An Immersive Virtual Kitchen Training System for People with Multiple Sclerosis: A Development and Validation Study

Rehabilitation via virtual reality (VR) training tools allows repetitive, intensive, and task-specific practice in a controlled and safe environment. Our goal was to develop and validate a novel immersive VR system based on the practice of real-life activities in a kitchen environment in people with multiple sclerosis (pwMS) with upper-limb dysfunction. The novel immersive VR kitchen application includes several tasks, i.e., tidying up the kitchen, preparing a hamburger and soup meal, and dish washing. Following the development phase, the system was tested for an 8-week intervention period on a small sample of pwMS suffering from upper-limb dysfunction. The Suitability Evaluation Questionnaire for VR systems served as the primary outcome. The scores for enjoyment, sense of comfort with the system, feelings of success and control, realism, easy-to-understand instructions, assists in rehabilitation therapy, were between 4.0 and 4.6, indicating a high satisfaction. The scores for eye discomfort, dizziness, nausea, and disorientation during practice were between 2.8 and 1.3, indicating a low-to-moderate interference of the system. The virtual kitchen training system is feasible and safe for upper-limb training in pwMS and paves the way for future RCTs to examine the benefits of the system compared with standard care, thus improving the functionality of the upper limbs in pwMS

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

Cognitive function in multiple sclerosis: A long-term look on the bright side.

BackgroundMultiple sclerosis (MS) may lead to cognitive decline over-time.ObjectivesCharacterize cognitive performance in MS patients with long disease duration treated with disease modifying drugs (DMD) in relation to disability and determine the prevalence of cognitive resilience.MethodsCognitive and functional outcomes were assessed in 1010 DMD-treated MS patients at least 10 years from onset. Cognitive performance was categorized as high, moderate or low, and neurological disability was classified according to the Expanded Disability Status Scale (EDSS) as mild, moderate or severe. Relationship between cognitive performance and disability was examined.ResultsAfter a mean disease duration of 19.6 (SD = 7.7) years, low cognitive performance was observed in 23.7% (N = 239), moderate performance in 42.7% (N = 431), and 33.7% (N = 340) had high cognitive performance, meeting the definition of cognitively resilient patients. Within the group of patients with low cognitive performance, severe disability was observed in 50.6% (121/239), while in the group of patients with high cognitive performance, mild disability was observed in 64.4% (219/340). Differences between the group of patients with high cognitive performance and severe disability (4.5%) and the group of patients with low cognitive performance and mild disability (5.0%) were not accounted for by DMD treatment duration.ConclusionsThe majority of DMD treated MS patients did not have cognitive decline that could impair their quality of life after disease of extended duration

sj-docx-1-jad-10.1177_10870547241232710 – Supplemental material for Attention Deficit/Hyperactivity Disorder in Children with Multiple Sclerosis

Supplemental material, sj-docx-1-jad-10.1177_10870547241232710 for Attention Deficit/Hyperactivity Disorder in Children with Multiple Sclerosis by Roy Aloni, Alon Kalron, Assaf Goodman, Amichai Ben-Ari, Talya Yoeli-Shalom and Shay Menascu in Journal of Attention Disorders</p

original articles 673 IMAJ • VOL the israeli retrospective Multicenter open-label study evaluating vagus nerve stimulation efficacy in children and adults

Background: The management of intractable epilepsy in children and adults is challenging. For patients who do not respond to anti-epileptic drugs and are not suitable candidates for epilepsy surgery, vagal nerve stimulation (VNS) is a viable alternative for reducing seizure frequency. Methods: In this retrospective multicenter open-label study we examined the efficacy and tolerability of VNS in patients in five adult and pediatric epilepsy centers in Israel. All patients had drug-resistant epilepsy and after VNS implantation in 2006-2007 were followed for a minimum of 18 months. Patients were divided into two age groups: &lt; 21 and &gt; 21 years old. results: Fifty-six adults and children had a stimulator implanted in 2006-2007. At 18 months post-VNS implantation, none of the patients was seizure-free, 24.3% reported a reduction in seizures of ≥ 75%, 19% reported a 50-75% reduction, and 10.8% a 25-50% reduction. The best response rate occurred in patients with complex partial seizures. Among these patients, 7 reported a ≥ 75% reduction, 5 patients a 50-75% reduction, 3 patients a 25-50% reduction, and 8 patients a &lt; 25% reduction. A comparison of the two age groups showed that the older group (&lt; 21 years old) had fewer seizures than the younger group. conclusions: VNS is a relatively effective and safe palliative method for treating refractory epilepsy in both adults and children. It is an alternative treatment for patients with drugresistant epilepsy, even after a relatively long disease duration, who are not candidates for localized epilepsy surgery. IMAJ 2013; 15: 673-677 vagal nerve stimulation (VNS), epilepsy, adults, children, seizure reductio

Modeling of Cognitive Impairment by Disease Duration in Multiple Sclerosis: A Cross-Sectional Study

<div><p>Background/Aims</p><p>Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years.</p><p>Methods</p><p>1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms.</p><p>Results</p><p>Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p = 0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p = 0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p = 0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years.</p><p>Conclusions</p><p>The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.</p></div

MindStreams Global Assessment Battery (GAB): Description of cognitive domains tested and outcome parameters obtained.

<p>Index scores explanation for GAB cognitive tests.</p><p>1. MEMORY: mean accuracies for learning and delayed recognition phases of Verbal and Non-Verbal Memory tests.</p><p>2. EXECUTIVE FUNCTION: composite scores (accuracy divided by average response time) for interference phase of the Stroop test and Go-NoGo test, mean weighted accuracy for Catch Game.</p><p>3. VISUAL SPATIAL: mean accuracy for Visual Spatial Processing test.</p><p>4. VERBAL: weighted accuracy for verbal rhyming test (part of Verbal Function test).</p><p>5. ATTENTION: mean response times for the Go-NoGo test and a no interference phase of the Stroop test, mean response time for a low-load stage of Staged Information Processing test, mean standard deviation of response time for the Go-NoGo test, mean accuracy for a medium-load stage of Information Processing test.</p><p>6. INFORMATION PROCESSING: composite scores (accuracy divided by average response time) for various low- and medium-load stages of the Staged Information Processing test.</p><p>7. MOTOR SKILLS: mean time until first move for Catch Game, mean inter-tap interval and standard deviation of inter-tap interval for Finger Tapping test.</p