Miraç Yıldırım

Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is a rare neurodegenerative disorder caused by pathogenic variants in NAXE gene. Movement disorders are among the clinical features of PEBEL1; however, no case presenting with paroxysmal exercise-induced dyskinesia (PED) has been reported. We reported the case of a 14-year-old girl who presented with PED episodes. Six months after the onset of episodes, she developed encephalopathy and focal status epilepticus. Exome sequencing analysis identified a homozygous pathogenic variant in NAXE gene, and she was diagnosed with PEBEL1. She was started on mitochondrial cocktail and multiple antiseizure medications; however, no response was observed. With the ketogenic diet (KD), seizure control was achieved and improvement in cognitive functions was observed. PED is a clinical feature not previously reported in PEBEL1 cases, and our case expands the phenotypic spectrum of this disorder. Additionally, our case highlights that KD may be a treatment option in PEBEL1.

Background Tubulinopathies encompass a clinically and neuroradiologically diverse group of neurodevelopmental disorders caused by mutations in genes encoding tubulins and microtubule-associated proteins. This study aims to delineate the extensive phenotypic and genotypic spectrum within a pediatric cohort. Methods We conducted a multicenter retrospective analysis of 15 pediatric patients from 12 unrelated families with genetically confirmed tubulinopathies across five tertiary centers in Turkey. Clinical data, seizure profiles, and neuroradiological findings were systematically evaluated. Results Genetic analysis identified 12 distinct pathogenic variants across seven genes (TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBG1, TUBGCP2), including four novel variants. The most prevalent clinical features included microcephaly (93.3%), global developmental delay (86.7%), and epilepsy (73.3%). Notably, one patient with TUBB2A-related tubulinopathy experienced a probable sudden unexpected death in epilepsy (SUDEP). Movement disorders were observed in 33.3% of the cohort, including dystonia and mirror movements. Neuroradiological assessment revealed corpus callosum anomalies (76.9%) and cortical malformations (76.9%) as the most frequent findings. Furthermore, we identified a rare case of TUBGCP2-related tubulinopathy presenting with cystic leukomalacia, expanding the known radiological spectrum. Conclusion Our findings underscore the profound genetic and phenotypic heterogeneity of tubulin-related disorders. The identification of rare variants and specific complications, such as SUDEP, highlights the necessity for comprehensive clinical monitoring and standardized management guidelines to optimize outcomes for this complex patient population.

Background: Human herpesvirus-6 (HHV-6) is a neurotropic virus that typically remains latent in immunocompetent individuals but may cause severe neurologic complications, including encephalitis, particularly in immunocompromised hosts. Rarely, HHV-6 encephalitis can also occur in immunocompetent children, often presenting with features of acute necrotizing encephalopathy. Cases: We report 2 cases of previously healthy toddlers who presented with fever, seizures and altered mental status. Neuroimaging revealed bilateral thalamic involvement consistent with acute necrotizing encephalopathy. HHV-6 DNA was detected in cerebrospinal fluid via polymerase chain reaction, confirming the diagnosis. Both patients received antiviral therapy with foscarnet, alongside immunomodulatory treatments including intravenous immunoglobulin, corticosteroids, plasmapheresis and, in 1 case, tocilizumab. Clinical outcomes varied, with 1 patient achieving full recovery and the other showing partial neurologic improvement. Conclusions: These cases highlight the potential for HHV-6 to cause severe encephalopathy in immunocompetent children. Early recognition, neuroimaging, and cerebrospinal fluid polymerase chain reaction testing are essential for diagnosis. Combined antiviral and immunomodulatory therapies may improve outcomes by addressing both viral replication and neuroinflammation.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder involving systemic inflammation and multi-organ damage, which often affects the central nervous system (CNS). Familial HLH, which is caused by mutations in genes such as PRF1 and UNC13D , impairs the function of cytotoxic cells, leading to uncontrolled immune activation. CNS involvement occurs in 30% to 73% of cases and manifests as seizures, encephalopathy or status epilepticus, which often mimics other neurologic conditions. This article presents the case of a 28-month-old boy with PRF1 -related HLH who developed super-refractory status epilepticus during CNS relapse, despite having undergone a prior hematopoietic stem cell transplantation (HSCT). An initial MRI scan revealed diffuse cortical and cerebellar abnormalities, whereas systemic HLH findings emerged later. Treatment included antiseizure medications, immunotherapy and etoposide, but severe neurologic deficits persisted. A review of the literature on 20 pediatric HLH cases presenting with status epilepticus revealed a variety of presentations, including focal, generalized and febrile infection-related epilepsy syndrome (FIRES). Neuroimaging showed white matter lesions, atrophy or diffusion abnormalities, whereas CSF findings ranged from normal to elevated protein and neopterin levels. Mortality was high (45%), with survivors often experiencing cognitive or motor impairments. HLH relapse can initially present with isolated CNS involvement, emphasizing the need for early neuroimaging and cerebrospinal fluid (CSF) analysis in suspected cases. Despite aggressive treatment, outcomes remain poor, highlighting the need for further research into optimal management strategies.