Canadian Practice and Recommendations on Functional MRI to Lateralize Language in Epilepsy.

BACKGROUND/OBJECTIVE: Identifying a patient's dominant language hemisphere is an important evaluation performed prior to epilepsy surgery and is commonly assessed using functional magnetic resonance imaging (fMRI). However, the lack of standardization and resultant heterogeneity of fMRI paradigms used in clinical practice limits the ability of cross-center comparisons to be made regarding language laterality results. METHODS: Through surveying Canadian Epilepsy Centres in combination with reviewing supporting literature, current fMRI language lateralization practices for the clinical evaluation of patients with epilepsy were assessed. To encourage standardization of this practice, we outlined a two-part paradigm series that demonstrates widespread acceptance, reliability and accessibility in lateralizing various aspects of language functioning in individuals with average or near-average IQ and normal literacy skills. RESULTS: The collected data confirm a lack of standardization in fMRI laterality assessments leading to clinical heterogeneity in stimulation and control tasks, paradigm design and timing, laterality index calculations, thresholding values and analysis software and technique. We suggest a Sentence Completion (SC) and Word Generation (WG) paradigm series as it was most commonly employed across Canada, demonstrated reliability in lateralizing both receptive and expressive language areas in supporting literature, and could be readily intelligible to an inclusive population. CONCLUSION: Through providing recommendations for a two-part paradigm series, we hope to contribute to the standardization of this practice across Canada to reduce clinical heterogeneity, encourage communicability between institutions, and enhance methodologies for the surgical treatment of epilepsy for the benefit of all individuals living with epilepsy in Canada.

Point biserial correlation symbiotic organism search nanoengineering based drug delivery for tumor diagnosis.

Nanoparticulate systems have the prospect of accounting for a new making of drug delivery systems. Nanotechnology is manifested to traverse the hurdle of both physical and biological sciences by implementing nanostructures indistinct fields of science, particularly in nano-based drug delivery. The low delivery efficiency of nanoparticles is a critical obstacle in the field of tumor diagnosis. Several nano-based drug delivery studies are focused on for tumor diagnosis. But, the nano-based drug delivery efficiency was not increased for tumor diagnosis. This work proposes a method called point biserial correlation symbiotic organism search nanoengineering-based drug delivery (PBC-SOSN). The objective and aim of the PBC-SOSN method is to achieve higher drug delivery efficiency and lesser drug delivery time for tumor diagnosis. The contribution of the PBC-SOSN is to optimized nanonengineering-based drug delivery with higher r drug delivery detection rate and smaller drug delivery error detection rate. Initially, raw data acquired from the nano-tumor dataset, and nano-drugs for glioblastoma dataset, overhead improved preprocessed samples are evolved using nano variational model decomposition-based preprocessing. After that, the preprocessed samples as input are subjected to variance analysis and point biserial correlation-based feature selection model. Finally, the preprocessed samples and features selected are subjected to symbiotic organism search nanoengineering (SOSN) to corroborate the objective. Based on these findings, point biserial correlation-based feature selection and a symbiotic organism search nanoengineering were tested for their modeling performance with a nano-tumor dataset and nano-drugs for glioblastoma dataset, finding the latter the better algorithm. Incorporated into the method is the potential to adjust the drug delivery detection rate and drug delivery error detection rate of the learned method based on selected features determined by nano variational model decomposition for efficient drug delivery.

Robotic assessment of sensorimotor and cognitive deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening. METHODS: 27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed. RESULTS: Across the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment. SIGNIFICANCE: Our findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment.

Clinical factors and vascular endothelial growth factor as determinants of disease progression in Indian patients with amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Prognostication remains sub-optimally defined. We aimed to assess clinical determinants of disease progression rates in Indian patients with ALS and to assess the role of vascular endothelial growth factor (VEGF) in disease progression. METHODS: In this cross-sectional study, consecutive patients with clinically definite/probable ALS according to the revised El Escorial criteria and controls were included. Patients were classified into fast or slow progressors based on disease progression rate (DPR). Serum and CSF VEGF level was assessed for patients and controls. RESULTS: Of 142 patients recruited, 93 (65.5%) were male. Mean age at enrollment was 49.37 ± 12.65 years. Mean duration of symptoms was 20.53 ± 20.88 months. Mean DPR was 1.14 ± 0.94. Based on DPR, 81 (57%) patients were slow progressors and 61 (43%) were fast progressors. Univariate analysis demonstrated a statistically significant association of DPR with age at onset, symptom duration, time to spread, wasting of small muscles of the hand, frontal release signs, and neurophysiologic bulbar abnormalities. On multivariate analysis, age at onset and symptom duration had a significant association with disease progression. The CSF VEGF levels of ALS patients (46.18 ± 27.8) were significantly elevated compared to controls (25.95 ± 25.64 pg/ml) (p = 0.001), but not serum VEGF. CONCLUSION: Age at symptom onset and duration of disease had a significant impact on disease progression in Indian patients with ALS. CSF VEGF levels were significantly elevated in ALS compared to controls, indicating the role of CSF VEGF as a potential biomarker.

Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. RESULTS: We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Comprehensive Outcome Assessment and Quality of Life Following Epilepsy Surgery.

BACKGROUND: Seizure freedom without deficits is the primary goal for epilepsy surgery. However, patients with medically refractory epilepsy commonly suffer from many co-morbidities related to mood, cognition, and sleep as well as social problems and resultant stigma. While epilepsy surgery literature does describe quality of life (QOL) and neuropsychological outcomes, there is a paucity of information on various common non-seizure outcomes, especially pertaining to mood, sleep, cognition, and social aspects. The objective of this study was to evaluate the role of various non-seizure parameters on post-epilepsy surgery QOL. METHODS: Consecutive adult patients operated for refractory epilepsy at least 1 year prior to initiation of this study were included and classified as seizure-free (group 1) or non-seizure-free (group 2). QOL was assessed using the QOLIE-31 instrument; patients with a T score less than 40 were categorized as "poor QOL." Non-seizure parameters assessed were cognition, mood disturbances, social improvement, social stigma, and sleep disturbances. Categorization into "good" and "poor" outcome subgroups on each item was carried out by dichotomization of scores. RESULTS: Thirty-seven patients (16 F) [mean age 23.5 ± 5.6 years] were evaluated; 26 were seizure-free (group 1). In this group, impaired memory, lower language scores, depression, not having been employed, not receiving education prior to surgery, and experiencing social stigma were factors significantly associated with poor QOL. In group 2, all patients had poor QOL scores. CONCLUSION: Non-seizure factors related to common epilepsy co-morbidities and social issues are highly prevalent among seizure-free patients reporting poor QOL after epilepsy surgery.

Chronic T Cell Encephalitis Responsive to Immunotherapy.

Chronic encephalitis manifesting as an epilepsy syndrome most commonly presents as Rasmussen's syndrome, usually characterized by epilepsia partialis continua, hemiparesis, and progressive cortical deficits such as aphasia, hemianopia, and cognitive decline. It is characterized by progressive hemispheric cortical atrophy on imaging and is usually seen in childhood. Adult-onset of the syndrome is rare, and only a few cases have been reported with bilateral symptoms. We present a patient with pseudobulbar affect and frontal lobe dysfunction who developed multifocal myoclonic jerks, right hemibody focal motor seizures, and right hemiparesis with bilateral cerebellar signs. Magnetic resonance imaging showed progressive hemispheric atrophy and bilateral features in Positron emission tomography-computed tomography (PET CT). Brain biopsy revealed chronic T-cell infiltrate. We discuss this case as the patient had several features that were atypical for Rasmussen's encephalitis (or syndrome).

Sleep and Temporal Lobe Epilepsy - Associations, Mechanisms and Treatment Implications.

In this systematic review, we aim to describe the association between temporal lobe epilepsy (TLE) and sleep, with bidirectional links in mechanisms and therapeutic aspects. Sleep stages may variably impact seizure occurrence, secondary generalization and the development, frequency and distribution of interictal epileptiform discharges. Conversely, epilepsy affects sleep micro- and macroarchitecture. TLE, the most frequent form of drug resistant epilepsy (DRE), shares an enduring relationship with sleep, with some intriguing potential mechanisms specific to anatomic localization, linking the two. Sleep characteristics of TLE may also inform localizing properties in persons with DRE, since seizures arising from the temporal lobe seem to be more common during wakefulness, compared to seizures of extratemporal origin. Polysomnographic studies indicate that persons with TLE may experience excessive daytime somnolence, disrupted sleep architecture, increased wake after sleep onset, frequent shifts in sleep stages, lower sleep efficiency, decreased rapid eye movement (REM) sleep, and possibly, increased incidence of sleep apnea. Limited literature suggests that effective epilepsy surgery may remedy many of these objective and subjective sleep-related concerns, via multipronged effects, apart from reduced seizure frequency. Additionally, sleep abnormalities also seem to influence memory, language and cognitive-executive function in both medically controlled and refractory TLE. Another aspect of the relationship pertains to anti-seizure medications (ASMs), which may contribute significantly to sleep characteristics and abnormalities in persons with TLE. Literature focused on specific aspects of TLE and sleep is limited, and heterogeneous. Future investigations are essential to understand the pathogenetic mechanisms linking sleep abnormalities on epilepsy outcomes in the important sub-population of TLE.

Relationship between location of epileptic focus and occurrence during sleep versus wakefulness.

Different sleep stages exert differential effects on interictal discharges, neural synchrony and seizure threshold. We sought to assess the relationship between localization of the epileptogenic focus and seizure distribution in sleep versus wakefulness among patients with refractory epilepsy. We conducted a retrospective chart review-based study. Video-electroencephalography of patients with refractory epilepsy, planned for resective surgery, were reviewed for seizure localisation and occurrence relative to stage of sleep/wakefulness. Demographic/clinical data, including details of surgery, were also recorded. Bivariate analysis was conducted using the chi-square test for proportions and unpaired t-test/ANOVA to compare the means within groups. We enrolled 175 patients (107 males) with a mean age of 26.1 + 9.8 years (range: 4-53 years). We analysed 1,282 seizures, of which 916 (71.5%) were temporal, 95 (7.4%) frontal, 144 (11.2 %) central/ parietal and 19 (1.5%) arose from the occipital lobe. Temporal lobe onset seizures were more frequent during wakefulness (77.7%) compared to extra-temporal localization (65%) (p<0.0001). Amongst temporal lobe onset seizures, those during wakefulness arose more frequently from the lateral temporal (88.6%) compared to the mesial temporal lobe (75.5%) (p=0.0003). A higher proportion of seizures evolved into secondary generalisation during sleep (23.5%) versus 8.7% during wakefulness (p<0.0001). Our study demonstrates that lobar location of epileptogenic foci is associated with a predilection of seizures to occur, as well as secondarily generalise, during sleep/wakefulness. Seizures with lateral temporal lobe as well as extratemporal lobe onset were more likely to occur during wakefulness. Overall, sleep related seizures were more likely to be of extratemporal lobe onset, though.

Does Bilateral Gap Arthroplasty Increase the Severity of Obstructive Sleep Apnea in Patients With Temporomandibular Joint Ankylosis?

PURPOSE: Obstructive sleep apnea (OSA) is common in patients with bilateral temporomandibular joint ankylosis (TMJA). The purpose of this study was to compare the preoperative and postoperative apnea-hypopnea index (AHI) in patients with TMJA undergoing bilateral gap arthroplasty (BGA). METHODS: The investigators implemented a prospective cohort study on patients with bilateral TMJA treated with BGA. The primary predictor variable was time (before and after BGA). The primary outcome variable was AHI and secondary outcome variable included posterior airway space, skeletal changes, Epworth sleepiness scale, minimum oxygen, average oxygen saturation, and maximal incisal opening at preoperative time (T0), 1 month (T1), and at 6 months (T2). The statistical test used were Greenhouse-Geisser test, repeated measure ANOVA (1 way), followed by post hoc Bonferroni test. The P-value was taken significant when <0.05 at a confidence interval of 95%. RESULTS: The study sample included 12 (m:f = 1:2) patients of bilateral TMJA with a mean age of 14.9 ± 4.8 years and mean follow-up of 6 months. Mean duration of ankylosis was 10.5 ± 6.9 years (median = 12). Trauma was the main etiological factor in 11 (91.7%) patients followed by infection in 1 (8.3%) patient. The mean increase in AHI was 8.6 (T0 to T1) with P-value = .002 and 23.4 (T1 to T2) and was statistically significant (P = .001). The mean decrease in posterior airway space was 4.5 ± 1.0 to 3.5 ± 0.5 (T0 to T2) and was statistically significant (P = .02). Mean difference in minimum oxygen was 6.8 (P-value = .015). Skeletal changes are consistent with clockwise rotation of the mandible and statistically significant changes in horizontal and vertical dimension. The mean change in average oxygen was statistically insignificant (P = 1.0). CONCLUSIONS: The present study concludes that gap arthroplasty in patients with bilateral TMJA can lead to development or worsening of pre-existing mild to moderate OSA. Ramus-condyle reconstruction should be performed to prevent the retropositioning of mandible and worsening of OSA.

A Randomized Controlled Trial to Assess the Effectiveness of Muscle Strengthening and Balancing Exercises on Chemotherapy-Induced Peripheral Neuropathic Pain and Quality of Life Among Cancer Patients.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is the presence of tingling, burning, itching, and unpleasant sensations in hands and feet due to nerve damage by chemotherapy. Exercise rehabilitation has potential to prevent or alleviate CIPN. OBJECTIVE: The aim of this study was to assess the effectiveness of muscle strengthening and balancing exercises on CIPN pain and quality of life (QOL) among cancer patients. METHODS: The randomized controlled trial included 45 cancer patients from a tertiary care hospital in India receiving chemotherapeutic drugs paclitaxel and carboplatin and found to have CIPN. Subjects were randomly allocated to exercise (n1 = 22) and usual care (n2 = 23) groups. The exercise group received home-based muscle strengthening and balancing exercise for 10 weeks. Data regarding demographic, clinical characteristics, CIPN, neuropathic pain, and QOL were collected by structured questionnaires Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, nerve conduction velocity, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: The 2 groups were homogenous regarding demographic variables. In clinical characteristics, the exercise group had larger body surface area and received a higher dose of paclitaxel. Significant reduction in neuropathic pain scores (P < .0001) and improvement in Functional QOL (P = .0002), Symptom QOL (P = .0003), Global Health Status QOL (P = .004) scores were observed after intervention in the exercise group than the usual-care group. CONCLUSION: Muscle strengthening and balancing exercises are effective in reducing CIPN pain and improving QOL among cancer patients. IMPLICATIONS FOR PRACTICE: Muscle strengthening and balancing exercises can be used as a complementary therapy for effective management of CIPN.

Magnetoencephalographic Identification of Epileptic Focus in Children With Generalized Electroencephalographic (EEG) Features but Focal Imaging Abnormalities.

PURPOSE: Children with generalized seizures are often excluded as epilepsy surgery candidates. This prospective study was conducted to evaluate the utility of magnetoencephalography (MEG) to refine the location of the "irritative zone" in children with single lesions on magnetic resonance imaging (MRI) but with generalized ictal electroencephalographic (EEG) findings. METHODS: Patients admitted with refractory epilepsy with imaging studies showing focal or hemispheric abnormalities but scalp video EEG showing generalized or multiregional epileptiform abnormalities were included. Patients were encouraged into natural sleep, and simultaneous whole-head MEG/EEG was recorded. Source localization of epileptic spikes on MEG was carried out while blinded to other results. Acceptable dipoles were classified into 3 groups: focal, hemispheric clusters, and single focal cluster with additional widespread dipoles. RESULTS: Nine patients (4 female, 5 males; ages 10 months to 15 years) were included. Two had focal features on clinical semiology, whereas all had generalized or multiregional interictal and ictal EEG. Etiologies included tuberous sclerosis complex (2), postencephalitic sequelae (1), focal cortical dysplasia (1), and unknown (2). Five patients had clear focal lesions on brain MRI whereas the other 2 had focal positron emission tomography (PET) abnormalities. An average of 38 spikes were accepted (average goodness of fit = 85.3%). A single tight cluster of dipoles was identified in 5 patients, 1 had dipoles with propagation from left occipital to right temporal. One patient had 2 distinct dipole clusters. MEG demonstrated focal findings 9 times more often than the simultaneously recorded scalp EEG, and 3 times more often than the associated multiday video EEG recordings. CONCLUSION: This study shows that neurophysiologic evidence of focal epileptiform abnormalities in patients with focal brain lesions and generalized EEG findings can be strengthened using MEG. Further feasibility of surgical candidacy should be evaluated in these patients.

Does antiepileptic drug withdrawal predispose patients undergoing temporal lobe epilepsy surgery to late onset of psychiatric morbidity? A report of three cases.

Surgery is an established and increasingly utilized treatment option in medically refractory temporal lobe epilepsy. Many psychiatric problems are known to complicate in the postoperative period. Most studies have a follow-up period of less than 24 months. We report the cases of three patients who developed severe psychiatric problems in the late postoperative period after successful temporal lobectomy for refractory epilepsy - Psychosis, major depression with psychosis, and severe anxiety disorder, respectively. None of the patients had past or family history of psychiatric disease. All three patients had undergone anterior temporal lobectomy on the right side for intractable epilepsy. They remained absolutely seizure-free after surgery. We conclude that psychiatric morbidity may arise de novo long after temporal lobectomy. This association between temporal lobectomy for epilepsy and late onset psychiatric morbidity should be carefully studied. Mechanisms underlying this late complication require deeper understanding of the effects of epilepsy surgery.

Remission And relapse of myasthenia gravis on long-term azathioprine: An ambispective study.

INTRODUCTION: Azathioprine (AZA) is commonly used in myasthenia gravis (MG). Treatment may be prolonged, entailing significant risks and avoidable costs. METHODS: We reviewed remission, relapse, and side-effect profiles in MG patients on AZA during treatment and after tapering off. We conducted an ambispective study and analyzed remission, relapse rates, and side-effect profiles in 117 MG patients on AZA. RESULTS: Thirty-nine patients (33.3%) achieved remission, and 36 (30.8%) achieved complete stable remission (CSR), with a 33% relapse rate. No AZA side effects were seen in 95 (81%) patients. Only duration of disease of >10 years (odds ratio 9.5, 95% confidence interval 2.4-36.9, P = 0.001) was significantly associated with remission. CONCLUSIONS: AZA is well tolerated by MG patients, and about 30% go into CSR on long-term AZA. Muscle Nerve, 2016 Muscle Nerve 54: 405-412, 2016.

Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection.

OBJECTIVES: The objective of our study was to describe the clinical characteristics, electrophysiology, MRI features and conduct viral assays in patients with Monomelic Amyotrophy (MMA) and follow them up over one year. METHODS: Consecutive patients with MMA who attended the Neurology services from April 2013 to March 2014 were included. Age and sex matched controls were taken for the purpose of viral assay analysis. The clinical evaluation was repeated at six months and one year. RESULTS: 109 cases and 109 controls were included in the study. The patients were predominantly males (98.2%; n=107/109) and had involvement of upper limbs (83.5%; n=91/109). 26 (23.8%) patients with clinically unilateral involvement had bilateral neurogenic changes in the electromyography. Serological assays of Japanese E, West Nile Virus, and Poliovirus 1, 2 and 3, HIV 1 and 2 were negative in all the cases and controls. CONCLUSIONS: Patients with MMA are predominantly young males with upper limb wasting and weakness. MRI of the cervical cord is normal in most of the patients (67.9%). The present study did not find any evidence of the association of viral infection in MMA.