Tropical Infections of the CNS: A worldwide problem

Neuroinfectious diseases continue to have a profound public health impact, particularly in resource-limited settings. Here we summarize the new research into pathophysiology, diagnosis, and treatment modalities for some of the most frequent and lethal infections affecting the central nervous system, including tuberculosis, malaria, and arboviral infections. Implementation of clinical trials targeting neuroinfectious diseases in resource-limited settings has unique challenges not found when identical research is performed in resource-rich areas. Travel, communications, and technology have improved the mobility of populations worldwide. Immigration and increased international travel make it likely that clinicians worldwide will see patients affected by infectious diseases such as malaria, tuberculosis, zika, dengue, chikungunya, and Ebola. Such infections may have devastating consequences for both the individual and the society, particularly if clinicians are not familiar with disease presentation and treatment.

EEG changes and their relationship with intellectual disability in children with autism spectrum disorders in a tertiary care hospital

Background: Autism in children is frequently associated with Intellectual disability (ID) and epilepsy. It is known that lower IQinfluences epilepsy rates; however, electroencephalographic (EEG) findings in different grades of intellectual functioning are less well studied. Objectives: This study aimed to evaluate the EEG findings and their association with the degrees of ID in children with autism. Methods: Fifty-two children, diagnosed with autism according to the DSM-IV-TR criteria, aged between 2 to 12 years, were included in the study. Participants were recruited from outpatient clinic in the Institute for Paediatric Neurodisorder and Autism (IPNA) in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. All of them were subjected to physical and neurological examination. Intelligence quotients (IQ) were measured in all the participants. Psychometric tests Bayley Scales of Infant and Toddler Development, Third edition (BSID III) or Weschler Intelligence Scale for Patients-Revised (WISC-R) were used for evaluating IQ. EEG recordings were done in all the participants. Results: The frequency of EEG abnormalities were observed in 51.9% participants. Among these abnormalities, 36.5% were epileptiform and 15.4% were non-epileptiform. Majority of the focal discharges, in this study were from temporal and frontal ((50% and 40% of focal discharge). Among generalized abnormalities, 89% were symmetrical spike-wave complexes. EEG abnormalities were associated with epilepsy in 66.7% of participants. ID was present in 84.6% and of them, 77% had moderate to severe ID. Mild, moderate or severe ID did not show significant association with EEG abnormalities (p>0.05). However, patients with moderate to severe ID (IQ <50) had a higher rate of EEG abnormalities compared to those without ID or mild ID (81.5% versus 18.5%) (P=0.03). Conclusion: Relatively large number of children with autism and ID had EEG abnormalities and there was a significant association with moderate to severe ID (IQ <50) and EEG abnormalities.

Pediatric Autoimmune encephalitis: Experience from a Tertiary Care Hospital in Bangladesh

Background: Autoimmune encephalitis (AIE) are distinct group of encephalitis where production of autoimmune antibody causes neuroinflammation. The core clinical features are encephalopathy, psychiatric disorder, movement disorder and seizure. The investigation and treatment modalities are different from that of infectious encephalitis. There are limited studies in pediatric population in particularly in developing country like Bangladesh. Thus this study has been done to describe patients with AIE from a tertiary care hospital. Method: This is a retrospective study done in children of 1-16 year from January 2018 to December 2019. AIE was diagnosed on the basis of clinical, electrographic and neuroimaging features and was confirmed with detection of autoantibody in CSF. Treatment was given according to the published literature with immunotherapy mainly. Results: Total 15 children were studied, 14 patients were antiNMDAR encephalitis and 1 was antiMOG antibody syndrome. Mean age was 5.98 and 4.5 year respectively. Seizure was the most common clinical feature, mostly focal in nature. Other manifestations were movement disorder, psychiatric disorder, loss of consciousness etc. Most of the patients had abnormal EE, focal epileptic discharge being the commonest. Eight out of 15 had abnormal MRI of brain. Cortical hyperintensity was important feature located mostly in temporal region. In the case of antiMOG antibody syndrome there was demyelinating lesion in multiple areas. Cornerstone of the treatment was mostly combination immunotherapy with IV methylprednisolone and IV immunoglobulin followed by oral steroid. Majority of the patients showed improvement however 3 patients had complete recovery. Complications observed were epilepsy, speech disorder, cognitive disorder, behavioural disorder, ataxia and visual impairment. Conclusion: Timely diagnosis and prompt treatment of AIE is very important as proper treatment can cause significant improvement.

Paediatric Acquired Demyelinating Syndromes

Paediatric acquired demyelinating syndromes (ADS) are characterised by neurological deficits persisting for at least 24 hours, involving the optic nerve, spinal cord or brain with a clinical spectrum of diagnoses including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab associated disease (MOGAD). Important strides have been made in delineating MS from other ADS subtypes over the past decade, including the discovery of serum aquaporin-4 (AQP4) and Myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). Both genetic (e.g. human leukocyte antigen, HLA-DRB1*1501 allele) and environmental risk factors (e.g. low serum vitamin D levels and prior exposure to Epstein–Barr virus) may contribute to risk of MS in children. Some of these risk factors not only confer increased susceptibility to MS but may also affect the disease course. Paediatric AQP4-Ab NMOSD is a rare disease worldwide but variations in incidence/prevalence have been described among different geographic regions and ethnicities. One-third of children who present with an ADS have MOG-Ab, and approximately half of patients with MOG-Ab have a relapsing disease course. It seems there is no racial or gender predominance in MOGAD, which is in contrast to the female and non-white predominance seen in both MS and NMOSD.‎ In this review, we examine the current literature regarding the epidemiology and demographics of these different ADS entities with a particular focus on the genetic and environmental risk factors for MS in children. While insights into disease pathophysiology in paediatric ADS have led recent therapeutic advances, well designed, collaborative large scale epidemiological studies are likely to provide the critical next step to a personalised approach to these conditions.

Rational Approach to Children with Drug-Resistant Epilepsy

Epilepsy is one of the most common neurological disorders to affect children, and has its highest incidence in infancy. Approximately one-quarter of children have seizures which are drug-resistant, and place the child at increased risk of cognitive delays, attention, behavior and psychiatric disorders, injury, sudden unexpected death and poor quality of life. This article presents a rational approach to the investigation and management of children with drug-resistant epilepsy.

Expensive molecular therapies for rare genetic disorders: carrier detection or newborn screening should be the strategy. A personal opinion.

Haluk Topaloglu,Yeditepe University School of MedicineDepartment of Pediatricsİstanbul, Turkey

Neuromuscular disease - Gene transfer for children

Successful gene transfer therapy (GTT) provides a functional copy of a gene to appropriate tissues for affected patients. While technically difficult, GTT holds great promise for treating and even curing previously fatal diseases. GTT for Spinal Muscular Atrophy is available commercially and ongoing studies continue to show it is safe and effective. Subclinical liver dysfunction is more common in older, heavier children receiving higher vial loads. Human trials support preclinical studies showing early timing of therapy is important. GTT for Duchene Muscular Dystrophy has required strategic approaches to create mini- and micro-dystrophin genes that will fit into available viral vectors. There are multiple ongoing studies that overall demonstrate good safety and efficacy. GTT for X-Linked Myotubular Myopathy is being studied in an ongoing trial that has shown improvement in respiratory function (including ventilator independence), neuromuscular function, and histopathological evaluation. Three patients with severe cholestatic liver dysfunction have died. Evaluation is ongoing to better understand these events. While GTT for neuromuscular disorders holds significant promise, it is not without risks and requires in-depth knowledge of the disease, abundant pre-clinical work, careful patient education, and ongoing patient care. There are a number of key questions that must be considered regarding the feasibility of expanding GTT to new disorders These examples illustrate how advances in GTT benefit children on a population level and may themselves benefit from early detection by NBS. By becoming involved in advocacy at state and federal levels, families and physicians can impact newborn screening policy and implementation regarding these disorders.

Dietary therapies for epilepsy in low resource settings: challenges and successes

The Ketogenic Diet (KD) is a high fat, low carbohydrate and restricted protein diet which has been used for the treatment of drug resistant epilepsy in children. It is considered the treatment of choice for refractory nonsurgical epilepsy in children. However, despite this being a very useful and relatively simple treatment, children from developing countries have not been able to benefit as much as their counterparts in more privileged settings. In this article, the challenges faced by pediatric neurologists and parents who wish to use the diet in children with refractory epilepsy are discussed, and also the simple low cost innovations which can be used to overcome these challenges are suggested. The evolution from the use of the classic ketogenic diet to the flexible use of the modified Atkins diet in low resource settings will be discussed.

Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

We report about a family with three of five siblings affected by a variable remitting-relapsing disease with epileptic seizures, coma and abdominal crises, and lethal outcome in all. In the youngest son and in one of his deceased brothers we identified two disease causing compound heterozygous POLG mutations. One of these was inherited from the mother, but the other was absent in the father`s blood, saliva, buccal swab and hair bulbs although his paternity was proven genetically. Thus, we assume germline mosaicism for this mutation in the father. Very low 5-methyltetrahydrofolate (5-MTHF) and absence of folate receptor-alpha was repeatedly found in the CSF of the youngest brother indicating a secondary cerebral folate transport deficiency. Folinic acid supplementation over 18 months resulted in some improvement of the neurological condition; however, it did not prevent progression of the systemic disease.

Convulsive status epilepticus in children in Mozambique: Is there a treatment gap?

Background: Optimal care of Convulsive status epilepticus (CSE) can be related to multiple barriers in resource-limited countries. Objectives and methods: Since limited data of CSE management are available from South-East Africa, we performed a retrospective analysis of the electronic records of pediatric patients with CSE admitted to the Maputo Central hospital from January 2016 until April 2019. Results: Our database consisted out of 39 patients. The average age was 5.15 (range 0.3-13.8) years and demographic characteristics did not show a relation to CSE characteristics or outcomes. However, the total stay in the hospital was negatively correlated with age (p=0.0314). Moreover, 14 patients needed to be admitted to the IC, which was correlated to having generalized motor seizures (p=0.0253), and a relatively higher need for a second AED to control their CSE (p=0.0131). Regarding AED use, the first AED was a IV benzodiazepine (BZD: midazolam (MIDA) or diazepam (DIAZ)) or IV phenytoin (PHEN) when BZDs were not available. There was no statistically significant difference between the efficacy of MIDA vs. DIAZ. Eleven patients received PHEN as a second-line drug, of which only two patients needed an additional dose of PHEN. None of the patients died and five patients (13.2%) had an extra comorbidity after CSE. Conclusions: Although limited AEDs were available in our study, compared to more AEDs in other developing and developed countries, we report the successful cessation of CSE in the majority of cases. We recommend strategies to improve prehospital management such as the use of non-IV BZD use, to limit the need for patients to be admitted to the IC and thereby potentially decreasing the number of AEDs, morbidity and hospital duration. Moreover, our data underline the conversion to second-line AEDs (PHEN) to be adequate in nearly all patients.