Primary and transitional progressive MS: a clinical and MRI cross-sectional study

BACKGROUND: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. METHODS: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.     

Multiple sclerosis amongst Chinese in Taiwan.

Twenty-five cases of multiple sclerosis (MS), including 2 autopsy cases, collected during the past 20 years from amongst the Chinese of Taiwan, are reported. These cases fulfilled all the clinical diagnostic criteria of MS. The following observations were made: (1) Multiple sclerosis does exist among Chinese in Taiwan. It is uncommon, but is by no means a very rare disease. The prevalence rate in northern Taiwan near Taipei is estimated as 0.8/100.000 population. (2) Female preponderence was conspicuous (F:M = 3.2.:1) in our MS cases as well as in other demyelinating diseases. (3) On the whole, the onset of the disease was earlier in female patients, and those who had their initial symptoms before the age of 20 years were all females. (4) The optic nerve was most frequently involved at the onset, and it was involved in the majority of patients during the whole clinical course. (5) Involvement of the optic nerve and spinal cord, with or without the brain stem, was the commonest form of our MS cases, especially among female patients. (6) More malignant forms of MS, with acute onset and rapid clinical course leading to severe incapacity or fatality, were more common among female patients. (7) Painful tonic spasms were relatively frequently encountered, and they were usually seen in patients with severe spinal cord involvement. (8) Marked elevation of the CSF total protein and of leukocytes was relatively frequent during severe relapses in patients with spinal cord lesions. (9) Severe and extensive demyelinating lesions, both old and recent, in the optic nerve and spinal cord were seen in 2 autopsy cases. The relationship between MS and NMO in Oriental patients is briefly discussed. (10) It seems likely that cases of MS which are atypical as compared with Western MS are more frequently seen in Oriental countries, and perhaps also in tropical regions where MS is known to be rare.     

Demyelinating lesions in the cervical cord in multiple sclerosis 10 years after onset of the disease. Correlation between MRI parameters and clinical course

BACKGROUND AND PURPOSE: Demyelinating lesions in spinal cord in multiple sclerosis (MS) are found in magnetic resonance imaging (MRI) in 47-90% of patients; spinal cord atrophy, however, which is a measure of axonal loss and correlates with disability, is found in 13-41% of patients. Presence and character of lesions depend on the duration and progression of the disease. The aim of this study was to estimate the presence, character and location of lesions and cervical cord atrophy in MRI performed 10 years after the onset of MS in relation to the clinical course. MATERIAL AND METHODS: 60 patients (41 females and 19 males) with definite MS according to McDonald's criteria were studied. The age of patients ranged from 29 to 62 years and disease duration ranged from 11 to 40 years. The MS group comprised 20 patients with secondary progressive MS (SPMS), 20 patients with primary progressive MS (PPMS) and 20 patients with benign form of MS (BMS). Spinal cord MRI was performed in conventional T1 and T2-weighted sequences. RESULTS: Demyelinating lesions were found in 62% of patients (50% of patients with BMS, 60% with PPMS and 75% with SPMS). 42 intrinsic focal lesions were identified in 18 patients and diffuse lesions of spinal cord were noted in 19 patients. Focal lesions were seen in patients with BMS, whereas SPMS patients had diffuse cervical cord abnormalities, and PPMS patients exhibited both forms of changes. 60% of intrinsic focal lesions were located at C3-C5 levels. Medium-sized lesions prevailed in BMS form; in PPMS form small and medium-size lesions, and in SPMS form large lesions (>10 mm) were more frequent. The spinal cord was atrophic in 8% of patients (10% of patients with PPMS and 15% with SPMS). In BMS no atrophy of the cervical cord was observed. We did not find focal demyelinating lesions in the cervical segment of patients with spinal cord atrophy. CONCLUSIONS: Presence and character of demyelinating lesions in cervical cord ten years after onset of MS is significantly related to the clinical form of the disease. The mid-cervical region of the spinal cord appeared to be the commonest location of the focal lesions. Cervical cord atrophy was more frequent in patients with PPMS and SPMS, but it was not accompanied with intrinsic focal cord lesions.     

Progressive ascending myelopathy: atypical forms of multiple sclerosis or what else?

The spinal cord can be affected by multiple heterogeneous disorders often difficult to diagnose. We describe ten patients affected by a progressive ascending myelopathy with a poor prognosis. The patients, during the follow-up period, underwent neurological examinations, cerebrospinal fluid analysis, hematological, microbiological, auto-antibodies screening, brain and spinal cord magnetic resonance imaging (MRI) and electroneurophysiological study. At disease onset spinal cord MRI showed ≥1 myelopathic lesions extended for <2 segments and then evidenced a progressive spinal cord atrophy without any new lesion. All patients showed an increase of the visual evoked potential P100 latency. All of them showed two or more clinical recurrences of myelitis and then, after a period ranging from 3 to 5 years from the disease onset, a progressive course. Five patients became unresponsive to intravenous high-dose steroid treatments and/or intravenous immunoglobulins and to any other therapeutic attempts, developed a progressive ascending myelopathy to tetraplegia and died from respiratory failure. The other five patients are in progressive phase of the disease with an initial involvement of the upper limbs and show mild cervical spinal cord atrophy at MRI, configuring the early stage of an ascending progressive myelopathy. In our opinion, the more suitable diagnosis is an atypical form of MS although is not possible to exclude a new nosological entity that could be included in the expanding range of spinal cord diseases.     

Clinical studies of multiple sclerosis in Japan: classical multiple sclerosis and Devic's disease

Eleven representative cases were selected from our 69 consecutive Japanese patients with probable multiple sclerosis (MS) seen in Kyushu University Hospitals, Fukuoka, Japan, so that these 11 cases demonstrated a spectrum of clinical presentations, ranging from that of classical MS to that of classical Devic's disease. Clinical analysis of the present series of cases revealed the existence of “intermediate” or “transitional” forms between classical MS and Devic's disease. These “intermediate” or “transitional” forms include: cases with bilateral visual impairment of severe degree at the onset followed by multifocal and multiphasic CNS lesions to give later a chronic, typical variety of MS; cases with frequent exacerbations and remissions of optic and spinal symptoms leading to severe disability within a relatively short period; cases with a rapidly-occurring, severe, extensive, transverse myelopathy associated with other CNS symptoms of mild degree; cases with classical Devic's disease showing remissions and exacerbations; and finally cases with Devic's disease followed by severe brain-stem symptomatology.These clinical observations suggest that the classical forms of MS and Devic's disease are the two extremes of a spectrum of the same disease, and that the opticospinal form of MS, which is most frequently encountered in Japan, might essentially be the same disease as MS seen in Western countries.     

High prevalence of restless legs syndrome in multiple sclerosis

Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 ± 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain–spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 ± 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.     

Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis

The importance of apolipoprotein E (ApoE) and myeloperoxidase (MPO) genotypes in the clinical characteristics of multiple sclerosis (MS) has been recently emphasized. In a large group of Polish patients we have tested the hypothesis that polymorphism in ApoE and MPO genes may influence the course of the disease. Genotypes were determined in 117 MS patients (74 females and 43 males; 99 sporadic and 18 familial cases) with mean EDSS of 3.6, mean age of 44. 1 years, mean duration of the disease 12.8 years and mean onset of MS at 31.2 years, and in 100 healthy controls. The relationship between ApoE and MPO genes' polymorphism and the MS activity as well as the defect of remyelination (diffuse demyelination) and brain atrophy on MRI were analysed. The ApoE epsilon4 allele was not related to the disease course or the ApoE epsilon2 to the intensity of demyelination on MRI. The genotype MPO G/G was found in all familial MS and in 57% (56/99) of sporadic cases. This genotype was also related to more pronounced brain atrophy on MRI. The MPO G/G subpopulation was characterized by a significantly higher proportion of patients with secondary progressive MS (P < 0.05) and by a higher value of EDSS. According to our results the MPO G allele is frequently found (in 96% of cases) among Polish patients with MS. More severe nervous tissue damage in the MPO G/G form can be explained by the mechanism of accelerated oxidative stress. It seems that MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in MS patients.     

视神经脊髓炎与多发性硬化的临床症状、脊髓MRI表现的对比分析

目的 结合视神经脊髓炎(NMO)与多发性硬化(MS)患者的临床症状和脊髓MRI特点探讨两者之间差异发生的机制.方法 回顾性分析中山大学附属第三医院自2004年1月至2007年1月收治的23例NMO患者及21例MS患者的临床资料,比较其临床症状及脊髓MRI上受损部位MRI上的差异.结果 NMO患者多为女性,且首次发病年龄、扩展病残状况评分(EDSS)评分均高于MS患者;双侧深感觉障碍、束带感、直肠或膀胱括约肌功能障碍3种临床症状在NMO、MS患者中的发生率不同,差异均有统计学意义(P<0.05);上述各临床症状基本能在脊髓MRI找到相应受损病灶.结论 NMO是不同于MS的脱髓鞘疾病,其特殊的发病机制导致其临床症状与脊髓MRI均有自己的特点.     

Epileptic seizures,cranial neuralgias and paroxysmal symptoms in remitting and progressive multiple sclerosis

The occurrence of a first epileptic seizure, spinal or brainstem paroxysmal symptom and cranial neuralgia during 25 years after onset was studied in a population-based multiple sclerosis (MS) cohort of 255 patients. Epileptic seizures occurred in 20, paroxysmal symptoms in 11 and cranial (trigeminal, intermedius, retroauricular or occipital) neuralgia in 11 patients. The yearly incidence of epileptic seizures in MS was estimated to be 349(+/-153)/100,000, approximately seven times higher than in the general population. The yearly incidence of a first paroxysmal symptom in the present material was calculated to be 190 cases in 100,000 MS patients, and the yearly incidence of cranial neuralgia was 189 cases in 100,000 MS patients. The epileptic seizures were more frequent during the progressive course than in the relapsing-remitting (RR) course. The frequencies of paroxysmal symptoms and cranial neuralgia did not differ between these two disease courses. A coincidence of epileptic seizures and a decline in cognitive functioning not seen among patients with paroxysmal symptoms was found The relatively late occurrence of epileptic seizures indicates that the frequency of epileptogenesis, known to involve neuronal damage, increases in the later stages of MS.     

Late onset multiple sclerosis

Multiple sclerosis (MS) with clinical onset after 50 years old is unusual and frequently misdiagnosed. Clinical presentation and course seem also to be different that in MS occurring between 20 and 50 years old. The aim of this study was to evaluate the clinical and paraclinical characteristics of late onset MS. We respectively studied MS patients older than 50 years at the onset of the disease. We evaluated demographical data, clinical symptoms, cerebrospinal fluid (CSF), visual evoked potentials (VEPs) and MRI of these patients. We also studied clinical data during the follow-up with the occurrence of new symptoms and the evolution of the disease by the index of progression (EDSS unit per year). In a population of 1 417 MS, 3.4 p.cent had their first symptoms at 50 years old or older and 0.45 p.cent after 59 years old. At the time of the study patients had more frequently a progressive form: 37 p.cent had a primary progressive form and 35 p.cent a secondary progressive MS. None of the patients with onset after 60 years old had relapsing remittent MS. Motor symptoms were the most common neurologic presentation (54 p.cent of patients). Very few patients had a clinical optic nerve involvement during the follow-up. The mean progression index was 1 suggesting a most severe evolution in this subgroup of MS patients. 76 p.cent of patients had oligoclonal banding detected by CSF electrophoresis. The VEPs were abnormal in 81 p. cent of patients tested. 71 p.cent of the brain MRI were consistent with the diagnosis of MS. 60 p.cent of patients had spinal cord MRI abnormal. This study highlights the differences between the late onset MS and earlier onset. As previously reported, our study underlines the high frequency of progressive course, motor function involvement and poor prognosis.     

多发性硬化226例临床分析

目的　总结国人多发性硬化 ( MS)的临床、影像及病理学特点。方法　从临床、影像学及组织病理学等多方面对 MS病例进行回顾性分析。结果　 2 2 6例 MS病例中 ,临床确诊 1 96例 ,实验室支持确诊 1 6例 ,临床或实验室可能 1 4例 ;男性 85例 ,女性 1 41例 ;发病年龄 4岁至 67岁 ,平均 3 2 .46岁 ,<1 5岁的早发型病例占 9.3 % ;3 0 .1 %病例病前有诱发因素 ,其中 77.9%与感染有关 ;首发症状以感觉异常、肢体无力及视力减退最为多见 ;88.1 %病例呈急性或亚急性起病 ,复发 -缓解型占 49.1 % ;病变部位中脊髓 1 5 1例 ,脑干 74例 ,小脑 2 4例 ,大脑半球 95例 ,视神经 98例 ;66.8%病例出现脊髓受累 ,5 0 .4%病例曾出现过尿便障碍 ,其中视神经脊髓炎占2 9.2 %。结论　国内 MS的发病年龄较西方国家早 ,起病急 ,病程短 ,视神经及脊髓易受侵犯 ,小脑、脑干较少受累 ,临床表现中以视神经受损及尿便障碍较为突出 ,致残率较高。诱发电位及 MRI检查有助于发现亚临床病变。急性、亚急性期应用激素疗效显著。     

Heterogeneity in multiple sclerosis: comparison of clinical manifestations in relatives

Once diagnosed to have MS, relatives of persons who have been previously diagnosed frequently ask whether their disease course will follow that of their relative(s) with MS. The present study compared the following clinical manifestations of MS among 43 index cases and 47 of their relatives, all of whom were diagnosed to have MS and regularly attended the MS Clinic in Vancouver, British Columbia: (i) age of onset of MS, (ii) clinical course, (iii) lesion site(s) and (iv) initial symptom(s) of MS. The results from the present study are preliminary because of the small size of the study group. However, these data suggest that apart from possibly age of onset between sibling pairs, the clinical manifestations of MS are not correlated among relatives who are assessed according to the same methodology. This is significant for counselling newly diagnosed relatives of longstanding MS patients.     

Early onset multiple sclerosis: a longitudinal study

OBJECTIVE: To evaluate the clinical course of MS in individuals with onset of MS before age 16. METHODS: Patients with onset of MS before age 16 (n = 116) with complete clinical information on the clinical course from the MS Clinic at The University of British Columbia (UBC) Site Hospital computerized database (MS-COSTAR) were included in this study. The data were compared to those from the Canadian natural history study for MS clinic attendees, regardless of age at onset. RESULTS: The mean duration of observation was 19.76 +/- 0.90 years; the mean age at MS onset was 12.73 +/- 0.25 years. Only three cases (2.6%) had a primary progressive (PP) MS course. To date, 60 (53.1%) of 113 subjects have developed secondary progressive (SP) MS. The 50% probability for SPMS was reached 23 years after onset. For patients with relapsing remitting (RR) or SPMS the mean disease duration from onset to the time of confirmed Expanded Disability Status Scale (EDSS) 3.0 was 16.03 +/- 1.17 years (at mean age 28.47 +/- 1.14); mean duration from onset to the time of EDSS 6.0 was 19.39 +/- 1.43 years (at mean age 32.32 +/- 1.44). Annual relapse rate was 0.54 +/- 0.05 per year. The correlation between the number of relapses during the first year of disease and the course of the disease was also significant. CONCLUSIONS: The prevalence of early onset MS (3.6%) in our study confirms the previous findings on early onset MS. A RR course was seen in the majority of cases of early onset MS. A high frequency of relapses, early age at permanent disability, and the presence of malignant cases raise the question of possible early use of disease-modifying therapy in patients with early onset MS.     

Familial clustering in Italian progressive-onset and bout-onset multiple sclerosis

Multiple sclerosis (MS) is a complex disease triggered by environmental and genetic agents, and clinically characterized by bout onset (BOMS) or progressive onset (PrMS). We collected clinical and familial aggregation data in a cohort of 518 Italian PrMS patients, and compared with 400 BOMS cases. An increased prevalence of MS in first-degree relatives of Italian PrMS was found. Familial aggregation is not influenced by probands’ clinical course, and there is no disease course concordance within MS families. These data are useful in counseling MS patients affected with different clinical courses of the disease.     

Clinical and demographical characteristics of primary progressive multiple sclerosis in Isfahan, Iran

Primary progressive multiple sclerosis (PPMS) is an uncommon form of multiple sclerosis (MS) in which the course of disease is progressive from onset. In a retrospective study amongst 1606 MS patients registered in Isfahan MS Society (IMSS) from April 2003 to 31 December 2005, 92 PPMS cases were identified. That means, the frequency of PPMS amongst all included MS patients would be 5.7% (95% CI: 6.7% and 4.7%). The mean expanded disability status scale (EDSS) for the group was 5.09 ± 1.3. The commonest mode of presentation was motor disturbance in 55 (59.8%), other modes of presentation were, vertigo in 15 (16.3%), visual problems in 12 (13%), sensory disturbances in six (6.5%), and diplopia in four (4.3%). The current existing symptoms were motor problems in all 92 (100%), cerebellar symptoms in 46 (50%), and cognitive impairment in only six (6.5%). Interestingly, two (2%) were affected by poliomyelitis during childhood and presenting symptom in both was limb weakness. Primary progressive form of MS is less common in Persian population and some of the rates observed in PPMS patients differ from those in other regions, these differences may be due to different ethnicity of Persian patients or to geographical differences.     

Epidemiological aspects of multiple sclerosis in Lublin (Poland)

BACKGROUND AND PURPOSE: The objective of this paper was to present an epidemiological analysis of multiple sclerosis (MS) in Lublin, identify MS prevalence as well as characterize the population of MS patients. MATERIAL AND METHODS: Information about the patients was gathered and they were examined from 1996 to the end of 2000, that is within a 5-year period. The patients' data were obtained from the neurological departments in Lublin, most often neurological (but also general and ophthalmic) clinics, as well as from the Lublin MS Society. The remaining patients' data were obtained from the doctors, family members, the Lublin MS Society members, as well as from the hospital and clinic files. The patients were interviewed in detail using a prepared questionnaire. The diagnosis and its degree of certainty were determined in accordance with the Poser's criteria. The control group included 111 healthy people who were Lublin residents on the day of examination. The obtained results were analyzed in epidemiological and statistical terms. RESULTS: On the prevalence day (31 December 1997) there were 204 MS cases in Lublin, including 141 women (69%) and 63 men (31%). The calculated incidence ratio was 57.3/105. The average age of MS onset was estimated to be 30.1 years. On 31 December 1997 the average duration of the illness was 15.4 years. The average age for the examined cases was 45.5 years. The average DSS (Disability Status Scale) score was 3.5. Most often the disease began with a single symptom, in 155 cases (75.9%), whereas several symptoms occurred in 37 patients (18.1%). The most common symptoms at the illness onset were sensory impairments (52 patients), optic neuritis (42 people) and pyramidal symptoms (34 patients). The most common form of the illness was a disseminated form, which was diagnosed in 131 patients (64.2%). In the examined patient population four types of MS were recognized. The relapsing-remitting MS (RR-MS) was observed in 62 patients (30.3%), the secondary progressive MS (SP-MS) in 83 patients (40.6%), and the primary progressive MS (PP-MS) was characteristic of 40 people (19.6%), while 19 patients (9.3%) experienced a benign course of MS. CONCLUSIONS: Our results are typical for the region of high incidence of MS. They are similar to the data achieved in other populations of that region.     

Aggressive course of cognitive impairment in multiple sclerosis: A new term for the management of patients

Multiple sclerosis (MS) can create different kinds of symptoms by involving different fields of the central nervous system. Cognitive impairment (CI) is one of the symptoms that can be caused by the onset of the disease and provide a change in the patient’s quality of life. Considering the course of the disease, CI usually worsens increasingly, and there is usually a severe CI in patients with end stage of MS. However, progressing CI can be so fast and severe in a few patients that it can disrupt the daily affairs of the individual. This paper plans to define the aggressive course of CIs in MS patients according to the reported cases. This definition explains that, the aggressive course of CI in MS patients happens in less than 5 years from the onset of the disease, and during this time, it causes dementia in the patient.     

Hydrosyringomyelia in demyelinating diseases

Spinal cord cavitation is a frequent finding in optic neuromyelitis (Devic's syndrome) (DS) but it is also, although rarely, observed in patients with multiple sclerosis (MS). The objective of our study was to compare the MRI characteristics of the syringomyelic cavities in 6 patients with DS and 3 patients with MS. All the patients with DS had a relapsing clinical form with normal brain MRI. Spinal MRI revealed unenhanced central cavities which extended more than 3 vertebral bodies and remained unchanged in follow-up studies. Two patients presented multiple cavities.MS patients suffered a relapsing remitting form of the disease, they all had hyperintense T2 enhancing lesions on their spinal MRI. Moreover spinal MRI also revealed non communicating cavities which extended less than 2 vertebral bodies. Follow-up studies in MS patients revealed a reduction of both the spinal lesions and the cavities. It is still debated whether DS represents a distinct clinical entity different from MS. These findings help distinguishing both disorders in cases when spinal cavities are present and also contribute to the therapeutic choice.     

Progression in multiple sclerosis: further evidence of an age dependent process

The relapsing-remitting phase and the progressive phase of multiple sclerosis (MS) seem to be the result of distinct pathophysiological processes. Previous research on the natural history of MS was largely focussed on relapses and disability scores. In this study we evaluated 438 patients with secondary or primary progressive MS. The influence of gender, initial disease course, onset manifestation and age at disease onset on age at progression and time to progression were evaluated with Kaplan-Meier survival analysis and Cox multivariate regression models. The analysis of these data showed that the initial disease course (SPMS or PPMS) had no influence on the age at progression. Gender had no influence on age at progression in PPMS and SPMS patients nor on time to progression in SPMS patients. PPMS patients with visual or brainstem/cerebellar onset had a significantly younger age at progression. SPMS patients with motor onset had a significantly higher age at progression and longer time to progression. Time to progression was significantly shorter in SPMS patients with higher age at disease onset. Our data give further support to the notion that progression in MS is an age dependent process independent of relapses.     

Influence of oligoclonal IgM specificity in multiple sclerosis disease course

Oligoclonal IgM bands (OCMB) against myelin lipids predict an aggressive multiple sclerosis (MS) course. However, the clinical significance of OCMB without lipid specificity, present in other MS patients, remains unknown. We describe here a characterization of these antibodies and study their role in MS progression. Fifty-four MS patients showing CSF-restricted OCMB were included in this study at disease onset and followed-up during 61.1 +/- 2.7 months. The specificity of OCMB and the CSF B-cell profile were investigated. A second CSF IgM study was performed in a group of eight patients. Thirty-eight patients showed OCMB against myelin lipids (M+L+) and other sixteen had OCMB lacking this specificity (M+L-). The CD5+ B cell subpopulation, responsible for most persistent IgM responses, was considerably higher in M+L+ than in M+L- patients (3.3 +/- 0.6% versus 0.8 +/- 0.2, P = 0.009). In addition, M+L+ bands persisted during disease course, while M+L- disappeared during follow-up. M+L+ patients suffered more relapses (4.2 +/- 0.6 versus 1.6 +/- 0.3, P = 0.002) and reached higher disability (EDSS score of 2.2 +/- 0.2 versus 1.2 +/- 0.2, P = 0.02) than M+L- group. These data corroborate that anti-lipid OCMB associate with an aggressive MS course and show that OCMB that do not recognize myelin lipids represent a transient immune response related to a more benign disease course.