Shelly Weiss

Epilepsy surgery can be successful in children with extensive congenital or early acquired focal or hemispheric brain lesion on magnetic resonance imaging (MRI) despite generalized interictal epileptiform discharges (IEDs). The aim of this study was to assess if rapid eye movement (REM) sleep reduced generalized IEDs and revealed lateralized IEDs to identify the epileptogenic hemisphere in children with generalized IEDs and normal/subtle changes on MRI. We studied 20 children with generalized IEDs on scalp electroencephalography (EEG) and normal/subtle changes on MRI who underwent intracranial video-EEG for epilepsy surgery. We assessed a minimum of 100 IEDs during REM, non-REM, and wakefulness, and assigned the distribution (generalized, left, or right hemisphere) to each IED. The number of lobes in the resected areas and seizure outcome were compared between 20 children with generalized IEDs and a comparison group of 28 children without generalized IEDs. The mean occurrence rate o...

Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome. Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic (ADOS-G). Of the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009). ASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome.

Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield in epileptic encephalopathy, we performed a retrospective cohort study in a single epilepsy genetics clinic. We included all patients with intractable epilepsy, global developmental delay, and cognitive dysfunction seen between January 2012 and June 2014 in the Epilepsy Genetics Clinic. Electronic patient charts were reviewed for clinical features, neuroimaging, biochemical investigations, and molecular genetic investigations including targeted next-generation sequencing of epileptic encephalopathy genes. Genetic causes were identified in 28% of the 110 patients: 7% had inherited metabolic disorders including pyridoxine dependent epilepsy caused by ALDH7A1 mutation, Menkes disease, pyridox(am)ine-5-phosphate oxidase deficiency, cobalamin G deficiency, methylenetetrahydrofolate reductase deficiency, glucose transporter 1 deficiency, glycine encephalopathy, and pyruvate dehydrogenase complex deficiency; 21% had other genetic causes including genetic syndromes, pathogenic copy number variants on array comparative genomic hybridization, and epileptic encephalopathy related to mutations in the SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, and SLC9A6 genes. Forty-five percent of patients obtained a genetic diagnosis by targeted next-generation sequencing epileptic encephalopathy panels. It is notable that 4.5% of patients had a treatable inherited metabolic disease. To the best of our knowledge, this is the first study to combine inherited metabolic disorders and other genetic causes of epileptic encephalopathy. Targeted next-generation sequencing panels increased the genetic diagnostic yield from <10% to >25% in patients with epileptic encephalopathy.

The relationship between epilepsy and sleep is bidirectional as seizures disrupt sleep and coexisting sleep disorders have detrimental effects on seizure control and quality of life for both the children and their families. Previous research has reported on sleep disturbance in children with epilepsy primarily by subjective parental reports. Actigraphy may provide a more accurate objective evaluation of sleep, but the validity of this sleep measure for children with epilepsy has not yet been assessed. The primary objective of this study was to validate the use of actigraphy as a tool in studying sleep patterns in children with epilepsy. This was a prospective study comparing sleep and wake epochs recorded for 24 h simultaneously by actigraphy and by continuous video-electroencephalography (VEEG) monitoring in 27 patients aged 2-18 years with medically refractory epilepsy. Strong correlations were found between actigraphy and VEEG sleep variables including night sleep period (r = 0.99), night sleep time (r = 0.96), duration of night wake time (r = 0.93) and number of significant wakings during the night (r = 0.81). The study results validate that actigraphy is a reliable and objective clinical and research tool for evaluating sleep and wakefulness in children with epilepsy.

The authors undertook this study to review their experience with cortical resections in the rolandic region in children with intractable epilepsy. The authors retrospectively reviewed the medical records obtained in 22 children with intractable epilepsy arising from the rolandic region. All patients underwent preoperative electroencephalography (EEG), MR imaging, prolonged video-EEG recordings, functional MR imaging, magnetoencephalography, and in some instances PET/SPECT studies. In 21 patients invasive subdural grid and depth electrode monitoring was performed. Resection of the epileptogenic zones in the rolandic region was undertaken in all cases. Seizure outcome was graded according to the Engel classification. Functional outcome was determined using validated outcome scores. There were 10 girls and 12 boys, whose mean age at seizure onset was 3.2 years. The mean age at surgery was 10 years. Seizure duration prior to surgery was a mean of 7.4 years. Nine patients had preoperativ...

The indications for operating on lesions in or near areas of cortical eloquence balance the benefit of resection with the risk of permanent neurological deficit. In adults, awake craniotomy has become a versatile tool in tumor, epilepsy and functional neurosurgery, permitting intra-operative stimulation mapping particularly for language, sensory and motor cortical pathways. This allows for maximal tumor resection with considerable reduction in the risk of post-operative speech and motor deficits. We report our experience of awake craniotomy and cortical stimulation for epilepsy and supratentorial tumors located in and around eloquent areas in a pediatric population (n=10, five females). The presenting symptom was mainly seizures and all children had normal neurological examinations. Neuroimaging showed lesions in the left opercular (n=4) and precentral or peri-sylvian regions (n=6). Three right-sided and seven left-sided awake craniotomies were performed. Two patients had a history ...

We report the finding of unique astrocytic inclusions in a series of pediatric epilepsy patients, all of whom presented with seizures in their first year of life and had mild-to-moderate developmental delay. All eventually underwent surgical treatment for refractory epilepsy and, on pathological examination, were found to have distinctive, eosinophilic, globular cytoplasmic inclusions confined to cortical astrocytes. These inclusions were almost exclusively juxtanuclear, highly refractile, spared distal subpial, or perivascular astrocytic processes and were strongly and exclusively immunopositive for filamin A, an actin binding protein involved in neuronal migration. Identical inclusions have been identified and characterized in cases of Aicardi syndrome, a rare neurodevelopmental disease. The presence of the same inclusions in the cortex of epilepsy patients, some of whom had concomitant brain anomalies related to migrational problems, prompted us to consider that these patients may lie within a spectrum of disease involving dysfunction of filamin or filamin-interacting proteins. The term "filaminopathy" is tentatively proposed as a distinct pathological entity for this condition in which clinical manifestations range from epilepsy in mildly neurologically impaired patients to severe mental and physical handicap in the Aicardi syndrome. Future studies will be necessary to unravel the exact nature of the filamin A protein or gene aberrations in these patients.

Moyamoya disease is a cerebrovascular disease characterized by stenosis and occlusion of the arteries of the circle of Willis, with abnormal telangiectatic collateral circulation at the base of the brain. An association between moyamoya disease and neurofibromatosis 1, a neurocutanoeus disorder, is well established in the literature. However, its association with other neurocutaneous syndromes is infrequently reported. Hypomelanosis of Ito, another neurocutaneous syndrome, is characterized by macular hypopigmented skin whorls and variable neurologic involvement. Only one case study of an association between hypomelanosis of Ito and moyamoya disease has been reported in the English literature. We report a 17-year-old girl with both hypomelanosis of Ito and angiographic moyamoya disease. She presented with intractable seizures, progressive left hemiparesis, and skin manifestations of hypomelanosis of Ito. Although one might consider a coincidental association, this second case points to an association between the two disorders. Detailed neuroimaging, in particular angiography, should be considered in children with hypomelanosis of Ito and abnormal neurologic findings.

The purpose of this study was to identify the pathologic features that predict postoperative outcome in children with cortical dysplasia adjacent to dysembryoplastic neuroepithelial tumors. We reviewed the records of children with dysembryoplastic neuroepithelial tumor who underwent epilepsy surgery and who had at least 1 year of surgical follow-up. We divided the dysembryoplastic neuroepithelial tumors into three pathology classes (simple, complex, and nonspecific), categorized adjunctive cortical dysplasia into four types, and compared histopathology with seizure outcomes. We identified 26 children with dysembryoplastic neuroepithelial tumors. Dysembryoplastic neuroepithelial tumors were complex in 19 patients (73%), simple in 6 (23%), and nonspecific in 1 (4%). Cortical dysplasia was adjacent to dysembryoplastic neuroepithelial tumors in 18 patients. Six patients had type IA cortical dysplasia, 5 had type IB, 3 had type IIA, and 1 had type IIB. The 3 remaining patients had repeated surgeries; of these, 2 patients had cortical dysplasias of type IA/IB and 1 was type IIA/IIB. Eight (39%) of 18 patients with dysembryoplastic neuroepithelial tumors and cortical dysplasia required further surgery for recurrent intractable seizures (P < .05), whereas none of 8 patients without cortical dysplasia required additional surgery. Of 13 patients with type I cortical dysplasia, only 4 had a poor seizure outcome, whereas all 5 patients with type II had a poor seizure outcome postoperatively (P < .05). Children with dysembryoplastic neuroepithelial tumor and cortical dysplasia often had recurrent intractable seizures postoperatively and required further epilepsy surgery. Cortical dysplasia adjacent to dysembryoplastic neuroepithelial tumor can play a role in the epileptogenicity of dysembryoplastic neuroepithelial tumor. Complete resection of a dysembryoplastic neuroepithelial tumor and its adjacent cortical dysplasia should be considered.