To examine the safety and efficacy of zonisamide in treating myoclonic seizures associated with progressive myoclonic epilepsy (PME), in an open-label setting. Thirty patients with refractory PME (aged > or = 5 years), who were taking... more
To examine the safety and efficacy of zonisamide in treating myoclonic seizures associated with progressive myoclonic epilepsy (PME), in an open-label setting. Thirty patients with refractory PME (aged > or = 5 years), who were taking up to three antiepileptic drugs, received adjunctive zonisamide (< or = 6 mg/kg/day) therapy for 16 weeks. Myoclonic seizures were recorded daily over a 24-hour period or in 10-minute epochs in the morning, afternoon, and evening. Safety was assessed via adverse events (AEs); efficacy was measured by the percentage of patients experiencing a > or = 50% decrease in myoclonic seizure frequency from baseline. Treatment-related AEs, experienced by 53% (n = 16/30) of patients, led to five patients discontinuing zonisamide. The most common AEs were decreased appetite, somnolence, and asthenia. Overall, 36% of patients (n = 10/28) had a > or = 50% reduction in myoclonic seizure frequency. These results suggest that zonisamide may be useful in the ...
Research Interests: Epilepsy, Adolescent, Medicine, Humans, Child, and 7 moreFemale, Male, Clinical Sciences, Adult, Seizures, Myoclonus, and Child preschool
To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind,... more
To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analy...
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Vagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people withdrug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessfulsurgery or are unsuitable for surgery. A... more
Vagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people withdrug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessfulsurgery or are unsuitable for surgery. A systematic review and meta-analysis were conducted todetermine the treatment effects of VNS Therapy as an adjunct to anti-seizure medications (ASMs) forthe management of adults with DRE.A literature search was performed in August 2020 of the Medline®, Medline® Epub Ahead of Print,Embase, and the Cochrane library databases. Outcomes examined included reduction in seizurefrequency, seizure freedom, ASM load, discontinuations, and serious adverse events (SAEs).Comparators included best medical practice, ASMs, low-stimulation or sham VNS Therapy.Four RCTs and six comparative observational studies were identified for inclusion. Against comparators,individuals treated with VNS had a significantly better odds of experiencing a ≥50% reduction in seizurefreq...
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Nineteen premature infants with progressive posthemorrhagic hydrocephalus with increased intracranial pressure were treated with external ventricular drainage. Progression of hydrocephalus was arrested during the drainage period in each... more
Nineteen premature infants with progressive posthemorrhagic hydrocephalus with increased intracranial pressure were treated with external ventricular drainage. Progression of hydrocephalus was arrested during the drainage period in each patient. Three of the 19 infants required no further therapy. Sixteen had recurrence of progressive ventricular dilatation, and all but one eventually had placement of a ventriculoperitoneal shunt, although under more favorable medical conditions than existed at the time of institution of external ventricular drainage. Three of the 19 infants died of causes unrelated to the external ventricular drainage. Of the 16 survivors, seven infants had a developmental quotient or formal IQ of over 75. Outcome was poorest for those infants with accompanying intracerebral hemorrhage. We consider ventriculostomy to be an effective temporizing measure in small infants with rapidly progressive posthemorrhagic hydrocephalus with increased intracranial pressure in whom ventricular decompression is necessary and placement of a ventriculoperitoneal shunt is not feasible.
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Assess perampanel's efficacy and safety as adjunctive therapy in adolescents (ages 12-17) with drug-resistant partial seizures. Adolescent patients enrolled in multinational, double-blind, placebo-controlled, phase III core studies... more
Assess perampanel's efficacy and safety as adjunctive therapy in adolescents (ages 12-17) with drug-resistant partial seizures. Adolescent patients enrolled in multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) completed 19-week, double-blind phase (6-week titration/13-week maintenance) with once-daily perampanel or placebo. Upon completion, patients were eligible for the extension (study 307), beginning with 16-week, blinded conversion, during which placebo patients switched to perampanel. Patients then entered the open-label treatment. Of 1480 patients from the core studies, 143 were adolescents. Pooled adolescent data from these core studies demonstrated median percent decreases in seizure frequency for perampanel 8 mg (34.8%) and 12 mg (35.6%) were approximately twice that of placebo (18.0%). Responder rates increased with perampanel 8 mg (40.9%) and 12 mg (45.0%) versus placebo (22.2%). Adolescents receiving concomitant enzyme...
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Herbs and dietary supplements enjoy widespread use in the treatment of epilepsy although supportive data yielding efficacy and safety are lacking. Ten specific products, American hellebore, betony, blue cohosh, kava, mistletoe, mugwort,... more
Herbs and dietary supplements enjoy widespread use in the treatment of epilepsy although supportive data yielding efficacy and safety are lacking. Ten specific products, American hellebore, betony, blue cohosh, kava, mistletoe, mugwort, pipsissiwa, skullcap, valerian, and melatonin, have either multiple-cited recommendations for use in epilepsy or a rationale for antiepileptic action and are discussed in detail. These items paradoxically often have a proconvulsant effect in addition to potentially serious adverse effects. Herb-drug interactions also occur at the level of the P450 hepatic enzyme system of drug catabolism and the P-glycoprotein transport system regulating the entry of exogenous compounds into the vasculature or blood-brain barrier. Thus, significant pharmacokinetic interactions may occur, in addition to pharmacodynamic interactions and proconvulsant effects of alternative medications themselves. Patients should be inquired as to the nature of any alternative medicine ...
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Over the past 10 years, the Food and Drug Administration has approved eight prophylactic antiepileptic drugs (AEDs). Although the goal of universal seizure control without side effects has not been reached, the tolerability of medications... more
Over the past 10 years, the Food and Drug Administration has approved eight prophylactic antiepileptic drugs (AEDs). Although the goal of universal seizure control without side effects has not been reached, the tolerability of medications has improved. This paper reviews the AEDs introduced since 1993 and tries to objectively present comparative data obtained in double-blind studies.
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Parkinsonism is an uncommon movement disorder in childhood. Six unusual cases of acquired parkinsonism in hospitalized children are described. Clinical manifestations included an akinetic-rigid syndrome with and without tremor, the... more
Parkinsonism is an uncommon movement disorder in childhood. Six unusual cases of acquired parkinsonism in hospitalized children are described. Clinical manifestations included an akinetic-rigid syndrome with and without tremor, the combination of parkinsonism and dystonia, and a parkinsonism-plus syndrome. Altered mental status, mutism, dysphagia, and sialorrhea were frequent associations. Etiologies included hypoxic-ischemic encephalopathy; haloperidol treatment with and without neuroleptic malignant syndrome; toxicity of cytosine arabinoside, cyclophosphamide, amphotericin B, and methotrexate; St. Louis encephalitis and other encephalitides; and a pineal tumor with hydrocephalus. Cranial magnetic resonance imaging results ranged from normal to profound cerebral and cerebellar atrophy with chemotherapeutic toxicity. The illnesses usually were severe enough to require pharmacotherapy. Incorrect diagnoses of depression or catatonia delayed treatment or aggravated the problem. Acute t...
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To study the evolution of cerebral glucose metabolism after partial seizure onset in children, and its relation to clinical variables. Thirty-eight children had 3.4 +/-.8 (18)FDG-PET scans over 3.0 +/- 1.3 years starting within a year... more
To study the evolution of cerebral glucose metabolism after partial seizure onset in children, and its relation to clinical variables. Thirty-eight children had 3.4 +/-.8 (18)FDG-PET scans over 3.0 +/- 1.3 years starting within a year after their third unprovoked partial seizure. (18)FDG-PET was analyzed with a region of interest template to measure normalized metabolism in 12 paired anatomic areas. Scans with absolute asymmetry index, |AI|, greater than 0.13 in at least one cortical region other than the cerebellum were considered abnormal. Standard clinical T1- and T2-weighted MRI (1.5 T) scans were obtained. Patients with initial normal PET (n = 28) were significantly more likely to remain in good seizure control than those with abnormal initial PET. Patients with initially normal PET scans that became abnormal had longer epilepsy duration before the first PET scan, but not greater seizure frequency, than those with PET always normal. There was no evidence for progression of hypometabolism. Patients with shorter time since last seizure and higher seizure frequency were more likely to have abnormal PET scans. Six of the seven patients whose PET scans were always abnormal had poor seizure control. Febrile seizure history did not affect PET findings. MRI was strongly predictive of initial PET results (chi(2) = 13.1; p &lt; 0.02) but did not predict fluctuation hypometabolism. A model combining MRI and initial PET was strongly predictive of clinical course. Initial imaging studies can help predict clinical course for children who have had at least three partial seizures. Serial FDG-PET is affected by seizure frequency and time since last seizure.
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We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks... more
We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks obtained at 1.5 or 3T with EPI BOLD techniques: verbal fluency, reading comprehension, and auditory comprehension. fMRI maps were visually interpreted at a standard threshold and rated as left or atypical language. Atypical language dominance occurred in 30 patients (29%) and varied with MRI type (p &lt; 0.01). Atypical language representation occurred in 36% (13/36) with normal MRI, 21% (6/29) with mesial temporal sclerosis, 14% (4/28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and all (6/6) with a history of stroke. Multivariate logistic regression analysis found handedness, seizure onset, and MRI type accounted for much of the variance in language activation patterns (chi(2) = 24.09, p &lt; 0.01). Atypical language was more prevalent in patients with early seizure onset (43.2%, p &lt; 0.05) and atypical handedness (60%, p &lt; 0.01). None of the three clinical factors were correlated with each other (p &gt; 0.40). Patients with atypical language had lower verbal abilities (F = 6.96, p = 0.01) and a trend toward lower nonverbal abilities (F = 3.58, p = 0.06). There were no differences in rates of atypical language across time, age groups, or MRI scanner. Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization.
Research Interests: Cognitive Science, Neurology, Semantics, Magnetic Resonance Imaging, Adolescent, and 15 moreLanguage disorders, Humans, Child, Female, Male, Verbal behavior, Infant, Clinical Sciences, Middle Aged, Adult, Retrospective Studies, Intelligence tests, Neurosciences, Age of Onset, and Functional Laterality
Research Interests: Pediatrics, Computed Tomography, Adolescent, Humans, Child, and 15 moreFemale, Male, Infant, The, Differential Diagnosis, Ct Scan, Retrospective Studies, Emergencies, Febrile Seizure, Seizures, Sensitivity and Specificity, X ray Computed Tomography, Gastroesophageal Reflux, Emergency Department, and Brain Diseases
Detailed preoperative electroencephalographic (EEG) studies are now recommended for children with seizures and cortical tumors to define seizure foci prior to surgery. To develop a historical perspective for better evaluation of results... more
Detailed preoperative electroencephalographic (EEG) studies are now recommended for children with seizures and cortical tumors to define seizure foci prior to surgery. To develop a historical perspective for better evaluation of results from series reporting tumor removal combined with resection of seizure foci, the authors reviewed seizure outcome in 60 children with seizures and low-grade neoplasms treated consecutively since 1981 by surgical resection without concomitant EEG monitoring or electrocortical mapping. Forty-seven of the 60 tumors were totally or near-totally resected; 45 patients were seizure-free and two were significantly improved 1 year following surgery. Of the 50 children in this series with more than five seizures prior to surgery, 36 were seizure-free, two were significantly improved, and 12 were not improved. Factors associated with poor seizure control included a parietal tumor location, a partial tumor resection, and a history of seizures for more than 1 year prior to surgery. The children at highest risk for poor seizure control at 2 years had experienced seizures for more than 1 year prior to surgery and had undergone partial resection of their parietal low-grade glial tumors or gangliogliomas. In contradistinction, the best seizure control was seen in patients with totally resected low-grade gliomas or gangliogliomas who had experienced seizures for less than 1 year (concordance rates for being seizure-free ranged from 78% to 86%). Long-term seizure control remained excellent. These results suggest that seizure control can be obtained 2 years following tumor surgery in the majority of children with presumed tumors after extensive tumor resection without concomitant EEG monitoring or electrocortical mapping.
Research Interests: Neurosurgery, Electroencephalography, Adolescent, Brain Mapping, Humans, and 17 moreChild, Glioma, Cerebral Cortex, Female, Male, Regression Analysis, Infant, Follow-up studies, Risk factors, Clinical Sciences, Adult, Prognosis, Risk Factors, Seizures, Neurosciences, Brain Neoplasms, and Low Grade Glioma
Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and... more
Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and tolerability data from the entire pediatric population in the rufinamide epilepsy clinical development program. The analysis population comprised 212 rufinamide-treated (age range 3-16 years) and 197 placebo patients (age range 4-17 years) in the double-blind studies, and 391 patients receiving rufinamide in the double-blind and/or open-label extensions. The most common adverse effects observed in rufinamide-treated patients in the double-blind studies were somnolence, vomiting, and headache. Changes in laboratory values, vital signs, and weight were generally clinically insignificant. This pooled analysis of data from pediatric patients in clinical studies of rufinamide for the treatment of seizures, mainly as adjunctive therapy, suggests a favorable safety and tolerability profile in this patient population.
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Anticonvulsant drugs are first-line treatments for both bipolar mood disorder and epilepsy; however, few studies have explored treatment options when these disorders co-occur. The aim of this study was to identify bipolar disorder... more
Anticonvulsant drugs are first-line treatments for both bipolar mood disorder and epilepsy; however, few studies have explored treatment options when these disorders co-occur. The aim of this study was to identify bipolar disorder symptoms common in pediatric epilepsy and to determine whether anticonvulsant monotherapy might be a practical treatment consideration. A retrospective chart review identified 38 children with bipolar spectrum disorder and epilepsy comorbidity. Two mental health clinicians independently assessed psychiatric diagnoses, symptoms, and assigned retrospective CGI-I ratings for psychiatric symptoms. Common bipolar symptoms included impulsivity, psychomotor agitation, and explosive rage. Forty-two medication trials with 11 different anticonvulsants were identified. Of the 30 instances in which anticonvulsant monotherapy was attempted, carbamazepine, divalproex sodium, lamotrigine, and oxcarbazepine were associated with better psychiatric CGI-I ratings than other monotherapies (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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;0.01). Results suggest that in many cases, selected anticonvulsants appeared to simultaneously treat both epilepsy and mood disorder. Controlled trials are necessary to further ascertain optimal anticonvulsant usage.
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Research Interests: Communication, Epilepsy, Adolescent, Chronic illness, Social behavior, and 16 moreHumans, Child, Adaptive behavior, RECREATION, Female, Male, Behavior change, Clinical Sciences, Longitudinal Studies, Analysis of Variance, Time Factors, Retrospective Studies, Age Factors, Social Behavior, Cooperative Behavior, and Self Esteem
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Children and adolescents with epilepsy have an overrepresentation of psychiatric illness. However, few studies in pediatrics have characterized specific psychiatric conditions associated with seizure localization. In addition, degree to... more
Children and adolescents with epilepsy have an overrepresentation of psychiatric illness. However, few studies in pediatrics have characterized specific psychiatric conditions associated with seizure localization. In addition, degree to which psychiatric illness may be more prominent in children refractory to standard medical treatment for epilepsy is not known. The aim of this study was to assess psychiatric symptoms in children with medically refractory epilepsy and ascertain whether symptoms were associated with specific localization. Case records were reviewed for 40 children with medically refractory epilepsy at the time of their referral for presurgical evaluation. Patients received a clinical psychiatric evaluation and parents completed the Child Behavioral Checklist (CBCL). Seizure localization was verified by pediatric epileptologists, and suitability for surgical procedures was verified by neurosurgical specialists. Groups were compared based on localization of seizure foci, either in the temporal lobe or predominantly extratemporal. The majority of the sample had psychiatric diagnoses and behavior problems, well beyond the level reported in chronic epilepsy populations. In addition, children with temporal lobe seizure foci had more CBCL behavioral problem categories rated in the clinically significant range, and also were more likely to have clinical diagnoses of depression. Routine psychiatric evaluation prior to epilepsy surgery may be important for pediatric patients with medically refractory epilepsy. Psychiatric illness, particularly depression, may be especially prominent for those with temporal lobe seizure foci.
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A chirp is a brief signal within which the frequency content changes rapidly. Spectrographic chirps are found in signals produced from many biological and physical phenomena. In radar and sonar engineering, signals with chirps are used to... more
A chirp is a brief signal within which the frequency content changes rapidly. Spectrographic chirps are found in signals produced from many biological and physical phenomena. In radar and sonar engineering, signals with chirps are used to localize direction and range to the signal source. Although characteristic frequency changes during epileptic seizures have long been observed, the correlation with chirps and chirp technology seems never to have been made. We analyzed 19404 s (1870 s of which were from 43 seizures) of intracranially (subdural and depth electrode) recorded digital EEG from 6 patients for the presence of spectral chirps. Matched filters were constructed from methods in routine use in non-medical signal processing applications. We found that chirps are very sensitive detectors of seizures (83%), and highly specific as markers (no false positive detections). The feasibility of using spectral chirps as matched filters was demonstrated. Chirps are highly specific and sensitive spectrographic signatures of epileptic seizure activity. In addition, chirps may serve as templates for matched filter design to detect seizures, and as such, can demonstrate localization and propagation of seizures from an epileptic focus.