Functional System Score Research Articles

Contribution of different relapse phenotypes to disability in multiple sclerosis

Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. Results: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (β = 0.27 (0.25–0.29)), cerebellar (β = 0.35 (0.30–0.39)) and bowel/bladder (β = 0.42 (0.35–0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains. Conclusion: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.

Neurostatus e-Scoring improves consistency of Expanded Disability Status Scale assessments: A proof of concept study

Background: To improve the consistency of standardized Expanded Disability Status Scale (EDSS) assessments, an electronic data capture tool and analysis tool was developed, Neurostatus e-Scoring (NESC). This tool allows real-time feedback by comparing entries with established scoring rules. Objective: To test whether using NESC reduces inconsistencies as compared to the paper-and-pencil version of the Expanded Disability Status Scale (pEDSS). Methods: In all, 100 multiple sclerosis (MS) patients were assessed in random order on the same day by pairs of neurologists, one using pEDSS and one NESC. We compared inter-rater reliability and frequency of inconsistencies in Neurostatus subscores, functional system (FS) scores, ambulation and EDSS steps. Results: Inconsistencies of any type were more likely to occur when using pEDSS (mean odds ratio (95% confidence interval (CI)) = 2.93 (1.62; 5.29)). This was also the case for FS score inconsistencies (2.54 (1.40; 4.61)) and more likely for patients in the lower EDSS range (⩽3.5 vs >3.5) (5.32 (1.19; 23.77)). Overall, inter-rater agreement for the assessed Neurostatus subscores was high (median and inter-quartile range = 0.84 (0.73, 0.81)). Conclusion: Our data provide class II evidence that the use of NESC increases consistency of standardized EDSS assessments, and may thus have the potential to decrease noise and increase power of MS clinical trials.

Validity of visual perceptive computing for static posturography in patients with multiple sclerosis

Background: Multiple sclerosis (MS) patients frequently have postural control impairment but quantitative posturography is difficult to perform in clinical care. Recent technology facilitates new posturography approaches. Objective: To evaluate construct validity of visual perceptive computing (VPC) for static posturography to study postural control in MS patients. Methods: A total of 90 MS patients and 59 healthy controls (HCs) performed three stance tests: open, closed and tandem stance. Static posturography was performed using a VPC system with Microsoft Kinect. Clinical assessments included Expanded Disability Status Scale (EDSS), Timed-25-Foot-Walk, Short-Maximum-Speed-Walk and 12-item MS Walking Scale (MSWS-12) questionnaire. Reliability was assessed with intra-class correlation coefficients at retest. Results: As a group, MS patients performed worse than HCs in all tests. The closed stance test showed best applicability and reliability. With closed eyes, in 36.7% of patients, the three-dimensional mean angular sway velocity (MSV-3D) was above HCs’ 95th percentile. Higher MSV-3D was associated with decreased walking speed (p < 0.001); worse clinical scores, mainly attributable to the cerebellar functional system score (p < 0.001); and reflected in self-reported walking disability (MSWS-12, p < 0.001). Conclusion: Postural control can be reliably assessed by VPC-based static posturography in patients with MS. Abnormal postural control seems to predominantly reflect involvement of cerebellar circuits with impact on gait and walking disability.

Alemtuzumab improves neurological functional systems in treatment-naive relapsing-remitting multiple sclerosis patients

BackgroundIndividual functional system scores (FSS) of the Expanded Disability Status Scale (EDSS) play a central role in determining the overall EDSS score in patients with early-stage multiple sclerosis (MS). Alemtuzumab treatment improves preexisting disability for many patients; however, it is unknown whether improvement is specific to certain functional systems. ObjectiveWe assessed the effect of alemtuzumab on individual FSS of the EDSS. MethodsCAMMS223 was a 36-month, rater-blinded, phase 2 trial; treatment-naive patients with active relapsing-remitting MS, EDSS ≤3, and symptom onset within 3years were randomized to annual courses of alemtuzumab or subcutaneous interferon beta-1a (SC IFNB-1a) 44μg three times weekly. ResultsAlemtuzumab-treated patients had improved outcomes versus SC IFNB-1a patients on most FSS at Month 36; the greatest effect occurred for sensory, pyramidal, and cerebellar FSS. Among patients who experienced 6-month sustained accumulation of disability, clinical worsening occurred most frequently in the brainstem and sensory systems. For patients with 6-month sustained reduction in preexisting disability, pyramidal and sensory systems contributed most frequently to clinical improvement. ConclusionsAlemtuzumab demonstrated a broad treatment effect in improving preexisting disability. These findings may influence treatment decisions in patients with early, active relapsing-remitting MS displaying neurological deficits. ClinicalTrials.gov Identifier NCT00050778.

The role and place of high-dose immunosuppressive therapy and autologous transplantation of hematopoietic stem cells for autoimmune diseases

To determine the possible boundaries of high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HDIT-autoHSCT) for autoimmune diseases (AUDs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). A long-term trial was conducted at one center to evaluate the efficiency and safety of HDIT-autoHSCT in patients with AUDs. The previous standard therapy was noted to be resistant or lowly effective. The age of 10 patients with systemic connective tissue diseases was 27.6±2.8 years; the pre-HDIT-autoHSCT disease duration was 5.9±1.3 years; the median posttransplantation follow-up was 39.3 months. The age of 49 patients with MS reached 34.9±1.33 years; the pretransplantation disease duration was 8.4±0.69 years; the median post-HDIT-autoHSCT follow-up was 42 months. The efficiency of transplantation was evaluated on the basis of clinical findings, by using scales, laboratory tests, and magnetic resonance imaging. Pretransplantation conditioning was carried out according to the protocols: a) BEAM + antilymphocyte globulin (ALG); b) fludarabine + melphalan + ALG. No fatal outcomes due to a transplant procedure were observed. Overall 5-year survival after transplantation was 80% for systemic connective tissue diseases and 95% for MS; 5-year progression-free survival rates were 30% in the RA and SLE groups and 45% in the MS group. HDIT-autoHSCT turned out safe and reduced the activity of the process and further disease progression for a long period of time, as confirmed by regression of clinical symptoms and/or status stabilization in 9 patients with SLE or RA and in all patients with MS. The favorable factors associated with the results of transplantation are age younger than 35 years in collagenoses with their short-term duration and moderate signs; age younger than 40 years in MS with a disease duration of less than 10 years and expanded disability status scale scores of not more than 6.5. Of importance are functional system scores, duration of first remission, and an index of disease progression in different types of MS.

Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis.

The motor cortex (MC) receives an excitatory input from the cerebellum which is reduced in patients with cerebellar lesions. High-frequency repetitive transcranial magnetic stimulation (rTMS) induces cortical facilitation which can counteract the reduced cerebellar drive to the MC. Our study included 24 relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients with dysmetria. The patients were divided into two groups: Group A received two sessions of real MC rTMS and Group B received one session of real rTMS and one session of sham rTMS. Ten healthy volunteers formed group C. Evaluation was carried out using the nine-hole pegboard task and the cerebellar functional system score (FSS) of the expanded disability status scale (EDSS). Group A patients showed a significant improvement in the time required to finish the pegboard task (P=0.002) and in their cerebellar FSS (P=0.000) directly after the second session and 1month later. The RRMS patients showed more improvement than the SPMS patients. Group B patients did not show any improvement in the pegboard task or the cerebellar FSS. These results indicate that MC rTMS can be a promising option in treating both RRMS or SPMS patients with cerebellar impairment and that its effect can be long-lasting.

Neuromyelitis optica shorter lesion can cause important pyramidal deficits

ObjectiveEvaluate the correlation between spinal cord lesion length and pyramidal function system score in a cohort of patients with NMO. MethodologyRetrospective retrieval of all exams performed in our center from January 2004 to December 2012 for patients with NMO. The exams were evaluated for lesion length, contrast enhancement and T1 hypointensity; these variables were correlated with the functional system score from the EDSS, performed no more than three months from the scan. Results41 patients were included. Although patients with lesion extension ≥2 vertebral segments did not present worse pyramidal scores in a direct comparison, the influence of lesion length was not so strong when patients were separated in 3 groups (≥2, ≥3 or ≥4 vertebral segments) and evaluated with a receiving operating characteristics (ROC) curves. Gadolinium enhancement also contributed to more severe pyramidal system scores, but T1 hypointensity did not. ConclusionAlthough patients with spinal cord lesion extending ≥3 vertebral segments had more pyramidal disability, its difference was not so strong when compared to patients with ≥2 or ≥4 vertebral segments. This suggests that lesion extension might not be the most important factor in favoring a worse prognosis in spinal cord lesions in NMO.

Relationship between Sustained Disability Progression and Functional System Scores in Relapsing-Remitting Multiple Sclerosis: Analysis of Placebo Data from Four Randomized Clinical Trials

Background: The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains. Methods: A post hoc analysis was performed on data from placebo-treated RRMS patients from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed. Results: The majority of patients experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains. Conclusion: The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression.

Rehabilitation outcomes in children with cerebral palsy during a 2 year period.

[Purpose] To observe motor and functional progress of children with cerebral palsy during 2 years. [Subjects and Methods] Pediatric cerebral palsy patients aged 3–15 years (n = 35/69) with 24-month follow-up at our outpatient cerebral palsy clinic were evaluated retrospectively. The distribution of cerebral palsy types was as follows: diplegia (n = 19), hemiplegia (n = 4), and quadriplegia (n = 12). Participants were divided into 3 groups according to their Gross Motor Functional Classification System scores (i.e., mild, moderate, and severe). All participants were evaluated initially and at the final assessment 2 years later. During this time, patients were treated 3 times/week. Changes in motor and functional abilities were assessed based on Gross Motor Function Measure-88 and Wee Functional Independence Measure. [Results] Significant improvements were observed in Gross Motor Function Measure-88 and Wee Functional Independence Measure results in all 35 patients at the end of 2 years. The Gross Motor Function Measure-88 scores correlated with Wee Functional Independence Measure Scores. Marked increases in motor and functional capabilities in mild and moderate cerebral palsy patients were observed in the subgroup assessments, but not in those with severe cerebral palsy. [Conclusion] Rehabilitation may greatly help mild and moderate cerebral palsy patients achieve their full potential.

Restless legs syndrome in multiple sclerosis.

There have been conflicting results in the literature regarding the relationship between functional system involvement, the expanded disability status scale (EDSS), and the presence of restless legs syndrome (RLS) in patients with multiple sclerosis (MS). Ninety-one patients with MS and 40 patients in a control group (headache, essential tremor, and benign positional paroxysmal vertigo) were studied. The patients underwent a complete neurological examination and Kurtzke functional system scores were calculated. In order to assess the temporal relation between the onset of RLS and MS, a semistructured interview guided by a questionnaire about RLS was applied to all of the patients. Sixteen (17.6%) of the patients with MS and 1 (2.5%) patient in the control group had RLS. The prevalence of RLS was higher in patients with MS, compared to the control group (P = 0.018). Among the patients with MS, none of them suffered from RLS before the onset of MS, whereas sixteen patients (16%) suffered RLS after the onset of MS. There was no significant relationship between functional system involvement and the presence of RLS. The prevalence of RLS was higher in MS patients than it was in the control group. No association was found between RLS and functional system involvement in MS patients.

Predictors of institutionalization for people with multiple sclerosis

BackgroundMultiple Sclerosis (MS) is a chronic, progressive disease of the central nervous system with a high prevalence in Canada. While the disease course is highly variable, a significant portion of people with MS may spend more than 10 years living with severe disability, and many of those will eventually require full time institutional care. Despite the high personal and economic cost of this care, little is known about predictors of institutionalization. ObjectiveThe objective of this study was to identify predictors of institutionalization. MethodsLongitudinal data from a university MS clinic database were extracted to explore nursing home placement over time of an urban subgroup. Cox regression analysis was performed with age of MS onset and sex, as well as baseline information obtained at the first MS clinic assessment: MS course, Kurtzke Expanded Disability Status Scale score, and functional system scores. ResultsOlder age of onset (p = .019) and higher baseline scores in specific functional systems (cerebellar, bowel/bladder, brainstem, and cerebral/mental) were significant (p = .000, p = .000, p = .001, p = .000 respectively) predictors of nursing home placement. ConclusionsPatients with older age of MS onset and those with baseline impairment in specific functional systems (cerebellar, bowel/bladder, brainstem, and cerebral/mental) may be at higher risk for future institutionalization and should be assessed with particular care to determine potential avenues of support to minimize this.

P059 - Clinical and radiologic correlates of quality of life measures in patients with relapse-onset multiple sclersosis

Objectives Several studies have reported reduced quality of life (QOL) scores in patients with multiple sclerosis (MS) even in absence of physical disability. Thus QOL measures could be served as an adjunct endpoints for clinical trials. In this study we assessed the relationship between QOL scores and brain structures' volume and magnetization transfer ratio (MTR) in patients with MS. Design and methods One hundred and twenty two patients with relapse-onset MS were recruited in the study. They underwent clinical examination and structural magnetic resonance imaging (MRI). QOL was evaluated using SF-36 questionnaire. Brain structure segmentation on lesion-filled T1-weighted images was performed using a multi-atlas algorithm, MAGeT Brain. Correlation between SF-36 physical and mental scores and expanded disability status scale (EDSS), brain structures' volumes (adjusted to intracranial volume) and MTR were assessed using general linear model (GLM) with age and gender as covariate. Results SF-36 physical score (PCS) was negatively correlated with EDSS (P>0.001), cerebellar (P=0.020) and pyramidal (P=0.001) Kurtzke functional system scores and multiple sclerosis functional composite (MSFC) score (P=0.006). Physical and mental Scores of SF-36 showed no significant correlation with total brain volume, volume of right and left thalamus, hippocampus, right and left hemispheres of cerebellum, corpus medullare of cerebellum and lesion load. The correlation between physical and mental subscores of SF-36 and MTR of corona radiate, internal capsule and corpus callosum were also non-significant. Conclusion Clinical measures predicted physical components of QOL. Neither clinical nor radiological measures of MS severity contribute significantly to mental QOL. Several studies have reported reduced quality of life (QOL) scores in patients with multiple sclerosis (MS) even in absence of physical disability. Thus QOL measures could be served as an adjunct endpoints for clinical trials. In this study we assessed the relationship between QOL scores and brain structures' volume and magnetization transfer ratio (MTR) in patients with MS. One hundred and twenty two patients with relapse-onset MS were recruited in the study. They underwent clinical examination and structural magnetic resonance imaging (MRI). QOL was evaluated using SF-36 questionnaire. Brain structure segmentation on lesion-filled T1-weighted images was performed using a multi-atlas algorithm, MAGeT Brain. Correlation between SF-36 physical and mental scores and expanded disability status scale (EDSS), brain structures' volumes (adjusted to intracranial volume) and MTR were assessed using general linear model (GLM) with age and gender as covariate. SF-36 physical score (PCS) was negatively correlated with EDSS (P>0.001), cerebellar (P=0.020) and pyramidal (P=0.001) Kurtzke functional system scores and multiple sclerosis functional composite (MSFC) score (P=0.006). Physical and mental Scores of SF-36 showed no significant correlation with total brain volume, volume of right and left thalamus, hippocampus, right and left hemispheres of cerebellum, corpus medullare of cerebellum and lesion load. The correlation between physical and mental subscores of SF-36 and MTR of corona radiate, internal capsule and corpus callosum were also non-significant. Clinical measures predicted physical components of QOL. Neither clinical nor radiological measures of MS severity contribute significantly to mental QOL.

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I–V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.

A 3 meter Timed Tandem Walk is an early marker of motor and cerebellar impairment in fully ambulatory MS patients

BackgroundMobility assessment in Multiple Sclerosis (MS) is crucial for trials and individual patient counseling. Up to now, standard tests as the Timed 25-Foot Walk (T25FW) are restricted by floor effects in mildly disabled patients. The 3-meter Timed Tandem Walk (TTW) as a possibly more sensitive measure has not been investigated yet. ObjectiveTo investigate sensitivity and specificity of the TTW and T25FW to detect mild clinical impairment in a large cohort of MS patients. MethodsWe extracted T25FW, TTW and EDSS from our UMC patient database (2009–2012). After randomization into an explorative (n=497) and validation (n=228) cohort, we calculated change rates and performed ROC analyses of gait tests and EDSS including Functional System Scores. ResultsBetween disability stages of EDSS 0–2.5 and EDSS 3.0–4.0, the mean TTW difference was 4s (T25FW=0.9s). The accuracy to separate between EDSS groups was moderate but identical for both tests (ROC–AUC T25FW=0.79, TTW=0.80, p=0.4). TTW had a higher sensitivity and specificity to differentiate between asymptomatic and symptomatic patients concerning FS motor/cerebellar scores (ROC–AUC T25FW=0.71, TTW=0.75, p<0.05). All hypotheses could be validated in the second cohort. ConclusionA 3-m Timed Tandem Walk is a standardized test that is easy to implement to detect impairment of the motor or cerebellar system in fully ambulatory MS patients. Based on the complex-task character, TTW is a potential new outcome measure for MS mobility in mildly disabled patients and can act as easily accessible and significant additional information in patient counseling.

Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study

Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing–remitting multiple sclerosis. This post hoc analysis of the Phase III TOWER study evaluated the effects of teriflunomide treatment on five severe relapse outcomes: relapses with sequelae defined by an increase in Expanded Disability Status Scale (EDSS)/functional system (FS) score (sequelae-EDSS/FS) 30 days post relapse; relapses with sequelae defined by the investigator (sequelae-investigator); relapses leading to hospitalization; relapses treated with intravenous corticosteroids; and intense relapses using the definition of Panitch et al. from the EVIDENCE study based on specified increases in EDSS for severe relapses. Adjusted annualized rates for the five severe relapse outcomes were derived using a Poisson model with robust error variance, with treatment, baseline EDSS strata and region as covariates. Compared with placebo, teriflunomide significantly reduced annualized rates of relapses with sequelae-EDSS/FS [14 mg, 36.6 % (p = 0.0021); 7 mg, 31.3 % (p = 0.0104)] and sequelae-investigator [14 mg only, 53.5 % (p = 0.0004)], relapses leading to hospitalization [14 mg only, 33.6 % (p = 0.0155)], relapses requiring intravenous corticosteroids [14 mg, 35.7 % (p = 0.0002); 7 mg, 21.5 % (p = 0.0337)], and intense relapses [14 mg only, 52.5 % (p = 0.0015)]. Patients treated with teriflunomide 14 mg spent significantly fewer nights in hospital for relapse (p = 0.009) and had lower annualized rates of all hospitalizations (p = 0.030). Taken together, the positive effects of teriflunomide on severe relapses indicate that teriflunomide may reduce relapse-related healthcare costs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-014-7395-7) contains supplementary material, which is available to authorized users.

Diffusion tensor imaging for characterizing white matter changes in multiple sclerosis

PurposeTo investigate the diagnostic values of quantitative diffusion tensor imaging parameters in detecting abnormalities in white matter of MS patients and correlate this with lesion load and clinical disability as prognostic factors. Patients and methodsDiffusion tensor imaging (DTI) was performed in 45 consecutive MS patients and 20 age-matched healthy control volunteers from March 2011 to November 2013. Mean diffusivity (MD), volume ratio (VR) and the fractional anisotropy (FA) were measured in normal appearing white matter (NAWM) and in different types of focal MS lesions during both activity and remission and compared with normal white matter (NWM) of the control group. Evaluation of lesion load was done by the semiautomated method. Clinical assessment of MS was established using the Kurtzke expanded disability status scale (EDSS) and the Kurtzke functional system score. ResultsSignificant increase of MD and decrease of FA and VR from normal appearing white matter of the patients to MRI detected active lesions and the least is inactive plaques comparing with NWM of the control group (P value 0.003 for MD, 0.013 for FA, and 0.014 for VR). Correlation and significant difference between {(increase in MD) and (decrease in FA and VR)} and lesion load (strongest in parietal lobes) and also Kurtzke expanded disability status scale (EDSS) and Kurtzke functional system score (KFS-p). ConclusionDTI–MRI quantitative parameters are good predictors of tissue damage not only in MRI-defined lesions but also in NAWM as a result of Wallerian degeneration and are helpful as diagnostic and prognostic tools.

The clinical impact of cerebellar grey matter pathology in multiple sclerosis.

BackgroundThe cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood.ObjectiveTo evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients.MethodsForty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS) and cerebellar functional system (FS) score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol-Digit Modalities Test (SDMT). Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes.ResultsAfter multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001), cerebellar FS (p = 0.002), arm function (p = 0.049), and for leg function (p<0.001). Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013), while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015).ConclusionsCerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

Evaluation of Brainstem Involvement in Multiple Sclerosis

the aim of the present study was to determine the optimum method to detect brainstem lesions in patients with Multiple Sclerosis (MS). 72 patients with the diagnosis of relapsing-remitting MS were prospectively included. brainstem functional system score (bSfS) (part of the expanded disability status scale (edSS) evaluating brainstem symptomatology) was calculated. Magnetic resonance imaging (Mri) was performed on 1.5t and t1, t2, pd and fluid-attenuated inversion recovery (flair) sequences were analyzed for presence of brainstem lesions. auditory evoked potentials (aep) and ocular and cervical vestibular evoked myogenic potentials (oVeMp and cVeMp) were performed according to the standardized protocol. from 72 patients, 18 (25%) had clinical involvement of the brainstem. Mri showed brainstem involvement in 29 (40%) patients. of the neurophysiological tests, aep showed pathological result in 16 (22%) patients, oVeMp in 36 (50%) patients, cVeMp in 18 (25%) patients, and VeMp (combination of oVeMp and cVeMp) in 45 (63%) patients. VeMp detected brainstem lesions in higher percentage than clinical examination, Mri and aep, which was statistically significant (< 0.0001, 0.012 and < 0.0001, respectively). results of the present study have shown that VeMps are the optimal method to detect brainstem lesions in multiple sclerosis and that they detect them significantly better than clinical examination, aep or Mri.

Relationship between Damage to the Cerebellar Peduncles and Clinical Disability in Multiple Sclerosis

To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P = .05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P = .03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P = .04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS.

Vestibular-evoked myogenic potentials, clinical evaluation, and imaging findings in multiple sclerosis

Vestibular-evoked myogenic potentials (VEMP), short-latency electromyographic responses elicited by acoustic stimuli, evaluate the function of vestibulocollic reflex and may give information about brainstem function. The aim of the present study is to evaluate the potential contribution of VEMP to the diagnosis of multiple sclerosis (MS). Fifty patients with MS and 30 healthy control subjects were included in this study. The frequency of VEMP p1-n1 and n2-p2 waves; mean p1, n1, n2, and p2 latency; and mean p1-n1 and n2-p2 amplitude were determined. The relation between clinical and imaging findings and VEMP parameters was evaluated. The p1-n1 and n2-p2 waves were more frequently absent in MS than in control subjects [p1-n1 wave absent: MS, 25 (25 %) ears; control, 6 (10 %) ears; P ≤ 0.02] [n2-p2 wave absent: MS, 44 (44 %) ears; control, 7 (12 %) ears; P ≤ 0.001]. The mean p1-n1 amplitude was lower in MS than in control subjects (MS, 19.1 ± 7.2 μV; control, 23.3 ± 7.4 μV; P ≤ 0.002). A total of 24/50 (48 %) MS patients had VEMP abnormalities (absent responses and/or prolonged latencies). VEMP abnormalities were more frequent in patients with than without vestibular symptoms (P ≤ 0.02) and with brainstem functional system score (FSS) ≥ 1 than FSS = 0 (P ≤ 0.02). In patients with MS, absence of p1-n1 wave was more frequent in patients with than without vestibular symptoms [absence of p1-n1 wave: vestibular symptoms, 9 (45 %) ears; no vestibular symptoms, 16 (20 %) ears; P ≤ 0.03] and patients with Expanded Disability Status Scale (EDSS) score ≥ 5.5 [absence of p1-n1 wave: EDSS ≥ 5.5, 7 (70 %) ears; EDSS <5.5, 18 (20 %) ears; P ≤ 0.001]. Abnormal VEMP may be noted in MS patients, especially those with vestibular symptoms and greater disability. The VEMP test may complement other studies for diagnosis and follow-up of patients with MS.