SUMMARYPurpose: Febrile infection-related epilepsy syndrome (FIRES) is an increasingly recognized epileptic syndrome that presents with multifocal refractory status epilepticus in previously normal children and evolves into a chronic, refractory, focal epilepsy with associated cognitive and behavioral difficulties. Herein we describe the features of the chronic epilepsy and critically review evidence for the etiology of this syndrome. Methods: Seven patients with FIRES were studied. The duration of follow-up in six survivors was 5-17 years. Clinical, electroencephalography (EEG), neuroimaging, and other investigative findings during the acute and chronic phases were reviewed. Key Findings: These previously normal children presented with a febrile illness and status epilepticus that was refractory to antiepileptic medications in all children, to immunotherapies (including immunoglobulin, corticosteroids, plasma exchange, and rituximab) in four, and to acute vagus nerve stimulation in one. Markers of cerebral inflammation were few and response to antiepileptic and immunomodulatory therapies was poor. Evolution to chronic epilepsy occurred without a silent period. Seizure characteristics in the chronic phase were strikingly stereotyped and similar to the acute phase, with head and eye version, unilateral facial jerking, asymmetric tonic posturing, and unilateral limb jerking in all patients. Electrographic ictal onset was lateralized in all recorded seizures, unilateral in one patient, and independent bilateral in three. Seizures were refractory to multiple antiepileptic medications in all patients and partly responsive to chronic vagus nerve stimulation in two patients. Moderate to severe intellectual impairment was noted in four patients, and borderline intellectual abilities were noted in two. Magnetic resonance imaging (MRI) in the chronic phase was normal in three patients and showed mild diffuse cortical atrophy and/or mild hippocampal atrophy or sclerosis in three. Significance: The similar perirolandic and perisylvian features of acute and chronic seizures, the lack of a silent period, the absence of evidence of cerebral inflammation, and the poor response to immunotherapies suggest FIRES is best conceptualized as a chronic epilepsy with explosive onset, not a remote-symptomatic epilepsy with an acute inflammatory antecedent.

Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. Methods: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.

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Background and Purpose:Clinical prediction rules (CPR) are clinical decision-making tools containing variables such as history, physical examination, diagnostic tests by developing scoring model from potential risk factors. This study is to establish clinical prediction scoring of drug-resistant epilepsy (DRE) in children using clinical manifestationa and only basic electroencephalography (EEG).Methods:Retrospective cohort study was conducted. A total of 308 children with diagnosed epilepsy were recruited. Primary outcome was the incidence of DRE. Independent determinants were patient characteristics, clinical manifestations and electroencephalography. CPR was performed based on multiple logistic regression.Results:The incidence of DRE was 42%. Risk factors were age onset, prior neurological deficits, and abnormal EEG. CPR can be established and stratified the prediction using scores into 3 levels such as low risk (score<6), moderate risk (score 6–12) and high risk (score>12) with positive likelihood ratio of 0.5, 1.8 and 12.5 respectively.Conclusions:CPR with scoring risks were stratified into 3 levels. The strongest risk is prior global neurological deficits.

BackgroundStroke is relatively rare in children but has a significant impact on long-term morbidity and mortality. There are limited data regarding the etiology, clinical manifestation, and prognosis of arterial ischemic stroke (AIS) and hemorrhagic stroke (HS) in children.ObjectiveThe aim of this study is to identify and compare etiology, risk factors, clinical manifestations, and prognostic outcomes between arterial ischemic and hemorrhagic pediatric stroke.MethodsWe retrospectively reviewed all hospital medical records and pediatric neurology database of 83 children who were first diagnosed with AIS and HS at the Pediatric Department, Chiang Mai University Hospital, Chiang Mai, Thailand between January 1, 2009, and December 31, 2018. All children were from 1 month to 18 years old.ResultsFifty-one AIS (56%) and 32 (35.2%) HS were identified. The median age of onset was 6.9 years for AIS and 5.3 years for HS. Moyamoya disease/syndrome was the most common cause in AIS (21.6%). Rupture of cerebral arteriovenous malformation was the most common cause in HS (21.9%). More than one-third (39%) of children had multiple risk factors associated with stroke. Iron deficiency anemia was commonly found in children with AIS (39.2%). The majority of clinical presentations were hemiparesis (80.4%) for AIS and alteration of consciousness (68.8%) for HS. The median time to diagnosis exceeded 6 hours in both AIS and HS. The overall mortality rate of acute stroke was 5.1 per 100 person-years (95% confidence interval [CI], 2.9–9). The mortality rate was higher in HS compared with that in AIS with statistical significance (16.6; 95% CI, 8.9–30.8 vs 1.1%; 95% CI, 0.3–4.6 per 100 person-years). Thirty children (36.1%) developed epilepsy during the follow-up (median duration, 26 months). Recurrent stroke occurred in 1 child with AIS and 1 child with HS.ConclusionsMoyamoya disease/syndrome and arteriovenous malformation rapture are the most common cause of AIS and HS, respectively. Iron deficiency anemia was commonly found in childhood AIS. The time to diagnosis in both AIS and HS was delayed. The mortality rate in HS was higher than in AIS. Neurological deficits are seen in 70% of childhood AIS during the follow-up. One-third of the children in our study developed epilepsy, which generally responds to a single antiseizure medication. The recurrence rate of childhood stroke was low compared with adult stroke.

Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients. Methods TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2). Results Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%). Conclusion Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.

We report a case of a perinatally HIV-infected patient aged 9 years, who presented with right-sided hemiplegia. His initial CD4 T-cell was of 0.21% (4 cells/μL) and plasma HIV RNA virus of 185 976 copies/mL (log 5.27). Plasma and CSF samples were subsequently positive for JCV. Twelve days after the initiation of highly active antiretroviral therapy (HAART), the MRI showed progressive white matter lesions with asymmetrical deep and subcortical white matter lesions over the left frontotemporoparietal region and the right frontal lobe. Immune Reconstitution Inflammatory Syndrome (IRIS) was suspected, and the patient was treated with methylprednisolone. His clinical symptoms worsened and despite therapy the patient deteriorated.

Background Febrile seizures are the most common seizures in children. Children with complex febrile seizures have a higher risk of subsequent epilepsy compared with children with simple febrile seizures. Multiple risks factors for epilepsy, including focal status epilepticus, family history of epilepsy, neurodevelopmental abnormalities and abnormal electroencephalogram findings, have been found with inconsistent results. The aim of this study is to identify risk factors for developing epilepsy in children with complex febrile seizures. Methods The study included 248 children aged 3–72‐months, diagnosed with complex febrile seizures at Chiang Mai University Hospital. Demographic data, seizure characteristics, electroencephalogram and neuroimaging findings were identified, and assessed to establish whether they were risk factors for subsequent epilepsy. Results Fifty‐five patients (22.1%) had subsequent epilepsy. Using Cox regression‐survival analysis, factors associated with epilepsy were prolonged seizures >15 min (P = 0.006; Hazard Ratio (HR): 2.475; 95% Confidence Interval (CI): 1.294–4.735), developmental delay (P = 0.019; HR: 4.476; 95% CI: 2.280–15.646), epileptiform discharges on electroencephalogram (P = 0.023; HR: 1.391; 95%CI: 1.174–1.876), and abnormal neuroimaging (computed tomography or magnetic resonance imaging; P = 0.028; HR: 1.355; 95% CI: 1.034–1.776). Age at onset, peak febrile temperature, duration between the onset of fever and the occurrence of seizure, recurrent seizures within 24 h, focal seizures, abnormal neurological exams and family history of febrile seizure or epilepsy were not associated with increased risk of subsequent epilepsy in this study. Conclusions Risk factors associated with increased risk of epilepsy in children with complex febrile seizures are prolonged seizures or febrile status epilepticus, developmental delay, electroencephalogram epileptiform discharges, and abnormal neuroimaging. Their presence would merit close clinical monitoring.