[Show abstract][Hide abstract] ABSTRACT: Distinguishing between seizures and nonepileptic events is a key challenge in pediatric neurology. The diagnostic gold standard is prolonged inpatient video electroencephalogram monitoring. However, little is known about preadmission characteristics that are predictive of recording an event during such monitoring.
This is a retrospective chart review of children undergoing prolonged inpatient video electroencephalogram monitoring between 2009 and 2012 at a tertiary referral center for the purpose of distinguishing between seizures and nonepileptic events. Demographic information, medical history, event characteristics, and inpatient monitoring course were abstracted.
Two-hundred thirteen children were identified. The median recording duration was 25 hours (interquartile range 22.4-48.5), and median time to event of interest (among those with an event recorded) was 4.5 hours (interquartile range 1.4-18.8). An event of interest was recorded in 66% of patients. At the event level, 20% of recorded events were associated with an electroencephalogram correlate, which refers to a change in the pattern seen on the electroencephalogram during a seizure. At the patient level, 112 (79.4%) with events recorded had only nonepileptic events recorded, 25 (17.7%) had only seizures recorded, and 4 (2.8%) had both recorded. Recording an event was predicted by the presence of intellectual disability (P = 0.001), greater preadmission event frequency (P < 0.001), and shorter latency since most recent event (P < 0.001).
Prolonged inpatient electroencephalogram monitoring captured an event of interest in two-thirds of patients, with most of these events captured within less than four and a half hours of recording onset. Several factors predict a greater yield with prolonged inpatient video electroencephalogram monitoring-including event frequency, latency since the most recent event, and the presence of intellectual disability-and can be used to counsel patients regarding this study for the purpose of event capture in the context of shared decision making.
[Show abstract][Hide abstract] ABSTRACT: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy.
We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency.
Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%).
These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy.
This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.
[Show abstract][Hide abstract] ABSTRACT: Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long-term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
[Show abstract][Hide abstract] ABSTRACT: An infant with infantile spasms is presented. Surgical treatment of spasms has increasingly become an option for the management of this difficult disease. This case reviews the issues related to, and the criteria necessary for the successful surgical management of infantile spasms.
[Show abstract][Hide abstract] ABSTRACT: Background
Mutations in the voltage-gated sodium channel SCN1A gene are responsible for the majority of Dravet syndrome cases. There is evidence that Nav1.1 channel coded by the SCN1A gene is involved in sleep regulation. We evaluated sleep abnormalities in children with Dravet syndrome using nocturnal polysomnography.
We identified six children at our institution with genetically confirmed Dravet syndrome who had also undergone formal sleep consultation with nocturnal polysomnography. Indications for polysomnography were parental concern of daytime fatigue or sleepiness, hyperactivity, inattention, disruptive behavior, nighttime awakenings or nocturnal seizures. Sleep studies were scored according to guidelines of the American Academy of Sleep Medicine and NREM cyclic alternating pattern was visually identified and scored according to established methods.
The mean age of the subjects at the time of polysomnography was 6 years. Standard polysomnography did not show any consistent abnormalities in the obstructive or central apnea index, arousal index, sleep efficiency or architecture. Cyclic alternating pattern analysis on 5 subjects showed an increased mean rate of 50.3% (vs 31-34% in neurological normal children) with a mild increase in A1 subtype of 89.4% (vs. 84.5%). A2/A3 subtype (5.3% vs. 7.3%), and B phase duration (22.4 vs. 24.7 seconds) were similar to previously reported findings in neurologically normal children.
Despite parental concerns for sleep disturbance in patients with Dravet syndrome, we could not identify abnormalities in sleep macroarchitecture. NREM sleep microarchitecture was, however, abnormal, with increased A1 subtype; resembling a trace´ alternant pattern of neonates and possibly suggestive of cortical synaptic immaturity in Dravet syndrome. Larger studies are needed to replicate these results.
[Show abstract][Hide abstract] ABSTRACT: Focal epilepsy accounts for approximately one-half to two-thirds of new-onset epilepsy in children. Etiologies are diverse, and range from benign epilepsy syndromes with normal neuroimaging and almost certain remission to focal malformations of cortical development or hippocampal sclerosis with intractable seizures persisting lifelong. Other important etiologies in children include pre-, peri-, or postnatal brain injury, low-grade neoplasms, vascular lesions, and neuroimmunological disorders. Cognitive, behavioral, and psychiatric comorbidities are commonly seen and must be addressed in addition to seizure control. Given the diverse nature of focal epilepsies in children and adolescents, investigations and treatments must be individualized. First-line therapy consists of prophylactic antiepileptic drugs; however, prognosis is poor after failure of two to three drugs for lack of efficacy. Refractory cases should be referred for an epilepsy surgery workup. Dietary treatments and neurostimulation may be considered in refractory cases who are not good candidates for surgery.
Adolescent Health, Medicine and Therapeutics 01/2014; 5:49-65.
[Show abstract][Hide abstract] ABSTRACT: Background
Predictors of ketogenic diet success in treating pediatric intractable epilepsy are not well understood. The aim of this study was to determine if initial body mass index and weight percentile impact early efficacy of the traditional ketogenic diet in children initiating therapy for intractable epilepsy.
This retrospective study included all children initiating the ketogenic diet at Mayo Clinic, Rochester from January 2001-December 2010 who had body mass index (children >2 years of age) or weight percentile (those <2 years of age) documented at diet initiation and seizure frequency recorded at diet initiation and one month. Responders were defined as achieving a >50% seizure reduction from baseline.
Our cohort consisted of 48 patients (20 male) with a median age of 3.1 years. There was no significant correlation between initial body mass index or weight percentile and seizure frequency reduction at one month (P = 0.72, r = 0.26 and P = 0.91, r = 0.03). There was no significant association between body mass index or weight percentile quartile and responder rates (P = 0.21 and P = 0.57). Children considered overweight or obese at diet initiation (body mass index or weight percentile ≥85) did not have lower responder rates than those with body mass index or weight percentiles <85 (6/14 vs 19/34, respectively, P = 0.41).
Higher initial body mass index and weight-for-age percentiles do not adversely affect the efficacy of the ketogenic diet.
[Show abstract][Hide abstract] ABSTRACT: Objective
This study aimed to identify long-term seizure outcome in pediatric nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs) due to lack of efficacy.
Children (1 month–17 years) with new-onset focal epilepsy not meeting the criteria for a defined electroclinical syndrome diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were retrospectively identified. Medical records of those followed for ≥ 2 years were reviewed to assess etiology, the number of AEDs that failed due to lack of efficacy, and seizure outcome at final follow-up. Etiology was classified into structural/metabolic, genetic, or unknown. Favorable outcome was defined as seizure freedom ≥ 1 year, on or off AEDs, without prior epilepsy surgery. Poor outcome was defined as ongoing seizures in the preceding year or having undergone prior epilepsy surgery.
Nonsyndromic focal epilepsy accounted for 275/468 (59%) of all patients with newly diagnosed epilepsy — of these, 256 (93%) were followed for a minimum of two years and were included in the study. Median duration of follow-up was 10.0 years. At least one AED had failed due to lack of efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%) children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED failures, the seizures of nearly one-quarter of children who had epilepsy with an unknown cause responded favorably to the third AED compared with only 7.8% of the cohort that had epilepsy with a structural/metabolic cause. Children with a remote brain insult had a significantly higher likelihood of favorable outcome with serial AEDs than those with other structural abnormalities.
Etiology is an important determinant of pharmacoresistance in nonsyndromic focal epilepsy. Surgical evaluation should be considered after failure of 1–2 AEDs in those who have epilepsy with structural causes, excluding remote brain insults. Conversely, as surgical success is lower with normal MRI or more diffuse brain insults, it appears reasonable to hold off surgical evaluation until 2–3 AEDs have failed in such children.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI) − negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data.
[Show abstract][Hide abstract] ABSTRACT: Medically intractable epilepsy involving drop attacks can be difficult to manage and negatively impact quality of life. Most studies investigating the effect of corpus callosotomy (CC) on seizures have been limited, focusing on the pediatric population, or drop seizures alone, with little attention to other factors influencing seizure outcome.
To assess seizure outcomes following CC in adults and children.
Retrospective analysis was performed on all patients who underwent CC (anterior two-thirds, 1-stage complete, or 2-stage complete) at our institution between 1990 and 2011. Change in frequency after CC was assessed for drop seizures and other seizure types. Multiple factors were evaluated for impact on seizure outcome.
Fifty patients met inclusion criteria. Median age was 1.5 years at seizure onset, and 17 at time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage complete in 17, and 2-stage complete in 5. All three groups experienced a significant decrease in drop seizures (p<0.001, p<0.001, and p=0.020, respectively), with 40% experiencing complete resolution, and 64% dropping at least one frequency category. Other seizure types significantly decreased in anterior 2/3 CC and 1-stage complete (p=0.0035, p=0.001, respectively). Decreasing age at surgery correlated with better seizure outcomes (p=0.043).
CC for medically refractory generalizing epilepsy is effective for both drop seizures and other seizure types. CC should be considered soon after a patient has been deemed medically refractory, as earlier age at surgery results in lower risk and better outcome.
[Show abstract][Hide abstract] ABSTRACT: Migrating focal seizures of infancy are characterized by seizure onset within 7 months of age, migrating focal motor seizures with multifocal ictal electroencephalography discharges intractable to conventional antiepileptic drugs, and poor prognosis. Reported genetic etiologies include SCN1A and KCNT1 mutations and homozygous deletion of the PLCB1 gene. Here we report a novel SCN2A mutation in a child with this syndrome.
A 7-week-old girl was admitted to our hospital for management of status epilepticus. She was the product of a full-term unremarkable pregnancy. Seizures started around 5 weeks of age and remained medically refractory. Electroencephalography showed multifocal epileptiform discharges as well as seizures arising from multifocal regions in both cerebral hemispheres. Based on her phenotype, a diagnosis of migrating focal seizures of infancy was made.
A novel de novo missense mutation was identified in the SCN2A gene, exon 22 (coding for voltage-gated sodium channel type II): c.3977T>A (p.V1326D). This mutation affects a highly evolutionarily conserved area of the gene and replaces hydrophobic nonpolar valine with polar aspartic acid; thus, it is predicted to affect protein function and is presumed pathogenic.
This report expands our knowledge of the genetic basis of migrating focal seizures of infancy to include mutations in SCN2A gene.
[Show abstract][Hide abstract] ABSTRACT: Mutations of the SCN1A subunit of the sodium channel is a cause of genetic epilepsy with febrile seizures plus (GEFS(+) ) in multiplex families and accounts for 70-80% of Dravet syndrome (DS). DS cases without SCN1A mutation inherited have predicted SCN9A susceptibility variants, which may contribute to complex inheritance for these unexplained cases of DS. Compared with controls, DS cases were significantly enriched for rare SCN9A genetic variants. None of the multiplex febrile seizure or GEFS(+) families could be explained by highly penetrant SCN9A mutations.
[Show abstract][Hide abstract] ABSTRACT: To review the efficacy and tolerability of stiripentol in the treatment of U.S. children with Dravet syndrome.
U.S. clinicians who had prescribed stiripentol for two or more children with Dravet syndrome between March 2005 and 2012 were contacted to request participation in this retrospective study. Data collected included overall seizure frequency, frequency of prolonged seizures, and use of rescue medications and emergency room (ER)/hospital visits in the year preceding stiripentol initiation, and with stiripentol therapy. We separately assessed efficacy in the following treatment groups: group A, stiripentol without clobazam or valproate; group B, stiripentol with clobazam but without valproate; group C, stiripentol with valproate but without clobazam; and group D, stiripentol with clobazam and valproate. In addition, adverse effects were recorded.
Thirteen of 16 clinicians contacted for study participated and provided data on 82 children. Stiripentol was initiated a median of 6.0 years after seizure onset and 1.2 years after diagnosis of Dravet syndrome. Compared to baseline, overall seizure frequency was reduced in 2/6 in group A, 28/35 in group B, 8/14 in group C, and 30/48 in group D. All children with prolonged seizure frequency greater than quarterly during the baseline period experienced a reduction in this frequency on the various treatment arms with stiripentol. Similarly, 2/4 patients in group A, 25/25 in group B, 5/10 in group C, and 26/33 in group D experienced reduction in frequency of rescue medication use and 1/1 in group A, 12/12 in group B, 3/5 in group C, and 18/19 in group D had reduction in frequency of ER/hospital visits. Adverse effects were reported in 38, most commonly sedation and reduced appetite. Four patients (5%) discontinued stiripentol for adverse effects and two (2%) for lack of efficacy.
Stiripentol is an effective and well-tolerated therapy that markedly reduced frequency of prolonged seizures in Dravet syndrome.
[Show abstract][Hide abstract] ABSTRACT: Although the pathophysiologic mechanism of sudden unexpected death in epilepsy (SUDEP) is unknown, autonomic dysfunction is thought to be the most likely. It has been hypothesized that respiratory depression resulting in SUDEP may be secondary to postictal generalized electroencephalography suppression (PGES). We sought to determine the characteristics of PGES in children. This included whether PGES was associated with ictally mediated autonomic changes and potential increased risk of SUDEP. Children admitted to our Pediatric Epilepsy Monitoring Unit between 3/2009 and 10/2011 were prospectively recruited. Clinical and electrophysiological data from children with PGES were compared to those without PGES. Data included the occurrence of peri-ictal tachycardia, bradycardia, and hypoxemia. Potential SUDEP risk was assessed using SUDEP-7 Inventory scores. Thirty seven children with 168 seizures were analyzed. PGES was observed following 27/168 (16.1%) seizures in 12/37 (32.4%) children. Only primary and secondarily generalized tonic clonic seizures were marked by PGES. PGES was significantly associated with peri-ictal tachycardia (p=0.019) and hypoxemia (p=0.005). Children with PGES had significantly higher SUDEP-7 Inventory scores than those without PGES (4.2±1.3 versus 2.8±1.4, p=0.007). SUDEP-7 scores were not significantly different between children with and without peri-ictal tachycardia (3.4±1.3 versus 2.5±1.6, p=0.12), bradycardia (4±2 versus 2.9±1.4, p=0.45), or hypoxemia (3.4±1.5 versus 2.4±1.3, p=0.051). Based on our data, PGES is not rare in children. Children with PGES may be at greater risk for SUDEP as measured by the SUDEP-7 Inventory.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES:Estimate the causes and risk of death, specifically seizure related, in children followed from onset of epilepsy and to contrast the risk of seizure-related death with other common causes of death in the population.METHODS:Mortality experiences from 4 pediatric cohorts of newly diagnosed patients were combined. Causes of death were classified as seizure related (including sudden unexpected death [SUDEP]), natural causes, nonnatural causes, and unknown.RESULTS:Of 2239 subjects followed up for >30 000 person-years, 79 died. Ten subjects with lethal neurometabolic conditions were ultimately excluded. The overall death rate (per 100 000 person-years) was 228; 743 in complicated epilepsy (with associated neurodisability or underlying brain condition) and 36 in uncomplicated epilepsy. Thirteen deaths were seizure-related (10 SUDEP, 3 other), accounting for 19% of all deaths. Seizure-related death rates were 43 overall, 122 for complicated epilepsy, and 14 for uncomplicated epilepsy. Death rates from other natural causes were 159, 561, and 9, respectively. Of 48 deaths from other natural causes, 37 were due to pneumonia or other respiratory complications.CONCLUSIONS:Most excess death in young people with epilepsy is not seizure-related. Mortality is significantly higher compared with the general population in children with complicated epilepsy but not uncomplicated epilepsy. The SUDEP rate was similar to or higher than sudden infant death syndrome rates. In uncomplicated epilepsy, sudden and seizure-related death rates were similar to or higher than rates for other common causes of death in young people (eg, accidents, suicides, homicides). Relating the risk of death in epilepsy to familiar risks may facilitate discussions of seizure-related mortality with patients and families.
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE A focal lesion detected by use of magnetic resonance imaging (MRI) is a favorable prognostic finding for epilepsy surgery. Patients with normal MRI findings and extratemporal lobe epilepsy have less favorable outcomes. Most studies investigating the outcomes of patients with normal MRI findings who underwent (nonlesional) extratemporal epilepsy surgery are confined to a highly select group of patients with limited follow-up. OBJECTIVE To evaluate noninvasive diagnostic test results and their association with excellent surgical outcomes (defined using Engel classes I-IIA of surgical outcomes) in a group of patients with medically resistant nonlesional extratemporal epilepsy. DESIGN A retrospective study. SETTING Mayo Clinic, Rochester, Minnesota. PARTICIPANTS From 1997 through 2002, we identified 85 patients with medically resistant extratemporal lobe epilepsy who had normal MRI findings. Based on a standardized presurgical evaluation and review at a multidisciplinary epilepsy surgery conference, some of these patients were selected for intracranial electroencephalographic (EEG) monitoring and epilepsy surgery. EXPOSURE Nonlesional extratemporal lobe epilepsy surgery. MAIN OUTCOMES AND MEASURES The results of noninvasive diagnostic tests and the clinical variables potentially associated with excellent surgical outcome were examined in patients with a minimum follow-up of 1 year (mean follow-up, 9 years). RESULTS Based on the noninvasive diagnostic test results, a clear hypothesis for seizure origin was possible for 47 of the 85 patients (55%), and 31 of these 47 patients (66%) proceeded to intracranial EEG monitoring. For 24 of these 31 patients undergoing long-term intracranial EEG (77%), a seizure focus was identified and surgically resected. Of these 24 patients, 9 (38%) had an excellent outcome after resective epilepsy surgery. All patients with an excellent surgical outcome had at least 10 years of follow-up. Univariate analysis showed that localized interictal epileptiform discharges on scalp EEGs were associated with an excellent surgical outcome. CONCLUSIONS AND RELEVANCE Scalp EEG was the most useful test for identifying patients with normal MRI findings and extratemporal lobe epilepsy who were likely to have excellent outcomes after epilepsy surgery. Extending outcome analysis beyond the resective surgery group to the entire group of patients who were evaluated further highlights the challenge that these patients pose. Although 9 of 24 patients undergoing resective surgery (38%) had excellent outcomes, only 9 of 31 patients undergoing intracranial EEG (29%) and only 9 of 85 patient with nonlesional extratemporal lobe epilepsy (11%) had long-term excellent outcomes.
[Show abstract][Hide abstract] ABSTRACT: Approximately 20% of children with epilepsy will be pharmacoresistant. The impact of intractable epilepsy extends far beyond just the seizures to result in intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death in epilepsy (SUDEP), and poor quality of life. Various predictors of pharmacoresistance have been identified; however, accurate prediction is still challenging. Population-based epidemiologic studies show that the majority of children who develop pharmacoresistance do so relatively early in the course of their epilepsy. However, approximately one third of children who initially appear pharmacoresistant in the first few years after epilepsy onset will ultimately achieve seizure freedom without surgery. The most significant predictor that early pharmacoresistance will not remit is the presence of a neuroimaging abnormality. Such children should be strongly considered for surgical evaluation.