Multiple sclerosis (MS) is a demyelinating inflammatory and degenerative disease that is the most frequent cause of disability in young adults 1. Genetic predisposition, unknown environmental factors, or a combination of both may explain the variable prevalence of MS in the world 23. Also, ethnicity may affect the frequency of MS among people living in the same area 4. Migration from a low to a high-risk area before the age of fifteen increases the MS risk 56.

MS in North Africa (NA) has seen epidemiological and phenotypic variation over the past few decades. Based on the Kurtzke classification, Algeria is located in a low-risk zone for MS 7. Over the past decade, MS is relatively common but scarcely documented in Algeria, but our experience in the practice suggests that the occurrence of MS is increasing. This notion was raised in a recent study that estimates up to 2.8 million people are living with MS worldwide (35.9 per 100,000 population) and that MS prevalence has increased in every region of the world since 2013,

A particularly severe profile of MS has been demonstrated in several studies in NA countries (Morocco, Tunisia and Algeria) 910111213. Some of these studies have been carried out on multicenter cohorts. Predicting this evolution at the onset of the disease will help in therapeutic management. Most of the studies evaluating the predictive factors of disability have been performed in Western populations and they are identical in all these populations 141516. A late onset disease, male gender, incomplete recovery from first episode, short interval between first and second episodes, high number of attacks during the first two years, and motor, cerebellar or sphincter symptoms at onset were associated with poor prognosis. However, these predictors of disability have not been studied in Arab populations, with the exception of the Yamout study which found that the predictors of disability in MS among the Lebanese population were not very different from predictors in western countries 17. The purpose of this study was to describe the clinical characteristics and to identify early predictors of long-term disability among MS patients in Algeria.

We performed a descriptive and retrospective study of MS patients seen at our MS clinic, followed over a 4-year period from July 2012 to July 2016 in the neurology department of University hospital Mustapha Bacha in Algiers. All patients gave informed consent for their data to be used and the study was approved by the local research ethics committee.

We systematically reviewed medical records of each subject. Subjects whose records were incomplete, did not confirm a diagnosis of clinically definite MS were excluded. Only the cases with definite MS according to Mc Donald’s classification were included in the cohort (dissemination in space and time were required: clinical presentation or additional data needed for MS diagnosis). These patients were classified according to international accepted disease course classification 18: relapsing-remitting (RR), secondary-progressive (SP) and primary progressive (PP).

A series of clinical variables were systematically assessed for each patient. They included: gender, medical history, key episodes in the course of Ms including relapses, onset of the progressive course, expanded EDSS, time of assignment of the successive scores of irreversible disability and type of disease modifying therapies, The initial demyelinating event was categorized by site (optic nerve, spinal cord, brain stem or cerebellum) and polysymptomatic signs. Recovery from the first relapse was classified as incomplete (persistence of neurologic signs) or complete (absence of neurologic signs). To determine the extent of neurologic disability, the EDSS score (range 0 to 10) was recorded during each visit of the patient to the neurologist. Disability was defined as irreversible when a given score persisted at least 6 months, excluding transient worsening of disability related to relapses. The Multiple Sclerosis Global Severity Score MSSS) was originally developed to compare the relative severity of disease across all levels of EDSS for a duration of disease, using a single clinical assessment at one point in time 19.

MRI of the brain was carried out in all patients, T1, T2 and flair sequences were performed. The cerebrospinal fluid (CSF) was examined to look for oligoclonal bands (OCB) to support the diagnostic in certain subjects.

Statistical analysis was conducted using SPSS for windows version 13.0, Comparison of categorical data was made according to the chi-squared test. The quantitative variables were presented as number of patients (%), the value of demographic data (gender, age, age at onset of MS), clinical data (course at onset of MS and initial symptoms, time to diagnosis, time from onset of MS to the second neurologic episode, extent of recovery from the first relapse, number of relapses during the first 2 years of the disease) were analyzed. The ANOVA test was used for the comparison of several means. The Kaplan-Meier technique was used for estimating the time to the assignment of an irreversible score of EDSS 4 and EDSS6. Survival curves were compared using the log-rank test.

Our study has shown that Algerian patients have similar characteristics to European and North Africans patients: predominantly female, average age of onset 30 years, relapsing–remitting onset in almost 90% of our cohort 202122. However, some specific features were found: Isolated motor dysfunction was the most frequent onset symptom, exceeding visual and sensory signs, an initial poly-symptomatic involvement was relatively as frequent (30%), and recovery from the initial neurological episode was found in about one-third of the patients. These phenotypic characteristics underline the particular severity of North African MS. Indeed, originating from North Africa has been described in some publications as a factor of severity for MS 9101123. The course of MS was more severe compared to European patients such that the EDSS 4 and 6 scores were readily reached presaging a more severe disease outcome. Thus, the study of Sidhom 12 revealed that the disability progression profile was more rapid in North African patients than in European patients. It was shown after statistical study by the Cox method that ethnic origin was a risk factor for reaching EDSS 6. The severity of the disease was more common in patients born in France and whose parents were of North African origin, reflecting genetic and environmental influences on the progression of the disease. For disability measures, the overall MSSS distribution in our cohort is similar to European and US data 1924. In a Tunisian and European study 12, the MSSS was 4.8 and 5.1. The same result is observed for the progression index which is similar to our cohort, it was 0.51 and 0.41. In contrast, the Moroccan study found a higher MSSS score and progression index (6.39 and 0.97) 10. The median time to reach EDSS 4 was similar to that reported in the North African studies and was shorter than in the European studies 10112224. The median time to EDSS 6 (19 years (95% CI = (14.2 - 23.7)) was relatively short compared with European cohorts. It was 27.9 years in Canada 26, 24 years in the United States 27 and between 20 and 24 years in France 2823. The evolution of MS is therefore very variable, ranging from a severe disease that is rapidly disabling to a mild form that causes minimal long-term disability. Predicting this evolution at the beginning of the disease will help in the therapeutic management. Most of the studies evaluating the predictive factors of disability have been performed in Western populations and they are identical in all these populations 2729. However, these predictive factors of long-term disability have not been studied in Arab populations, with the exception of the Yamout study in Lebanon 17.

Late age at onset is considered predictive of early progression to disability in most studies 293031. The presence of pyramidal and cerebellar signs has been described in several studies as a fact associated with a poor long-term prognosis 312125. Incomplete recovery after the first attack is also predictive of poor long-term disability and secondary progression 2832. We also confirmed that the median time to irreversible disability (EDSS 4 or 6) was shorter in patients with a progressive form than in those with a remittent form. This result is in agreement with previous studies 33. A short interval between the first and second attacks (P1-P2) was also considered to be a poor prognosis. Scalfari et al. found a statistically significant association between P1-P2 interval and disability outcome 34. However, these authors described this result as a less predictive factor than the number of relapses in the first two years. Other studies 2528 reported similar results, showing that a longer P1-P2 interval was correlated with a longer time to disability and passage to secondary progressive form.

It has been described that MSSS-based analysis identifies more risk factors for severity than when the EDSS is used alone. For example, in the two American studies using MSSS, the male gender was correlated with the severity of the disease 3536. While the studies that used the EDSS alone did not identify gender as a risk factor for severity 37. These observations support the suggestion that the MSSS was a more nuanced indicator of disease severity than the EDSS, since it incorporates two factors that are not accounted for by raw EDSS scores: duration of the disease and change in EDSS score over time. This hypothesis was confirmed by the study of Pachner et al, which showed that disease severity as measured by the MSSS was practically stable over several years of follow-up, thus predicting individual-level disease severity over time 38. Benign MS is defined by an EDSS ≤ 2 or ˂3 after 10 years or more of disease progression 3940. In a recent study the authors propose an alternative definition (EDSS ≤1.0, absence from any disability, and the ability to work after 15 years of disease duration) which might truly reflect 41. In our series we found 31 patients (8%) meeting this definition. Although the definition of benign forms remains debated, it is generally admitted that they are characterized by the absence of significant ambulatory impairment 10 to 20 years after the onset of the disease. However, the practical impact of this concept remains limited for two reasons: on the one side, it is a progressive modality that can only be determined a posteriori, and on the other side, epidemiological studies with sufficient hindsight tend to show that a significant proportion of initially "benign" patients nevertheless end up worsening with time, following the usual evolution of other MS patients 41. The suggestion that MS is progressing more slowly than previously thought may represent a change in the type of patient with MS being seen in MS clinics today, perhaps driven by an increased recognition of MS, new diagnostic techniques, availability of immunomodulatory drugs to treat MS and increased survival (related to better health care and management of chronic diseases). All these factors might contribute to the differences between older and newer natural history studies. In fact, the specific component of these factors remains to be determined, in particular the impact of immunomodulatory drugs on long term disability progression 42. There were some limitations to our study that require discussion: we did not study the impact of disease-modifying drugs therapy. Moreover, considering variability in the duration and type of treatment in our population, it may be very hard to include this component in our evaluation. The accessibility of medical care in some centres, a less awareness of MS in the general public and the low socio-economic among some patients may have influenced this time of diagnosis, the time of treatment and the severity of the disease but those data which were not assessed in this study. Nevertheless, this is a detailed study of MS patients in Algeria, and it should provide baseline characteristics of MS patients in this region, since environmental and genetic factors are thought to have significant roles in MS 6.

We wish that in the future other epidemiological studies from other centers in the country will appear to clarify the characteristics and evolution of the disease in our region where multiple sclerosis is little studied. A national registry is strongly recommended, as well as long-term follow-up epidemiological and genetic studies.