It is well documented that children with autistic spectrum disorder (ASD) have an increased preva... more It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome.
Epilepsy surgery can be successful in children with extensive congenital or early acquired focal ... more 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 dis... more 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.
Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Académie canadienne de psychiatrie de l'enfant et de l'adolescent, 2014
Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield ... more 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.
Introduction: Occipital lobe epilepsy (OLE) poses a diagnostic challenge to clinicians. Here, we ... more Introduction: Occipital lobe epilepsy (OLE) poses a diagnostic challenge to clinicians. Here, we present our experience in the surgical management of OLE in children using magnetoencephalography (MEG) in the pre-operative evaluation. Methods: Retrospective chart review was performed from 2000 to 2010 to identify patients with OLE. Patients were analyzed in two categories: isolated OLE (11 patients) and extended OLE (parietooccipital, temporooccipital, and temporoparietooccipital; 30 patients). Survival analysis and multivariate Cox proportional hazards regression were used to identify independent predictors of seizure outcome. Results: Forty-one patients with a mean follow-up of 3.1 years were identified with an overall 68% rate of satisfactory seizure outcome. Patients with extended OLE had younger ages at seizure onset and different seizure semiologies compared with those with isolated OLE. None of the latter underwent insertion of subdural grid electrodes for localization of the epileptogenic zone compared with 77% of the former (p < 0.001). On multivariate analysis, the strongest independent predictor of unsatisfactory outcome was MEG dipoles in the occipital lobe contralateral to resection. G.M. Ibrahim et al.
Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onse... more Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onset epilepsy, brain structural anomalies, and developmental delay, which indicates that it may represent a unique clinicopathologic entity. To further characterize this condition we use proteomics to investigate differentially expressed proteins in epileptic brain tissue from three pediatric epileptic patients with cerebral hyaline astrocytic inclusions, ranging in age from 5-13 years, and compare to brain tissue from two normal controls. Catalase and carbonic anhydrase I both exhibited increased expression in epileptic brain tissue compared to controls. These findings were confirmed by Western blot analysis. Furthermore, both proteins were localized to astrocytes and in epileptic brain were located within the cerebral hyaline astrocytic inclusions, suggesting a potential role in the generation of this pathologic feature of early onset epilepsy with cerebral hyaline astrocytic inclusions.
Objective To evaluate the effectiveness of a behavioural-educational sleep intervention delivered... more Objective To evaluate the effectiveness of a behavioural-educational sleep intervention delivered in the early postpartum in improving maternal and infant sleep.
Background: Sleep problems are common among children with chronic illnesses such as Juvenile Idio... more Background: Sleep problems are common among children with chronic illnesses such as Juvenile Idiopathic Arthritis (or JIA). However, little is known about the frequency and severity of sleep disturbance(s) and the factors that are associated with sleep problems in children with JIA. The mechanism(s) of the relationships characterizing the development or exacerbation of sleep problems in children with JIA are still unknown, however studies have reported an association. The purpose of this study was to synthesize existing research related to sleep problems in children with JIA. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. An experienced librarian conducted searches in MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to January 2012, to identify potentially relevant citations. Two members independently selected, rated methodological quality using the QUIPS tool, and extracted data from included studies. Results: Ten studies were included and findings varied across studies; studies were mostly cross-sectional, or casecontrolled designs, with only one cohort study available. Four studies found that children and adolescents diagnosed with JIA had significantly more sleep disturbances when compared to healthy controls. Pain was most often associated with sleep disturbances. The heterogeneous findings highlight the complex relationships between JIA and sleep, and low methodological quality of studies in the field. Conclusions: This review supports an association between poor sleep and increased symptoms related to JIA, specifically the experience of pain. However, results need to be interpreted cautiously given the inconsistent findings regarding factors associated with sleep problems in JIA, the limited evidence available, and its low quality. Furthermore it is not yet determined if the poor sleep patterns predate the symptoms reported with JIA. More research is vital to understanding the factors that predict or perpetuate poor sleep in children and adolescents diagnosed with JIA.
The relationship between epilepsy and sleep is bidirectional as seizures disrupt sleep and coexis... more 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.
Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In t... more Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. We reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. The mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous...
The authors undertook this study to review their experience with cortical resections in the rolan... more 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...
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2014
The indications for operating on lesions in or near areas of cortical eloquence balance the benef... more 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 ...
Journal of the International Neuropsychological Society, 2007
We investigated language representation in nine children (six male, three female; 5.6-17.7 years ... more We investigated language representation in nine children (six male, three female; 5.6-17.7 years of age) who underwent surgical treatment of medically intractable epilepsy of the left hemisphere. Although interhemispheric reorganization has been previously documented in similar groups, this is the first study to systematically evaluate possible intrahemispheric effects of early insult. All cases had left hemisphere seizure foci and underwent extraoperative stimulation mapping (ESM) for language localization prior to receiving cortical resections. To compare ESM findings across subjects and to assess intrahemispheric reorganization, we developed a novel coregistration technique whereby independent raters plotted two-dimensional (2D) ESM findings in 3D standard space. Expressive language sites identified with ESM were compared with a structural probability map of pars opercularis, or Broca's area. The average difference between independent raters' estimates of 28 language sites was 3.9 mm (SD 5 2.0), indicating excellent agreement; the coregistration procedure permitted assessment of 2D ESM findings in 3D standard space. We observed language sites in regions substantially anterior and superior to canonical Broca's area, possibly reflecting intrahemispheric reorganization. Findings suggest that left hemisphere insult in young children may result in anterior displacement of language within the frontal cortex. (JINS, 2007, 13, 505-516.)
Journal of Neuropathology and Experimental Neurology, 2008
We report the finding of unique astrocytic inclusions in a series of pediatric epilepsy patients,... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;filaminopathy&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 arte... more 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 objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin... more The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism.
It is well documented that children with autistic spectrum disorder (ASD) have an increased preva... more It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome.
Epilepsy surgery can be successful in children with extensive congenital or early acquired focal ... more 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 dis... more 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.
Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Académie canadienne de psychiatrie de l'enfant et de l'adolescent, 2014
Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25% in patients with epileptic encephalopathy.
Introduction: Occipital lobe epilepsy (OLE) poses a diagnostic challenge to clinicians. Here, we ... more Introduction: Occipital lobe epilepsy (OLE) poses a diagnostic challenge to clinicians. Here, we present our experience in the surgical management of OLE in children using magnetoencephalography (MEG) in the pre-operative evaluation. Methods: Retrospective chart review was performed from 2000 to 2010 to identify patients with OLE. Patients were analyzed in two categories: isolated OLE (11 patients) and extended OLE (parietooccipital, temporooccipital, and temporoparietooccipital; 30 patients). Survival analysis and multivariate Cox proportional hazards regression were used to identify independent predictors of seizure outcome. Results: Forty-one patients with a mean follow-up of 3.1 years were identified with an overall 68% rate of satisfactory seizure outcome. Patients with extended OLE had younger ages at seizure onset and different seizure semiologies compared with those with isolated OLE. None of the latter underwent insertion of subdural grid electrodes for localization of the epileptogenic zone compared with 77% of the former (p < 0.001). On multivariate analysis, the strongest independent predictor of unsatisfactory outcome was MEG dipoles in the occipital lobe contralateral to resection. G.M. Ibrahim et al.
Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onse... more Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onset epilepsy, brain structural anomalies, and developmental delay, which indicates that it may represent a unique clinicopathologic entity. To further characterize this condition we use proteomics to investigate differentially expressed proteins in epileptic brain tissue from three pediatric epileptic patients with cerebral hyaline astrocytic inclusions, ranging in age from 5-13 years, and compare to brain tissue from two normal controls. Catalase and carbonic anhydrase I both exhibited increased expression in epileptic brain tissue compared to controls. These findings were confirmed by Western blot analysis. Furthermore, both proteins were localized to astrocytes and in epileptic brain were located within the cerebral hyaline astrocytic inclusions, suggesting a potential role in the generation of this pathologic feature of early onset epilepsy with cerebral hyaline astrocytic inclusions.
Objective To evaluate the effectiveness of a behavioural-educational sleep intervention delivered... more Objective To evaluate the effectiveness of a behavioural-educational sleep intervention delivered in the early postpartum in improving maternal and infant sleep.
Background: Sleep problems are common among children with chronic illnesses such as Juvenile Idio... more Background: Sleep problems are common among children with chronic illnesses such as Juvenile Idiopathic Arthritis (or JIA). However, little is known about the frequency and severity of sleep disturbance(s) and the factors that are associated with sleep problems in children with JIA. The mechanism(s) of the relationships characterizing the development or exacerbation of sleep problems in children with JIA are still unknown, however studies have reported an association. The purpose of this study was to synthesize existing research related to sleep problems in children with JIA. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. An experienced librarian conducted searches in MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to January 2012, to identify potentially relevant citations. Two members independently selected, rated methodological quality using the QUIPS tool, and extracted data from included studies. Results: Ten studies were included and findings varied across studies; studies were mostly cross-sectional, or casecontrolled designs, with only one cohort study available. Four studies found that children and adolescents diagnosed with JIA had significantly more sleep disturbances when compared to healthy controls. Pain was most often associated with sleep disturbances. The heterogeneous findings highlight the complex relationships between JIA and sleep, and low methodological quality of studies in the field. Conclusions: This review supports an association between poor sleep and increased symptoms related to JIA, specifically the experience of pain. However, results need to be interpreted cautiously given the inconsistent findings regarding factors associated with sleep problems in JIA, the limited evidence available, and its low quality. Furthermore it is not yet determined if the poor sleep patterns predate the symptoms reported with JIA. More research is vital to understanding the factors that predict or perpetuate poor sleep in children and adolescents diagnosed with JIA.
The relationship between epilepsy and sleep is bidirectional as seizures disrupt sleep and coexis... more 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.
Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In t... more Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. We reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. The mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous...
The authors undertook this study to review their experience with cortical resections in the rolan... more 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...
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2014
The indications for operating on lesions in or near areas of cortical eloquence balance the benef... more 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 ...
Journal of the International Neuropsychological Society, 2007
We investigated language representation in nine children (six male, three female; 5.6-17.7 years ... more We investigated language representation in nine children (six male, three female; 5.6-17.7 years of age) who underwent surgical treatment of medically intractable epilepsy of the left hemisphere. Although interhemispheric reorganization has been previously documented in similar groups, this is the first study to systematically evaluate possible intrahemispheric effects of early insult. All cases had left hemisphere seizure foci and underwent extraoperative stimulation mapping (ESM) for language localization prior to receiving cortical resections. To compare ESM findings across subjects and to assess intrahemispheric reorganization, we developed a novel coregistration technique whereby independent raters plotted two-dimensional (2D) ESM findings in 3D standard space. Expressive language sites identified with ESM were compared with a structural probability map of pars opercularis, or Broca's area. The average difference between independent raters' estimates of 28 language sites was 3.9 mm (SD 5 2.0), indicating excellent agreement; the coregistration procedure permitted assessment of 2D ESM findings in 3D standard space. We observed language sites in regions substantially anterior and superior to canonical Broca's area, possibly reflecting intrahemispheric reorganization. Findings suggest that left hemisphere insult in young children may result in anterior displacement of language within the frontal cortex. (JINS, 2007, 13, 505-516.)
Journal of Neuropathology and Experimental Neurology, 2008
We report the finding of unique astrocytic inclusions in a series of pediatric epilepsy patients,... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;filaminopathy&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 arte... more 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 objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin... more The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism.
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Papers by Shelly Weiss