Hüseyin Kılıç

Objective: Childhood cerebrovascular diseases (CVDs) comprise a heterogeneous group of disorders associated with significant neurological morbidity and long-term functional impairment. Despite increasing awareness, epidemiological and outcome data in pediatric populations remain limited. This study aimed to evaluate the demographic characteristics, etiological distribution, clinical presentation, neuroimaging findings, treatment approaches, and long-term outcomes of pediatric patients diagnosed with CVD in a tertiary pediatric neurology center. Methods: This retrospective single-center study included 25 pediatric patients diagnosed with CVD and followed up between 2010 and 2026. Demographic data, clinical findings, etiological factors, neuroimaging characteristics, treatment strategies, and follow-up outcomes were retrospectively reviewed. Functional outcomes were assessed using the Modified Rankin Scale (mRS). Results: The mean age at diagnosis was 8.4 years, and 60% of patients were male. Ischemic stroke was identified in 68% of patients, whereas 32% had hemorrhagic stroke. Hematologic/thrombophilic disorders and vasculopathies represented the most common etiological subgroups. Acute-onset hemiparesis, headache, and seizures were the leading presenting symptoms. Neuroimaging abnormalities were detected in all patients, with multiple lesions observed in 68% and bilateral involvement in 44% of cases. Pediatric intensive care unit admission was significantly more frequent among patients with hemorrhagic stroke (P < .001), and was significantly associated with long-term neurological sequelae development (P = .004). Long-term neurological sequelae were identified in 60% of patients, and post-stroke epilepsy developed in 52%. Mortality was 4%, while the median mRS score at the last follow-up visit was 2. Conclusion: Pediatric CVDs are associated with substantial long-term neurological burden despite relatively low mortality rates. Hemorrhagic events were linked to more severe clinical outcomes and higher intensive care requirements. Early recognition, comprehensive neurovascular imaging, and multidisciplinary long-term follow-up are essential for improving neurological outcomes in affected children. Cite this article as: Sengenc E, Tunc A, Guler S, et al. From acute events to chronic burden: a 16-year single-center experience in pediatric cerebrovascular diseases. Cerrahpaşa Med J 2026, 50, 0098, doi: 10.5152/cjm.2026.26098.

Background/Objectives: Pediatric Takayasu arteritis (PTA) is a rare large-vessel vasculitis with limited data regarding neurological involvement. This study aimed to evaluate neurological manifestations and associated neuroimaging findings in a cohort of children with PTA. Methods: In this retrospective observational study, 22 patients diagnosed with PTA and followed at a tertiary center between January 2000 and April 2025 were included. Neurological symptoms, examination findings, and neuroimaging data were reviewed. Angiographic involvement was classified according to the Numano classification. Results: Neurological involvement was identified in 5 patients (22.7%), including ischemic stroke (n = 3) and hypertensive encephalopathy (n = 2). Neurological symptoms were present in 15 patients (68.2%), with headache being the most common manifestation (54%). Other symptoms included dizziness, paresthesia, visual disturbances, syncope, and seizures. Neuroimaging revealed ischemic lesions in a subset of patients, as well as nonspecific white matter changes. Angiographic evaluation showed a predominance of extensive disease patterns, particularly Type V and Type IV involvement. Conclusions: Neurological manifestations in pediatric Takayasu arteritis are common but often nonspecific. However, severe complications such as stroke and hypertensive encephalopathy may occur and can be the initial presentation. Careful neurological evaluation and the use of neuroimaging are essential for early detection and appropriate management.

Primary hereditary microcephaly (MCPH) comprises a group of genetically heterogeneous disorders characterized by severe microcephaly and mild intellectual disability. It differs from syndromic primary microcephaly (PM) by the lack of syndromic features and major brain malformations. We evaluated the genetic diagnostic yield, pathogenic mechanisms, and clinical features of these two PM groups in 87 patients from 64 families. Exome sequencing was performed on probands, 52 of whom had consanguineous parents. The diagnostic yield was 53.1%. Of the 34 disease‐causing variants identified, 15 were novel, with 83.7% being biallelic. MCPH‐associated genes were found in 17.2% of families, while syndromic PM accounted for 35.9%. Most patients in both groups had speech delay. In the MCPH group, borderline to mild intellectual disability, independent of microcephaly severity, and behavioral abnormalities were prominent, whereas severe intellectual disability was more common in the syndromic group. Notably, most genes associated with MCPH are involved in mitotic division and DNA repair pathways, while those in syndromic PM are involved in transcription regulation and cell trafficking pathways. A bird‐like facial gestalt was observed in patients from both groups with genes related to mitotic division and DNA repair. In addition, we expanded the genetic heterogeneity to include a potential candidate gene, KNTC1 .

Background: Therapeutic plasma exchange (TPE) removes circulating pathogenic antibodies, immune complexes, cytokines, and complement components. While established in adult neurology, evidence on its safety and efficacy in pediatric neurocritical care remains limited. Objective: To evaluate the indications, clinical efficacy, and safety of TPE in children with acute or subacute immune‐mediated neurological disorders admitted to the pediatric intensive care unit (PICU). Methods: A retrospective cohort of 24 pediatric patients (aged 1–18 years) treated with TPE between February 2023 and October 2025 was analyzed. Diagnoses included multiple sclerosis ( n = 8), Guillain–Barré syndrome ( n = 5), acute disseminated encephalomyelitis ( n = 3), transverse myelitis ( n = 3), autoimmune encephalitis ( n = 3), optic neuritis ( n = 1), and myasthenia gravis ( n = 1). Patients received 3–7 TPE sessions. Clinical response was measured using the modified Rankin Scale (mRS) and GBS disability scores before and after treatment. Results: A total of 130 sessions were performed. Clinical improvement occurred in 20 of 24 patients (83%)—moderate in 8 (33%) and mild in 12 (50%). Median mRS/GBS scores decreased from 4.0 to 3.0 ( p = 0.001). Early initiation of TPE (≤ 7 days from symptom onset) was associated with a higher likelihood of neurological improvement in multivariable analysis. No life‐threatening complications were observed. Transient, reversible events included hypocalcemia (2.3%), hypotension (1.5%), and urticaria (1.6%). Conclusion: TPE appears to be a safe and potentially beneficial intervention for severe or refractory pediatric neuroimmunological disorders. Earlier initiation of TPE was associated with improved neurological outcomes; however, these findings should be interpreted cautiously given the small sample size and heterogeneous disease groups. These findings support integrating TPE into multidisciplinary PICU management and add to the growing evidence supporting its use in pediatric neuroimmunology.

Background: Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype–phenotype correlations and diagnostic yield vary substantially across disease entities. Methods:We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology–based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Results: Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Conclusions: Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype–phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice.

Neurodevelopmental disorders (NDDs) with ataxia are genetically heterogeneous and remain a diagnostic challenge. Recent advances in genomic technologies have facilitated the identification of rare, potentially causative variants in genes not traditionally associated with classic NDD phenotypes. The DNAH14 gene, encoding a dynein axonemal heavy chain involved in ciliary motility, has recently emerged as a novel candidate in neurological syndromes. Here, we report two Turkish siblings presenting with late-onset balance disorder, progressive ataxia, and cognitive impairment. Initial genetic analysis revealed that both siblings also harbor FXN GAA repeat expansions consistent with pathogenic Friedreich’s ataxia (FRDA). To elucidate the molecular basis of the patients’ cognitive impairment, whole-exome sequencing was performed. This analysis identified a novel homozygous frameshift variant in the DNAH14 gene, located within the conserved linker domain upstream of the motor core, which is critical for ATP hydrolysis and microtubule interactions. The variant is absent from population databases, predicted to be deleterious by multiple in silico algorithms, and segregates in the family in a manner consistent with autosomal recessive inheritance. The coexistence of FRDA expansions and a truncating DNAH14 variant suggests a potential dual genetic contribution to the observed phenotype, in which FRDA-associated pathology likely underlies the ataxia, while DNAH14 disruption may contribute to additional neurodevelopmental features. This is the first report describing the co-occurrence of FRDA and a homozygous truncating DNAH14 variant in the same individuals, broadening our understanding of overlapping neurogenetic mechanisms. Our findings expand the phenotypic spectrum of DNAH14-related disorders and highlight the importance of considering multilocus pathogenic variants in patients with complex or atypical ataxia presentations.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterised by defi-cits in social communication and stereotyped, restrictive behaviour. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a rare, autosomal recessive neurogenetic dis-order associated with a range of neurodevelopmental disorders, particularly ASD. We report the case of a 4.5-year-old boy with failure to thrive, microcephaly and global developmental delay. Plasma amino acid analysis revealed significantly reduced branched-chain amino acid (BCAA) concentrations. Whole-exome sequencing identified a homozygous nonsense variant in BCKDK. A multidisciplinary programme was initiated that included individualised high-protein medical nutrition therapy and oral BCAA supplementation titrated according to serial plasma levels. After eight months, plasma BCAA levels approached the lower limit of the normal range and behavioural improvements were sustained. Targeted dietary optimisation with additional BCAA supplementation partially normalised amino acid profiles and led to a measurable improvement in neurobehaviour in BCKDK deficiency, even when treatment was initiated after the diagnosis of ASD. Early metabolic screening of children with unexplained developmental delay or ASD is advisable, as timely nutrition-based intervention can improve both biochemical and neurodevelopmental outcomes.