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Aim: To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP). Method: Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug‐responsive (n = 83) and drug‐resistant groups (n = 147) using logistic regression and hierarchical cluster analysis. Results: Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug‐resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77–0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy. Interpretation: Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment. What this paper adds: Severe motor and non‐motor impairments in cerebral palsy (CP) increase epilepsy risk.Epilepsy more likely resolves in bilateral spastic and milder CP impairments.Epilepsy in CP often manifests at an early age with multiple seizure types and high drug resistance.Children with a known genetic cause and CP epilepsy surgery group represent distinct clinical subgroups. [ABSTRACT FROM AUTHOR]

Objective: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features and the functional effects of GABRA1 variants to establish genotype–phenotype correlations. Methods: Genetic and electroclinical data of 27 individuals (22 unrelated and 2 families) harboring 20 different GABRA1 variants were collected and accompanied by functional analysis of 19 variants. Results: Individuals in this cohort could be assigned into different clinical subgroups based on the functional effect of their variant and its structural position within the GABRA1 subunit. A homogenous phenotype with mild cognitive impairment and infantile onset epilepsy (focal seizures, fever sensitivity, and electroencephalographic posterior epileptiform discharges) was described for variants in the extracellular domain and the small transmembrane loops. These variants displayed loss‐of‐function (LoF) effects, and the patients generally had a favorable outcome. A more severe phenotype was associated with variants in the pore‐forming transmembrane helices. These variants displayed either gain‐of‐function (GoF) or LoF effects. GoF variants were associated with severe early onset neurodevelopmental disorders, including early infantile developmental and epileptic encephalopathy. Interpretation: Our data expand the genetic and phenotypic spectrum of GABRA1 epilepsies and permit delineation of specific subphenotypes for LoF and GoF variants, through the heterogeneity of phenotypes and variants. Generally, variants in the transmembrane helices cause more severe phenotypes, in particular GoF variants. These findings establish the basis for a better understanding of the pathomechanism and a precision medicine approach in GABRA1‐related disorders. Further studies in larger populations are needed to provide a conclusive genotype–phenotype correlation. ANN NEUROL 2024;95:27–41 [ABSTRACT FROM AUTHOR]

Objective: Infection‐triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes. Methods: We measured CSF neopterin, quinolinic acid, kynurenine and kynurenine/tryptophan ratio using a liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) system. The CSF of 18 children with ITES were compared with acute encephalitis (n = 20), and three control groups, namely epilepsy (n = 20), status epilepticus (n = 18) and neurogenetic controls (n = 20). Results: The main ITES phenotypes in 18 patients were acute encephalopathy with biphasic seizures and late restricted diffusion (AESD, n = 4), febrile infection‐related epilepsy syndrome (FIRES n = 4) and other ITES phenotypes. Influenza A was the most common infectious trigger (n = 5), and 50% of patients had a preceding notable neurodevelopmental or family history. CSF neopterin, quinolinic acid and kynurenine were elevated in ITES group compared to the three control groups (all p < 0.0002). The ROC (area under curve) for CSF neopterin (99.3%, CI 98.1–100) was significantly better than CSF pleocytosis (87.3% CI 76.4–98.2) (p = 0.028). Elevated CSF neopterin could discriminate ITES from other causes of seizures, status epilepticus and febrile status epilepticus (all p < 0.0002). The elevated CSF metabolites normalised during longitudinal testing in two patients with FIRES. Interpretation: CSF neopterin and quinolinic acid are neuroinflammatory and excitotoxic metabolites. This CSF metabolomic inflammatory panel can discriminate ITES from other causes of new onset seizures or status epilepticus, and rapid results (4 h) may facilitate early immune modulatory therapy. [ABSTRACT FROM AUTHOR]

Aim: To investigate the psychosocial impact of genetic testing for childhood‐onset developmental and epileptic encephalopathies (DEEs) in order to identify parents' information and support needs. Method: In this mixed‐methods study, we conducted in‐depth semi‐structured interviews with parents (n=25) of children, recruited from the Sydney Children's Hospital Network, Australia, who had received genetic testing. Thematic saturation was reached; interviews were transcribed, deidentified, line‐by‐line coded, and thematically analysed by three coders, using an inductive approach. We also quantitatively assessed the impact of genetic testing on quality of life outcomes and parents' satisfaction with genetics services. Results: Qualitative and quantitative analysis revealed that compassionate genetic counselling and consistent clinician–parent partnerships facilitated parents' capacity to process their child's genetic diagnosis. Parents believed that a sparsity of diagnosis‐specific information to contextualize their child's genetic DEE, combined with limited psychosocial resources to support coping with ongoing prognostic uncertainty, contributed to chronic psychological stress. Access to diagnosis‐specific resources and peer support was considered necessary to support parents in communicating their child's genetic DEE and to reduce social isolation. Interpretation: Integrated psychosocial resources, including tailored psychological supports, diagnosis‐specific information, and peer‐to‐peer supports, are priority areas to complement genetic services. podcast : (https://youtu.be/3tFjqndfQuI) This original article is commented by Tumiene on page 13 of this issue. [ABSTRACT FROM AUTHOR]

Byline: Kavitha. Kothur, Subhash. Kaul, S. Rammurthi, V. C. S.. Bandaru, Suvarna Alladi. Suryaprabha, K. Mrudula Cerebral venous thrombosis developing concurrently with active ulcerative colitis poses a therapeutic dilemma. We [...]

Byline: Kavitha. Kothur, Munni. Ray, Prahbhjot. Malhi Tuberous sclerosis complex (TSC) is an inherited genetic disorder commonly associated with neuropsychiatric complications like epilepsy, mental retardation, autism and other behavioral problems [...]

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Aim To determine the role of inflammation in pediatric transient focal cerebral arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. Methods We measured 32 cytokine/chemokines in acute cerebrospinal fluid collected from children with stroke due to focal cerebral arteriopathy (n = 5) using multiplex immunoassay and compared with two patients with arterial ischemic stroke due to other causes (non-focal cerebral arteriopathy group, vertebral dissection, n = 1; cryptogenic, n = 1), pediatric encephalitis (n = 43), and non-inflammatory neurological disease controls (n = 20). Results Median age in the focal cerebral arteriopathy group was 9.3 years (range, 2.8–13 years). In the focal cerebral arteriopathy group (n = 5), four patients had middle cerebral ± distal carotid arteriopathy; one patient had posterior circulation arteriopathy. The median time from symptom onset to cerebrospinal fluid sampling was four days (range, 0.6–7 days). Only IL-6, IL-8, CXCL1, and CXCL10 levels were significantly higher in the acute cerebrospinal fluid of focal cerebral arteriopathy patients compared to non-inflammatory neurological disease controls and non-focal cerebral arteriopathy stroke. In contrast to focal cerebral arteriopathy, a broad array of Th1, Th2, Treg, Th17, B-cell related, and other broad spectrum cytokine/chemokines were elevated in encephalitis. Conclusion The elevated cerebrospinal fluid cytokine/chemokines support innate, T cell, and granulocyte inflammatory mechanisms in children with focal cerebral arteriopathy. This warrants larger cohort studies to discriminate primary inflammatory signals of the arteriopathy from secondary inflammation due to the stroke itself. [ABSTRACT FROM AUTHOR]

Objectives: There is no information available on the follow-up of children with Kawasaki disease (KD) in developing countries. This prospective study was undertaken to evaluate the cardiac abnormalities in a cohort of children with KD from a tertiary care centre in Northern India., Methods: Twenty children with diagnoses of KD and followed-up for at least 3 months in the Pediatric Rheumatology and Immunology Clinic of the Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh were evaluated between July 2002 to January 2006. Age of onset of disease ranged from 12 months to 10 years. The male: female ratio was 4:1. All patients had received intravenous immunoglobulin (IVIG) administration in the acute stage. Chest radiography showed no abnormalities in the 15 patients in whom it was done. Electrocardiographic abnormalities were seen in 3 patients in the form of T wave inversion in 3, ST segment changes in 2, and prolonged PR interval in 1 patient which normalized on follow-up. The mean time interval between the diagnosis of KD and first follow-up echocardiography was 7.9 +/- 3.5 months (range 4.4-11.4 months), which was repeated at 1 year and 2 years follow-up in patients who had abnormal findings. When we analyzed coronary artery diameters using Japanese Ministry of Health criteria, none of our patients could qualify for a diagnosis of coronary aneurysm. However, 3 had coronary artery diameters more than + 2 SD when the body surface area adjusted coronary dimensions were used., Results: One of our patients also had increased left ventricular dimensions but also had normal ejection fraction and shortening fraction, and there were no regional wall motion abnormalities. Mitral valve was thickened in 2 patients and trivial mitral regurgitation was noticed in 1 patient. Repeat echocardiography done 1 year and 2 years later on follow-up, showed persistence of thickening of the mitral valve leaflet in one of these but there was no regurgitation. None of our patients had evidence of cardiac failure, arrhythmia or myocardial infarction. There was no mortality in this series. Thallium scans were carried out during follow-up on 14 patients in this cohort and 2 patients showed perfusion defects in anterior wall, septum and posterior wall of lateral ventricle., Conclusions: We conclude that significant myocardial dysfunction and coronary artery changes due to KD were uncommon in our cohort. We speculate that this can be attributed to the IVIG given to the patients during the acute phase of the illness. To the best of our knowledge, this is the first study on detailed cardiac follow-up of children with KD from a developing country.

Pulmonary manifestations of sarcoidosis are common and may be initially confused with other common diseases like tuberculosis. We report an 11 yr old girl who presented with chronic cough, low grade fever, recent exposure to tuberculosis and hilar lymphadenopathy. She was provisionally diagnosed as pulmonary tuberculosis and treated accordingly. As she had poor response to anti tubercular therapy, diagnosis was subsequently revised to sarcoidosis by lung biopsy. Treatment with steroids resulted in significant clinical improvement.