Mean Progression Index Research Articles

Pediatric-onset multiple sclerosis in Brazilian patients: Clinical features, treatment response and comparison to pediatric neuromyelitis optica spectrum disorders

BackgroundMultiple Sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are acquired demyelinating syndromes of the central nervous system more frequently in young adults and their beginning before 18 years of age is rare. They are autoimmune diseases with distinct pathophysiology, clinical presentation, treatment and prognoses. During childhood these conditions often present similar clinical features and differential diagnosis among pNMOSD, pMS and acute disseminated encephalomyelitis (ADEM) is still difficult at disease onset. The aim of this article is to describe the epidemiologic and clinical features, to evaluate the response to treatment and to compare the mains characteristics between the patients with MS and NMOSD who had the first event prior to 18 years of age followed at the Universidade Federal de São Paulo (UNIFESP). MethodsRetrospective analysis of patients with MS and NMOSD who started the disease before 18 years of age followed for at UNIFESP. All patients fulfilled the McDonald 2010 criteria for MS and the IPND 2015 criteria or 2006 diagnostic criteria for NMOSD. For treatment analysis, we select patients with a follow-up of more than 6 months. ResultsSixty-eight patients fulfilled the inclusion criteria for MS and were selected for analysis. Mean age of onset was 15 years, 73.5% were female and the mean follow-up was 6.7 years. Mean annualized relapse rate (aRR) observed was 0,82 relapse/year and mean progression index (PI) was 0.31 EDSS points/year. The multivariate analysis showed a significant association between the EDSS on first appointment and total number of relapses with neurological disabilities in long term in patients with MS. The treatment with interferon-beta (IFN-β) and glatiramer acetate (GA) was safe and patients treated with high dose IFN-β and GA had a statistically significant reduction in disability progression. Eleven patients fulfilled the inclusion criteria for NMOSD: mean age of onset was 14 years, 72.7% were female and the mean follow-up was 6.3 years. Mean aRR observed was 1.5 relapse/year and mean PI was 2.2 EDSS points/year. The treatment with azathioprine was safe and significant halts disability progression. Patients with NMOSD reached EDSS 6 prior than those with MS. ConclusionsPediatric demyelinating diseases in Brazil are similar to the diseases described abroad. In patients with pMS, the EDSS score at the first appointment and the total number of relapses were associated with poor prognosis. NMOSD is more severe than MS in pediatric patients. Treatment with DMD and azathioprine was well tolerated and effective in reducing relapse rate and disability.

NEW INSIGHTS IN THE NATURAL HISTORY OF EARLY-ONSET MULTIPLE SCLEROSIS

Background. The early onset forms of Multiple Sclerosis (Paediatric MS, P-MS) have a low frequency, occurring in 2% to 10% of all MS cases. Age at diagnosis is a key feature for disease progression and prognosis in MS patients. Objective. To evaluate the clinical features and course of MS in patients having the disease onset before the age of 18, according to age at diagnosis. Methods. Patients with MS onset before age of 18 identified from Basse-Normandie MS regional registry, were included in the study. Patients were divided in two groups according to the age at MS diagnosis: the first group (group A) of patients in whom MS diagnosis was set before age of 18 and the second group (group B) including patients older than 18 years at MS diagnosis. Data related to clinical features and disease course were evaluated and compared between the two groups and also with some clinical data of adult MS patients included in the same regional database. Results. A total of 41 patients with P-MS were included in the study, represented by 20 patients in group A and 21 patients in group B. Patients from group A had a more rapid progression to mild handicap (EDSS 3.0) than patients from group B (time to reach EDSS 3.0 of 6.34 vs 14.36 years; p=0.02) and they reached this level of disability at a younger age (21.17 vs 29.79 years; p=0.002). The duration of the first remission was significantly shorter in group A (1.44 vs 5.14 years; p<0.001) and the evolution to secondary-progressive (SP) form was faster when compared to group B (14.97 vs 27.57 years; p=0.01). Patients from group A had a greater risk to reach EDSS 3.0 or EDSS 6.0 as well as a greater probability to reach SP form (p<0.001) than patients from group B. Progression index (PI) of the entire paediatric group was significantly lower than mean PI in the adult group (0.29 vs 0.45; p=0.003) but not significantly different between the two groups (0.37 in group A vs 0.21 in group B). Conclusion. P-MS forms show some clinical peculiarities, especially those with the age of diagnosis less than 18 years. They seem to have a more severe clinical MS course and a faster progression of disability.

Is multiple sclerosis more disabling in North African patients?

Ethnic and environmental factors are major determinant of prevalence and severity of Multiple Sclerosis (MS). Data relating to the severity of MS in North-African are scarce and conflicting and concern mainly migrants to Europe. To Answer this question, the authors have conducted a multicenter study enrolling patients with MS (Revised Mc Donald Criteria 2005) seen between 1998 and 2010 in the university hospitals of Casablanca, Fes and Marrakesh. Severity of MS was evaluated by the Progression Index (PI), time to reach an EDSS of 6.0 and the Multiple Sclerosis Severity Score (MSSS). The study included 460 patients. The sex ratio was 2.1. The mean age of MS onset was 30.2 years, with a mean follow up of 88.8 months. The relapsing-remitting MS accounted for 82.1% and the primary progressive form represented 17.9%. The median MSSS was 6.39, fast progressor (MSSS>5) represented 62.6%.The mean PI was 0.97 with 20% of Malignant forms (PI>1.2). Time to reach an EDSS score of 6 was 18 years (16.5–19.5). Previous studies comparing the MS severity between Caucasian and NA migrants in Europe have concluded to more severe disease in NA population. Our study is the first conducted in the autochthone population (Morocco) founding a similar result with a rapidly disabling disease. Subsequent Multicenter study from Algeria corroborates these findings. The Authors review and discuss possible factors and bias that could explain these data.

Late-onset multiple sclerosis in Isfahan, Iran.

Multiple sclerosis (MS) typically affects young adults; however, the first symptoms can occur after age 50 and is classified as late-onset MS (LOMS). In this retrospective study, we extracted the records of 3522 MS patients (2716 females and 806 males) registered in the Isfahan MS Society (IMSS) from 2003 to 2010. Next, we searched for LOMS cases. We aimed to compare these cases with 1698 non-LOMS subjects also extracted from the IMSS database. We found 48 LOMS patients (28 females and 20 males), which gave a crude frequency of 1.36%. The frequency by sex of LOMS in males (2.4%) was significantly greater than in females (1.0%, P = 0.002). The mean age at onset was 55.1 ± 4.3 years. The female to male ratio of 1.4:1 in these patients was significantly lower than in non-LOMS subjects (3.37:1, P = 0.003). The leading pattern of MS was relapsing-remitting (RR) in 62.5%, followed by primary progressive (PP) in 27.1%, and secondary progressive (SP) in 10.4%. Predominant presenting symptoms and signs were motor disturbances (35.4%), followed by brainstem (25%), optic neuritis (22.9%), and sensory related deficits (18.7%). The mean progression index (PI) in LOMS patients (0.88 ± 0.48) was significantly higher than in non-LOMS cases, 0.37 ± 0.17 (P < 0.0001). In comparing LOMS patients with the non-LOMS cohort, there was a higher frequency of the PP pattern and a higher PI in the LOMS group. In comparing other high-risk populations with the Isfahan cohort, LOMS formed a lower percentage of the total Isfahan MS population.

Treatment of Neuromyelitis Optica with Intravenous Immunoglobulin: Report of 8 Patients (P04.141)

Objective: Report the effect of IV immunoglobulin (IVIG) as a rescue therapy for patients with relapsing neuromyelitis optica (NMO) that have failed adequate immunosuppression. Background Treatment of NMO is based on case series that evidence benefit with immunosuppressive drugs (prednisone, azathioprine, micophenolate and rituximab). Plasmapheresis is recommended for patients with severe relapses or that keep on relapsing while on immunosuppressants. Because plasmapheresis is not immediately available in some Brazilian hospitals, requires a central line and the blood derived products, we implemented a program to use IVIG as a rescue therapy for those that kept on relapsing after an adequate immunosuppressant course. Design/Methods: Evaluation 8 patients with NMO that fulfilled the Wingerchuk 2006 criteria, followed at UNIFESP, that first received prednisone (0.5-1mg/kg) and azathioprine (2-3mg/kg) for preventing relapses and further received pulse IV immunoglobulin (IVIG) 2g/kg in five days every three to four months up to 5 years as rescue therapy. Efficacy was evaluated comparing annualized relapse rate (ARR) and progression index (PI) before and after IVIG use. Results: There were seven women and one man with mean age of 30 years and mean disease duration of 7.6 years; five were positive for the NMO-IgG. Reasons for IVIG indication were either severe relapse not improving after 5g IV methylprednisolone, inefficacy to reduce ARR or EDSS worsening. Two to ten cycles of IVIG were implemented to these eight patients; mean ARR decreased from 1.8 (±1.6) to 0.1 (±0.2) and mean PI from 1.5 (±1.6) to 0.9 (±0.6). One patient died due to severe encephalitic and brainstem relapse. Conclusions: IVIG provided additional short and long-term benefits in patients with NMO that have failed immunosuppression or suffered a severe relapse. The study for its use as a rescue therapy in places where plasmapheresis is unavailable should be encouraged based on these 7 patients that presented a positive response. Disclosure: Dr. Bichuetti has nothing to disclose. Dr. Boulos has nothing to disclose. Dr. Shinosaki has nothing to disclose. Dr. Souza has nothing to disclose. Dr. Oliveira has nothing to disclose. Dr. Gabbai has nothing to disclose.

Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity

It is still unclear whether chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS), because substantial methodological differences have been claimed by Zamboni to account for the lack of results of other groups. Furthermore, the potential role of venous malformations in influencing MS severity has not been fully explored. This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses. In the present study, CCSVI was studied in 84 MS patients and in 56 healthy subjects by applying the Zamboni method for CCSVI identification. We found no significant differences (p = 0.12) in CCSVI frequency between MS and control subjects. Furthermore, no differences were found between CCSVI-positive and CCSVI-negative patients in terms of relevant clinical variables such as disease duration, time between onset and first relapse, relapsing or progressive disease course, and risk of secondary progression course. Statistically significant differences were not found between CCSVI-positive and CCSVI-negative MS subjects by analyzing direct measures of disability such as mean Expanded Disability Status Scale (EDSS) (p = 0.07), mean progression index (p > 0.1), and mean MS severity score (p > 0.1). The percentage of subjects who reached EDSS 4.0 and 6.0 milestones was not different among CCSVI-negative and CCSVI-positive subjects, and no significant correlation was found between severity of disability and number of positive CCSVI criteria. Our results indicate that CCSVI has no role in either MS risk or MS severity.

The course of early-onset multiple sclerosis in Iraqi children

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system that is increasingly recognized worldwide in children and adolescents. The current study aimed at identifying the clinical characteristics of MS with onset under 18 years of age. This cross-sectional study was conducted in the Multiple Sclerosis Center archive system in Baghdad Teaching Hospital during the period from March 1 to May 15, 2008. The records of 1125 MS patients from 2000 to 2008 were reviewed. Among them 77 patients had the onset of MS under 18 years of age. Two thirds of the patients were female (a female/male ratio of 1.6:1). The mean age of the patients at the onset of the disease was 14.95 ± 3.21 years, and the mean time between the first and second attacks was 3.06 ± 4.09 years. Seventy patients (90.9%) had an initial course of relapse remitting MS. Among them 9 (12.9%) progressed to secondary progressive MS after a mean duration of 9.87 ± 4.14 years. The remaining 7 patients had primary progressive MS associated with optic neuritis and brain stem lesion. Fifty-nine (76.6%) patients had monofocal signs and 18 (23.4%) had polyfocal signs. The mean extended disability status scale score was 4.15 ± 2.17 and the mean progression index was 1.44 ± 2.31. There was a strong inversed correlation between the progression index and interval between the first and second attacks (P=0.0001). The results of the present study show that the course of MS in Iraqi children and adolescents is more aggressive than in children from other countries. This finding needs to be evaluated by further studies.

Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS.

The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS.

Short Communication: Treatment of Relapsing-Remitting Multiple Sclerosis 96 Patients with IFN-β1b: Results of a 6-Year Follow-Up

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.

Late-onset multiple sclerosis.

The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. A retrospective chart review. The Multiple Sclerosis Center at Sheba Medical Center, Israel. 640 patients with a definite diagnosis of MS. Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.

Familial factors influence disability in MS multiplex families. French Multiple Sclerosis Genetics Group.

Both genetic and environmental factors play a role in the pathophysiology of MS and may influence the clinical expression of the disease. To determine the contribution of familial factors to the clinical expression of MS. The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded. Disability was determined by the progression index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years. Statistical analyses were performed either with a group of patients (clinical features, relation between human leukocyte antigen and clinical features) or with a group of sibpairs (concordance for clinical features). The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03). This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of disability might be partly influenced by familial factors (environmental or genetic).