Vagus nerve stimulation in pediatric patients: Is it really worthwhile?

Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case-control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group - 1.33±1.45years; controls - 3.23±3.11; p=0.0001), abnormal findings in neurological examination (p=0.01), history of previous ineffective epilepsy surgery (p=0.03), and baseline seizure frequency (p=0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Hemispheric dysplasia and hemimegalencephaly: imaging definitions.

BACKGROUND AND PURPOSE: Hemispheric dysplasia (HD) and hemimegalencephaly (HME) are both brain malformations with early clinical manifestation including developmental delay and intractable epilepsy. Sometimes the differentiation of these conditions is not simple. HME is an anomaly of cortical development caused by a combination of neural proliferation and cell migration dysfunction, showing lobar or hemispheric enlargement. On the other hand, HD shows no brain hypertrophy, and even brain atrophy, eventually. PATIENTS AND METHODS: To compare both conditions, we reviewed clinical, MRI, and histopathology of 23 patients with developmental delay and refractory epilepsy treated with hemispheric surgery. RESULTS: Histologically, both groups presented polymicrogyria, focal cortical dysplasia, gray matter (GM) heterotopia, pachygyria, and agyria. The white matter (WM) showed different degrees of gliosis and myelin impairment. Even though with no specificity in histopathology, the degree of lesion was more impressive on HME. The combination of WM dysmyelination and hypertrophy leads to the so called hamartomatous appearing. Although not all HME showed brain enlargement and some HD might show no size changes or atrophy, the size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions. CONCLUSION: Brain MRI was the best diagnostic tolls because it allowed together high contrast resolution, whole brain coverage and spatial distribution analysis. HD and HMD showed brain asymmetry tendency, but in opposite directions. The size of affected hemisphere and the hamartomatous appearance of the WM were the more relevant signs to differentiate both conditions.

Surgery for focal cortical dysplasia in children using intraoperative mapping.

OBJECTIVE: Children with malformation of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. Here, we describe a single-center experience with pediatric patients who underwent surgery for intractable epilepsy due to focal cortical dysplasia (FCD). METHODS: Clinical data of 78 patients under 18 years of age with diagnosis of intractable epilepsy due to FCD who underwent surgery from January 1996 to January 2012 were reviewed comparing data of patients submitted to electrocorticography (ECoG) with those without ECoG. RESULTS: Patients' mean age at surgery was 8.52 ± 4.99 years; mean age at epilepsy onset was 2.55 ± 3.01 years. Almost 80 % of the patients underwent ECoG register that was essential for delimitation of surgical resection in 66 out of 78 patients. ECoG was performed in all patients with extratemporal lesions, and the most common FCD found was type II. Seizure outcome was similar in groups with or without ECoG. CONCLUSIONS: Tailored resection of FCD lesions for intractable epilepsy can be safely performed in children with a good seizure outcome and low complication rate. Epilepsy surgery should be considered for all patients with FCD and refractory epilepsy.

The Important Role of Hemispherotomy for Rasmussen Encephalitis: Clinical and Functional Outcomes.

BACKGROUND: Rasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes. METHODS: All patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes. RESULTS: Forty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS. CONCLUSIONS: Considering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life.

Sudden unexpected death in epilepsy: from the lab to the clinic setting.

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids.

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy.

Pediatric epilepsy surgery and sudden unexpected death epilepsy: the contribution of a Brazilian epilepsy surgery program.

BACKGROUND AND PURPOSE: Individuals with epilepsy are at higher risk of death than those from the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Epilepsies in the pediatric group are more frequently associated with known potentially risk factors for SUDEP, and a treatment resulting in an improved seizure control may also decrease mortality. The aim of this study is to identify the incidence of SUDEP in a group of operated-on children and adolescents. METHODS: We analyzed 267 patients up to 18 years old, with medically intractable epilepsy submitted to surgery. We considered the age at surgery, the seizure type, the pathological findings, and the seizure outcome. Data were prospectively collected, according to the protocols of our institution's ethics committee. RESULTS: The percentage of boys was 58.05. A good outcome was achieved in 72.6% of the cases and a bad outcome in 27.4%. Nine patients died during follow-up, six from clinical complications, and one from SUDEP. All patients who died during the long-term follow-up had persisted with refractory postoperative seizures. The patient who died from SUDEP died during a generalized tonic-clonic seizure. CONCLUSIONS: Of the patients, 72.6% had excellent postoperative outcome, and one patient died of SUDEP. All patients who died had had disabling seizures' persistence. The surgical treatment of epilepsy in children and adolescents is an efficient therapy for the medically intractable symptomatic epilepsies and also for the reduction of mortality and SUDEP risks.

From Galapagos to the labs: Darwinian medicine and epilepsy today.

In 1991, a mummy frozen in ice was found by climbers in the Tyrolean Alps. Otzi the Iceman has since been studied in the light of evolutionary explanations for diseases. This year, which marks Charles Darwin's 200th birthday and the 150th anniversary of his publication On the Origin of Species, should re-ignite discussion of the importance of the correlation between nutritional diet and diseases. Epilepsy is one of the commonest diseases in the world. Individuals with epilepsy are at higher risk of death than the general population, and sudden unexpected death (SUDEP) is the most important direct epilepsy-related cause of death. A number of factors may influence the risk for SUDEP. Along these lines, several studies have demonstrated that polyunsaturated (omega-3) fatty acids may reduce the risk of cardiovascular mortality, and diminish neuronal excitability. Also, omega-3 fatty acids may decrease seizure frequency, contributing to the reduction of SUDEP risk. Reconstruction of the nutritional patterns of Stone Age humans and optimal human nutrition in the present may be relevant to the prevention and treatment of chronic diseases such as epilepsy and the catastrophic evolution into epilepsy refractoriness and SUDEP.

Physical exercise in epilepsy: what kind of stressor is it?

Stress has been considered the most frequently self-reported precipitant of seizures in people with epilepsy. The literature documents that physical stress, that is, physical exercise, can have beneficial effects in people with epilepsy. In view of evidence indicating that sensitivity to stress is reduced after a physical exercise program, physical activity could be a potential candidate for stress reduction in people with epilepsy. This review considers how physical exercise could contribute to reduce seizure susceptibility and, hence, seizure frequency. Possible mechanisms by which exercise can be beneficial for people with epilepsy are highlighted. Hypothalamic-pituitary-adrenal axis adaptation, neurotransmitter system modulation, and metabolic and neuroendocrine changes may interfere with seizure susceptibility. The psychological stress of different sports activities is an important concern that must also be taken into account. Overall, among stress reduction therapies for the treatment of seizures, exercise might be a potential candidate.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: a case study.

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased, it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental studies in the literature that show an effect of omega-3 supplementation on epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy.

Do psychiatric comorbidities predict postoperative seizure outcome in temporal lobe epilepsy surgery?

Clinical and demographic presurgical variables may be associated with unfavorable postsurgical neurological outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, few reports include preoperative psychiatric disorders as a factor predictive of long-term postsurgical MTLE-HS neurological outcome. We used Engel's criteria to follow 186 postsurgical patients with MTLE-HS for an average of 6 years. DSM-IV criteria and psychiatric comorbidity criteria specific to epilepsy (interictal dysphoric disorder, postictal and interictal psychosis) were used to assess presurgical psychiatric disorders. Kaplan-Meier event-free survival and adjusted hazard ratios were estimated with unconditional logistic regression. Seventy-seven (41.4%) patients had a preoperative Axis I psychiatric diagnosis. Thirty-six patients had depression, 11 interictal dysphoric disorder, 14 interictal psychosis, 6 postictal psychosis, and 10 anxiety disorders. Twenty-three (12.4%) patients had Axis II personality disorders. Regarding seizure outcome, preoperative anxiety disorders (P=0.009) and personality disorders (P=0.003) were positively correlated with Engel class 1B (remaining auras) or higher. These findings emphasize the importance of presurgical psychiatric evaluation, counseling, and postsurgical follow-up of patients with epilepsy and psychiatric disorders.