Sigride Thome-Souza

A Controlled Clinical Trial of Cathodal DC Polarization in Patients with Refractory Epilepsy

Summary:  Purpose: To study the effects of cathodal DC polarization in patients with refractory epilepsy and malformations of cortical development (MCDs) as indexed by seizure frequency and epileptiform EEG discharges.

Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.

Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy

Physicians have become aware of the high prevalence of psychiatric disorders (PDs) in children and adolescents with epilepsy; however, there are many controversies as to which factors may have an important role in the different types of PD. This study was designed to assess the main PD; verify the age of onset compared with the age of diagnosis of the PD; and determine which factors may be correlated with the type of PD described. For this purpose, a multidisciplinary team evaluated children and adolescents (4-18 years) with epilepsy and analyzed patient-related factors such as age (grouped according to Piagets cognitive scale: <6 years, 7-13 years, >13 years), sex, family history of PDs, and cognitive status. With respect to epilepsy features, we considered age of onset, duration, seizure control at the time of psychiatric evaluation, refractoriness, antiepileptic drugs (mono- vs polytherapy), seizure type (generalized vs focal), and epilepsy type (idiopathic vs symptomatic/probably symptomatic). Depression occurred in 36.4% and attention-deficit hyperactivity disorder (ADHD) in 29.1%, these being the most frequent PDs in this series. Focal epilepsy was significantly more frequent in children and adolescents with PDs. As to the type of PD, age was an important factor, with a predominance of ADHD in children and depression in adolescents (P<0.0001). Family history was contributory for depression, but not for others PDs (P<0.0001). Depression remained underdiagnosed and untreated for a longer period. Impact of early diagnosis and treatment remains unknown.

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study.

Objective: To study the effects of repetitive transcranial magnetic stimulation (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and malformations of cortical development (MCDs). Methods: Eight patients with MCD and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600 pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after as well as 15 and 30 days after rTMS treatment. Results: Stimulation significantly decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction of 46.4%, 95% CI 12.7–80.2%, and mean reduction of 42.1%, 95% CI 8.2–75.7%, respectively). This was associated with a significant reduction in the number of seizures reported as compared with the 4-week period preceding rTMS (mean reduction of 57.3%, 95% CI 33.1–80.3%, and mean reduction of 51.2%, 95% CI 27.9–74.9%, respectively). Conclusion: This open study shows a significant antiepileptic effect of rTMS based on clinical and electrophysiological criteria and supports the therapeutic utility of rTMS for patients with well-localized epileptogenic cortical malformations.

Risk factors for psychogenic nonepileptic seizures in children and adolescents with epilepsy

There is evidence that psychogenic nonepileptic seizures (PNES) remain underdiagnosed, especially in children and adolescents. Diagnosis of such events is even more difficult in patients that do have epilepsy, leading to delayed diagnosis and treatment and, consequently, iatrogenic complications. This study aimed to evaluate possible risk factors in children with epilepsy who had PNES. Seizures and epileptic syndromes were classified according to International League Against Epilepsy guidelines. Patients were evaluated with a structured psychiatric anamnesis and classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research; and Schedule for Affective Disorders and Schizophrenia for School-Age Children--Epidemiological Version. Risk factors such as head trauma, physical, sexual and psychological abuse, and psychiatric diagnoses, among others, were investigated. Family history of epilepsy and psychiatric illness were detected by review of medical records and/or follow-up interviews. Gender was not a predictive factor, and although older children had a higher risk for PNES, younger children also presented truly psychogenic events mimicking epileptic seizures. The most common associated psychiatric diagnosis was depression. Family histories for epilepsy and psychiatric illness were a frequent finding. An inadequate family environment was more common than sexual or physical abuse. Current knowledge obtained from adults with PNES has been used to understand children with PNES. However, this study of children with epilepsy revealed some similarities and many differences. These features may help to identify predictive factors in a population in need of adequate diagnosis of and therapy for this long-lasting pathology.

Temporal Lobe Epilepsy in Childhood: Comprehensive Neuropsychological Assessment

The neuropsychological features of children with temporal lobe epilepsy are not yet well defined. The aim of this study was to identify the neuropsychological deficits in children with temporal lobe epilepsy. We evaluated 25 patients and compared them with 25 normal children. All children underwent a comprehensive neuropsychological assessment. We found a significant difference in favor of the control group in the following measures: IQ; forward digit; Trail Making Test for Children B; Wisconsin Card Sorting Test; block design; Boston naming test, verbal fluency; and Wide Range Assessment of Memory and Learning verbal learning, visual learning, verbal memory, visual memory, delayed recall of verbal learning, delayed recall of stories, and recognition of stories. Our findings show that children with temporal lobe epilepsy present with several neuropsychological deficits, despite normal IQ. These findings point to a dysfunction of cerebral areas other than temporal lobe, particularly the frontal lobes.

Executive dysfunction in children and adolescents with temporal lobe epilepsy: is the Wisconsin Card Sorting Test enough?

The Wisconsin Card Sorting Test (WCST) is the gold standard in the evaluation of executive dysfunction (ED) in patients with temporal lobe epilepsy (TLE). We evaluated 35 children with TLE and 25 healthy controls with the WCST and with a more comprehensive battery. Among the children with TLE, 77.14% showed impairment on the WCST. On other tests (Wechsler Intelligence Scale for Children-Digit Forward, Matching Familiar Figures Test, Trail Making Test, Word Fluency, Finger Windows, and Number-Letter Memory), impairment was demonstrated in 94.29%. The authors concluded that the WCST is a good paradigm to measure executive impairment in children with TLE; however, it may be not enough. Evaluation performed only with the WCST not only underestimated the number of patients with ED, but also missed relevant information regarding the type of ED.

Autonomic changes following generalized tonic clonic seizures: An analysis of adult and pediatric patients with epilepsy

OBJECTIVE Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients. METHODS Patients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented. RESULTS Twenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response (β=+0.67, p=0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power (β=-12.65, p=0.0036). CONCLUSION Sympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.

Chronopharmacology of Anti-Convulsive Therapy

Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of ‘zeitgebers’ that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues.

Lamotrigine and valproate: efficacy of co-administration in a pediatric population

This study aimed to assess the risks and benefits of the co-administration of lamotrigine and valproate in a pediatric population with refractory epilepsy. Twenty-eight children who received lamotrigine and valproate during co-medication were evaluated. Outcome measurements were established according to efficacy in seizure control, adverse effects, and tolerability. Treatment was considered effective when >50% frequency reduction was obtained. Adverse effects were also analyzed and in patients who presented them the mode of administration was compared with those who did not to verify the importance of this factor. Association of lamotrigine and valproate was considered effective in 64.3% of all patients, regardless of the seizure type. Seizure-free status was obtained in six patients. Drop attacks and secondary generalized tonic-clonic seizures were reduced in five patients, who remained under treatment despite less than the satisfactory (<50%) seizure decrease. Tremor occurred in six patients; urinary incontinence and ataxia in one. Skin rash also occurred, as an early manifestation, in two patients, both with a previous history of hypersensitivity to antiepileptic drugs. Causes for discontinuation were inefficacy of treatment in six patients and presence of adverse effects in two. In our series, seizure control was obtained in most children with refractory epilepsy, some of whom had a previous history of unsatisfactory response to lamotrigine and valproate, either in monotherapy or polytherapy. Adverse effects were uncommon, but skin rash was observed in higher proportions than in other series with lamotrigine or valproate. Nevertheless, these risks may be lessened with slow introduction and by exclusion of patients with a previous history of hypersensitivity.