Recording of single-unit activities with flexible micro-electrocorticographic array in rats for decoding of whole-body navigation.

OBJECTIVE: Micro-electrocorticographic (µECoG) arrays are able to record neural activities from the cortical surface, without the need to penetrate the brain parenchyma. Owing in part to small electrode sizes, previous studies have demonstrated that single-unit spikes could be detected from the cortical surface, and likely from Layer I neurons of the neocortex. Here we tested the ability to use µECoG array to decode, in rats, body position during open field navigation, through isolated single-unit activities. Approach: µECoG arrays were chronically implanted onto primary motor cortex (M1) of Wistar rats, and neural recording was performed in awake, behaving rats in an open-field enclosure. The signals were band-pass filtered between 300 to 3000 Hz. Threshold-crossing spikes were identified and sorted into distinct units based on defined criteria including waveform morphology and refractory period. Body positions were derived from video recordings. We used gradient-boosting machine to predict body position based on previous 100 ms of spike data, and correlation analyses to elucidate the relationship between position and spike patterns. Main results: Single-unit spikes could be extracted during chronic recording from µECoG, and spatial position could be decoded from these spikes with a mean absolute error of prediction of 0.135 and 0.090 in the x- and y- dimensions (of a normalized range from 0 to 1), and Pearson's r of 0.607 and 0.571, respectively. Significance: µECoG can detect single-unit activities that likely arise from superficial neurons in the cortex and is a promising alternative to intracortical arrays, with the added benefit of scalability to cover large cortical surface with minimal incremental risks. More studies should be performed in human related to its use as brain-machine interface.

Role of Perampanel in the Management of Pediatric Epilepsies in Asia: Expert Opinion.

Management of pediatric epilepsies poses unique challenges around diagnosis, treatment options, comorbidities, and the potential for these factors to interact with processes in the developing brain. In pediatric patients, broad-spectrum antiseizure medications (ASMs) with minimal potential for adverse events (AEs) and limited impact on cognition and behavior are preferred. Perampanel is a first-in-class ASM with broad-spectrum efficacy, a tolerable safety profile, minimal negative impact on cognitive function, and other features that make it a viable treatment option in this patient population. However, evidence and experience of its use in pediatric patients are less extensive than in adult patients. Experts in pediatric epilepsy across the region convened at a series of meetings to discuss the use of perampanel in pediatric patients, including dose optimization, AE prevention and management, and considerations in particular groups. This article summarizes key evidence for perampanel in the pediatric population and consolidates the experts' recommendations for using the ASM in managing pediatric epilepsies.

Comparison of functional outcome scales in paediatric acute encephalitis: Responsiveness and outcome predictors.

PURPOSE: To compare scoring systems and their ability to capture short and long-term recovery of paediatric patients with acute encephalitis. To identify clinical predictors of short-term outcomes by correlating functional outcome measures at 1 month post diagnosis of acute encephalitis. METHODS: Patients with encephalitis diagnosed between July 2011 and 2016 based on Granerod's criteria were studied in this retrospective cohort study. Functional outcome scores on WeeFIM, LOS, GOS-E, mRS and ICF at initial presentation and 1, 3, 6 and 12 months later were compared. RESULTS: WeeFIM and LOS scores both showed maximum change in the first 3 months, reflecting highest recovery in this period. With WeeFIM, the greatest change occurred within the first month following diagnosis. On univariate analysis, seizure frequency in the first month, presence of movement disorder, presence of autonomic dysfunction and lower baseline functional score was associated with poorer WeeFIM scores at 1 month. The latter three variables remained statistically significant on multivariate analysis. CONCLUSION: WeeFIM is a potentially preferred functional outcome assessment tool as it demonstrated greatest recovery within the first month due to a trend of high responsiveness and relatively low ceiling effect. Presence of autonomic dysfunction and movement disorders at diagnosis correlated with poorer outcome at 1 month post diagnosis.

Hospital-based observational study of neurological disorders in patients recently vaccinated with COVID-19 mRNA vaccines.

PURPOSE: We describe the spectrum of acute neurological disorders among hospitalized patients who recently had COVID-19 mRNA vaccination. METHOD: We performed a prospective study at 7 acute hospitals in Singapore. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system (CNS) syndromes, cerebrovascular disorders, peripheral nervous system (PNS) disorders, autonomic nervous system (ANS) disorders and immunization stress-related responses (ISRR). RESULTS: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273); 915,344(65.5%) completed 2 doses. Four hundred and fifty-seven(0.03%) patients were referred for neurological complaints [median age 67(20-97) years, 281(61.5%) males; 95.8% received BNT162b2 and 4.2% mRNA-1273], classified into 73(16.0%) CNS syndromes, 286(62.6%) cerebrovascular disorders, 59(12.9%) PNS disorders, 0 ANS disorders and 39(8.5%) ISRRs. Eleven of 27 patients with cranial mononeuropathy had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis; none were vaccine-induced thrombotic thrombocytopenia. Five had mild flares of immune-mediated diseases. CONCLUSION: Our observational study does not establish causality of the described disorders to vaccines. Though limited by the lack of baseline incidence data of several conditions, we observed no obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

Serial outcomes in acute necrotising encephalopathy of childhood: A medium and long term study.

OBJECTIVE: Acute necrotising encephalopathy (ANEC) is a severe, debilitating childhood disorder. We used the ANEC scoring system (ANE-ss) and standardised neurodevelopmental scores to objectively characterise medium and long term outcomes. METHODS: Retrospective review of children with ANEC at KK Women's and Children's Hospital, Singapore, from 2005 to 2012. ANE-ss was determined from clinical features and neuroimaging, and neurodevelopmental scores (Pediatric Glasgow Outcome Scale Extended, Pediatric Cerebral Performance Category scale and Pediatric Overall Performance Category scale) were applied at 1, 6, 12 and 24months post diagnosis. RESULTS: Seven patients with ANEC were studied. All had a viral prodrome with fever, and encephalopathy at presentation, and received immunotherapy (steroids or immunoglobulin). ANE-ss scores were medium risk in 4 patients and high risk in 3 patients. One died (high risk ANE-ss) and outcome was determined in the 6 survivors. At 1month post diagnosis, 3 patients (50%) were mildly affected and 3 (50%) were severely affected. Morbidity rates improved by 12months, with 67% and 33.3% scoring in the mildly affected and severely affected ranges, respectively. Medium risk patients did well with majority having little or no neurological deficits and good outcome scores. CONCLUSION: Mortality and severe morbidity correlated well with high risk ANE-ss. However, our patients with medium risk ANE-ss had good neurodevelopmental sequelae. Serial disability scoring is useful in evaluating the progress of ANEC patients on follow up. Assessment at 1month post diagnosis can aid prognostication of long term outcome.

Guiding follow-up of paediatric idiopathic intracranial hypertension with optical coherence tomography.

Idiopathic intracranial hypertension (IIH) is uncommon in the paediatric population. Papilloedema is the hallmark sign and patients can suffer permanent vision loss as a consequence. We describe the role of optical coherence tomography (OCT) in the follow-up of two paediatric patients with newly diagnosed IIH. Patient A presented with vomiting and examination showed ophthalmoplaegia and papilloedema. She was treated with acetazolamide, furosemide and therapeutic lumbar punctures. Patient B presented with incidental papilloedema and was treated with acetazolamide and she reported intermittent headache during follow-up. Fundoscopic examinations for both patients showed persistent blurred disc margins but OCT examinations documented improvement of average retinal nerve fibre layers. OCT may be of value in monitoring for recurrence in paediatric IIH.

Hemophagocytic lymphohistiocytosis with isolated central nervous system reactivation and optic nerve involvement.

Hemophagocytic lymphohistiocytosis is a rare childhood disorder characterized by uncontrolled proliferation of benign lymphocytes and histiocytes in multiple organs. Neurological presentations of central nervous system involvement are highly variable. The authors present a case of familial hemophagocytic lymphohistiocytosis in an 8-month-old girl with isolated central nervous system reactivation and optic nerve involvement. She presented with fever and hepatosplenomegaly at 2 months of age. Genetic studies confirmed familial hemophagocytic lymphohistiocytosis. There were no clinical features of central nervous system involvement at presentation. While on maintenance chemotherapy awaiting bone marrow transplant, she presented with new-onset seizures. Magnetic resonance imaging of the brain revealed extensive areas of abnormal signal and a thickened and enhancing left optic nerve. Ocular manifestations of hemophagocytic lymphohistiocytosis have rarely been described. To the authors' knowledge, this is the first case report of magnetic resonance imaging findings of optic nerve involvement in a child with hemophagocytic lymphohistiocytosis.