Young Multiple Sclerosis Patients Research Articles

Cognitive dysfunction characteristics of multiple sclerosis with aging

BackgroundWe aimed to investigate the characteristics of cognitive impairment in older people with multiple sclerosis (MS). MethodsCross-sectional study that included participants that were examined with a common and comprehensive neuropsychological protocol. The subjects were matched by sociodemographic variables and the following groups were generated for comparisons: young MS versus healthy controls (HC) (n = 246), old MS versus HC (n = 198), young MS vs old MS (n = 226), MS vs Alzheimer's disease (AD)(n = 70), and MS vs Parkinson's disease (PD) (n = 62). The ICCoDiMS criteria were used to define cognitive impairment in MS. ResultsCognitive impairment was more frequent in young than old patients (70.8 % vs 52.2 %). Attention and speed processing is the most frequent cognitive domain impaired in MS (54.9 % of young MS vs 32.7 % of old MS). The frequency of impairment in attention/processing speed (54.9 % vs 32.7 %) and episodic memory (27.9 % vs 14.3) was higher in the young group than in the old group. There were no statistically significant differences in the distribution of impairment in executive function (46.0 % vs 35.3 %), visuospatial (17.9 % vs 9.5 %), and language (12.4 % vs 17.7 %). In those patients meeting the criteria for cognitive impairment, young MS patients showed lower performance in attention/processing speed tests. Conversely, old MS patients showed lower performance in episodic memory, verbal fluency, and planning. There were no differences in the correlations between SDMT and other neuropsychological tests in young and old patients, which suggests similar cognitive processes underlying SDMT performance in both groups. There were differences between old MS and prodromal AD, especially in episodic memory, while the cognitive profile of old MS was largely shared with PD. ConclusionsOur study found that the cognitive profile of MS is defined by a characteristic impairment in attention and processing speed, which is present during the lifespan. The impairment in processing speed is less prominent in old age, whereas the impairment of other cognitive functions becomes more relevant. These findings suggest potential differences in the pathophysiological processes associated with cognitive impairment between young and old ages that warrant further investigation.

Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis.

Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients. To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients. Prospective single-centre observational study collecting information on occurrence, type and grade of infections in patients followed at the MS centre, Lugano (Switzerland). Associations with infection risk were tested using multivariable Poisson and Cox regressions. A total of 503 patients were included (injectables/untreated, n = 127; orals, n = 139; monoclonal antibodies (MAB), n = 237) and 326 infections recorded over 12.6 (11.6-14.0) months. As compared to injectable DMTs/no treatment, MAB and oral DMTs were positively associated with infection incidence (IRR = 2.32, 95% confidence interval (CI) = 1.39-3.89, p = 0.001; IRR = 2.04, 95% CI = 1.19-3.49, p = 0.009, respectively). After excluding COVID-19, the effect of MAB was stronger among patients <50 years (IRR = 5.90, 95% CI = 2.80-12.45, p < 0.001) than >50 years (IRR = 1.95, 95% CI = 0.91-4.15, p = 0.084). Higher disability and male sex were the only variables associated with severe infections. Treatment with MAB and oral DMTs is associated with higher incidence of infections, with a stronger effect in young MS patients. Disability appears the main predictor of severe infections regardless of treatment.

Telomere Length as a biomarker in Multiple Sclerosis (S9.002)

Telomere Length as a biomarker in Multiple Sclerosis (S9.002)

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation

Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Predictors of Disease Activity and Worsening in Relapsing-Remitting Multiple Sclerosis.

Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening. The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of follow-up including relapse, MRI activity, and disease worsening. One thousand eight participants were randomized, with 959 eligible for assessment of disease activity and worsening on follow-up. In multivariable models, the risk of relapse was higher in participants younger than 38 years at BL than in those older (HR range 1.36-1.43), with the presence of gadolinium (Gd)+ lesions at BL (HR 1.38, [95% confidence interval, CI 1.14, 1.67]) and with BL EDSS ≥3.5 vs <3.5 (HR range 1.63-1.67). The risk of new MRI activity was higher in younger participants (HR range 1.58-1.84), with higher preexisting lesion counts greater than the median lesion count with ≥71 T2 hyperintense lesions vs <71 (HR 1.50, [95% CI 1.27, 1.77]), with the presence of BL Gd+ lesions (HR 1.75, [95% CI 1.49, 2.06]), and higher BL T2 lesion volume (HR 1.02 for every unit increase in baseline volume, [95% CI 1.01, 1.03]). The risk of new MRI activity was lower in those receiving combination therapy compared with those that in those receiving either glatiramer acetate (HR range 0.67-0.68) or interferon beta-1a (HR range 0.68-0.70). The risk of disease worsening was higher for those with higher T2 volume (HR for 1 unit increase in volume 1.01, 95% CI 1.004, 1.03) and BL EDSS <2 (HR range 2.79-2.96). There were no associations between sex, race, and disease duration on relapse, MRI activity, or disease worsening in the multivariable analysis. Prospective data from a large clinical trial cohort show that younger MS patients with high BL relapses and MRI lesion burden have the highest risk of subsequent disease activity. Clinical trial registration number NCT00211887. CombiRx was registered at ClinicalTrials.gov (NCT00211887) on September 21, 2005. Study enrollment began in January 2005.

Vitamin D supplementation in multiple sclerosis: an expert opinion based on the review of current evidence

ABSTRACT Introduction Vitamin D has long been known for its immune-modulating effects, next to its function in calcium metabolism. As a consequence, poor vitamin D status has been associated with many diseases including multiple sclerosis (MS). Epidemiological studies suggest an association between a poor vitamin D status and development of MS and a poor vitamin D status is associated with more relapses and faster progression after patients are diagnosed with MS. Area’s covered The aim of the authors was to review the role of vitamin D supplementation in the treatment of MS. Pubmed was used to review literature with a focus of vitamin D supplementation trials and meta-analyses in MS. Expert opinion There is no solid evidence to support the application of vitamin D therapy, based on current available supplementation trials, although there are some promising results in the clinically isolated syndrome (CIS) patients and young MS patients early after initial diagnosis. The authors recommend further larger clinical trials with selected patient groups, preferable CIS patients and young patients at the time of diagnosis, using vitamin D3 supplements to reach a 100 nmol/l level, to further investigate the effects of vitamin D supplementation in MS.

Secular trends in disease modifying treatment and expenditure in multiple sclerosis: A longitudinal population study in the north of Ireland

BackgroundThe epidemiology of multiple sclerosis (MS) is important for planning disease modifying therapy (DMT). Secular changes in the use of DMT in MS can guide future service development. MethodsA population study of the prevalence of multiple sclerosis was completed in the west of Northern Ireland – a defined geographic area making up the Western Health and Social Care Trust (WHSCT). The use, category and cost of DMT for the MS population in the WHSCT were measured over 11 years. ResultsThe WHSCT had a recorded prevalence of MS of 238.4/100,000 (95%CI 221.5–256.5) in 2018. DMT use increased over threefold in 11 years. Four hundred and nine (57%) of 720 MS patients were taking a DMT by 2018. The annual expenditure of DMT drugs had increased sixfold over ten years to £5,301,198 in 2018 (using 2018 prices), reflecting both an increase in DMT use and a switch to more intensive DMTs. Younger MS patients were more likely to be taking a DMT (P<0.001). ConclusionDMT use and cost have been increasing among the MS population in the Northern Ireland. There has been a temporal switch to more efficacious DMTs. Future research should monitor the cost-effectiveness and equity of treatment of MS patients.

Comorbid pathology of the cardiovascular system in young patients with relapsing-remitting multiple sclerosis

To study the state of the cardiovascular system and peripheral microcirculation in young patients with relapsing-remitting multiple sclerosis (MS). The study included 45 MS patients (17 men and 28 women, age 28 [24; 32] years, disease duration 5.5 [2; 7] years). The control group included healthy controls (age 30 [25; 33] years). Neurological and cardiologic examinations included 24-hour Holter ECG monitoring and 24-hour blood pressure monitoring with determination of the daily arterial vascular stiffness, echocardiography, laser doppler flowmetry followed by an occlusive test to assess the state of microvasculation, levels of serum vascular cellular adhesion molecule-1 (VCAM-1). In MS group, the results of 24-hour blood pressure monitoring showed that the variability of systolic blood pressure and diastolic blood pressure during daytime hours was reduced compared to the control group (p<0.026 and p<0.002, respectively). The indicators of daily arterial stiffness in MS group were significantly increased (p<0.001). According to the results of Holter ECG monitoring, no heart rhythm disorder was detected in both groups, except an increase in the number of supraventricular extrasystoles in MS patients compared to the control group (p<0.005). There were no between group differences in echocardiography indicators. The level of VCAM-1 was significantly increased in MS group compared to controls (p<0.001). Young MS patients are at risk of cardiovascular diseases associated with the variability of blood pressure and indexes of daily arterial vascular stiffness.

Comorbid pathology of the cardiovascular system in young patients with relapsing-remitting multiple sclerosis

To study the state of the cardiovascular system and peripheral microcirculation in young patients with relapsing-remitting multiple sclerosis (MS). The study included 45 MS patients (17 men and 28 women, age 28 [24; 32] years, disease duration 5.5 [2; 7] years). The control group included healthy controls (age 30 [25; 33] years). Neurological and cardiologic examinations included 24-hour Holter ECG monitoring and 24-hour blood pressure monitoring with determination of the daily arterial vascular stiffness, echocardiography, laser doppler flowmetry followed by an occlusive test to assess the state of microvasculation, levels of serum vascular cellular adhesion molecule-1 (VCAM-1). In MS group, the results of 24-hour blood pressure monitoring showed that the variability of systolic blood pressure and diastolic blood pressure during daytime hours was reduced compared to the control group (p<0.026 and p<0.002, respectively). The indicators of daily arterial stiffness in MS group were significantly increased (p<0.001). According to the results of Holter ECG monitoring, no heart rhythm disorder was detected in both groups, except an increase in the number of supraventricular extrasystoles in MS patients compared to the control group (p<0.005). There were no between group differences in echocardiography indicators. The level of VCAM-1 was significantly increased in MS group compared to controls (p<0.001). Young MS patients are at risk of cardiovascular diseases associated with the variability of blood pressure and indexes of daily arterial vascular stiffness.

PREVALENCE AND PREDICTORS OF LOW BONE MINERAL DENSITY IN PATIENTS WITH MULTIPLE SCLEROSIS IN YOUNG AGE

Актуальность. Рассеянный склероз – хроническое аутоиммунное прогрессирующее заболевание нервной системы, характеризующееся повышенным риском переломов, обусловленным рядом причин, включая низкую минеральную плотность костной ткани (МПКТ). Согласно данным литературы, больные рассеянным склерозом уже в молодом возрасте могут иметь МПКТ ниже возрастной нормы. Факторы, ассоциирующиеся с низкой МПКТ у таких больных, нуждаются в изучении. Цель – установить распространенность низкой МПКТ у больных рассеянным склерозом в молодом возрасте и выявить факторы, вызывающие ее снижение. Материал и методы. Критерием включения в исследование являлся возраст мужчин – от 18 до 50 лет, женщин – от 18 лет до периода наступления менопаузы. Обследовано 163 пациента с рассеянным склерозом, их средний возраст составил 36,1±7,6 года. Женщин было 111 (68,1%), мужчин – 52 (31,9%). Ремиттирующий рассеянный склероз был у 121 (74,2%) больного, вторично-прогрессирующий – у 37 (22,7%), первично-прогрессирующий – у 5 (3,1%). Медиана балла по расширенной шкале инвалидизации (Expanded Disability Status Scale – EDSS) составила 3,5 [интерквартильный размах Q25; Q75 – 2,0; 5,5]. Медиана продолжительности заболевания была 8,5 [5,0; 14,0] года. Измерение МПКТ проводилось методом двуэнергетической рентгеновской абсорбциометрии. Исследование проведено в двух точках скелета: поясничном отделе позвоночника и проксимальном отделе бедра. Результаты. Снижение МПКТ ниже возрастной нормы по Z-критерию выявлено у 30 (18,4%) пациентов. Индекс массы тела (отношение шансов (OШ) 0,8; 95% доверительный интервал (ДИ) 0,7-0,9; p=0,001), продолжительность заболевания (OШ 1,1; 95% ДИ 1,0-1,2; p=0,023), число курсов глюкокортикостероидов (ОШ 1,3; 95% ДИ 1,0-1,6; р=0,03), курение (ОШ 2,7; 95% ДИ 1,0-7,2; р=0,04) являются независимыми факторами низкой МПКТ в исследованной популяции больных рассеянным склерозом. Заключение. У каждого четвертого больного рассеянным склерозом в молодом возрасте снижена МПКТ. Значимыми факторами, влияющими на МПКТ в исследованной популяции больных рассеянным склерозом молодого возраста, оказались продолжительность заболевания, низкий индекс массы тела, прием глюкокортикостероидов и курение.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

PP13.9 – 2836: Variants in the NR3C2 gene as possible genetic predisposition for the development of multiple sclerosis

Objective Due to the incidental finding of two NR3C2 gene variants in young MS patients, we investigated the possibility that NR3C2 might be a suspectibility gene for multiple sclerosis (MS) and autoimmune disease. Methods In two unrelated MS cases we found respectively a deletion and a point mutation within the coding region of the NR3C2 gene using array-comparative genomic hybridization (Agilent 180k) and Sanger sequencing of NR3C2. The latter was also performed in an independent cohort of 100 MS probands. Results Case 1 is a male 12 years-old MS patient. Array-comparative genomic hybridization revealed a 112–181 kb deletion in NR3C2, compatible with the diagnosis of type 1 pseudohypoaldosteronism. He had no symptoms of this disease but serial blood investigations confirmed a mild elevation of aldosterone. Segregation analysis revealed that his mother and maternal aunt, both of which developed autoimmune thyroiditis, carried the same microdeletion. Case 2 is the mother of a child with pseudohypoaldosteronism. She presented at age 28 with MS and was known to carry the same mutation (c.1757+1G>C) as her daughter in the splice donor site of intron 2 of NR3C2. The mother had elevated aldosterone levels. In an independent MS cohort, we detected a loss-of-function mutation (p.Ser585X) in a single patient with early-onset MS and a positive familial history. She had no symptoms of pseudohypoaldosteronism but a mild but reproducible elevation of aldosterone was detected. Conclusion Our data suggest that NR3C2 loss-of-function variants may associate with a genetic predisposition for developing autoimmune disease, particularly for MS. Though further validation of our findings in a larger cohort is necessary the possible involvement of the renin-angiotensin-aldosterone system in the pathogenesis of MS may have important implications in counselling and follow up of patients with NR3C2 mutations and opens novel perspectives for MS treatment.

Cyclophosphamide Does Not Affect Fertility in Young Multiple Sclerosis Patients (P02.133)

Cyclophosphamide Does Not Affect Fertility in Young Multiple Sclerosis Patients (P02.133)

Risk of vascular disease in patients with multiple sclerosis: a review

Objective: Vascular dysfunction and shared risk factors may lead to an increased risk of arterial and venous vascular disease in patients with multiple sclerosis (MS). The aim of this review was to describe studies examining the risk of vascular diseases in MS patients.Methods: A PubMed search combined with review of reference lists and table of contents revealed eight relevant studies describing the occurrence or risk of one or more vascular diseases.Results: One cohort study and three cross-sectional studies described stroke occurrence in 898 to 13 963 MS patients. MS was associated with an increased risk of stroke and cerebrovascular diseases compared with the general population and other hospitalized patients, particularly within the first years after MS diagnosis and in young and middle-aged MS patients. In contrast, data are conflicting with regard to the association between MS and coronary artery disease including myocardial infarction. Cross-sectional studies found a lower prevalence of coronary artery disease in MS patients, while the only cohort study found an increased risk within the first year after MS diagnosis only. MS was, however, associated with an increased risk of venous thromboembolism, including deep venous thromboembolism and pulmonary embolism, in particular within the first years after MS diagnosis.Discussion: MS is associated with an increased risk of vascular diseases within the first years after a first-time MS diagnosis compared with the general population. The risk declines thereafter, but remains elevated for stroke and venous thromboembolism. Shared risk factors, linked pathogenesis, and bias may contribute to the association.

The risk of fracture in patients with multiple sclerosis: The UK general practice research

Patients with multiple sclerosis (MS) may be at an increased risk of fracture owing to a greater risk of falling and decreased bone mineral density when compared with the general population. This study was designed to estimate the relative and absolute risk of fracture in patients with MS. We conducted a population-based cohort study using data from the UK General Practice Research Database linked to the National Hospital Registry (1997–2008). Incident MS patients (n = 5565) were matched 1:6 by year of birth, sex, and practice with patients without MS (controls). Cox proportional-hazards models were used to derive adjusted hazard ratios (HRs) for fracture associated with MS. Time-dependent adjustments were made for age, comorbidity, and drug use. Absolute 5- and 10-year risks of fracture were estimated for MS patients as a function of age. Compared with controls, MS patients had an almost threefold increased risk of hip fracture [HR = 2.79, 95% confidence interval (CI) 1.83–4.26] and a risk of osteoporotic fracture that was increased 1.4-fold (HR = 1.35, 95% CI 1.13–1.62). Risk was greater in patients who had been prescribed oral/intravenous glucocorticoids (GCs; HR = 1.85, 95% CI 1.14–2.98) or antidepressants (HR = 1.79, 95% CI 1.37–2.35) in the previous 6 months. Absolute fracture risks were low in younger MS patients but became substantial when patients were older than 60 years of age. It is concluded that MS is associated with an increased risk of fracture. Fracture risk assessment may be indicated in patients with MS, especially those prescribed GCs or antidepressants. © 2011 American Society for Bone and Mineral Research

Cognitive rehabilitation in children and adolescents with multiple sclerosis

Cognitive impairment can be detected in a sizeable proportion of pediatric multiple sclerosis (MS) patients. It involves memory, complex attention, information processing speed, executive functions, linguistic abilities, and intelligent quotient. It has a great impact on school, everyday and social activities, and significantly progresses overtime in the great majority of the subjects. These findings highlight the importance of a comprehensive and systematic assessment of MS-related cognitive difficulties in pediatric cases. Moreover, despite the acknowledged relevance of cognitive impairment in this age range, specific interventions for pediatric MS are lacking. As for rehabilitative strategies, there is some evidence of efficacy in other diseases, in particular brain trauma, tumor, and stroke. The development of effective rehabilitative strategies tailored to the needs of young MS patients is a priority for future research in the field.

Peripheral Arterial Compliance Is Compromised In Young Multiple Sclerosis Patients

Peripheral Arterial Compliance Is Compromised In Young Multiple Sclerosis Patients

P02-211 Depression, anxiety and health status in patients with multiple sclerosis

Aims:Multiple sclerosis (MS) is the most common cause of neurological disability in young adults and is frequently accompanied by symptoms of depression and anxiety. The aim of this study was to explore the association of depression and anxiety with health status in younger and older MS patients.Method:223 MS patients (67.3% female; mean age 38.9±10.8 years; mean disease duration 5.8±5.2 years) were divided into younger and older age groups (&lt; 45 and ≥45 years). They completed questionnaires focusing on sociodemographic data, depression and anxiety (HADS), and physical and mental health status (SF-36). Functional disability (EDSS) was assessed by a neurologist. To analyse the data, a U-test and multiple linear regression analyses were performed.Results:A model consisting of age, gender, marital status, EDSS, depression and anxiety explained 46.6% of the variance in physical health status and 60.8% of the variance in mental health status (p≤.001). Depression was a significant predictor of physical health status in older MS patients and was associated with mental health status in both age groups (p≤0.001). Anxiety was related to worse physical and mental health status in younger MS patients, but not in the older ones.Conclusion:Depression in MS patients is associated with mental health status and with physical health status only in the older group; anxiety is associated only in younger MS patients with regard to their health status. Psychiatric diagnostics focusing on depression and anxiety might be important for treatment of MS patients in order to contribute to improving a patient's health status.

Primary headache and multiple sclerosis: preliminary results of a prospective study

The aim of this study was to explore the association between different types of headache (HA) and the clinical features of multiple sclerosis (MS). The relationship between HA and MS-specific therapies was also analysed. A total of 102 MS patients were recruited at the MS Centre of S. Andrea Hospital in Rome. According to International Headache Society criteria, the lifetime prevalence of primary HA was 61.8%. Migraine was observed more often in young relapsing-remitting MS patients, whilst tension-type HA was associated with older age, male gender and a secondary progressive course. Sixty-four patients had a history of ongoing or past interferon beta (IFNb) exposure. Of these, 17 subjects did not have a history of HA, while 24 complained of an increase in frequency of migraine attacks and 7 reported an IFNb-induced HA. Investigating and treating HA in MS patients starting IFNb therapy may improve MS-specific medication compliance.

The safety profile of cyclophosphamide in multiple sclerosis therapy

Cyclophosphamide (Cyc) is an alkylating agent used to treat malignancies and autoimmune diseases, such as lupus nephritis, rheumatoid arthritis and immune-mediated neuropathies. Over the past 40 years, Cyc has also been applied to treat multiple sclerosis (MS) and the effective stabilisation of rapidly progressive forms of MS has been demonstrated in several studies. Cyc has a dose-dependent bimodal effect on the immune system. High doses have been demonstrated to induce an anti-inflammatory immune deviation (i.e., suppression of T helper 1 and enhancement of T helper 2 activity), affect CD4CD25high regulatory T cells and establish a state of marked immunosuppression. Data from the literature suggest that Cyc is particularly indicated in the treatment of young MS patients, suffering from a very active inflammatory disease characterised by frequent relapses and rapid accumulation of disability and displaying gadolinium-enhancing lesions on brain magnetic resonance. The most common Cyc-based therapeutic protocol applied in MS consists of monthly intravenous pulses for 1 year followed by bimonthly pulses for the second year, with or without prior infusion of corticosteroids. This protocol is usually well tolerated by the patients. Indeed, most of the side effects (mild alopecia, nausea and vomiting, cystitis) are dose dependent, transient and completely reversible. Definitive amenorrhoea is observed only in older female patients (aged > 40 years). Cyc has a safety and efficacy profile similar to that of mitoxantrone and can be used in patients whose disease is not controlled by IFN-β or glatiramer acetate. Short course (6 – 12 months) of Cyc therapy can precede the initiation of immunomodulatory treatment in selected patients with an aggressive MS onset.