Diagnosis and management of neurofibromatosis type 1 in Arabian Gulf Cooperation Council Region: challenges and recommendations.

Neurofibromatosis type 1 (NF1) is a complex multisystem genetic disorder that requires long-term, age-specific monitoring and multidisciplinary care. NF1 symptom burden can significantly affect the quality of life and impose a substantial economic burden on patients and their families. The approval and widespread availability of mitogen-activated protein kinase (MEK) inhibitors such as selumetinib for NF1-related plexiform neurofibromas have revolutionized the standard of care for patients with NF1, however their effective utilization hinges on early recognition of NF1. We present a consensus manuscript describing the challenges observed in the Arabian Gulf Cooperation Council (GCC) for diagnosing and managing NF1. Experts from the GCC also present recommendations for the early recognition and management of NF1 and its complications. A referral pathway that can play a crucial role in helping primary healthcare providers refer their patients to experts is also proposed. Increasing the availability and accessibility of genetic testing at an affordable cost and optimizing personalized NF1 care are essential for NF1 management. Developing regional guidelines for NF1 management and establishing NF1 centers of excellence may facilitate better care and outcomes for patients with NF1 in the GCC region.

Evaluation of adherence to pediatric status epilepticus management guidelines in Saudi Arabia.

OBJECTIVE: To assess compliance with the 2017 Saudi pediatric status epilepticus management guidelines and to printout the main obstacle for adherence to the guidelines. METHODS: A cross sectional study conducted in September 2019, using electronic survey. The survey sent to all the Pediatric Emergency physicians practicing in Kingdom of Saudi Arabia (KSA) through emails and WhatsApp and the questionnaire based on clinical scenario written in English language. RESULTS: One hundred and three (70%) of 147 physicians working in KSA and covering pediatric emergency departments responded to the survey. Only 20% of the physicians reported full compliance to all 4 guideline components; 57% reported that they were not aware of the published guidelines. CONCLUSION: Pediatric emergency physicians reported poor compliance to the 2017 published guidelines for the treatment of children with convulsive status epilepticus in KSA.

Metabolic and genetic disorders mimicking cerebral palsy.

Cerebral palsy is a syndrome that encompasses a large group of childhood movement and posture disorders that result from a lesion occurring in the developing brain. The clinical presentation of many metabolic and genetic conditions, particularly in highly consanguineous populations, can mimic cerebral palsy particularly at early age. The aim of this review article is to identify the clinical features that should alert the physician to the possibility of disorders that resemble cerebral palsy, the clinical and neuroimaging red flags, and highlight some metabolic and genetic conditions which may present with spasticity, ataxia and dyskinesia. In the case of metabolic or genetic disorder, making a precise diagnosis is particularly important for the possibility of treatment, accurate prognosis and genetic counseling.

Recessive AFG3L2 Mutation Causes Progressive Microcephaly, Early Onset Seizures, Spasticity, and Basal Ganglia Involvement.

BACKGROUND: Mutations in AFG3L2, a gene encoding a subunit of the mitochondrion m-AAA protease, cause spinocerebellar ataxia type 28 and recessive spastic ataxia type 5. Neuroimaging shows cerebellar atrophy. METHODS: Retrospective review of the patient charts including their clinical evaluation and molecular genetic, neurodiagnostic, and neuroradiological investigations. RESULTS: We describe five members of a large consanguineous family with a severe mitochondrial disease phenotype in the form of regression of the developmental milestones in the first year of life, refractory epilepsy, progressive microcephaly, increased blood lactate, basal ganglia involvement, and premature death. Exome sequencing showed homozygous mutation of the AFG3L2 gene in all individuals: c.1714G>A (p.Ala572Thr). CONCLUSIONS: Our findings add to the phenotypic, neuroradiological, genetic, and biochemical spectrum of AFG3L2 mutations.

Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

BACKGROUND: Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. CASE DESCRIPTION: In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). CONCLUSION: This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy.

Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone.

OBJECTIVE: To compare the combination of biotin plus thiamine to thiamine alone in treating patients with biotin-responsive basal ganglia disease in an open-label prospective, comparative study. METHODS: twenty patients with genetically proven biotin-responsive basal ganglia disease were enrolled, and received for at least 30 months a combination of biotin plus thiamine or thiamine alone. The outcome measures included duration of the crisis, number of recurrence/admissions, the last neurological examination, the severity of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and the brain MRI findings during the crisis and after 30 months of follow-up. RESULTS: Ten children with a mean age of 6 years(1/2) were recruited in the biotin plus thiamine group (group 1) and ten children (6 females and 4 males) with a mean age of 6 years and 2 months were recruited in the thiamine group (group 2). After 2 years of follow-up treatment, 6 of 20 children achieved complete remission, 10 had minimal sequelae in the form of mild dystonia and dysarthria (improvement of the BFMDRS, mean: 80%), and 4 had severe neurologic sequelae. All these 4 patients had delayed diagnosis and management. Regarding outcome measures, both groups have a similar outcome regarding the number of recurrences, the neurologic sequelae (mean BFMDS score between the groups, p = 0.84), and the brain MRI findings. The only difference was the duration of the acute crisis: group 1 had faster recovery (2 days), versus 3 days in group 2 (p = 0.005). CONCLUSION: Our study suggests that over 30 months of treatment, the combination of biotin plus thiamine is not superior to thiamine alone in the treatment of biotin-responsive basal ganglia disease.