductions in total nerve fibre densities were entirely accounted for by reductions in small nerve fibres (cross sectional area less than 5 microm2 ). No significant reductions were seen in large fibre (cross sectional area 5 microm2 or more) densities. It is concluded that substantial axonal loss and spinal cord lateral column white matter atrophy occur at C3 and T2 in MS, and that these changes can be detected in some patients from early in the course of the disease.     

Thymectomy in multiple sclerosis: a 3-year follow-up

We studied 34 MS patients who were treated experimentally by thymectomy with or without 1 year of azathioprine therapy. After 3 years, there was no evidence of benefit. Relapsing-remitting patients had done as well or better clinically than controls, and the chronic progressive group did less well statistically than controls.     

Anxiety and depressive symptoms in clinically isolated syndrome and multiple sclerosis

Depression and anxiety have been reported in patients with multiple sclerosis (MS) and in patients with clinically isolated syndrome (CIS). However, the precise mechanisms that lead to depressive and anxiety symptoms in these patients are still unclear. In this study we evaluated with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) patients with MS and CIS and compared them to controls. We also correlated BDI and BAI scores with clinical parameters. Kruskall-Wallis followed by Dunn's Multiple Comparison Test, Chi-square and Spearman test were used. Patients with MS had higher depressive and anxiety scores than controls. The BDI and BAI scores of patients with CIS were not significantly different from controls. There was a positive correlation between BDI, BAI and EDSS. Our results corroborate the view that MS patients have higher depression and anxiety levels than control subjects. Anxiety and depressive symptoms also seem to progress according to the severity of the disease.     

An exploratory study on emotion recognition in patients with a clinically isolated syndrome and multiple sclerosis

Objectives

Multiple sclerosis (MS) is a chronic multifocal CNS disorder which can affect higher order cognitive processes. Whereas cognitive disturbances in MS are increasingly better characterised, emotional facial expression (EFE) has rarely been tested, despite its importance for adequate social behaviour.

Patients and methods

We tested 20 patients with a clinically isolated syndrome suggestive of MS (CIS) or MS and 23 healthy controls (HC) for the ability to differ between emotional facial stimuli, controlling for the influence of depressive mood (ADS-L). We screened for cognitive dysfunction using The Faces Symbol Test (FST).

Results

The patients demonstrated significant decreased reaction-times regarding emotion recognition tests compared to HC. However, the results also suggested worse cognitive abilities in the patients. Emotional and cognitive test results were correlated.

Conclusion

This exploratory pilot study suggests that emotion recognition deficits might be prevalent in MS. However, future studies will be needed to overcome the limitations of this study.     

Clinical isolated syndrome: a 3-year follow-up study in China

Objective

To summarize the characteristics of Chinese clinically isolated syndrome (CIS) patients and their 3-year follow-up results. Investigate the relationship between CIS features and clinical outcomes.

Methods

Forty-nine CIS patients were recruited and 42 of them were able to be followed up for a mean of 38 months (range 26-48 months). We recorded baseline features including patient demographics, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCB) and MRI lesions in brain and spinal cord. The incidence of conversion to clinically definite MS (CDMS) or neuromyelitis optica (NMO) after CIS was calculated, and the relationship between baseline features and CDMS was explored. All data were statistically processed with SPSS for Windows Version 11.5.

Results

After a mean follow-up of 38 months, 10/42 patients had converted to CDMS (24%), and one patient had developed definite NMO. The other 31 patients remained in CIS status. A spinal cord syndrome was the initial CIS manifestation in 57% of patients. The conversion rates to MS were 22% (5/23) for patients presenting with a spinal cord syndrome and 27% (3/11) for multi-focal manifestations. The three-year CDMS conversion rates were 70% (7/10) for patients who fulfilled the MRI dissemination in space criteria (2005 revised McDonald) at onset of CIS, while only 9% (3/32) of patients who did not fulfill these criteria converted to CDMS. Females had significantly higher conversion rate than males.

Conclusion

A spinal cord syndrome was the most common initial presentation of our Chinese CIS group. After a mean follow-up of 38 months, the conversion rate to MS was approximately 25%. The 2005 revised McDonald MRI criteria for dissemination in space is a key prognostic factor for conversion to MS in CIS in Chinese patients.     

Cancer incidence in multiple sclerosis: a 35-year follow-up

The risk of cancer among multiple sclerosis (MS) patients was evaluated emphasising cancers with a potentially infectious aetiology. Cancer incidence was estimated among incident MS patients in 1964-1993 (n = 1,597) in Finland. The cohort was followed up for cancer incidence through the Finnish Cancer Registry until 1999. A total of 85 cancer cases were diagnosed showing a standardised incidence ratio (SIR) of 1.0 (95% CI 0.8-1.2) for all cancers. The risk (SIR) of haematological tumours was 1.1 and that of central nervous system (CNS) tumours 1.3. The small excess risk of haematological malignancies is consistent with infectious aetiology, whereas the association between MS and CNS tumours may be due to misclassification.     

Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis

Atrophy of the spinal cord is known to occur in multiple sclerosis but the cause and the timing of its onset are not clear. Recent evidence suggests that atrophy may start to occur early in the disease. The aim was to determine whether atrophy of the spinal cord could be detected in vivo using MRI techniques, in patients presenting with a clinically isolated syndrome, which in many cases is the earliest clinical stage of multiple sclerosis. The cross sectional area of the spinal cord was measured in 43 patients presenting with a clinically isolated syndrome and 15 matched controls. T2 weighted imaging of the brain was also performed to determine the number and volume of high signal lesions consistent with disseminated demyelination. Both patients and controls were restudied after 1 year. The spinal cord area was significantly smaller in the 74% of patients with an abnormal brain MRI at presentation than in controls (mean areas 73.9 mm(2) and 78.1 mm(2) respectively, p=0.03). No significant difference was found in the spinal cord area between controls and patients with normal baseline brain imaging. The annual rate of change in patients did not differ significantly from controls. In conclusion, the finding of a smaller cord area in the subgroup of patients with clinically isolated syndrome with the highest risk of developing multiple sclerosis-that is, with an abnormal brain MRI, suggests that atrophy has developed in some patients with multiple sclerosis even before their first clinical symptoms. However, the lack of a detectable change in cord area over 1 year of follow up contrasts strikingly with the results of an earlier study of patients with relapsing-remitting multiple sclerosis, suggesting that the rate of atrophy increases as the disease becomes more established.     

Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study

In 2001, we followed up all patients from the 1991 Olmsted County Multiple Sclerosis (MS) prevalence cohort. We found that the longer the duration of MS and the lower the disability, the more likely a patient is to remain stable and not progress. This is particularly powerful for patients with benign MS with Expanded Disability Status Scale score of 2 or lower for 10 years or longer who have a greater than 90% chance of remaining stable. This is important because these patients represent 17% of the entire prevalence cohort. These data should assist in the shared therapeutic decision-making process of whether to start immunomodulatory medications.