Neurological disorders associated with COVID-19 in Sri Lanka.

BACKGROUND: Neurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka. METHODS: COVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 - May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations. RESULTS: One hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain-Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 - 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 - 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period. A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046). CONCLUSIONS: The spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.

Impact of COVID-19 pandemic on caregivers of persons with epilepsy - A systematic review.

PURPOSE: To describe the impact of COVID-19 pandemic on caregivers of persons with epilepsy. METHODS: This systematic literature review was conducted according to the Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA) guidelines. The PECO (Patient, Exposure, Comparison, Outcome) framework criteria were as follows: caregivers of persons with epilepsy; exposed to the COVID-19 pandemic; and outcomes, evaluated under 4 domains- Difficulties faced by caregivers during the COVID-19 pandemic, physical, emotional and behavioural impacts, diagnosed health conditions, and impact on clinical management and follow-up). Literature was searched in PubMed, Google Scholar, CINAHL, Medline, and Cochrane Library Databases. Appraisal tool for Cross-Sectional Studies (AXIS) was used to assess the methodological quality of studies. RESULTS: Data were extracted from 21 eligible articles from 199 and included 5810 caregivers of persons with epilepsy. In the domain of difficulties faced by caregivers during the COVID-19 pandemic, the most significant effect was related to difficulties in obtaining and affording anti-seizure medications. Appointment cancellations also affected most caregivers (4/7 studies). Seizure exacerbation was not a major concern to them. Anxiety, reported by most caregivers in 5/7 studies, depression in 2/5 studies, stress by majority of caregivers in 4/6 studies, and increased substance use in one study were other significant bad experiences. Social isolation increased for the majority in 2/7 studies. Financial difficulties were described in two studies. Under caregivers' health conditions, there was only one study to review. Emotional issues affected majority in 3/7 studies, physical issues in 2/4 studies, and worsened behavior in one. With regards to clinical management and follow-up, most caregivers (4/5 studies) adopted self-management strategies, but 3/8 studies reported difficulties in accessing medications and healthcare services. Additionally, 4/8 studies highlighted communication and coordination difficulties with healthcare providers. Caregivers' attitude towards telemedicine varied across studies. SIGNIFICANCE: COVID-19 pandemic had a profound impact on caregivers of persons with epilepsy, affecting their emotional, physical, and behavioral health. It limited their access to healthcare and impacted financial stability. Caregivers of persons with epilepsy need comprehensive support and resources during crisis situations.

Validation of the Sri Lankan Health-Related Quality-of-Life Index for pre-schoolers (SLHQL-P) and school age (SLHQL-S) children with epilepsy.

INTRODUCTION: Health-related quality of life (HRQL) in children and adolescents remains an underappreciated problem in Asian region, due to lack of culturally sound HRQL measures. This paper describes the validation process of two age-specific, proxy-rated HRQL indexes namely Sri Lankan Health-Related Quality-of-Life Index for preschoolers (SLHQL-P) and school age children (SLHQL-S) with epilepsy. METHODS: Primary caregivers of children and adolescents with epilepsy aged 1-18 years from three districts in Sri Lanka were invited to fill the SLHQL-P (for 1-5 years) and SLHQLS (for 6-18 years). It was re-administered to a subset of consenting primary caregivers after an interval of two weeks. Scientific soundness of SLHQL-P and SLHQL-S were established based on causal indicator model. RESULTS: Total of 98 and 169 primary caregivers responded to SLHQL-P, SLHQL-S respectively. Final questionnaires of SLHQL-P and SLHQL-S consists of 26, 57 items respectively in three multi-item domains measuring the child's physical functioning (6, 9 items), psychological functioning (6, 31 items) and social functioning (14, 17 items) with higher scores reflecting better HRQL. Construct validity was established by several methods including strong relationship with seizure severity. Good test-retest reliability was also demonstrated for both SLHQL-P and SLHQL-S (r = 0.77, 0.938) CONCLUSIONS: Both SLHQL-P and SLHQL-S are feasible, reliable and valid instruments to measure HRQL in children and adolescents with epilepsy in clinical as well as research settings in Sri Lanka.

Quality of life at 6 years in children treated for West syndrome with hormonal therapy.

INTRODUCTION: West syndrome is a severe epileptic encephalopathy occurring in infancy. Majority of affected children suffer from poor epilepsy control in later life and are dependent on care-givers for daily living. There is no previous study evaluating the Quality of Life (QOL) in children suffered from WS. METHOD: A prospective cohort study was performed at six years in a group of children with West syndrome, followed up in the Sri Lanka Infantile Spasm Study (SLISS). The quality of life was evaluated using Sri Lankan Health-Related Quality-of-Life Index for school children (SLHRQ-S), an age-specific, primary caregiver proxy-rated, validated questionnaire for Sri Lankan children with epilepsy. Information on epilepsy, medication, and daily activities was obtained from the parents. RESULTS: Fifty parents of initial 97 children treated for WS participated. The majority had no ongoing epilepsy (56%) at time of evaluation. The mean QOL was 67.22 (SD 15.68). Mean QOL scores for individual domains showed that physical domain was the worst affected (58.51 (SD = 22.11)). Psychological and social function domains were 68.73 (SD = 17.74) and 75.2 (SD = 14.87), respectively. Male sex (0.02), using multiple anti-seizure medications (0.00) and lower ILAE epilepsy control scale (0.02) were significantly associated with a poor quality of life. Age at onset, delay in treatment, and early spasm control were among the factors that did not influence quality of life. CONCLUSION: Despite having control of their epilepsy in the majority, these children suffered from poor quality of life. The greater impact on the physical domain possibly is related to the effect of underlying pathologies.

Cornea Verticillata in classical Fabry disease, first from Sri Lanka: a case report.

BACKGROUND: Fabry disease is a rare inborn error of metabolism with profound clinical consequences if untreated. It is caused by the deficiency of α galactosidase A enzyme and is the only lysosomal storage disorder with an X linked inheritance. Confirmation requires genetic analysis of Galactosidase Alpha (GLA) Gene, which is often a challenge in resource-poor settings. Despite these technological limitations, specific clinical features in this condition can establish the diagnosis. CASE PRESENTATION: We report on a 13-year old male who presented with an afebrile convulsion with a background history of chronic burning sensation of hands and feet and anhidrosis for 2 years duration with a similar history of episodic acroparesthesia in the other male sibling. The early clinical diagnosis was based on the history and detection of Cornea Verticillata on eye examination. Biochemical confirmation was established with detection of low α galactosidase A enzyme levels and a missense mutation of the Galactosidase Alpha (GLA) Gene (c.136C > T) established the genetic confirmation. CONCLUSION: This is the first case of Fabry disease reported in Sri Lanka. Awareness of specific clinical features aided clinical diagnosis long before access to genetic confirmation was available.

Developmental profile at initial presentation in children with infantile spasms.

AIM: To describe the baseline developmental profile and influence of clinical and demographic factors on the developmental skills of infants diagnosed with infantile spasms. METHOD: Ninety-five infants (55 males, 40 females) newly diagnosed with infantile spasms were recruited for a cross-sectional, longitudinal study. All infants underwent Bayley Scales of Infant and Toddler Development assessments in the cognitive, receptive communication, expressive communication, and fine and gross motor developmental domains; they also underwent visual, auditory, and social behaviour assessments. Infants were categorized as 'early' (<6mo) or 'late' (≥6mo) presenters; if presented within 28 days, this was considered as 'early presentation', whereas a delay greater than 28 days was considered as a 'delay in presentation'. Antenatal, perinatal, and postnatal risk factors were identified. RESULTS: Over 90% of infants showed impairment in all domains, with the majority having severe delay; 99% showed cognitive impairment. Delayed presentation was significantly associated with receptive communication delay (odds ratio [OR]=5.35; 95% confidence interval [CI]=1.05-27.32). Onset at 6 months or less influenced auditory (OR=2.8; 95% CI=1.16-6.8) and visual (OR=3.03; 95% CI=1.22-7.57) behaviours. Neonatal infections impacted both receptive (OR=1.12; 95% CI=1.04-1.2) and expressive communication (OR=1.08; 95% CI=1.02-1.14) delay. Neonatal seizures significantly influenced visual, auditory, and social impairments. Expressive communication and gross motor development shared common perinatal risk factors. INTERPRETATION: Adverse developmental status at presentation, associated with delayed presentation and neonatal risk factors should alert clinicians to the surveillance of at-risk infants and seek out timely interventions. WHAT THIS PAPER ADDS: Ninety per cent of infants showed impaired cognitive, communication, and motor skills at presentation. Visual, auditory, and social behaviour impairments were significantly associated with perinatal risks. Visual, auditory, and social behaviour impairments were significantly associated with neonatal seizures.

PERFIL DE DESARROLLO DURANTE LA PRESENTACIÓN INICIAL DE LOS ESPASMOS INFANTILES EN NIÑOS: OBJETIVO: Describir el perfil de desarrollo basal y la influencia de factores clínicos y demográficos sobre las habilidades de desarrollo en niños diagnosticados con espasmos infantiles. METODO: Se reclutaron 95 niños recientemente diagnosticados con espasmos infantiles en una corte transversal, de un estudio longitudinal. Se realizaron Escalas de Bayley (Bayley Scales of Infant and Toddler Development) para el desarrollo de lactantes y preescolares a todos los niños, evaluando cognición, comunicación receptiva, comunicación expresiva, y los dominios del desarrollo motor, grueso y fino; también se sometieron a evaluaciones visuales, auditivas y de comportamiento social. Los niños fueron clasificados como presentación Temprana'(< 6 meses) o Tardía (≥ 6 meses); si los espasmos se presentaron dentro de los primeros 28 días, se consideró como presentación temprana, mientras que un retraso mayor de 28 días fue considerado como un retraso en la presentación. Se identificaron los factores de riesgo prenatales, perinatales y postnatales. RESULTADOS: Más del 90% de los lactantes mostró discapacidad en todos los dominios, la mayoría con retraso severo; 99% mostró deterioro cognitivo. El retraso en la presentación está significativamente asociado con retraso en la comunicación receptiva (razón de probabilidades [OR]= 5,35; 95% intervalo de confianza [CI]= 1,05-27,32). El inicio a los 6 meses o menos influenció en el comportamiento auditivo (OR = 2,8; 95% CI = 1,16-6,8) y visual (OR = 3,03; 95% CI = 1,22-7,57). Las infecciones neonatales impactaron tanto en el retraso de la comunicación receptiva (OR = 1,12; 95% CI=1,04-1,2) como en la expresiva (OR =1,08; 95% CI = 1,02-1,14). Las convulsiones neonatales influenciaron significativamente en discapacidades visuales, auditivas, y sociales. La comunicación expresiva y el desarrollo motor grueso tuvieron factores de riesgo perinatales comunes. INTERPRETACIÓN: Un estado de desarrollo adverso al momento de la presentación de espasmos infantiles, asociado con un retraso en la presentación y los factores de riesgo neonatal deben alertar a los clínicos a la vigilancia de niños en riesgo y buscar intervenciones oportunas.

PERFIL DE DESENVOLVIMENTO NA APRESENTAÇÃO INICIAL EM CRIANÇAS COM ESPASMOS INFANTIS: Xxx. OBJETIVO: Descrever o perfil de desenvolvimento inicial e a influência de fatores clínicos e demográficos nas habilidades do desenvolvimento de crianças diagnosticadas com espasmos infantis. MÉTODO: Noventa e cinco lactentes diagnosticados com espasmos infantis foram recrutados para um estudo transversal longitudinal. Todas as crianças foram submetidas a avaliações pela Escala Bayley de Desenvolvimento para bebes e crianças nos domínios Cognitivo, comunicação receptiva e expressiva, e desenvolvimento motor fino e grosso; eles também foram submetidos a avaliações: visual, auditivo e comportamento social. Os bebês foram categorizados como "precoces" (<6 m) ou "atrasados" (≥6 m); se apresentada no prazo de 28 dias, foi considerado como "precoces", enquanto que superior a 28 dias foi considerado como "atrasados". Fatores de risco pré-natais, perinatais e pós-natais foram identificados. RESULTADOS: Mais de 90% dos lactentes apresentaram comprometimento em todos os domínios, sendo a maioria com atraso grave; 99% apresentaram comprometimento cognitivo. A apresentação tardia foi significativamente associada ao atraso na comunicação receptiva (odds ratio [OR] = 5,35; intervalo de confiança de 95% [IC] = 1,05-27,32). O início aos 6 meses ou menos influenciou os comportamentos auditivos (OR = 2,8; 95% IC = 1,16-6,8) e visuais (OR = 3,03; IC95% = 1,22-7,57). As infecções neonatais impactaram no atraso na comunicação receptiva (OR = 1,12; 95% IC = 1,04-1,2) e expressiva (OR = 1,08; 95% IC = 1,02-1,14). As convulsões neonatais comprometeram significativamente as áreas: visual, auditiva e social. Comunicação expressiva e desenvolvimento motor grosso ambos demostraram fatores de risco perinatais comuns. INTERPRETAÇÃO: O estado de desenvolvimento adverso, associado à atraso na apresentação e fatores de risco neonatais devem alertar os clínicos para a vigilância de bebês de risco e buscar intervenções oportunas.

Development of outcome criteria to measure effectiveness of antiepileptic therapy in children.

PURPOSE: Clinical trials of antiepileptic drugs frequently measure outcomes of seizure control, which demonstrate efficacy. Yet, functional status, quality of life, and long-term treatment effects reflecting effectiveness are scarcely assessed. We sought to use a consensus method to help identify which outcome criteria key stakeholders consider should be used to measure effectiveness in trials of antiepileptic treatments for children. METHOD: A two-round Delphi survey was used; parents of children with epilepsy and local, international experts comprising academics and clinicians participated in the survey. In the first round, 32 experts, 50 parents, and 15 children with epilepsy aged >13years suggested outcomes that they considered important in determining effectiveness of antiepileptic therapy in children, separately for preschool and school age. In the second round, 29 experts and 42 parents scored the importance of outcomes from the list suggested by at least 10% of round 1 respondents and also proposed five most important outcomes. RESULTS: Complete seizure freedom (67%), seizure frequency (48%), ability to perform normal day-to-day activities (45%), and quality of life (40%) were identified as the most important outcomes of antiepileptic therapy in children of both age groups. Additionally, effect on developmental milestones (47%) and child's compliance to treatment regimen (39%) were identified as most important in preschool age group and school performance (49%); adverse effects (39%) were identified as most important in school age group. CONCLUSION: For the first time, this study has identified outcome priorities regarding antiepileptic treatment in children based on the key stakeholders' perspectives. It could be used as a provisional list of outcomes for inclusion in a core outcome set for children with epilepsy.

Gillespie syndrome in a South Asian child: a case report with confirmation of a heterozygous mutation of the ITPR1 gene and review of the clinical and molecular features.

BACKGROUND: Gillespie syndrome is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia, non-progressive cerebellar ataxia and intellectual disability. Homozygous and heterozygous pathogenic variants of the ITPR1 gene encoding an inositol 1, 4, 5- triphosphate- responsive calcium channel have been identified in 13 patients recently. There have been 22 cases reported in the literature by 2016, mostly from the western hemisphere with none reported from Sri Lanka. CASE PRESENTATION: A 10-year-old girl born to healthy non-consanguineous parents with delayed development is described. She started walking unaided by 9 years with a significantly unsteady gait and her speech was similarly delayed. Physical examination revealed multiple cerebellar signs. Slit lamp examination of eyes revealed bilateral partial aniridia. Magnetic resonance imaging of brain at the age of 10 years revealed cerebellar (mainly vermian) hypoplasia. Genetic testing confirmed the clinical suspicion and demonstrated a heterozygous pathogenic variant c.7786_7788delAAG p.(Lys2596del) in the ITPR1 gene. CONCLUSION: The report of this child with molecular confirmation of Gillespie syndrome highlights the need for careful evaluation of ophthalmological and neurological features in patients that enables correct clinical diagnosis. The availability of genetic testing enables more accurate counseling of the parents and patients regarding recurrence risks to other family members.

Viral aetiologies of acute encephalitis in a hospital-based South Asian population.

BACKGROUND: The aetiological spectrum of acute encephalitis shows inter- and intra-geographical variations. We aimed to identify the viruses that cause infectious encephalitis in Sri Lanka, which represents a South Asian population. METHODS: A cross-sectional study was conducted among 99 patients with encephalitis/meningoencephalitis admitted to two tertiary-care hospitals in Colombo. Cerebrospinal fluid and serum were tested for conventional and emerging encephalitogenic viruses. Specific nucleic acid amplification and antibody assays were used to identify viruses. Plaque reduction neutralization test was done to confirm the diagnosis of West Nile virus (WNV). RESULTS: Patients' age ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male:female ratio of 1.75:1. A viral aetiology was identified in only 27.3%. These included dengue virus (40.7%), Japanese encephalitis virus (25.9%), varicella zoster virus, WNV and probable Epstein Barr virus (11.1% each). None were positive for herpes simplex viruses or cytomegalovirus. Screening for bacterial aetiologies was negative for all patients. There were no distinguishable clinical or laboratory findings between the different viral aetiologies. The case fatality rate was 7%, which was higher among patients with an identified viral aetiology. CONCLUSIONS: A viral aetiology was identified in only about a quarter of patients with encephalitis. Dengue virus accounted for the majority.

Surgical Outcome of Pharmaco Refractory Epilepsy in the National Epilepsy Center of Sri Lanka.

BACKGROUND: The National Epilepsy Center (NEC) in Sri Lanka was established in 2017. Seizure outcome, effects on quality of life (QOL) and surgical complications among nonpediatric patients who underwent epilepsy surgery from October 2017 to February 2023 are described. METHODS: Nineteen patients (≥14 years) underwent epilepsy surgery at the NEC. We used Engel classification and Quality of Life in Epilepsy 31 (QOLIE-31) questionnaire to assess seizure outcome and QOL respectively. Surgical complications were categorized into neurological and complications related to surgery. RESULTS: Nine female and 10 male patients underwent surgery (mean age 27.5 years (range 14-44 years). The mean follow-up duration was 10.5 months (range 6-55 months). Twelve patients underwent temporal lobe resections. At 6-months follow-up, 83.3% (10/12) had favorable seizure outcomes with Engel class I/II. At 1-year follow-up 6/8 patients (75.0%) and at 2-year follow-up, 5/7 patients (71.4%) had a favorable outcome. Seven patients had extra-temporal lobe surgeries and one defaulted. Seizure freedom was observed in 6/6 at 6 months, 3/3 at 1-year, and 2/2 at 2-year follow-up. Five patients (26.3%) experienced minor post-operative surgical site infection. Two (11.1%) had persistent quadrantanopia. Meaningful improvement in QOL (change in QOLIE-31 score ≥11.8) was observed irrespective of seizure outcome or type of surgery (P < 0.001). CONCLUSIONS: Epilepsy surgery is effective in developing countries. Seizure outcomes in our patients are comparable to those worldwide. Clinically important QOL improvement was observed in our series. This is the first published data on epilepsy surgery outcomes in nonpediatric patients from Sri Lanka.

Life-Saving Treatments for Spinal Muscular Atrophy: Global Access and Availability.

Background and Objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disorder manifesting with progressive muscle weakness and atrophy. SMA type 1 used to be fatal within the first 2 years of life, but is now treatable with therapies targeting splicing modification and gene replacement. Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi improve survival, motor strength, endurance, and ability to thrive, allowing many patients to potentially attain a normal life; all have been recently approved by major regulatory agencies. Although these therapies have revolutionized the world of SMA, they are associated with a high economic burden, and access to these therapies is limited in some countries. The primary objective of this study was to compare the availability and implementation of treatment of SMA from different regions of the world. Methods: In this qualitative study, we surveyed health care providers from 21 countries regarding their experiences caring for patients with SMA. The main outcome measures were provider survey responses on newborn screening, drug availability/access, barriers to treatment, and related questions. Results: Twenty-four providers from 21 countries with decades of experience (mean 26 years) in treating patients with SMA responded to the survey. Nusinersen was the most available therapy for SMA. Our survey showed that while genetic testing is usually available, newborn screening is still unavailable in many countries. The provider-reported treatment cost also varied between countries, and economic burden was a major barrier in treating patients with SMA. Discussion: Overall, this survey highlights the global inequality in managing patients with SMA. The spread of newborn screening is essential in ensuring improved access to care for patients with SMA. With the advancement of neurotherapeutics, more genetic diseases will soon be treatable, and addressing the global inequality in clinical care will require novel approaches to mitigate such inequality in the future.

An international pilot study of an Internet-based platform to facilitate clinical research in epilepsy: the EpiNet project.

PURPOSE: We created an epilepsy patient database that can be accessed via the Internet by neurologists from anywhere in the world. The database was designed to enroll and follow large cohorts of patients with specific epilepsy syndromes, and to facilitate recruitment of patients for investigator-initiated clinical trials. METHODS: The EpiNet database records physician-derived information regarding seizure type and frequency, epilepsy syndrome, etiology, drug history, and investigations. It can be accessed from any country by approved investigators via a secure, password-protected Website. All data are encrypted. The database is for both research and clinical purposes. Investigators were invited to register any patient with epilepsy, but were particularly encouraged to register patients when uncertain of the optimal management. Participation required approval from investigators' ethics committees and institutional review boards, and all patients or their caregiver provided written informed consent. Patients were not enrolled in clinical trials in this pilot study. KEY FINDINGS: The international pilot study recruited patients from September 2010 to November 2011. Sixty-four investigators or research assistants from 25 centers in 13 countries registered 1,050 patients. Patients with a wide range of epilepsy syndromes and etiologies were registered. Patients' ages ranged from 2 weeks to 90 years. SIGNIFICANCE: The Website was successfully used by doctors working in different health systems. The pilot study confirmed that this low-cost, collaborative approach to research has great potential. Large, multicenter cohort studies will commence in 2012, and randomized clinical trials are being planned. All epileptologists are invited to join this project.

Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections.

Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population. Methods: Ninety-nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary-care hospitals in Sri Lanka were studied. PCR and ELISA were used to screen viruses while Gram stain and culture were used to screen bacteria. Sera were tested for antibodies binding to primary embryonic rat hippocampal neuronal cultures and cell-based assays for antibodies to NMDAR, LGI1, CASPR2, Contactin2, AMPAR, GABAAR, GABABR, aquaporin-4 and MOG. Results: Patient ages ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral etiology was identified in 27.3% and bacterial meningoencephalitis was diagnosed in 17.1%. Sera of nine patients had antibodies binding to live primary neurons, but only five had specific antibodies to CASPR2 (n = 1), NMDAR (n = 2) or GABABR-antibodies (n = 2). Moreover, the patients with CASPR2 antibodies and NMDAR-antibodies were also positive for dengue antibodies. Only the two patients with NMDAR-antibodies had features and responses to immunotherapy consistent with AE. Conclusions: Identified infectious forms of meningoencephalitis (44.4%) greatly exceeded the occurrence of neuronal autoantibodies (9.1%) and AE (2%) in Sri Lanka, and this may be common in those regions where infections are prevalent.

Autoimmune epilepsy due to N-methyl-D-aspartate receptor antibodies in a child: a case report.

INTRODUCTION: Seizures of autoimmune etiology may occur independent of or predate syndromes of encephalitis. We report a child with "pure" autoimmune epilepsy followed up for 7 years to highlight long-term effects of this epilepsy and the importance of early initiation and appropriate escalation of immunosuppression to achieve a good long-term outcome. CASE PRESENTATION: A previously healthy 5-year-old Sri Lankan boy presented with acute, frequent, brief focal seizures of temporal-lobe semiology without clinical and investigatory findings suggestive of central nervous system infection, tumor, structural abnormality, or metabolic causes. His epilepsy showed poor response to increasing doses and combinations of antiseizure medications. Further investigations detected N-methyl-D-aspartate receptor antibodies in serum, but not cerebrospinal fluid. Treatment with intravenous methyl prednisolone and maintenance on mycophenolate resulted in a rapid reduction, with seizure freedom achieved within 5-6 weeks. He relapsed when immunotherapy and anti seizure medications were reduced after seizure freedom for 24 months. This, and subsequent relapses, showed poor response to modification of anti-seizure medications, but treatment with immunotherapy (methyl prednisolone and rituximab) achieved complete seizure freedom. At 7-years of follow-up, he remains free of seizure for over 3 years, and has average academic performance and satisfactory quality of life. CONCLUSIONS: Autoimmune epilepsy is a recognized independent entity. Diagnostic criteria have been suggested for its early recognition and confirmation of diagnosis. Early diagnosis and initiation of immunosuppression, with prompt escalation of treatment when necessary, remains key to good patient outcome.

Herpes Simplex Virus-2 Encephalitis Complicated with Multiple Cranial Neuritis and Dysautonomia.

Introduction: Herpes simplex encephalitis (HSE) is mainly caused by herpes simplex virus-1 infection (HSV-1). Herpes simplex virus-2 (HSV-2) infection is rare except in neonates or the immune-compromised. Cranial neuritis is rarely reported in association with HSE. This case study in an eleven-month-old followed by a literature review on cranial neuritis in HSE in children is presented due to the rarity of both situations. Case Report: An eleven-month old otherwise healthy infant presented with encephalitis due to HSV-2 infection which was complicated with dysautonomia manifesting as blood pressure fluctuations and tachycardia, and cranial neuritis manifesting as unilateral ptosis and palatal palsy. The clinical presentation of brain stem encephalitis was confirmed by the Magnetic Resonance Imaging findings of hyperintense foci and contrast enhancement in the medulla oblongata. Following treatment with acyclovir, he made a complete recovery. He did not have any clinical or laboratorial evidence suggestive of immune deficiency. Conclusion: HSV-2 infection can occur beyond the neonatal age group even in the absence of immune compromise. The brainstem encephalitis manifesting as cranial neuritis and autonomic dysfunction made a complete recovery.

Epilepsy Outcome at Four Years in a Randomized Clinical Trial Comparing Oral Prednisolone and Intramuscular ACTH in West Syndrome.

BACKGROUND: This article explores the role of initial treatment on control of spasms and other epilepsies at four years in children previously treated for West syndrome. METHODS: The Sri Lanka Infantile Spasm Study is a prospective clinical trial evaluating response to intra-muscular adrenocorticotropic hormone (ACTH) versus oral prednisolone. A previous report documented response through age 12 months. This article provides four-year follow-up data. RESULTS: At age four years, 65 of the original 97 were available for follow-up; another 13 had died, and 19 moved and could not be contacted. Of the 65 children, 37 (57%) continued to have seizures and 28 were seizure free. In the 37 children with ongoing epilepsy, 32.4% continued to have spasms, either alone or in combination with other seizure types. The epilepsy types seen in these children were focal epilepsy (59.4%), mixed focal and generalized epilepsy (24%), generalized epilepsy only (10.8%), and uncertain (5%). The majority of those still having epilepsy (66.7%) were controlled on medication. There was no significant difference in the rate of epilepsy or spasms or their control by medication between those treated with ACTH or oral prednisolone. Spasm control at day 14 did not influence the four-year spasm or epilepsy outcome. CONCLUSIONS: A majority of children diagnosed with West syndrome continued to have seizures at age four years, although most were controlled on antiseizure medication. The long-term risk of developing epilepsy or its control was the same, regardless of whether ACTH or prednisolone was initially used as treatment.

Effect of intramuscular ACTH versus oral prednisolone on the developmental trajectories of children with West syndrome over 24 months: A randomised control study.

OBJECTIVE: To assess the developmental progression and compare the developmental attainments of children treated with two hormonal therapies for infantile spasms (IS) over two years (seizure and EEG outcomes of this RCT published previously). METHODS: Newly diagnosed infants with IS were randomised to receive adrenocorticotrophin (ACTH) or prednisolone for 14 days. All underwent Bayley III Infant and Toddler Assessments in cognitive (Cog), receptive (RC) and expressive (EC) communication, fine (FM) and gross (GM) motor developmental subsets at baseline (T0), one-year (T1) and two-years (T2). RESULTS: 95 infants randomised to prednisolone (n = 48) and ACTH (n = 47) groups were eligible for developmental assessments. Mean age at initial assessment was 8.75 months (SD = 6.37, range 1.46-34.4 months). 48 children presented for all three assessments. Mean composite scores of each developmental domain improved across the three time points; but the progression was significant only in relation to motor development (p = 0.04). When comparing the treatment outcomes at 2-years, mean composite scores of children treated with ACTH were significantly lower in motor domain (p = 0.023). As for developmental delay, the ACTH group (n = 32) showed significant delay in expressive communication (adjusted OR 5.46, 95% CI: 1.1, 28.57; p = 0.04) and fine motor (adjusted OR 9.4, 95% CI: 1.1, 83.3; p = 0.04) at T2 compared to the prednisolone (n = 30) in a regression analysis. CONCLUSION: The number of children with delay at the 2 year follow up were significantly higher in two domains in the ACTH group compared to the prednisolone group. Overall results do not show a significant advantage of ACTH over prednisolone for developmental outcomes at two years, but further comparative studies over longer periods are required for more definitive conclusions.

Classifying etiology of infantile spasms syndrome in resource-limited settings: A study from the South Asian region.

OBJECTIVE: Etiological classification of infantile spasms syndrome (ISS) is important, considering the influence on prognosis based on the presence or absence of a known etiology. This study was performed to describe the limitations and difficulties experienced within the South Asian region when classifying the etiology of ISS according to the current recommendation. METHOD: Data on healthcare indices and facilities related to management of ISS for the nine countries in the South Asian region were gathered by the South Asian West Syndrome Research Group. A Google survey was performed among three hundred and thirty pediatric neurologists in the region. The capacity within each country for investigating etiology of ISS according to current described benchmarks was evaluated. The difficulties experienced in this regard and the potential solutions were investigated. RESULTS: One hundred and sixty pediatric neurologists (response rate 48%) from Bangladesh (19/25), India (94/255), Myanmar (11/11), Nepal (6/8), Pakistan (19/25), and from Sri Lanka (7/8) responded. Three countries had no pediatric neurology services. Fifty-six percent attempted to classify ISS etiology according to classification outlined by International League Against Epilepsy in 2017. The facilities to perform metabolic, genetic, and immunological investigations were very limited. Lack of funding for investigations and poor laboratory support were the two most frequent barriers encountered. Sixty percent indicated that a separate classification is suitable for low-income setting; 78% suggested inclusion of separate category as "incompletely investigated" as an alternative solution to mitigate the barrier of achieving a better understanding of the etiological subtypes seen more frequently in this region. SIGNIFICANCE: The resources in South Asian region are limited to meet the recommendations for investigating etiology of ISS. Including the etiological subcategory "incompletely investigated" is proposed as an alternative to understand the true proportions of children in this region, with a definite known etiology and those with an unknown etiology.