Benign childhood epilepsy with centrotemporal spikes: is it always benign?

Most children with benign childhood epilepsy with centrotemporal spikes have few seizures, and some have only one. We describe two children with interictal and ictal findings consistent with this epileptic syndrome but with severe intractable seizures and cognitive decline that resulted in consideration for epilepsy surgery. Spontaneous remission occured in one child; the other is still young. Despite the high seizure burden and cognitive decline, surgical consideration should be withheld, as these seizures are likely to remit.     

How should we be searching for genes for common epilepsy? A critique and a prescription

Despite enormous data collection and analysis efforts, the genetic influences on common epilepsies remain mostly unknown. We propose that reasons for the lack of progress can be traced to three factors: (1) A reluctance to consider fine-grained phenotype definitions based on extensive and carefully collected clinical data; (2) the pursuit of genetic analysis methods that are popular but poorly conceived and are inadequate to the task of resolving the problems inherent in common disease studies; (3) preconceived ideas about the genetic mechanisms that cause epilepsy (which we have discussed elsewhere). We propose a paradigm for finding epilepsy-related loci and alleles that has proven successful in other common diseases.     

Does status epilepticus in children cause developmental deterioration and exacerbation of epilepsy?

The aims of this study were to determine predictors of abnormal outcome, neurodevelopmental deterioration, new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus in children presenting with status epilepticus. For all children presenting to Royal University Hospital, Saskatoon, Saskatchewan, Canada, with status epilepticus between January 1987 and December 1996, demographic data, details of status epilepticus (etiology, duration, treatment, and investigations), developmental milestones, seizures prior to and following status epilepticus, recurrent status epilepticus, and neurologic examination findings at status epilepticus and at follow-up were collected by chart review, patient interview, and neurologic examination. Neurodevelopmental outcome was determined for all subjects except those who died during the initial hospitalization. Predictors of new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus were determined for children followed for 3 months or more after status epilepticus. At follow-up, 79% were abnormal neurologically. Predictors included etiology (nonfebrile or nonidiopathic), perinatal difficulties, preceding developmental delay, abnormal initial neurologic examination; and abnormal neuroimaging. Thirty-four percent showed neurodevelopmental deterioration; predictors included etiology (nonidiopathic or nonfebrile), young age at status epilepticus (12 months or less), and abnormal neuroimaging. Thirty-six percent with no history of seizures preceding status epilepticus developed epilepsy and 25% developed refractory epilepsy. Fifty percent of children had recurrent status epilepticus. In conclusion, very few children presenting in status epilepticus were normal at follow-up. Sequelae were seen predominantly in those with a nonidiopathic, nonfebrile etiology, whereas those with idiopathic or febrile status epilepticus did well.     

Which outcomes should we measure in adult epilepsy trials? The views of people with epilepsy and informal carers

ObjectiveSo that informed treatment decisions can be made, clinical trials need to evaluate treatments against domains that are important to people with epilepsy (PWE), their carers, and clinicians. Health professionals have identified domains of importance to them via the International League Against Epilepsy's Commission on Outcome Measurement (COME). However, patients and carers have not been systematically asked.MethodsVia the membership of the British Epilepsy Association, we recruited and surveyed 352 PWE and 263 of their informal carers. They were presented with 10 outcome domains (including the 5 identified by COME) and asked to rate their importance using a 9-point Likert scale. They were also asked to identify any additional domains of importance.ResultsThe patients' mean age was 49 years, the median number of years since diagnosis was 20, and 65% had experienced seizures in the prior 12 months. Most carers were the spouse or parent. Patients' and carers' mean ratings indicated that their outcome priorities were similar, as were those of patients who had and had not experienced recent seizures. There was consensus among patients that 6 domains were of critical importance. These included the 5 identified by COME (namely, and in order of importance, the effects of the treatment on “Seizure severity”, “Seizure frequency”, “Quality of life”, “Cognitive function”, and “Adverse events”), as well as one additional domain (“Independence/need for support”). There was consensus among carers that the 5 COME domains were also critically important. They, however, identified 3 further domains as critically important. These were the effects of the treatment on patient “Depression”, “Anxiety”, and “Independence/need for support”.ConclusionsOur study found some overlap between the priorities of PWE, carers, and health professionals. They, however, highlight additional areas of importance to patients and carers. Our results could inform a core outcome set for epilepsy that represents the domains that should be reported as a minimum by all trials. This could promote trials which produce meaningful results and consistency in measurement and reporting.     

Does a normalizing electroencephalogram in benign childhood epilepsy with centrotemporal spikes abort attention deficit hyperactivity disorder?

This retrospective study delineated the efficacy of antiepileptic drugs in preventing the need for methylphenidate in patients with benign childhood epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder. Seventeen patients were identified. A reduction of electroencephalogram pathologic activity by more than 50% was achieved in some patients with the antiepileptic drugs levetiracetam, sulthiame, lamotrigine, clobazam, and valproic acid. Complete normalization was achieved in two patients with sulthiame. Improvement in attention along with the reduction of pathologic electroencephalogram activity was observed in four patients, two with sulthiame, and one each with lamotrigine and levetiracetam (which was ceased because of suicidal tendencies). However, this improvement in attention was either temporary or not significant enough to discontinue methylphenidate. Methylphenidate was eventually prescribed to all patients.     

How should we measure delayed sleep phase shift in severe, refractory obsessive-compulsive disorder?

Objective. A previous study, based upon direct nursing observations, showed almost half of a cohort of inpatients with severe, enduring OCD also suffered from delayed sleep phase shift. Males, younger patients and those with more severe symptoms were most likely to be affected. However, the ward environment may have had a direct effect on sleeping patterns. In this study we compared the accuracy of actigraphic measurements with that of the "gold standard" of direct nursing observation, and other clinical sleep scales. We postulated that actigraphy would prove a reliable, acceptable, and valid alternative. Methods. All patients admitted over 29 months to a specialized treatment unit for severe, chronic refractory OCD were invited to participate. We collected demographic data, clinical measures of OCD and depressive symptom severity, self-rated measures of social and occupational disability and sleep, nursing records based upon direct observation of sleep onset and duration, and actigraphy records. Results. Evaluable data was obtained from 36 patients (22 males) with an average age of 37 years and profound OCD symptoms measured by the Yale-Brown Obsessive-Compulsive Scale. According to direct nursing observation, 12 patients (33%) showed delayed sleep phase shift. Actigraphic recordings demonstrated good agreement (kappa =?0.63) with nursing observation as did the St George's Insomnia Questionnaire (kappa =?0.66). Conclusion. This study demonstrates that actigraphy is a reliable method of recording sleep/activity cycles in severe, enduring OCD.     

How cautious should we be when assessing apathy with the Unified Parkinson's Disease Rating Scale?

Current practice often assesses apathy with a single item from the Unified Parkinson's Disease Rating Scale (UPDRS, item 4). Yet, the relationship between the UPDRS item 4 and the validated Apathy Scale (AS) is unknown. The purpose of this study was to evaluate the operating characteristics of UPDRS item 4 in relation to the AS. Three hundred and one patients with PD were administered the AS and the UPDRS. We compared the UPDRS item 4 to the standard AS classification of ≥14 as apathetic. A receiver operating characteristics (ROC) curve was obtained, and sensitivity, specificity, positive, and negative predictive power were calculated. The ROC curve showed area under the curve as 0.75. A cut‐off of 1 had good sensitivity (81%) but poor specificity (53%; high false positive rate). A cut‐off point of 2 had acceptable specificity (87%) but poor sensitivity (52%, high false negative rate). Continuing to increasing the cut‐off point (e.g., 3, 4) continues to increase specificity at the expense of dramatically reducing sensitivity. These findings suggest the use of caution when screening for apathy with item 4 due to its poor sensitivity in relation to the AS. © 2009 Movement Disorder Society     

How should we deal with missing data in clinical trials involving Alzheimer's disease patients?

Missing data are frequent in Alzheimer's disease (AD) trials due to the age of participants and the nature of the disease. This can lead to bias and decreased statistical power. We assessed the level and causes of missing data in a 2-year randomised trial of an AD patient management program (PLASA study), and conducted sensitivity analyses on the primary endpoint (functional decline), using various methods for handling missing data: complete case, LOCF, Z-score LOCF, longitudinal mixed effects model, multiple imputation. By 2 years, 32% of the 1131 subjects had dropped out, with the commonest reasons being death (28% of dropouts) and refusal (22%). Baseline cognitive and functional status were predictive of dropout. All sensitivity analyses led to the same conclusion: no effect of the intervention on the rate of functional decline. All analyses demonstrated significant functional decline over time in both groups, but the magnitude of decline and between-group (intervention versus usual care) differences varied across methods. In particular, the LOCF analysis substantially underestimated 2-year decline in both groups compared to other methods. Our results suggest that data were not "missing completely at random", meaning that the complete case method was unsuitable. The LOCF method was also unsuitable since it assumes no decline after dropout. Methods based on the more plausible "missing at random" hypothesis (multiple imputation, longitudinal mixed effects models, z-score LOCF) appeared more appropriate. This work highlights the importance of considering the validity of the underlying hypotheses of methods used for handling missing data in AD trials.     

How wrong can we be? The effect of inaccurate mark-up of EEG/fMRI studies in epilepsy

ObjectiveThe aim of this investigation was to determine the effect of inaccurate or inconsistent marking up of events in the EEG on statistical analysis of EEG/fMRI studies of patients with epilepsy.MethodsEEGs obtained during EEG/fMRI studies conducted on 10 patients with epilepsy and six normal control subjects were reviewed. All clear epileptiform events were marked up in the patient EEGs, as were all small movement-related artefacts in the patient and control subject EEGs. We then considered the effect on the numbers of voxels above threshold in the resulting Statistical Parametric Mapping (SPM) analysis if events were omitted, mislabelled, or if event times were inconsistently marked up.ResultsOmitting true epileptiform events resulted in a decrease in the number of voxels that survive statistical threshold. Mixing epileptiform and non-epileptiform events in the SPM analysis generally (but not always) decreased the number of voxels that survived threshold. Inconsistent event mark-up had little effect if the inconsistency was small (<200 ms), but had more effect if it was large (>500 ms).ConclusionIt is important to accurately mark-up EEGs acquired during EEG/fMRI studies in order to get the best results from subsequent analyses.SignificanceOur study reveals the consequences of inaccurate review of the EEG in EEG/fMRI studies and suggests guidelines for the review of EEG in these investigations which, if followed, should result in studies of acceptable quality.     

Non-convulsive status epilepticus and generalised tonic–clonic seizures persisting in old age in a patient with idiopathic generalised epilepsy: a long-term observation

Abstract  Persisting non-convulsive status epilepticus in a man with idiopathic generalised epilepsy is reported. After a first generalised tonic/clonic seizure on awakening one day at the age of 20, the patient experienced rare nonconvulsive status epilepticus until the age of 73, when the frequency of the episodes increased, in spite of the initiation of treatment with antiepileptic drugs. No significant cognitive decline was documented when the patient was 83. The existence of such conditions in the context of idiopathic generalised epilepsy shows the problems of syndromic diagnosis and of age dependency of some epileptic phenomena over the course of life with potential bidirectional influences between epileptic manifestations and senile processes The online version of the article unfortunately contained some mistakes. R. Manni was not listed among the authors. The spelling of the title was incorrect, please find the correct title above. The online version of the original article can be found at:     

Treating anxiety disorders in children and adolescents with epilepsy: What do we know?

Children with epilepsy are at significant risk of psychiatric disorders, which can in turn negatively impact social skills development, academic achievement, and quality of life. The most commonly reported psychiatric comorbidities in pediatric epilepsy are ADHD, depression, and anxiety. The prevalence rates of anxiety disorders in pediatric epilepsy range from 5 to 49%, and in the general population, anxiety disorders are the most common psychiatric disorder in childhood. For the purposes of this review, anxiety disorders will be examined in order to 1) examine rates of anxiety disorders in children and adolescents with epilepsy, 2) review treatment options for anxiety disorders in children with epilepsy, and 3) identify future avenues for the development of evidence-based practices for the treatment of anxiety disorders in youth with epilepsy.     

Internet use and looking up information online in adults with epilepsy varies by epilepsy status — 2013 National Health Interview Survey

We estimated US national prevalences of Internet use and looking up health information online among adults with epilepsy and those without, overall (age-standardized) and by three age groups (18–44, 45–59, and ≥ 60 years) using the 2013 National Health Interview Survey. Results showed that both overall and across all age groups, a significantly lower percentage of adults with active epilepsy reported using the Internet compared with that of adults without epilepsy. However, among Internet users, the percentage of looking up health information online did not differ by epilepsy status or age. Ensuring access to the Internet and encouraging use of quality, secure, and easy-to-access resources and e-tools might help adults with epilepsy to optimize their self-management and improve their quality of life.