Chellamani Harini

Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen's encephalitis.

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussens encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.

Continuous Spikes and Waves during Sleep: Electroclinical Presentation and Suggestions for Management

Continuous spikes and waves during sleep (CSWS) is an epileptic encephalopathy characterized in most patients by (1) difficult to control seizures, (2) interictal epileptiform activity that becomes prominent during sleep leading to an electroencephalogram (EEG) pattern of electrical status epilepticus in sleep (ESES), and (3) neurocognitive regression. In this paper, we will summarize current epidemiological, clinical, and EEG knowledge on CSWS and will provide suggestions for treatment. CSWS typically presents with seizures around 2–4 years of age. Neurocognitive regression occurs around 5-6 years of age, and it is accompanied by subacute worsening of EEG abnormalities and seizures. At approximately 6–9 years of age, there is a gradual resolution of seizures and EEG abnormalities, but the neurocognitive deficits persist in most patients. The cause of CSWS is unknown, but early developmental lesions play a major role in approximately half of the patients, and genetic associations have recently been described. High-dose benzodiazepines and corticosteroids have been successfully used to treat clinical and electroencephalographic features. Corticosteroids are often reserved for refractory disease because of adverse events. Valproate, ethosuximide, levetiracetam, sulthiame, and lamotrigine have been also used with some success. Epilepsy surgery may be considered in a few selected patients.

Localization of the Epileptogenic Foci in Tuberous Sclerosis Complex: A Pediatric Case Report

Tuberous sclerosis complex (TSC) is a rare disorder of tissue growth and differentiation, characterized by benign hamartomas in the brain and other organs. Up to 90% of TSC patients develop epilepsy and 50% become medically intractable requiring resective surgery. The surgical outcome of TSC patients depends on the accurate identification of the epileptogenic zone consisting of tubers and the surrounding epileptogenic tissue. There is conflicting evidence whether the epileptogenic zone is in the tuber itself or in abnormally developed surrounding cortex. Here, we report the localization of the epileptiform activity among the many cortical tubers in a 4-year-old patient with TSC-related refractory epilepsy undergoing magnetoencephalography (MEG), electroencephalography (EEG), and diffusion tensor imaging (DTI). For MEG, we used a prototype system that offers higher spatial resolution and sensitivity compared to the conventional adult systems. The generators of interictal activity were localized using both EEG and MEG with equivalent current dipole (ECD) and minimum norm estimation (MNE) methods according to the current clinical standards. For DTI, we calculated four diffusion scalar parameters for the fibers passing through four ROIs defined: (i) at a large cortical tuber identified at the right quadrant, (ii) at the normal appearing tissue contralateral to the tuber, (iii) at the cluster formed by ECDs fitted at the peak of interictal spikes, and (iv) at the normal appearing tissue contralateral to the cluster. ECDs were consistently clustered at the vicinity of the large calcified cortical tuber. MNE and ECDs indicated epileptiform activity in the same areas. DTI analysis showed differences between the scalar values of the tracks passing through the tuber and the ECD cluster. In this illustrative case, we provide evidence from different neuroimaging modalities, which support the view that epileptiform activity may derive from abnormally developed tissue surrounding the tuber rather than the tuber itself.

Current and emerging potential for magnetoencephalography in pediatric epilepsy

Magnetoencephalography (MEG) is a noninvasive neuroimaging tool that is increasingly becoming useful for presurgical delineation of epileptogenic zones and eloquent cortex in both lesional and non-lesional pediatric cases. During the past 10 yrs, the use of MEG in pediatric epilepsy research has increased. This paper starts with a review of the use of MEG in pediatric epilepsy. We then describe the protocol used for epilepsy patients at the pediatric MEG facility in Boston Children’s Hospital and present two case studies of intractable epilepsy obtained in our laboratory -cortical dysplasia and tuberous sclerosis complex -to illustrate our methodology in localizing epileptiform generators. In both cases, we are able to localize generators of interictal spikes in the irritative zone just outside the lesion. We also present results on localization of the somatosensory cortex based on our pediatric MEG system to illustrate the utility of MEG for identification of the eloquent cortex. We complete this review by considering advantages and limitations of MEG in children with epilepsy, its future developments and research applications. Application of MEG in pediatric epilepsy will accelerate during the coming years as different types of pediatric whole-head MEG systems and more advanced data analysis methods become available to the researchers and clinicians. These advances will lead to greater use of MEG as a complement to clinical electroencephalography, with improved noninvasive delineation of the epileptogenic zone.

Safety and retention rate of rufinamide in 300 patients: A single pediatric epilepsy center experience

Reports of studies evaluating rufinamide as an add‐on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long‐term follow‐up period.

Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy.

BACKGROUND Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. We evaluated the efficacy and safety of clobazam in a large sample of patients with refractory epilepsy at a tertiary pediatric center. METHODS We retrospectively reviewed patients treated with clobazam between January 2001 and July 2013 who had a follow-up visit at least one month after starting clobazam. Response was defined as ≥50% reduction in seizure frequency compared with baseline seizure frequency during the 3 months before the introduction of clobazam. We examined the relationship between dose range and response rate. RESULTS Four-hundred twenty-five patients were prescribed clobazam, of whom 300 (median age 9.1 years, interquartile range 4.7-13.3 years) had follow-up data greater than 1 month. Median follow-up was 5 months (interquartile range 3-11 months). Response to treatment with clobazam was observed in 203 of 300 (67.7%) patients, of whom 84 (28%) became seizure-free. The median starting dose was 0.2 (interquartile range 0.13-0.33) mg/kg/day with a target dose of 0.48 (0.26-0.80) mg/kg/day. Twenty-seven (9%) patients discontinued clobazam, 16 (59.3%) because adverse effects, 10 (37%) because of a lack of efficacy, and one (3.7%) because of a combination of adverse effects and lack of efficacy. The most common adverse effects were tiredness in 44 of 300 (14.6%) and mood or behavioral changes in 23 (7.7%). CONCLUSIONS Clobazam is a well-tolerated antiepileptic drug with good response rates in pediatric patients with refractory epilepsy.

Rasmussen's encephalitis presenting as focal cortical dysplasia

Rasmussens encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussens encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic.

Neurological maturation of late preterm infants at 34 wk assessed by amplitude integrated electroencephalogram

Background:This study tested if measures of central nervous system (CNS) immaturity reflected by amplitude integrated electroencephalogram (aEEG) and associated clinical morbidities are determinants of length of hospitalization among late preterm infants born at 34 wk.Methods:This was a prospective cohort study of infants with a gestational age of 34 wk 0–6 d who had a single aEEG recording acquired over 6 h in a neonatal intensive care unit within 72 h of birth (n = 80). Infants were followed for predefined morbidities (classified as CNS or non-CNS) and length of hospitalization (determined by the clinical care team). aEEG variables were correlated with length of hospitalization.Results:Eighty infants were enrolled and 75 aEEG recordings were analyzed. The average length of hospitalization was 10.4 ± 7.2 d (range 3–46 d). The total number of cycles recorded in the first 72 h following birth were inversely correlated with the length of hospitalization (r2 = 0.44, P < 0.001). Kaplan–Meier curves indicated that morbidities consistent with neurological immaturity were associated with a longer length of hospitalization (P < 0.001).Conclusion:Neurological maturation as indicated by aEEG and specific clinical morbidities is an important determinant of length of hospitalization among late-preterm infants.

Utility of initial EEG in first complex febrile seizure

OBJECTIVE The risk of developing epilepsy following febrile seizures (FS) varies between 2% and 10%, with complex febrile seizures (CFS) having a higher risk. We examined the utility of detected epileptiform abnormalities on the initial EEG following a first CFS in predicting subsequent epilepsy. METHODS This was a retrospective study of consecutive patients (ages 6-60 months) who were neurologically healthy or mildly delayed, seen in the ED following a first CFS and had both an EEG and minimum of 2-year follow-up. Data regarding clinical characteristics, EEG report, development of subsequent epilepsy, and type of epilepsy were collected. Established clinical predictors for subsequent epilepsy in children with FS and EEG status were evaluated for potential correlation with the development of subsequent epilepsy. Sensitivity, specificity, and positive and negative predictive values of an abnormal EEG (epileptiform EEG) were calculated. RESULTS A group of 154 children met our inclusion criteria. Overall, 20 (13%) children developed epilepsy. The prevalence of epilepsy was 13% (CI 8.3-19.6%). Epileptiform abnormalities were noted in 21 patients (13.6%), EEG slowing in 23 patients (14.9%), and focal asymmetry in six (3.8%). Epileptiform EEGs were noted in 20% (4/20) of patients with epilepsy and 13% (17/134) of patients without epilepsy (p=0.48). At an estimated risk of subsequent epilepsy of 10% (from population-based studies of children with FS), we determined that the PPV of an epileptiform EEG for subsequent epilepsy was 15%. None of the clinical variables (presence of more than 1 complex feature, family history of epilepsy, or status epilepticus) predicted epilepsy. CONCLUSIONS An epileptiform EEG was not a sensitive measure and had a poor positive predictive value for the development of epilepsy among neurologically healthy or mildly delayed children with a first complex febrile seizure. The practice of obtaining routine EEG for predicting epilepsy after the first CFS needs clarification by well-defined prospective studies.

Clinical and Neuroimaging Profile of Children with Lesions in the Corpus Callosum

T2‐hyperintense signal changes in corpus callosum (CC) have been described in epilepsy and encephalitis/encephalopathy. Little is known about their pathophysiology. The aim of this study was to examine the clinical presentation and evolution of CC lesions and relationship to seizures.