Profile of paediatric sleep patients and polysomnography findings: Experience from an exclusive paediatric sleep clinic in India

Objectives: The objectives of the study were to describe the profile of patients attending an exclusive paediatric sleep clinic in India. Materials and Methods: Children aged 1 month–18 years, attending an exclusive paediatric sleep clinic, were assessed using standardized questionnaires. Children underwent sleep coaching, were treated medically, or underwent polysomnography based on the decision of the paediatric pulmonologist. Level 1 polysomnography was conducted by trained personnel. Results: Of 186 children, 36.5% were for infant sleep issues, 24.7% suspected obstructive sleep apnea (OSA), 18.2% neuromuscular diseases with sleep problems, 15.6% genetic disorders with sleep problems, 4.3% parasomnias, and 0.5% abnormal movements during sleep. Of the 85 paediatric polysomnographies conducted, 9.4% were normal studies, 87% had OSA, 1.1% restless leg syndrome, and 2.3% were inadequate studies. Conclusion: Sleep disorders in children are not uncommon and paediatricians need to be aware and identify them early. More number of exclusive paediatric sleep clinics need to be established in India.

Approach to Common Sleep Disorders

Sleep disorders are highly relevant in clinical practice given their prevalence as well as their impact on health outcomes and quality of life. The most common concerns are excessive daytime sleepiness, insomnia, disordered breathing, and abnormal movements or behaviors during sleep. A detailed but targeted history is vital, particularly from the sleep partner/witness. In-laboratory sleep testing (polysomnography and multiple sleep latency test) remains vital in the diagnosis of certain sleep disorders (such as sleep-disordered breathing and central hypersomnia) and in specific populations (such as in children and individuals with comorbid medical disorders). Advances in technology have allowed for a variety of methods in assessing a patient's sleep, from compact devices to evaluate for sleep apnea, wrist actigraphy, and mobile device-based applications. As the pathophysiology of various sleep disorders becomes better elucidated, disease-specific medications have been developed for these conditions. Nonetheless, a multidisciplinary approach to management is necessary, including improving sleep hygiene and cognitive behavioral therapy.

Personality Changes, Cognitive Decline, and Jerking Movements

A 64-year-old man had development of abnormal movements characterized by grimacing of the left hemiface and posturing of the ipsilateral arm. He had a generalized tonic-clonic seizure, followed by cognitive decline requiring assistance for most activities of daily living. He was readmitted to the hospital for neurologic evaluation. His heart rate was 120 beats/min, he was afebrile. On neurologic examination, he had a Mini-Mental State Examination (MMSE) score of 16/30. The patient was oriented to person only, and he had multiple, frequent, left hemibody jerks during examination. Cerebrospinal fluid analysis indicated increased protein concentration but otherwise normal findings. Laboratory abnormalities included a serum sodium and antibodies to leucine-rich, glioma-inactivated protein 1. Electroencephalography revealed diffuse slowing and bilateral temporal lobe epileptiform discharges. Magnetic resonance imaging of the brain showed T2/fluid-attenuated inversion recovery hyperintensities in the bilateral hippocampi and amygdalae and gadolinium enhancement in the same regions. Brain 18F-fludeoxyglucose–positron emission tomography demonstrated hypermetabolism in the mesiotemporal lobes bilaterally. A diagnosis of limbic encephalitis associated with leucine-rich, glioma-inactivated protein 1-immunoglobulin G antibodies was. The unilateral facial and arm movements were consistent with faciobrachial dystonic seizures and are pathognomonic of the disorder. The patient’s seizure frequency did not improve with antiepileptic drug therapy. The patient was treated with intravenous methylprednisolone, followed by plasmapheresis. This resulted in substantial improvement of his cognitive dysfunction and decrease in the faciobrachial dystonic seizures frequency. Therapy was transitioned to oral prednisone and the patient was discharged from the hospital. This patient had classic features of leucine-rich, glioma-inactivated protein 1 antibody encephalitis: faciobrachial dystonic seizures, personality changes, subacute cognitive decline, hyponatremia, and improvement with immunotherapy.

Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants

Background Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features. Case-report A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe). Conclusion This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.

Prevention of oral and maxillofacial trauma secondary to orofacial dyskinesias associated with anti-N-methyl-d-aspartate receptor encephalitis: a case series

Background Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is a multi-stage autoimmune-mediated disease associated with a multitude of neuropsychiatric and dysautonomic features. Orofacial dyskinesias are frequently associated with this condition and manifest as abnormal movements of the orofacial musculature. These involuntary movements may result in significant trauma to the oral and maxillofacial complex including the avulsion of the dentition and orofacial lacerations. Case presentation We describe the course of two female patients with anti-NMDARE in whom significant involuntary self-inflicted maxillofacial trauma was suffered despite the use of complex parenteral sedation regimens. The application of traditional maxillomandibular wiring techniques and pharmacologic strategies, including botulinum toxin, to immobilize the mandible were initially unsuccessful. These difficulties led to the fabrication and wire-based fixation of a patient-specific acrylic oral appliance that maintained the mandible in a depressed position and mitigated all lateral and protrusive movements. Discussion and conclusions These cases illustrate the first known successful use of an appliance-based therapy for managing orofacial dyskinesias in the anti-NMDARE patient population through an adaptation of traditional maxillomandibular fixation techniques. This approach eliminated further orofacial trauma and afforded physicians with safer means to manage and assess patients afflicted with this condition during their protracted intensive care unit admissions.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort

ABSTRACT:Objective:To identify the prevalence of EEG abnormalities in patients with COVID-19 with neurologic changes, their associated neuroimaging abnormalities and rates of mortality.Methods:A retrospective case series of 192 adult COVID-19 positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced- montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications, metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed.Results:EEG indications included encephalopathy (54.7%), seizure (18.2%), coma (17.2%), focal deficit (5.2%), and abnormal movements (4.6%). Epileptiform abnormalities occurred in 39.6% of patients: focal intermittent epileptiform discharges in 25.0%, lateralized periodic discharges in 6.3%, and generalized periodic discharges in 19.3%. Seizures were recorded in 8 patients, 3 with status epilepticus. Antiseizure medication administration, epilepsy history, and older age were associated with epileptiform abnormalities. Only 26.3% of patients with any epileptiform abnormality, 37.5% with electrographic seizures, and 25.7% patients with clinical seizures had known epilepsy. Background findings included generalized slowing (88.5%), focal slowing (15.6%), burst suppression (3.6%), attenuation (3.1%), and normal EEG (3.1%). Neuroimaging pathology was identified in 67.1% of patients with epileptiform abnormalities, over two-thirds acute. In-hospital mortality was 39.5% for patients with epileptiform abnormalities, 36.2% for those without. Risk factors for mortality were coma and ventilator support at time of EEG.Significance:This article highlights the range of EEG abnormalities frequently associated with acute neuroimaging abnormalities in COVID-19. Mortality rates were high, particularly for patients in coma requiring mechanical ventilation. These findings may guide the prognosis and management of patients with COVID-19 and neurologic changes.

Parkinson’s disease diagnosis using convolutional neural networks and figure-copying tasks

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that causes abnormal movements and an array of other symptoms. An accurate PD diagnosis can be a challenging task as the signs and symptoms, particularly at an early stage, can be similar to other medical conditions or the physiological changes of normal ageing. This work aims to contribute to the PD diagnosis process by using a convolutional neural network, a type of deep neural network architecture, to differentiate between healthy controls and PD patients. Our approach focuses on discovering deviations in patient’s movements with the use of drawing tasks. In addition, this work explores which of two drawing tasks, wire cube or spiral pentagon, are more effective in the discrimination process. With $$93.5\%$$ 93.5 % accuracy, our convolutional classifier, trained with images of the pentagon drawing task and augmentation techniques, can be used as an objective method to discriminate PD from healthy controls. Our compact model has the potential to be developed into an offline real-time automated single-task diagnostic tool, which can be easily deployed within a clinical setting.

Classification of Functional Movement Disorders with Resting State fMRI

Functional movement disorder (FMD) is a type of functional neurological disorder characterized by abnormal movements that patients do not recognize as self-generated. Prior imaging studies show a complex pattern of altered activity, linking regions of the brain involved in emotional responses, motor control, and agency. This study aimed to better characterize these relationships by building a classifier via support vector machine (SVM) to accurately classify 61 FMD patients from 59 healthy controls using features derived from resting state functional MRI (rs-fMRI). First, we selected 66 seed regions based on prior related studies, then calculated the full correlation matrix between them, before performing recursive feature elimination to winnow the feature set to the most predictive features and building the classifier. We identified 29 features of interest that were highly predictive of FMD condition, classifying patients from controls with 80% accuracy. The features selected by the model highlight the importance of the interconnected relationship between areas associated with emotion, reward and sensorimotor integration, potentially mediating relationships between regions associated with motor function, attention and executive function. Exploratory machine learning was able to identify this distinctive, abnormal pattern, suggesting that alterations in functional linkages between these regions may be a consistent feature of the condition in many FMD patients.

Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified NMDA receptor antibodies from encephalitis patients to mice precipitated seizures, thereby confirming that antibodies are directly pathogenic for seizures. Although different repertoires of anti-NMDA receptor antibodies could contribute to the distinct clinical manifestations in encephalitis patients, the role of specific antibodies in the expression of seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived monoclonal antibodies with distinct epitopes within the N-terminal domain (NTD) of the NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11 antibodies for 2 weeks precipitated seizures, as measured with continuous EEG using cortical screw electrodes. The seizure burden was comparable in all three antibody-treated groups. The seizures were accompanied by increased hippocampal C-C chemokine ligand 2 (CCL2) mRNA expression 3 days after antibody infusion had stopped. Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal antibodies targeting different epitopes within the NMDA receptor may result in a similar seizure phenotype.

An Automated Approach for General Movement Assessment: A Pilot Study

Objective: The objective of the study was to develop an automatic quantitative approach to identify infants with abnormal movements of the limbs at term equivalent age (TEA) compared with general movement assessment (GMA).Methods: GMA was performed at TEA by a trained operator in neonates with neurological risk. GMs were classified as normal (N) or abnormal (Ab), which included poor repertoire and cramped synchronized movements. The signals from four micro-accelerometers placed on all limbs were recorded for 10 min simultaneously. A global index (KC_index), quantifying the characteristics of individual limb movements and the coordination among the limbs, was obtained by adding normalized kurtosis of the distribution of the first principal component of the acceleration signals to the cross-correlation of the jerk for the upper and lower limbs.Results: Sixty-eight infants were studied. A KC_index cut-off of 201.5 (95% CI: 199.9–205.0) provided specificity = 0.86 and sensitivity = 0.88 in identifying infants with Ab movements.Conclusions: KC_index provides an automatic and quantitative measure that may allow the identification of infants who require further neurological evaluation.