Characteristics of Devic's disease (neuromyelitis optica) in Mexico

OBJECTIVE: To report clinical and epidemiological data of Devic's disease in Mexico. DESIGN : Retrospective study of hospital case records. SETTING: The medical records were those of the National Institute for Neurology and Neurosurgery (INNN), a tertiary care referral center in Mexico City. PATIENTS: There were 424 medical histories available for review among 561 discharges with diagnoses of multiple sclerosis (MS), neuromyelitis optica (NMO), or equivalents. 390 met the diagnostic criteria of MS and 34 the NMO criteria. MAIN OUTCOME MEASURES: We recorded clinical signs, visual acuities, and the Expanded Disability Status Scale (EDSS) at the initial diagnostic admission and during follow-up. All patients had examination of cerebrospinal fluid (CSF) at diagnosis; head and spine magnetic resonance imaging (MRI) were performed at diagnosis and at follow-up. RESULTS: All 34 patients were Mexican Mestizos, who comprise 79 % of the residents of Mexico City. There were 23 monophasic and 11 relapsing cases. Intervals between initial and defining events for the 8 ON and 12 myelitis onsets were 17 and 24 months (means) and 15 and 17 months (medians), respectively. Mean follow- up from onset was 70.2 months and 42.9 months from diagnostic examination. No patient showed improvement in EDSS scores. Visual loss was severe. CONCLUSION: A provisional prevalence rate of about 1 per 100,000 population for NMO in Mexican Mestizos might be offered. The disease seems more severe in our population than in other recent series.     

Incidence of seroconversion and sero-reversion in patients with multiple sclerosis (MS) who had been treated with natalizumab: A systematic review and meta-analysis

BackgroundNatalizumab is a medication of choice for some patients with relapsing remitting (RR) form of multiple sclerosis (MS). John Cunningham virus (JCV) antibody status is important in cases who are treating with natalizumab. Different studies reported various rates of seroconversion and sero-reversion in patients who had been treated with natalizumab. As there is no systematic review reporting incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab, we aimed to conduct this systematic review and meta-analysis to find pooled incidence of seroconversion and seroreversion in MS cases who were treated with natalizumab.MethodsPubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, and google scholar were systematically searched. We also searched the gray literature including references from included studies, and conference abstracts which were published up to April 2019.ResultsThe incidence of seroconversion was reported between 6% and 41% and the incidence of seroreversion was reported between 1% and 11%.The pooled estimate of seroconversion incidence was 19% (95% CI: 13%–25%) (I² = 96.8%, P < 0.001) and the pooled estimate of seroreversion incidence was 5% (95% CI: 3%–8%) (I² = 72.2%, P < 0.001).Subgroup analysis by considering the country of the origin showed that the pooled incidence of seroconversion incidence during the studies was 6% in Asian countries and 21% in European/American countries. The incidence difference between subgroups was significant (p < 0.001).ConclusionIncidence of seroconversion in MS patients who had been treated with natalizumab is higher in European/American countries than Asian countries.     

Incidencia y prevalencia de la esclerosis múltiple en China y países asiáticos

The prevalence of multiple sclerosis (MS) in Asian countries is thought to be lower than in Western countries, with Asian populations presenting 80% less risk of MS than white populations. Incidence and prevalence rates in Asian countries are therefore not well defined and their association with rates in neighboring countries, as well as with ethnic, environmental, and socioeconomic factors, are not well understood.We performed a comprehensive literature review of epidemiological data from China and neighbouring countries to study the frequency of the disease, focusing on prevalence, and the progression over time and the influence of sex-related, environmental, dietary, and sociocultural factors.Prevalence rates in China range between 0.88 cases/100,000 population in 1986 and 5.2 cases/100,000 population in 2013, with a non-significant upwards trend (p = .08). The increase observed in Japan, where figures ranged between 8.1 and 18.6 cases/100,000 population was highly significant (p < .001). Prevalence rates in countries with predominantly white populations are considerably higher and have increased over time, reaching 115 cases/100,000 population in 2015 (r² = 0.79, p < .0001).In conclusion, the prevalence of MS in China appears to have risen in recent years, although Asian populations (including Chinese and Japanese populations, among others) appear to present less risk than other populations. Within Asia, geographical latitude appears not to be a determining factor for developing MS.     

我国北方地区多发性硬化164例的临床特点

目的通过分析总结我国北方地区164例多发性硬化(MS)的临床资料,探寻MS的临床特点。方法从临床表现和影像学等多方面对164例MS病例进行回顾性分析。结果164例MS病例中,男48例,女116例;发病年龄4．5个月-66岁,平均29．2s岁;<15岁的早发型占9．8％,发病高峰在20-40岁;39％的患者有明确诱因;主要以急性或亚急性起病(73．1％);首发症状以肢体无力(36．6％)、肢体感觉障碍(25．6％)和视力减退(22．6％)最常见;复发缓解型占58．5％。本组头部MRI阳性率为93．5％,脊髓MRI阳性率为87．5％,以半卵圆中心、脑室周围、基底节和脑干等处多见。结论本组MS患者的临床特点表现为发病早,起病急,病程短,视神经易受侵犯,小脑较少受累。MRI对于发现MS病灶有很高的敏感性。     

Mitochondrial mutations of Leber's hereditary optic neuropathy: a risk factor for multiple sclerosis

Multiple sclerosis (MS) and Leber's hereditary optic neuropathy (LHON) have been found to occur in combination. Based on an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS. All three primary LHON mutations occurring in the European and North American populations have been found to be associated with an MS-like syndrome. The neurological characteristics of MS associated with LHON are indistinguishable from those of MS in general, but the severe and bilateral visual symptoms and signs justify considering these patients as a clinical subgroup of MS and screening them for LHON mutations. However, screening LHON patients for MS appears to be more rewarding. Received: 21 July 1999, Received in revised form: 10 January 2000, Accepted: 8 March 2000     

Epilepsy and multiple sclerosis in Sicily: a population-based study

PURPOSE: To evaluate the association between epilepsy and multiple sclerosis (MS), we analyzed the incidence of epilepsy in a population-based incidence cohort of MS in Catania, Sicily. METHODS: According to Poser's diagnostic criteria, 170 incident cases of MS have been identified from 1975 to 1994 in the city of Catania. All these subjects underwent a complete neurological examination to confirm the diagnosis of MS and to identify those patients with a history of seizures. Diagnosis of epilepsy was based on the criteria proposed by the International League Against Epilepsy (ILAE) in 1993, and seizures were classified according to the classification of the ILAE, 1981. RESULTS: From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence of MS was 2.3/100,000 (95% CI, 2.0-2.6). Of the 170 defined MS patients, four developed epilepsy after the onset and also diagnosis of MS, giving an incidence rate of epilepsy of 285/100,000 person years at risk (95% CI, 119-684) and 147.8/100,000 when age adjusted to the world standard population. The cumulative risk of developing epilepsy after the onset of MS, evaluated by using the life-table methods, was zero at 1 year and 1.76% at 5 years. Of these four patients, three were classified as having partial seizures with secondary generalization and one with tonic-clonic seizures. CONCLUSIONS: Our data are consistent with those reported in literature suggesting that the risk of developing epilepsy is threefold higher among MS patients than in the general population.     

Which syringomyelia is truly associated with multiple sclerosis?

Necrosis of the spinal cord within multiple sclerosis (MS) lesions was suggested as a putative cause of syringomyelic cavity development in MS. A number of evidences suggest however that mechanisms other than necrosis are pathogenetically relevant for cavity formation, possibly depending on the atypical topographical distribution of the demyelinative lesion and on the increased cerebrospinal fluid pressure into the central canal below the compression. Not coincidentally, the hypothesis of post-necrotic and ex-vacuo mechanisms leading to cavitation derives from Japanese studies where MS is characterised by high tissue destructive capability and, besides its rarity, has many differences from the more common Western MS type and similarities with the acute disseminated encephalomyelitis (ADEM). Our opinion is that different MS types (Asian and Western) are accompanied by nonuniform mechanisms of syrinx formation and that the Asian MS type shares common, post-necrotic mechanisms with ADEM.     

Prevalence and pattern of multiple sclerosis in Benghazi, north-eastern Libya

A search for Libyan patients with multiple sclerosis (MS) was made in Benghazi, located on the southern Mediterranean coast at a latitude of 32 degrees N. Twenty-one clinically definite and probable cases were detected during the period July 1982-June 1984. On the basis of 2 probable incidental cases, the incidence for 1983 was 0.8 per 100 000 of the population at risk (10-50 years). On July 1st, 1984, the rough prevalence rate for the total population was 4 per 100 000 and the age-adjusted prevalence rate was 5.9 per 100 000. This study suggests that Benghazi falls within the medium frequency band for MS. High prevalence of brainstem involvement and cerebellar dysfunction and infrequent occurrence of the severe optic-spinal form and sphincter disturbance indicates that the present group of patients resembles Western pattern of MS as opposed to Asian MS.     

The reliability of specific primary progressive MS criteria in an ethnically diverse population

Three different diagnostic criteria for primary progressive MS were recently proposed for Caucasian population of Western European region. OBJECTIVE: The objective of the study was to apply these criteria to a series of Brazilian patients with high ethnic diversity background to evaluate reproducibility and reliability. METHODS: 52 patients classified as form of the disease that is progressive from onset and followed between 2000 and 2006 were included. Thompson, McDonald and Polman criteria were applied based in clinical date and complementary exams. Results: 72% fulfilled all three criteria with moderate agreement (p<0.001). Ten patients fulfilled at least one criterion and four failed to fulfill any of the three criteria. Strong agreement was found between Thompson and McDonald criteria (p<0.001), agreement was moderate between Thompson and Polman criteria (p<0.001) and weak agreement occurred between McDonald and Polman criteria (p=0.042). CONCLUSION: The main difference between these criteria is the change in the role of CSF, previously a prerequisite for diagnosis. Rigid diagnostic criteria as Thompson have higher specificity, should be used in clinical research protocols, while more flexible criteria as Polman facilitate the diagnosis of PPMS in neurological practice, particularly in initial stages of the disease, because of their potentially higher sensitivity.     

MRI criteria in MS patients with negative and positive oligoclonal bands: equal fulfillment of Barkhof’s criteria but different lesion patterns

In multiple sclerosis (MS) more than 95% of the patients have positive oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Previous studies have reported differences between patients with and without OCB mainly with regard to clinical parameters such as age, gender, disease duration, and clinical severity. However, several MRI characteristics have also been hypothesized to be distinct, and a varying lesion load in OCB-negative and -positive patients is proposed. In this study, we aimed to evaluate whether Barkhof’s diagnostic MRI criteria are unequally frequently fulfilled in OCB-negative and -positive MS patients. We screened our database for all OCB-negative MS patients who had (1) been treated with the diagnosis of a clinical definite relapsing-remitting MS in our institution as well as (2) undergone CSF analysis and MR brain imaging during hospital stay between January 2004 and December 2007. Eleven OCB-negative patients were identified who fulfilled these criteria. In a second step, we carefully matched each of them to two OCB-positive controls according to age, gender, EDSS, and disease duration. The separate analysis of the several parameters of Barkhof’s criteria revealed a less frequent prevalence of infratentorial (3/11 vs. 18/22; P = 0.005) and a more frequent occurrence of juxtacortical lesions (10/11 vs. 10/22; P = 0.022) in OCB-negative as compared to OCB-positive patients. The overall fulfillment of the Barkhof criteria did not differ in OCB-negative and -positive patients (7/11 vs. 16/22; P = 0.696). Further analyses of MRI findings between OCB-negative and -positive MS patients might contribute to a better pathophysiological understanding of the genesis and evidence of OCB in the CSF of MS patients.     

La SEP de l’enfant : est-elle différente de celle de l’adulte ?

IntroductionMultiple sclerosis (MS) is not uncommon in children. The aim of this study was to compare early onset MS (EOMS) with adult onset MS (AOMS).MethodsA retrospective study including MS cases between 1997 and 2010. EOMS was defined by age at MS onset < 18 years. Data were collected using the EDMUS database (European Database of Multiple Sclerosis) including: sex, age at onset, disease duration, EDSS, score after relapse. The MSSS and the Progression Index were calculated. Patients with disease duration less than one year were excluded. MS symptoms at onset and at further relapses were also noted. These parameters were compared between the EOMS and the AOMS groups.ResultsTwo hundred fifty-nine cases were included including 31 EOMS (11.96%). The mean follow-up was 96 months. The relapsing-remittent form was significantly more frequent in the pediatric group (94% vs 79%). Mean EDSS and MSSS scores and the percentage of fast progressors (MSSS > 5) were lower in the EOMS group. Analysis of neurological symptoms at the first MS attack and further neurological events showed a lower frequency of gait disturbances, motor symptoms and bladder symptoms in the EOMS group compared with the AOMS group. The 10-year mean EDSS score was 1.9 for EOMS and 4.1 for AOMS, after 25 years it was 4.5, and 7.27 respectively.ConclusionThis study highlights the relative frequency of EOMS in our MS population. However, different severity scores showed less disability progression in EOMS patients compared with AOMS patient; irreversible disability was reached at an early age.     

Gene polymorphism at position –308 of the tumor necrosis factor α promotor is not associated with disease progression in multiple sclerosis patients

Tumor necrosis factor-α (TNFα) is a pluripotent proinflammatory cytokine and is thought to play an important role in the inflammatory process of multiple sclerosis (MS). A G→A transition in the TNFα promotor at position –308 (TNF2 allele) has been shown to be associated with increased TNFα production. This study was designed to detect wether the TNF2 allele is associated with disease progression in MS. We examined the TNFα–308 polymorphism with an allelic discrimination PCR to detect the G→A transition in the genomic DNA of 283 MS patients from Germany and in 72 patients with amyotrophic lateral sclerosis (ALS) and 66 with stroke from the same genetic background who served as controls. Disease severity was defined by the progression index (PI) and by progression to the important clinical landmarks of Extended Disability Status Score (EDSS) 3.5 and 6. In addition, we evaluated the TNFα mRNA expression in whole blood with quantitative PCR. No differences were found between the presence of the TNF2 allele in MS, ALS, or stroke patients. Among the MS patients the TNF2 allele was not associated with a certain disease course. No association was found between the accumulation of neurological deficits and progression to clinical landmarks. Although MS patients with the TNF2 allele tended to progress more rapidly from EDSS 3.5 to EDSS 6 this difference was nonsignificant (P = 0.2). Nevertheless, we observed significantly higher TNFα mRNA expression in blood cells of stable patients carrying the TNF2-allele in comparison to the group with the wild type (P = 0.024). To examine the effect of genetic background we examined the DNA of 60 MS patients and 20 healthy controls in a Cypriot population of Greek origin. There was a significantly lower frequency of the TNF2 allele in the Cyprus population than in Germans (P = 0.01). No significant differences were found between the frequencies of the TNF2 allele in Cypriot MS patients and controls. Although the TNF2 allele is associated with higher TNFα mRNA baseline levels, our data indicate that this allele appears not to contribute to MS susceptibility or severity. In addition our data demonstrate that the TNFα–308 polymorphism is segregated differentially in two European populations of different genetic origin. Received: 30 November 1998 Received in revised form: 8 April 1999 Accepted: 13 May 1999     

The SMile Card: a computerised data card for multiple sclerosis patients

The SMile Card was developed as a means for computerising clinical information for the purpose of transferability, accessibility, standardisation and compilation of a national database of demographic and clinical information about multiple sclerosis (MS) patients. In many European countries, centres for MS are organised independently from one another making collaboration, consultation and patient referral complicated. Only the more highly advanced clinical centres, generally located in large urban areas, have had the possibility to utilise technical possibilities for improving the organisation of patient clinical and research information, although independently from other centres. The information system, developed utilising the Visual Basic language for Microsoft Windows 95, stores information via a ‘smart card’ in a database which is initiated and updated utilising a microprocessor, located at each neurological clinic. The SMile Card, currently being tested in Italy, permits patients to carry with them all relevant medical information without limitations. Neurologists are able to access an update, via the microprocessor, the patient's entire medical history and MS-related information, including the complete neurological examination and laboratory test results. The SMile Card provides MS patients and neurologists with a complete computerised archive of clinical information which is accessible throughout the country. In addition, data from the SMile Card system can be exported to other database programs. Received: 27 April 1999 / Accepted in revised form: 10 March 2000     

Genetics and familial distribution of multiple sclerosis: A review

Purpose of reviewThis article reviews the genetics of multiple sclerosis (MS), as well as intra-familial concordance and clinical correlations between different members of a family. Indeed, significant findings have been made on these topics in recent years.Recent findingsThe influence of specific genes on the clinical or radiological presentation of MS has been described as well as preliminary findings in the field of pharmacogenomics. Within familial forms of MS, correlations on specific aspects of the disease have been described, such as the age of onset or the clinical course between siblings.SummaryThe genetic contribution to the risk of developing MS is now estimated to be about 50%, with the genes involved mainly located within the major histocompatibility complex. Familial MS represents 12.6% of all MS cases, with the risk depending on the degree of genetic proximity to the index case. Furthermore, these familial cases seem to have a different clinical presentation from sporadic cases such as earlier worsening of disability and more severe long-term disability. Clinical correlations between different members of a family with MS have also been described, such as a similar age of onset between siblings, but deep clinical and radiological phenotyping is warranted to investigate MS disease severity concordance within familial cases of MS.     

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT 03375177).MethodsThe eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset.ResultsA total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7–4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively).Conclusion3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.     

Gene expression profiling in multiple sclerosis brain

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system and the leading cause of non-traumatic neurological disability in young adults in the United States and Europe. The clinical disease course is variable and starts with reversible episodes of neurological disability in the third or fourth decade of life. Microarray-based comparative gene profiling provides a snapshot of genes underlying a particular condition. Several large scale microarray studies have been conducted using brain tissue from MS patients. In this review, we summarize existing data from different gene expression profiling studies and how they relate to understand the pathogenesis of MS.     

Region with persistent high frequency of multiple sclerosis in Croatia and Slovenia

OBJECTIVE: The aim of this study was to evaluate the prevalence of multiple sclerosis (MS), and to determine the clinical characteristics and the occurrence of familial MS in the Gorski kotar-Kocevje region, which was previously considered to be a region of high prevalence of MS. METHODS: All clinically and laboratory supported definite cases of MS according to Poser's criteria, living residents of the chosen area on June 1, 1999 were included in the study. The patients were ascertained through national case registers for MS at the University Medical Centers (Rijeka and Ljubljana), registries of the national associations of MS patients, as well as from the medical records of regional outpatient clinics. RESULTS: The crude annual prevalence per 100,000 population was 151.9 (95% CI 123.2-187.4). 28.7% of patients had a history of MS among first-, second-, or third-degree relatives. The frequency of primary progressive course of disease was 23.5%. The sex ratio (F/M) was 1.41. CONCLUSION: A stable high prevalence of MS as well as a high number of familial MS cases was identified in the neighbouring regions of Slovenia and Croatia.     

Clinical characteristics of multiple sclerosis in Lebanon

The epidemiologic, clinical, radiological and laboratory characterization of multiple sclerosis (MS) is very well documented in Caucasian and Japanese populations, but very little is known about MS in the Arab world. Such knowledge is becoming of paramount importance, with the recent advances in therapies, MRI techniques and other diagnostic procedures. We report a cohort of Lebanese MS patients, including details of their clinical and laboratory characteristics. The medical records of 202 patients fulfilling the Mc Donald's diagnostic criteria, and followed in our tertiary care center were reviewed. This cohort is highly representative of the disease in Lebanon where the number of MS patients is estimated to be between 1200 and 1700. The peak age of onset of MS in our cohort was in the third decade with 62.4% of patients developing their first symptoms between 20 and 39 years. The female/male ratio was 1.8/1.0. A positive family history for MS was present in 5% of patients. The most frequent presenting symptoms were brainstem-cerebellar (46.2%) followed by sensory (42.5%), motor (33.9%) and visual (29.6%). Of the total number of patients, 85.1% had relapsing remitting MS at onset, and 7.9% primary progressive MS. Benign MS defined as EDSS<=2.0 after 10 years from onset was present in 20% of patients. The mean time from onset to secondary progressive MS was around 9 years. Visual, brainstem, and somatosensory evoked potentials were abnormal in 65.6%, 27.8%, and 50.7% of patients tested respectively. Cerebrospinal fluid showed pleocytosis in 32.6%, increased IgG synthesis in 45.2%, positive oligoclonal bands in 40%, and elevated protein in 34% of patients tested. Although some of the clinical characteristics of our MS population were different compared to western series, the natural history of the disease was similar.     

Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis

There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.     

Asymptomatic MS

“Asymptomatic multiple sclerosis (MS)” or “subclinical MS” describes “a clinically silent disease state of MS” discovered by chance either by imaging or at autopsy, or with incidental findings shown by other diagnostic tools that are consistent or suggestive of MS, and that cannot be explained by any other disease or condition.Since the early 1960s there have been a number of autopsy studies reporting cases, in which histopathological brain changes consistent with MS were found, despite that none had any clinical symptom or sign of the disease during their lifetime. Several reports have also shown that asymptomatic first-degree relatives of MS patients may have oligoclonal bands in their cerebrospinal fluids or may turn out to have abnormal evoked potential studies.With the extensive availability of MRI lately, the incidence of individuals having these studies performed for indications other than suspicion of inflammatory demyelinating disease of the central nervous system (CNS) such as primary headaches or trauma, revealing unsuspected brain and/or spinal cord lesions compatible with MS had raised. A number of such case-series reported recently had resulted in increased awareness of this finding and to its relationship to clinical multiple sclerosis. This situation is now referred as “radiologically isolated syndrome (RIS)” and is the most common type of “asymptomatic MS”.Since it is well known that MS has an asymptomatic period of unknown duration in many individuals preceding its initial presentation, either as a clinically isolated syndrome or in rare instances as primary progressive-MS, it is likely that a number of MS patients will be diagnosed by chance as RIS at an early stage before converting to clinical disease. Currently this issue has gained a wide interest as there are no established protocols regarding how to study and follow these individuals or whether they should be treated or not! However, not all patients with RIS are predestined to develop clinical disease and it was recently shown that the rate of conversion to clinical MS is about one-third of RIS cases at five years. Although that there may be some risk factors suggestive of a higher or earlier conversion to clinical disease, none are definite and the current evidence is not supportive of initiating treatment in patients diagnosed as RIS.