Higher EDSS Scores Research Articles

The prevalence of lower urinary tract symptoms based on individual and clinical parameters in patients with multiple sclerosis

BackgroundMost patients with multiple sclerosis (MS) suffer from bladder dysfunction during the course of the disease. This study was conducted to examine the prevalence of these complications among patients with MS.MethodsThis cross-sectional study was performed on 602 patients with MS who referred to the neurology clinics of Kashani and Alzahra Hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Multistage random cluster sampling was performed and the informed consent form was signed by the subjects. Then, all the data were collected through interviews using the Lower Urinary Tract Symptom Score (LUTSS) developed in accordance with the definitions presented by the International Continence Society (ICS) and the International Prostate Symptom Score (I-PSS) and DASS-21 questionnaire. The data were analyzed using descriptive and inferential statistical tests in SPSS.ResultsThe prevalence rate of lower urinary tract symptoms (LUTS) was 87.6% among all the subjects, with a similar rate among women (88.0%) and men (86.0%). There was a significant difference between men and women in terms of the prevalence of stress urinary incontinence (SUI), intermittent urine flow, hesitancy, straining, and dribbling (P < 0.050). There was no significant difference between women and men in terms of the prevalence of other symptoms (P > 0.050). A significant difference was observed in the degree of LUTS with age, marital status, marriage duration, education, illness duration, clinical course, disability, anxiety, depression, and stress (P< 0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a urinary problems among patients with MS and a high EDSS score [0.67 (0.507–0.903), P = 0.008].ConclusionsA high prevalence of LUTS was found among patients with MS. There was a higher probability of a urinary tract problem among patients with MS and a high EDSS score. Therefore, it is recommended that the health system take the necessary measures regarding timely detection and treatment of LUTS among these patients in order to prevent secondary outcomes and improve the quality of life (QOL) of patients with MS.

Cognitive functions in pediatric multiple sclerosis: 2-years follow-up

ABSTRACTObjective: To assess the neuropsychological status of pediatric multiple sclerosis (MS) patients and its relationship with clinical variables in a longitudinal study.Methods: Patients with MS (n = 46) and age- and gender-matched healthy control subjects (HCs, n = 53) were given tests of non-verbal reasoning, attention/concentration, visuospatial judgement and verbal fluency at baseline visit and after 2 years of follow-up. Cognitive impairment was defined as a failure on at least three of the four tests. Patients were grouped according to the age of disease onset (≤12 years as group 1 and > 12 years as group 2).Results: Cognitive impairment was detected in 22 of 46 patients at follow-up (47.8%). Patients with cognitive worsening had higher EDSS scores at follow-up compared to cognitively improved/stable group (0.68 ± 1.16 vs 0.04 ± 0.2, p = 0.01). The most affected domains were attention/concentration and non-verbal reasoning. Comparison between baseline and follow-up tests showed impairment in non-verbal reasoning over time in group 1 patients while other functions improved over time in patient and control groups as expected.Conclusion: Pediatric MS is likely to affect patients’ cognition concurrently with their disability levels. This effect is significant in the non-verbal reasoning area in patients with disease onset before age 12 years. A practical method assessing this function should be part of these patients’ regular follow-up for optimal treatment, prevention and rehabilitation.

Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function

We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.

Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors.

BackgroundMany potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS.ObjectiveThe aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities.MethodsWe included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao’s battery and Stroop test, cognitive reserve (premorbid intelligence quotient–IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire.Results150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02–1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88–0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02–1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23–1.05)ConclusionsOur findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies.

Prevalence of sleep disorders in Parkinson\u2019s disease patients in two neurology referral hospitals in Ethiopia

BackgroundNon motor symptoms (NMS) of Parkinson’s disease (PD) are common and can be more disabling than motor symptoms. Sleep disorders can be seen in up to 98% of patients with Parkinson disease. Poor sleep quality has been associated with poverty and race, and yet there has been no prior report on sleep disorders in those with PD living in sub Saharan Africa. We wished to document the prevalence of sleep disorders in PD patients in Ethiopia.MethodsWe conducted a cross-sectional point prevalence study from July 1 to October 30, 2015 of all patients attending the neurology outpatient department in Tikur Anbessa and Zewuditu Memorial Hospitals, Addis Ababa, Ethiopia. Demographic data, clinical history and physical examination findings were collected from participants using a structured questionnaire. We used the Parkinson’s disease sleep scale version two (PDSS-2) and Epworth Sleepiness Scale (ESS) to assess the sleep symptoms.ResultsOf the 155 patients surveyed, all patients reported some sleep problem. Over 43.9% of patients had a PDSS score > 18. The median score of ESS was 9 (IQR = 5–12), with 77/155 (49.7%) of the patients having possible or definite excessive daytime somnolence. A high EDSS score significantly associated with a Hoehn & Yahr score > 4 (p = 0.02).ConclusionsIn Ethiopian PD patients, the prevalence of those with severe sleep disorders is the highest reported to date. The prevalence of possible/definite EDS is amongst the highest in the world. Further investigation into whether poverty or race explains this finding is needed.

Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: Multi-center, controlled trial

BackgroundCognitive impairment (CI) is a common problem in multiple sclerosis (MS), may occur either in early or late phase of the disease, and impairs quality of life. ObjectivesThis study aimed to determine the prevalence of CI and related risk factors in relapsing-remitting MS (RRMS) patients in Turkey. MethodsThe present cross-sectional, multi-center, and nationally representative study included RRMS patients. Sociodemographic characteristics, cognitive functions and additional outcomes were compared between patients with and without CI. ResultsThe analyses included 487 RRMS patients. According to the BRB-N battery results, CI prevalence was 53.7%. There was a negative significant correlation of BRB-N subtests with age, disease duration, and EDSS and MSNQ-patient rated scores. On the logistic regression analysis, increased age, living in village/rural area, high income level, and high EDSS score were significant increasing risk factors in the development of CI. ConclusionsThis is the first national cognitive data obtained from MS in Turkey, which is a country between Europe and Asia and thus has characteristics of both continents. The similarity of the results of the present study obtained from Turkey to the Western-based data indicates that CI is universal in MS and the main factors affecting CI have not changed.

Effect of comorbidities on the course of multiple sclerosis

ObjectiveThe clinical condition of multiple sclerosis (MS) patients depends not only on the course of MS but also on their lifestyle and comorbidities. This study aimed to assess the effect of selected comorbidities, lifestyle-related factors and clinical data available at the time of MS diagnosis, on the disease activity and the disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). Patients and methodsBased on clinical relapses over a period of 12 months of observation and the results of MRI scans, 138 patients with RRMS were qualified into two groups: ‘active’ or ‘stable’ course of the disease. Patients from both groups were compared regarding the clinical data determined at diagnosis, comorbidities and lifestyle-related factors. Similar comparisons were carried out between patients with EDSS < 3 vs, patients with EDSS ≥ 3. ResultsNo significant differences in comorbidities and lifestyle-related data between the stable and active group were detected. Arterial hypertension, hyperlipidemia, higher BMI values, older age and a lower education level, were found more frequently in patients with EDSS ≥ 3. Oligoclonal bands, multifocal clinical manifestation as the first relapse, higher EDSS score and many T2 MRI lesions at the diagnosis were detected significantly more often in the active group. Motor or brainstem/cerebellum damage symptoms as the first relapse were observed more frequently in patients with EDSS ≥ 3. ConclusionsCardiovascular diseases may exacerbate disability progression in MS patients. Relapses and radiological activity do not depend on chronic comorbidities. Clinical data available at the diagnosis may be useful in forecasting a distant course of MS.

Comparison of Double Inversion Recovery and FLAIR Sequences in Diagnosing Multiple Sclerosis Infratentorial Plaques

Fluid–Attenuated Inversion Recovery (FLAIR) is the most commonly used sequence in routine practice for MS. Recent studies employ alternative sequences such as Double Inversion Recovery (DIR) in addition to conventional MRI techniques. In this study we compared these two sequences for their sensitivity in detecting infratentorial lesions in MS. A total of 24 patients with 3D DIR and 3D FLAIR sequences were included in this study. Plaques were classified according to their localization such as brainstem and cerebellar plaques. The relationship between number of infratentorial plaques and age, gender, MS type, disease duration, average annual number of attacks, cerebellar atrophy existence and EDSS score was also analyzed. DIR sequence detected higher number of lesions compared to FLAIR sequence in brainstem (59 vs 45 plaque in 24 cases) and cerebellum (50 vs 25 plaque in 24 cases). In detecting cerebellar lesions, superiority of DIR sequence compared to FLAIR sequence was statistically significant (p=0.049). Patients with longer disease duration had less cerebellar lesion load in FLAIR sequence at a statistically significant rate. Patients with longer disease duration and higher number of attacks had higher EDSS scores. There was no relationship between brainstem plaques number of cerebellum plaques and EDSS score. Comparing groups with and without cerebellar atrophy, cerebellar atrophy was also more frequent in patients with higher level of cerebellar lesion load in DIR sequence (p=0.028). Our findings suggest that DIR sequence is superior to FLAIR sequence in detecting cerebellar lesions. Cerebellar lesion load detected in DIR sequence was correlated to cerebellar atrophy. For this reason, especially during early period of disease, DIR sequence may be more useful than FLAIR sequence in distinguishing definite MS from clinical isolated syndromes and also for determining atrophy risk.

Long-term disability and progression in spinal onset multiple sclerosis.

The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12months. Eventually, 476 MS patients were included. Data regarding the demographics, initial symptoms, the degree of recovery from the initial relapse, neuroimaging, cerebrospinal fluid analysis, long-term disability, and progression were collected from the medical registry. The mean duration of follow-up was 7.49±5.30years. The percentage of patients entering the progressive disease course was 23.3 in the whole group. A total of 157 patients (33.0%) had SC involvement during the first clinical relapse. These patients were significantly older at disease onset (31.69±10.18 vs. 29.55±9.49; p=0.028), had higher rates of progression (32.5 vs. 18.8%; p=0.001), and had higher disability scores in long-term follow-up (3.41±2.19 vs. 2.62±1.81; p<0.001). Mean age at the transition of progressive phase was 41.4±11.2years. The degree of recovery from the initial relapse significantly affected the long-term disability. The poor recovery from the initial relapse was associated with older onset age and higher EDSS scores. Being older than 40years during MS onset and poor recovery from the initial relapse exerted an increased risk for progression. The initial SC involvement was related to a more severe relapse with less chance of complete recovery and higher risk for progression. Confirmation of risk factors in different MS cohorts would increase our understanding of the complex disease mechanisms.

Prevalence of cognitive impairment among Hungarian patients with relapsing-remitting multiple sclerosis and clinically isolated syndrome

BackgroundCognitive impairment (CI) is a frequent symptom of multiple sclerosis (MS); its prevalence is reported to be 43–70%. It is one of the most important determinants of MS patients’ quality of life, as it is one of the main factors for MS patients becoming unemployed. AimWe aimed to determine the prevalence of CI among the relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS) patients in Hungary, to evaluate the predicting factors of CI and to assess the differences between sexes and patients with different educational levels. Patients and methodsFive-hundred and fifty-three CIS and RRMS patients were enrolled to our study from three Hungarian MS centers. Age at screening, age at disease onset, disease duration, EDSS score, sex and educational levels were analyzed as socio-demographic factors. The BICAMS battery was used to assess their cognitive state, the BDI-II battery to assess depression. For statistical analysis, we utilized logistical regression, and used Fisher exact tests, chi-square tests and one-way ANOVA. ResultsThe mean age of our patients was 44.93 ± 11.69 years, mean age at disease onset was 31.95 ± 10.01 years, the mean disease duration was 13.05 ± 8.05 years and the median EDSS score 2.0 (Range: 6.5, IQR:2.0) points. Three-hundred and sixteen (57.1%) patients had CI. Sex, educational level and EDSS score proved to be significant predictors of CI (OR: 2.71, p < 0.001; OR: 1.94, p = 0.023; OR: 0.47, p = 0.003 respectively). CI was significantly (p < 0.001) more frequent among men (70.1%) than women (52.0%). We found, that educational level and EDSS score were only a significant predicting factor among women. Thus, the prevalence of CI among women with college or university degree was significantly (p < 0.001) less common (39.4%) than women with 12–15 years of education (57.4%) and women without a high school degree (66.7%). Also, we found that among women with higher EDSS score than 2 points, the prevalence of CI is 69.9% as compared to women with EDSS score between 0 and 2 points, where the prevalence is 42.8% (p < 0.001). No such differences were observed among man. DiscussionOur prevalence data is similar to those reported in the literature (43–70%), and almost identical to the one assessment using the BICAMS battery. We found that men are more vulnerable to CI than women in MS, as was reported recently. We are the first to report however, that higher educational level and lower EDSS scores are only associated with better cognitive performance in women.

Participation Restriction in People With Multiple Sclerosis: Prevalence and Correlations With Cognitive, Walking, Balance, and Upper Limb Impairments

ObjectivesTo calculate the percentage of participation restrictions according to disability level in multiple sclerosis (MS), and to assess the relationship between participation restrictions and cognitive, gait, balance, and upper limb deficits. DesignCross-sectional study. SettingRehabilitation unit. ParticipantsParticipants (N=125) consisted of people with MS (n=105) and healthy subjects (HS; n=20). InterventionsNot applicable. Main Outcome MeasuresThe Community integration Questionnaire was used to assess participation in home, social, and productive activities. Percentages of people with MS having Community Integration Questionnaire scores lower than the 10th percentile of those of HS were calculated for each subscale to categorize the persons with participation restrictions. Cognitive deficits (Symbol Digit Modalities Test), walking disability (25-ft walking test/Expanded Disability Status Scale [EDSS]), balance disorders (Bohannon Standing Balance Test), and manual dexterity (Nine Hole Peg Test) were recorded. ResultsSeventy-seven percent of participants showed participation restrictions, which increased with higher EDSS scores from 40% (EDSS<4) to 82% (EDSS>5.5). Social participation was more restricted than home integration, with <20% of participants shopping for groceries alone. Cognitive deficits were more highly associated (r=.60) with participation restrictions than balance (r=.47), gait (r=−.45), and hand dexterity (r=.45) limitations. ConclusionsParticipation restrictions are present in MS and increase with disability level. However, the results also show that MS does not restrict participation in all domains. Participation restrictions at home are less restricted compared with social participation. Cognitive disorders are more associated with participation restrictions than physical limitations.

Fatigue evaluation in fingolimod treated patients: An observational study

BackgroundFatigue is one of the most disabling symptoms in Multiple Sclerosis (MS) patients and is associated with a low quality of life. Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, is the first oral MS disease modifying treatment. Little is known about its effect on fatigue. To assess the impact of Fg on fatigue within the first 6 months of treatment in MS patients, we conducted a prospective, open label study, in real life setting. MethodsChange of Modified Fatigue Impact Scale (MFIS) between Fg treatment start and at 6 months was used as a first outcome. Secondary outcomes were changes of MFIS subscales, Fatigue severity scale (FSS) and Visual Analogic Scale of Fatigue (VAS-F) scores, Results54 completed the study at M6. No significant change was noted in global MFIS (and neither in sub analysis of MFIS), FSS or VAS-F at M6. Patients with high level of fatigue (MFIS or ≥38) had a higher EDSS score than patients with lower level of fatigue (MFIS <38), (mean 3.3, [SD 1.6] versus 1.6 [SD1.1], p=0.0002) but showed no significant difference in MFIS evolution at M6. There was no significant statistical difference in fatigue parameters evolution at M6 within patients Nz+ or Nz-. ConclusionThere is no significant impact of Fg on fatigue after 6 months of treatment.

Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis.

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986-2016) were included. Nine studies were included (3 retrospective cohort and 6 case-control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means=-5.42years, 95% CI -7.19 to -3.66, p<0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means=0.45, 95% CI -0.01 to 0.91, p=0.054). No differences were observed in sex distribution (OR=0.94, 95% CI 0.51-1.72, p=0.83) and clinical form (OR=1.03, 95% CI 0.33-3.21, p=0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR=7.06, 95% CI 2.39-20.8; p<0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR=2.6, 95% CI 1.0-6.5; p=0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures.

A lesion topography-based approach to predict the outcomes of patients with multiple sclerosis treated with Interferon Beta

BackgroundWith increasing availability of effective disease-modifying treatments for multiple sclerosis (MS), an early identification of patients who do not adequately respond to Interferon Beta (IFNB) is relevant to decide the future strategy. ObjectiveTo investigate the predictive role of new lesion location on the risk of breakthrough disease in IFNB-treated patients with MS. MethodsWe analysed data from 392 patients starting IFNB and regularly followed up to 5 years. Before and after one year of IFNB treatment, all patients underwent a conventional brain and spinal cord magnetic resonancer imaging (MRI) scan with the same 1.5T magnet to obtain the count and location of new MRI lesions. Relapses and MRI activity occurred in the first year of IFNB treatment (year 0–1) were included in the set of potential predictors for relapses and disability worsening in the subsequent four years (year 2–5). ResultsWe found that 96 (24.5%) patients had relapses and/or MRI activity in the first year of IFNB treatment, while 41.6% of the patients experienced relapses and 17.8% experienced disability worsening. from year 2 to 5. The risk of relapses (year 2–5) was associated with ≥2 relapses (HR=5.65, p<0.001) and new T2-hyperintense lesions (for 2 new lesions: HR=1.96, p=0.011; for ≥3 new lesions: HR=3.55, p<0.001) in the first year of treatment. Other than male sex (HR=2.01, p=0.01) and higher EDSS score (HR=2.17, p<0.001), the risk of disability worsening (year 2–5) was associated with ≥2 relapses (HR=4.33, p<0.001) and new spinal cord or infratentorial lesions (HR=4.45,p<0.001) in the first year of treatment. ConclusionsOur findings suggest a dose-effect relationship between the lesion count and the risk of future relapses, while the occurrence of new MRI lesions in sites representing anatomical bottle-necks was better than lesion count at predicting the future risk of disability worsening despite IFNB treatment.

Absence of MxA induction is related to a poor clinical response to interferon beta treatment in multiple sclerosis patients.

The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-β administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-β treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or -non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-β in naïve MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-β treatment are more likely to be non-responders to this therapy.

Prevalence and incidence of cognitive impairment in multiple sclerosis: a population-based survey in Catania, Sicily.

Cognitive impairment (CIm) is a frequent finding in multiple sclerosis (MS) affecting up to 65% of patients. The aim of this study was to evaluate the prevalence and incidence of CIm in a population-based cohort of MS patients identified in the city of Catania from 1995 to 2004. One-hundred and twenty-five patients experiencing the onset of MS during 1995-2004 were enrolled. Cognitive performance was assessed through the Brief Repeatable Battery (BRB) of neuropsychological tests and the Stroop word-color task (ST). CIm was defined as the failure on at least three tests involving at least two different domains. Patients without CIm at baseline were followed up after over 3 years. The most impaired tests were the Symbol Digit Modalities Test (36%) and the Paced Auditory Serial Addition Test 3 (35%). At baseline the prevalence of CIm was 44% (95% CI 35.2-53.1). An almost sixfold increased risk of developing CIm was found among MS patients aged 40 and above at the time of the NPS examination (OR 5.84; 95% CI 2.57-13.2; p value <0.0001) and a threefold increased risk for patients with an EDSS score >3 (OR 3.51; 95% CI 1.30-9.46, p value 0.01). At the follow-up out of the 70 MS patients without CIm at baseline evaluation, 26 (37.1 %) developed CIm. The total person-years at risk was 269 person-years giving an incidence rate of CIm of 96.6/1,000 person-year (95% CI 57.3-128.7). The overall prevalence of CIm in MS is 44% and the incidence after 4 years is 37.1%. CIm affects more frequently patients older than 40 years and with a higher EDSS score.

81. Motor evoked potential as a predictor of clinical response in multiple sclerosis patients treated with 4 aminopyridine

4-Aminopyridine (4-AP) has been recently introduced as a symptomatic treatment of walking impairment in MS patients. The clinical benefits have been reported in about 1/3 of patients. The study was intended to verify in patients treated with 4-AP: – the ability of motor-evoked potentials (MEPs) in identifying patients responding to treatment; – if there are MEP parameters changes related to clinical improvement. Patients were enrolled in a prospective study. Patients underwent neurological examination, in order to determine: EDSS, T25WF (a walking test, measuring speed). MEPs have been recorded at lower limb, central motor conduction time (CMTT) and CMAP/MEPs ratio have been evaluated before starting and after 30 days of 4-AP treatment. We enrolled 14 patients. Patients with high EDSS score (>4) and bilateral CMTT alteration were most likely responding to therapy. MEP parameters changes observed in some patients were not related to clinical effect measured with T25WF. The response to 4-AP occurs only in 35% of MS patients. Given the drug’s side effects and its high cost, it would be useful to have predictor of response to treatment. Joining together EDSS score and CMTT value we could identify a great number of patients responding to therapy (nearly 85%).

SPINAL CORD GLUTAMATE-GLUTAMINE IS ELEVATED IN MS RELAPSE

<h3>Background</h3> 1.5Tesla 1H-magnetic resonance spectroscopy (MRS) demonstrates reduced spinal cord (SC) N-acetyl-aspartate (NAA) following SC relapses in MS but it remains unknown whether glutamate-glutamine (Glx) metabolism is also affected, as in the brain. Using 3Tesla MRS, we quantified Glx following SC relapse and assessed the clinical relevance of metabolite changes. <h3>Methods</h3> SC metabolites were quantified in 20 RRMS patients (14F; mean age 41 yrs.) within 4 weeks of cervical SC relapse and 22 controls (17F; mean age 44 yrs.) using a cardiac-gated PRESS sequence; TE=30 ms; MOIST water suppression on a 3T Philips scanner. MSFC and EDSS scores were obtained for patients. <h3>Results</h3> SC NAA was reduced (p=0.023) and Glx was elevated (p=0.036) compared to controls. In patients, higher EDSS scores were independently predicted by higher creatine (p=0.032) and choline (p=0.041) and longer timed walk was independently predicted by higher creatine (p=0.002), myoinositol (p=0.025) and choline (p=0.044). <h3>Conclusions</h3> Higher choline, creatine and myoinositol are associated with disability and may reflect important pathological processes. Elevated Glx wasn9t predictive of disability but may cause excitotoxicity and hinder recovery; longitudinal study is therefore needed.

Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis

ObjectiveThe purpose of this study was to assess the safety and efficacy of mitoxantrone (MX) in pediatric patients with aggressive multiple sclerosis (MS). MethodsA retrospective analysis on pediatric MS patients treated with MX was performed with regards to demographic/clinical parameters and magnetic resonance imaging (MRI) findings. Results19 definite pediatric MS cases with mean ± SD age of 15.4 ± 2.8 years underwent 20 mg MX for control of their severe/frequent relapses, high EDSS score or new and active brain MRI lesions. After a median [IQR] follow-up period of 30[12–60] months, 14 cases (73%) were relapse free; the EDSS score decreased by at least 0.5 in 16 cases (84.2%); and gadolinium-enhancing lesion volume fell by 84.2% in 16 cases. Adverse events included nausea and vomiting, fatigue, alopecia, palpitation, cardiomyopathy and mild leukopenia. All adverse events were mild and transient. ConclusionOur results suggest MX is a good candidate for treatment of children with worsening RRMS and SPMS. Recommendations regarding patient selection, treatment administration, and close follow-up should be considered. Continuing research is needed to establish its efficacy and safety profile in a multinational collaboration with careful follow-up of adverse events.

Central nervous system inflammatory demyelinating disorders among Hong Kong Chinese

Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2–5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.