Electronic Neurostatus-EDSS increases the quality of expanded disability status scale assessments: Experience from two phase 3 clinical trials.

BACKGROUND: The Neurostatus-eEDSS is an electronic tool providing automated real-time feedback on inconsistencies of Neurostatus-EDSS calculations. OBJECTIVE: To analyze the performance of the Neurostatus-eEDSS in two multicenter phase 3 multiple sclerosis (MS) trials. METHODS: All assessments captured with the Neurostatus-eEDSS web service during a period of 2.5 years were analyzed. RESULTS: Of the total 10,789 assessments, 40.1% had inconsistencies after first entry, reduced to 22.1% due to the real-time feedback. The entire checking process resulted in a change of the expanded disability status scale (EDSS) score in 14.8% of the assessments. CONCLUSION: The Neurostatus-eEDSS can increase consistency and reliability of EDSS assessments in clinical MS trials.

Tasks of activities of daily living (ADL) are more valuable than the classical neurological examination to assess upper extremity function and mobility in multiple sclerosis.

BACKGROUND: Accurate clinical assessment in multiple sclerosis (MS) is challenging. The Assess MS system is being developed to automatically quantify motor dysfunction in MS, including upper extremity function (UEF) and mobility. OBJECTIVE: To determine to what extent combinations of standardized movements included in the Assess MS system explain accepted measures of UEF and mobility. METHODS: MS patients were recruited at four European MS centres. Eight movements were selected, including tasks of activities of daily living (ADL) and classical neurological tests. Movements were recorded on video and rated by experienced neurologists (n = 5). Subsequently, multivariate linear regression models were performed to explain the variance of the Nine-Hole Peg Test (9HPT), Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and Timed-25 Foot Walk test (T25WT). RESULTS: In total, 257 patients were included. The movements explained 62.9% to 80.1% of the variance of the 9HPT models, 43.3% and 44.3% of the AMSQ models and 70.8% of the T25WT. In all models, tasks of ADL contributed most to the variance. CONCLUSION: Combinations of movements are valuable to assess UEF and mobility. Incorporating ADL tasks into daily clinical practice and clinical trials may be more valuable than the classical neurological examination of UEF and mobility.

Effects of cenobamate on cognitive performance of epilepsy patients.

PURPOSE: Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. METHOD: Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. RESULTS: The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. CONCLUSION: Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

A subgaleal electrode array for neurostimulation allows the recording of relevant information in closed loop applications.

BACKGROUND: Neurostimulation is an emerging treatment option for patients resistant to pharmacotherapy and ineligible for neurosurgical intervention. Compared to intracranial stimulation placement of electrodes in the subgaleal space offers a minimally invasive option for long-term seizure monitoring for responsive systems. NEW METHOD: It was investigated, whether electrode contacts of a device being developed as a stimulation system placed in the subgaleal space are suited for recording of EEG activity for seizure detection. EEG was recorded intraoperatively in four participants participating in a clinical trial during the insertion of the device. Quantitative parameters like electrode impedance, signal amplitude ranges and amplitude spectra were determined. Epileptiform patterns in the recordings were compared to patterns occurring in scalp EEG prior to device implantation. RESULTS: Electrode impedances, amplitude ranges for artefact free intervals and intervals containing artefacts were determined. Spectral analysis showed typical properties of EEG recordings with high amplitude content at low frequencies and a peak in the alpha band. No major noise except at power line frequency disturbed the recordings. In two patients, typical epileptiform patterns could be identified having similar characteristics as their respective scalp EEG recordings prior to device implantation. COMPARISON WITH EXISTING METHODS: New and less invasive electrode system compared to existing solutions for responsive neurostimulation. CONCLUSIONS: The subgaleal electrode system allows for high quality EEG recordings even in an hostile unfavorable environment like an operation theatre. For the design of a signal acquisition unit of a responsive system using subgaleal electrodes, specifications could be obtained.

PIMIDES I: a pilot study to assess the feasibility of patient-controlled neurostimulation with the EASEE® system to treat medically refractory focal epilepsy.

The study design of PIMIDES, a trial based on patient-individualized transcranial electric neurostimulation of epileptic foci, is reported. Inclusion criteria include a predominant epileptic focus and pharmacoresistance to two antiepileptic drug treatments. The study is prospective, unblinded, and serves to assess the safety of subgaleal implantation and transcranial stimulation.

Reference videos reduce variability of motor dysfunction assessments in multiple sclerosis.

Motor dysfunction, particularly ataxia, is one of the predominant clinical manifestations in patients with multiple sclerosis (MS). Assessment of motor dysfunction suffers from a high variability. We investigated whether the clinical rating of ataxia can be improved through the use of reference videos, covering the spectrum of severity degrees as defined in the Neurostatus-Expanded Disability Status Scale. Twenty-five neurologists participated. The variability of their assessments was significantly lower when reference videos were used (SD = 0.12; range = 0.40 vs SD = 0.26; range = 0.88 without reference videos; p = 0.013). Reference videos reduced the variability of clinical assessments and may be useful tools to improve the precision and consistency in the clinical assessment of motor functions in MS.