Seizure Reduction In Patients Research Articles

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Effects of long-term supplementation of probiotics on cognitive function and emotion in temporal lobe epilepsy.

Cognitive impairment and neuropsychiatric disorders are very common in patients with temporal lobe epilepsy (TLE). These comorbidities complicate the treatment of epilepsy and seriously affect the quality of life. So far, there is still no effective intervention to prevent the development of epilepsy-associated comorbidities. Gut dysbiosis has been recognized to be involved in the pathology of epilepsy development. Modulating gut microbiota by probiotics has shown an antiseizure effect on humans and animals with epilepsy. Whether this treatment strategy has a positive effect on epilepsy-associated comorbidities remains unclear. Therefore, this study aimed to objectively assess the effect of probiotics on cognitive function and neuropsychiatric performance of patients with TLE. Participants enrolled in an epilepsy clinic were randomly assigned to the probiotic and placebo groups. These two groups were treated with probiotics or placebo for 12 weeks, and then the cognitive function and psychological performance of participants were assessed. We enrolled 76 participants in this study, and 70 subjects were finally included in the study (35 in the probiotics group and 35 in the placebo group). Our results showed significant seizure reduction in patients with TLE treated with probiotics. No significant differences were observed on cognitive function (including intelligence and memory) between groups. For neuropsychiatric performances, supplementation of probiotics significantly decreased the Hamilton Anxiety Rating and Depression Scale scores and increased the 89-item Quality of Life in Epilepsy Inventory score in patients with TLE. In conclusion, probiotics have a positive impact on seizures control, and improve anxiety, depression, and quality of life in patients with TLE.

Comparison of efficiency between VNS and ANT-DBS therapy in drug-resistant epilepsy: A one year follow up study

Vagus nerve stimulation (VNS) and anterior thalamic deep brain stimulation (ANT-DBS) have both been used for treatments of drug-resistant epilepsy (DRE). However, there is no comparative study on the effectiveness of two methods from one single center. 17 patients with DRE who underwent VNS therapy and 18 patients who underwent DBS were enrolled. A retrospective study was performed starting from baseline before operation extending to 12 months after operation. The seizure types, duration of epilepsy, age at implantation, failed numbers of antiepileptic drugs (AEDs) before operation, history of craniotomy, stimulation parameters and response rate were described. The analysis of liner regression on the age of onset, duration of epilepsy, numbers of AEDs, and the seizure reduction at 12 months after operation was applied. The mean seizure reduction in patients with DBS at 3, 6, 9 and 12 months after the operation was 57.22%, 61.61%, 63.94% and 65.28%, and that in cases with VNS was 36.06%, 39.94%, 45.24% and 48.35%, respectively. At 1 year after the operation, the patients with older operation age, focal seizures and older age of onset responded better to VNS; and those older operation age, focal generalized seizures, history of craniotomy and longer duration of disease responded better to DBS. The efficiency of ANT-DBS was higher than that of VNS at each follow up time point. Patients can choose the appropriate treatment according to the individual clinical characteristics.

Fenfluramine for treatment-resistant epilepsy in Dravet syndrome and other genetically mediated epilepsies.

Fenfluramine hydrochloride, initially utilized as a weight loss drug in the 1970s and later removed from the market for adverse cardiopulmonary side effects, has since been repurposed as an antiseizure medicine (ASM). The potential antiseizure effects of fenfluramine were first identified in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. Compared with other ASMs, fenfluramine offers a novel mechanism by acting on serotonin and σ1 receptors, demonstrated in vitro and in vivo in animal models of Dravet syndrome. Results from a large double-blind, placebo-controlled trial demonstrated robust efficacy for seizure reduction in patients with Dravet syndrome, and met its primary endpoint with the 0.7 mg/kg/day fenfluramine treatment group experiencing a 62.3% or greater reduction in mean monthly convulsive seizure frequency (MCSF) compared with placebo. Here we provide a comprehensive review of the preclinical and clinical activity of fenfluramine, a recently approved drug for treatment of epilepsy in patients with Dravet syndrome.

Discovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders.

Recent clinical evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications. Given that everolimus is an incomplete inhibitor of the mTOR function, we sought to develop a new mTOR inhibitor that has improved properties and is suitable for CNS disorders. Starting from an in-house purine-based compound, optimization of the physicochemical properties of a thiazolopyrimidine series led to the discovery of the small molecule 7, a potent and selective brain-penetrant ATP-competitive mTOR inhibitor. In neuronal cell-based models of mTOR hyperactivity, 7 corrected the mTOR pathway activity and the resulting neuronal overgrowth phenotype. The new mTOR inhibitor 7 showed good brain exposure and significantly improved the survival rate of mice with neuronal-specific ablation of the Tsc1 gene. These results demonstrate the potential utility of this tool compound to test therapeutic hypotheses that depend on mTOR hyperactivity in the CNS.

Successful treatment of intractable life-threatening seizures with perampanel in the first case of early myoclonic encephalopathy with a novel de novo SCN1A mutation

PurposeEarly myoclonic encephalopathy (EME) is a form of developmental and epileptic encephalopathy with myoclonic seizures and a suppression burst on electroencephalogram, which occurs during the neonatal or early infantile period and is characterized by highly intractable seizures and severe development impairment. Although multiple genetic aetiologies of EME have been identified, no SCN1A mutation has been reported. MethodsWe described a female patient with EME due to an SCN1A mutation. ResultsShe developed frequent myoclonic and apnoeic seizures during the neonatal period. As her seizures were refractory to many antiepileptic drugs, she underwent a tracheotomy and has since been treated with continuous mechanical ventilation. Eventually, perampanel was added, which resulted in the cessation of the apnoeic seizures. Genetic analysis revealed a heterozygous de novo missense mutation in the SCN1A gene (c.2588 T > C:p.Leu863Ser). ConclusionThis is the first patient with EME due to anSCN1A mutation to be successfully treated with perampanel. Recently, perampanel was reported to be effective in treating Dravet syndrome, including cases with an SCN1A mutation. Perampanel may contribute to seizure reduction in patients with intractable epilepsy carrying the SCN1A mutation.

The Wada test might predict postoperative fine finger motor deficit after hemispherotomy

IntroductionCerebral hemispherotomy is a surgical method with a high rate of seizure reduction in patients with intractable epilepsy. However, there is a probability of postoperative motor deficits. The objective of this study was to investigate whether the Wada test can help predict motor function outcomes after hemispherotomy and, therefore, may be useful in decision-making and patient selection. Patients and methodA total of 13 patients with hemispherical intractable epilepsy underwent hemispherical disconnection surgeries. Six of them underwent the Wada test to evaluate motor function and language function followed by peri-insula hemispherotomy. The patients’ age ranged from 11 to 45years (mean 27years). ResultsThree of six patients had reduced dexterity on the Wada test. The finger motor function in the other patients did not change on the Wada test. Postoperatively, all patients who had decreased fine motor movement on the Wada test showed postoperative clumsiness of their hands and fingers. ConclusionsThe Wada test might predict postoperative fine finger motor deficit after hemispherotomy. This study showed that gross motor function was compensated in the ipsilateral hemisphere, whereas fine finger motor movement function remained in the contralateral frontal cortex.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6months or longer and 14% experienced at least one seizure-free period of 1year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p=0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Subdural electrodes in focal epilepsy surgery at a typical academic epilepsy center.

To assess the use of subdural intracranial EEG (iEEG) on postoperative outcomes at an epilepsy center. Ninety-one epilepsy patients underwent iEEG. Array design was compared with noninvasive EEG with over 1 year of outcome. Patient demographics, implanted brain sites, electrodes, contacts/site, and surgical location were correlated with outcome. Fisher exact test and logistics regression were used to evaluate significance (P ≤ 0.05). Of ninety-one women, 55 (mean age, 32.3 years; range, 11-60) underwent tailored iEEG. Seventy of ninety-one (76.9%) resections (70% temporal) yielded 24/91 (26.4%) seizure free (SF). Strips (57.1%), grids (5.5%), or both (37.4%) for iEEG use was commonly bilateral (58.2%; 65.3% bitemporal) but did not predict outcome (P = NS). A lesion (28/91) did predict a SF outcome (42.9%). The iEEG localized 45.7% of seizures beyond scalp EEG and changed the localization or lateralization in 75.7% of resected patients. Electrode design, localization, lateralization, and site of resection did not correlate with outcome (P = NS). Overall, iEEG use portended a non-SF outcome (P ≤ 0.0001). The use of iEEG selected 46% additional patients for surgery, yet only 26% became SF. A magnetic resonance imaging lesion predicted a SF or seizure-improved outcome. Although iEEG changed the localization and lateralization of scalp ictal EEG in three quarters of patients, its use was a negative predictor for a favorable outcome. Preoperative counseling should emphasize expectations for seizure reduction in patients requiring iEEG.

Predictors of Ketogenic Diet Efficacy in Children Based on the Electroencephalogram (EEG).

It is unclear whether electrographic features are predictive of ketogenic diet efficacy and how evolution of electroencephalogram (EEG) findings correlates with clinical improvement. We aimed to identify predictors for clinical seizure reduction on the diet as it correlates with serial EEGs. We reviewed 89 patients on the diet at Children's Medical Center from 2005 to 2012. We developed scoring criteria to analyze EEG characteristics (2 scales: 0-3 for encephalopathy; 0-6 for interictal discharges). Those with the lowest encephalopathy scores on last EEG strongly correlated with seizure reduction in patients with >95% seizure reduction (P = .002). A change in encephalopathy scores in those with moderate-severe encephalopathy on first EEG also correlated with >95% reduction in seizures (P = .009). This supports the theory that serial EEGs can be helpful in predicting positive therapeutic outcomes on the diet. Of 43 patients with both initial and follow-up EEGs, 27 had a decrease in interictal epileptic discharge frequency, though this was not significant (P = .434).

Sustained reduction of seizures in patients with intractable epilepsy after self-regulation training of slow cortical potentials - 10 years after.

The aim of this study was to determine whether the reduction of seizures in patients with intractable epilepsy after self-regulation of slow cortical potentials (SCPs) was maintained almost 10 years after the end of treatment. Originally, 41 patients received training with SCP-neurofeedback. A control group of 12 patients received respiratory feedback while another group of 11 patients had their anticonvulsant medications reviewed. Nineteen patients in the experimental group participated at least in parts of the long-term follow-up, but only two patients from each control group agreed to do so. The follow-up participants completed the same seizure diaries as in the original study. Patients of the experimental group also took part in three SCP-training sessions at the follow-up evaluation. Due to the small sample size, the results of participants in the control groups were not considered in the analysis. A significant decrease in seizure frequency was found about 10 years after the end of SCP treatment. The clinical significance of this result is considered medium to high. All patients were still able to self-regulate their SCPs during the feedback condition. This success was achieved without booster sessions. This is the longest follow-up evaluation of the outcome of a psychophysiological treatment in patients with epilepsy ever reported. Reduced seizure frequency may be the result of patients continued ability to self-regulate their SCPs. Given such a long follow-up period, the possible impact of confounding variables should be taken into account. The small number of patients participating in this follow-up evaluation diminishes the ability to make causal inferences. However, the consistency and duration of improvement for patients who received SCP-feedback training suggests that such treatment may be considered as a treatment for patients with intractable epilepsy and as an adjunct to conventional therapies.

Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide

Lennox-Gaustaut syndrome is an electroclinical epilepsy syndrome characterized by the triad of electroencephalogram showing diffuse slow spike-and-wave discharges and paroxysmal fast activity, multiple intractable seizure types, and cognitive impairment. The intractability to seizure medications and cognitive impairment gives rise to eventual institutionalized patient care. Only a small subset of seizure medications has been shown to be helpful in seizure control. Most patients take up to 3 medications at high therapeutic dosing and are susceptible to medication-induced side effects. The lack of medication efficacy in seizure control has led one meta-analysis to conclude that there is no single medication that is highly efficacious in controlling seizures in this syndrome. On this background, a new and structurally novel seizure medication, rufinamide, has been found to be beneficial in the treatment of seizures in this syndrome. In a multicenter, double-blinded, randomized, placebo-controlled study, rufinamide was found to reduce seizures by over 30%. More importantly, it reduced the frequency of the seizure type that induces most of the morbidity of this syndrome, the drop seizure, by over 40%. There were few side effects, the medication was well tolerated, and in the open labeled extension study, tolerance was not found. In this review, we describe the main electroclinical features of Lennox-Gaustaut syndrome and summarize the few controlled studies that have contributed to its rational treatment. Currently, there is no single agent or combination of agents that effectively treat the multiple seizure types and co-morbidities in this syndrome. Our focus will be on the role of the new medication rufinamide in seizure reduction in patients with Lennox-Gaustaut syndrome.

Talampanel

Talampanel is a novel anticonvulsant that acts as an allosteric inhibitor of the AMPA receptor. Talampanel has a broad spectrum of action in animal models of epilepsy and neuroprotection. Clinical experience to date has been able to show effectiveness in reduction of seizures in patients with refractory partial seizures.

Effect of lamotrigine on depressive symptoms in adult patients with epilepsy

In this investigation, the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive lamotrigine ( n = 32) or placebo ( n = 38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic–clonic (PGTC) seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell Dysthymia Rating Scale—Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score (lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P = 0.01) and POMS total score (lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P = 0.03) and numerically greater with lamotrigine than placebo for CDRS score (lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P = 0.50). Among the subset of patients with at least mild depression (BDI-II score ⩾ 10), mean improvement from baseline was numerically, but not statistically significantly, greater with lamotrigine (11.5, n = 13) than placebo (3.1, n = 18) ( P = 0.054). Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood ( r = 0.1, P = ns). Compared with placebo, lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures. Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms.

Effect of vagal nerve stimulation on patients with bitemporal epilepsy.

Patients with bitemporal epilepsy are characterized by the existence of independent bitemporal seizure onset zones. The aim of this study was to evaluate the effect of chronic vagal nerve stimulation (VNS) on eight patients with bitemporal epilepsy. We demonstrated the gradually increased effect of VNS on the reduction of seizures as compared with baseline seizure frequency in patients with bitemporal epilepsy. The average seizure reduction increased from 4.2% at the 3-month follow-up visit to 18.2, 34.4 and 42.2% at the 6, 12 and 18-month follow-up visits. Similarly, a >or=50% reduction of complex partial seizures was reported at the 3-month follow-up visit in no patients (0%); at the 6-month follow-up visit in one patient (12.5%); at the 12-month follow-up visit in three patients (37.5%); and at the 18-month follow-up visit in five patients (62.5%). These data demonstrate the positive and long-lasting effect of VNS on seizure reduction in patients with intractable bitemporal epilepsy. The main mechanism of this chronic effect is not fully understood.

Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy.

We studied the effect of vagus nerve stimulation (VNS) on seizure reduction in patients with intractable epilepsy with bilateral independent temporal lobe foci. Ten patients who met the criterion of the presence of two distinctive clinical and ictal EEG seizure patterns were identified and followed up for 1 year. Six patients had >50% reduction in their seizure frequency that persisted up to > or =1 year of follow-up, whereas four patients reported small or no reduction in their partial seizures. VNS is often effective and well tolerated in this select group of intractable epilepsy patients.