Improvement In Seizure Frequency Research Articles

Effectiveness of dose-escalated topiramate monotherapy and add-on therapy in neurosurgery-related epilepsy: A prospective study.

Background:Lesional and symptomatic causes of epilepsy are the most common neurological disorders of the brain. Topiramate effectively controls newly diagnosed epilepsy and refractory focal seizures, but high-dose topiramate does not improve seizure control. This study aimed to evaluate the clinical efficacy and safety of dose-escalated topiramate as first-line monotherapy and add-on therapy in patients with neurosurgery-related epilepsy.Material and Methods:A total of 55 neurosurgical patients with epilepsy were divided into monotherapy and add-on therapy groups and both groups received topiramate via the dose-escalation method. The primary efficacy outcomes were seizure-free rate and seizure response rate. Adverse events and seizure frequency were recorded.Results:The seizure response rate in the first month of monotherapy was significantly better than that of add-on therapy (89% vs 65%, P < .05), but no significant differences were found in seizure response rates between the 2 groups after 2 months of treatment. Both monotherapy and add-on therapy were effective in controlling seizures, with mean seizure frequency of 0.725 vs 0.536 and seizure-free rate of 88% vs 78.6%. Both treatments showed good improvement of seizure frequency in patients without tumor. The efficacy of monotherapy was better than that of add-on therapy (80% vs 29.2%) in patients with body mass index (BMI) ≤24. However, add-on therapy was better than monotherapy (76.7% vs 21.4%) in patients with BMI > 24. Dizziness (25.5%) and headache (16.4%) were the most common adverse events. No severe adverse event such as cognitive impairment was observed.Conclusions:Dose-escalated topiramate monotherapy and add-on therapy demonstrate good efficacy and safety, with fewer adverse events in seizure control in neurosurgical patients.

Altered amplitude of low-frequency fluctuations and regional homogeneity in drug-resistant epilepsy patients with vagal nerve stimulators under different current intensity.

BackgroundThe mechanisms of vagal nerve stimulation (VNS) for the treatment of drug‐resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting‐state functional MRI (rs‐fMRI).MethodsThe rs‐fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t‐test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t‐test.ResultsThe significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus.ConclusionsThe spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS‐induced improvement in seizure frequency.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions

The term ‘implantation effect’ is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

A resting-state functional MRI study on the effect of vagal nerve stimulation on spontaneous regional brain activity in drug-resistant epilepsy patients

PurposeTo explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). Methods15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t-test or paired sample t-test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. ResultsThe voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. ConclusionsAltered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency.

‘In the best case seizure-free’ – Parental hopes and worries before and satisfaction after their child's epilepsy surgery

ObjectiveThe objective of this study was to gain a better understanding of parental hopes and worries before and subsequent experiences two years after their child had undergone epilepsy surgery. MethodsThe parents of 107 children and young people who underwent epilepsy surgery at a single center completed surveys focusing on hopes and concerns before surgery and subsequent experiences at two-year follow-up. Responses were analyzed by thematic analysis. ResultsBefore surgery, parental hopes focus on not only seizure freedom or reduction but also potential improvements in child development and emotional–behavioral functioning. Worries before surgery include not only potential injury or loss of skills but also a concern that the surgical procedure would not lead to an improvement in the child's seizures. The vast majority of parents experienced positive aspects at the two-year follow-up including seizure freedom or reduction but also perceived improvements in behavior, development, and sleep. This suggests that for many, expectations for the surgery were met. A small number of parents reported negative effects of surgery including loss of skills, worsening/lack of improvement in seizure frequency, or negative impact on development. SignificanceFor the majority of parents whose children undergo surgery, expectations are met, and fears are not realized. Knowledge of parental hopes and worries before surgery as well as experiences after the operation is useful for improving pre- and postsurgical counseling.

1270 Wobbly Knees: Cataplexy Or Seizure? A Case Report

Abstract Introduction Cataplexy (associated with narcolepsy) is difficult to differentiate from conditions such as seizure, syncope or TIA, but using validated clinical tools can help. We report a case that was mistakenly diagnosed as cataplexy, delaying diagnosis and treatment of his underlying seizures. Report of Case A 42 years old male presented with “freezing spells” described as spontaneous episodes of weakness in his knees. He may stagger and drop objects but had never fallen. He denies loss of consciousness. Post-ictally, he takes a moment to readjust his body and returns to baseline. There was no warning or aura before the episodes. These spells initially occurred 1-2 times/year in 2002, then progressed to 1/month by 2006 and then increased to 15 times/day in Jan 2019, lasting 5-10 seconds at a time. He became hesitant to drive. He was evaluated by a pulmonologist/sleep specialist. PSG showed Mild OSA but MSLT wasn’t suggestive of Narcolepsy. He was prescribed CPAP but stopped after 6 months since it didn’t improve his symptoms. He was prescribed Venlafaxine to treat presumptive Cataplexy, without any benefit. Eventually, he was referred to neurology/sleep clinic. Cataplexy questionnaire was administered and was negative: specifically, there were no emotional triggers of his episodes, such as hearing a joke, laughing or crying. Due to the stereotyped nature of his spells, he was referred to epilepsy specialist. He underwent 72 hours video EEG monitoring which showed that his clinical episodes were associated with EEG abnormality, suggestive of frontal lobe epilepsy. He was placed on Keppra and Oxcarbazepine. On follow up visit, he reported improvement in seizure frequency from 10-20/day to 1-2/day. Conclusion A validated1 clinical Tool such as Stanford Cataplexy questionnaire helps in differentiation of Cataplexy from other forms of transient muscle weakness. It can prevent 15 years delay in diagnosis and treatment of patients, or use of unnecessary medication.

1229 Management of Severe Sleep Related Disordered Breathing in a Pediatric Case of Vagal Nerve Stimulation

Abstract Introduction Vagal nerve stimulator (VNS) can be an effective treatment for refractory epilepsy but can lead to sleep related disordered breathing in the form of obstructive and central sleep apnea. We describe a pediatric case with VNS developing severe obstructive sleep apnea (OSA) and the course of management. Report of Case A 10-year-old boy with history of cerebral palsy, medically intractable epilepsy secondary to Lennox-Gastaut syndrome, and noted improvement in seizure frequency with VNS placement, presented to the pediatric sleep clinic with concern for sleep disordered breathing in the setting of snoring and witnessed gasping at night. The polysomnogram (PSG) showed severe OSA with apnea/hypopnea index (AHI) of 21.8 events/hour and associated hypoxemia. He subsequently underwent adenotonsillectomy. Post procedural PSG demonstrated persistent severe OSA. The obstructive events had rhythmicity temporally coincident with the VNS cycling. Subsequent PSG, after turning VNS off, showed a reduction in AHI to 11 events/hour without hypoxemia. Positive airway pressure (PAP) was initiated during this PSG, however titration was rendered unsuccessful due to VNS activation. A final titration PSG was performed with optimal resolution of OSA with VNS turned off. Since the patient did not have nocturnal seizures, it was recommended to turn the VNS off at nighttime with CPAP use. Patient was noted to have less sleep disruptions at night and more alertness during the day. Conclusion This case poses a challenging situation where patient’s epilepsy responded to VNS but the device contributed to OSA and affected PAP titration. One strategy to improve OSA in such cases is to change VNS parameters at the risk of changing stimulation settings effective for seizure control. Turning VNS off during sleep provided a simpler solution while ensuring effective treatment. Thus, clinicians should be vigilant about concomitant OSA treatment in the setting of vagal nerve stimulation, which can improve quality of life.

Systematic review of corpus callosotomy utilizing MRI guided laser interstitial thermal therapy

Corpus callosotomy is a palliative surgical option for patients with refractory epilepsy and frequent drop attacks, decreasing seizure frequency and severity by disconnecting the cerebral hemispheres. Though often successful, open surgery is not without risk. Corpus callosotomy by MRI-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to the standard open procedure. This report aims to present an illustrative case and systematically review the current literature on the surgical technique. A systematic review of the English literature through January 2019 was performed. Articles were searched by title utilizing the following key word combinations: “laser” and “callosotomy”, “callosotomy” and “ablation”, “laser” and “corpus”, “callosotomy” and “thermal”, and “stereotactic” and callosotomy”. The articles recovered were then classified by level of evidence and summarized. Fifteen papers were reviewed, of which 6 met inclusion and exclusion criteria. All included studies were classified as level IV evidence. There was a total of 13 patients ranging from 13 months to 44 years old (mean 23.5 years old). The number of laser fibers utilized ranged from 1 to 3. Engel class I was achieved in 5 patients, II in 4, III in 2, IV in 1. Reported patient follow up was 4–39.7 months (mean 15.43). Corpus callosotomy utilizing MRI-guided laser interstitial thermal therapy results in improvement in seizure frequency and severity with minimal complications. Prospective trials are needed to compare its seizure control and long-term outcomes to that of standard open callosotomy.

Various Aspects of Tiagabine Effectiveness as Add-on Therapy in Patients with Refractory Epilepsy.

The aim of the present study was to investigate various aspects of tiagabine (TGB) effectiveness in Bulgarian patients with drug-resistant epilepsy. This open, prospective study recruited the patients with epilepsy attending the Clinic of Neurology at the University Hospital of Plovdiv, Bulgaria. The patients completed diaries about the seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with TGB and at 6 months or 1 year afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. TGB was applied as an add-on treatment in 43 patients (24 males, mean age 39 years). There was relatively mild and transient dynamic improvement of seizure severity, satisfactory seizure frequency reduction in 32.6% of participants, stable mean seizure frequency reduction (40-50%) from month 6 to month 24 and a stable response rate (52.3-50%) during the same period. New seizure types (myoclonic, myoclonic-atonic) occurred in 2 patients. The final clinical efficacy was higher in patients with initial monotherapy. There were adverse events (dizziness/vertigo, sedation, memory impairment, loss of appetite and weight, confusion, psychosis, insomnia, transient diplopia, lymphadenomegaly, rash, nausea, depression, anxiety, tremor of hands, unstable gait, legs edema, thrombocytopenia, cervical muscles tightening) in 26.19% of patients. In conclusion, TGB treatment is associated with low and transient improvement of seizure severity, good and stable improvement of seizure frequency, possible worsening of seizure control, possible appearance of new seizure types, and acceptable safety and tolerability.

Vagus nerve stimulation in pediatric patients with failed epilepsy surgery.

Adequate control of pharmacoresistant epilepsy continues to be a challenge. Multiple studies have reported the benefits of epilepsy surgery and vagus nerve stimulation for children with pharmacoresistant epilepsy. Little is known about the role of vagus nerve stimulation for children with failed epilepsy surgeries. The aim of this study was to examine the effects of vagus nerve stimulation on seizure frequency reduction for children with failed epilepsy surgeries. We retrospectively reviewed 85 children with pharmacoresistant epilepsy who underwent vagus nerve stimulation. Six of these patients underwent epilepsy surgery before vagus nerve stimulation (group I) and 79 patients received only vagus nerve stimulation (group II). We recorded seizure frequency at 3, 12, 24 and 36months after vagus nerve stimulator implantation. Both groups had reduced seizure frequencies at the 3-, 12-, 24- and 36-month follow-up (p = 0.044 for group I trends and 0.008 for group II trends). Vagus nerve stimulator implantations significantly improve seizure frequency for children with or without previous epilepsy surgery at 3, 12, 24 and 36months. These findings suggest that vagus nerve stimulation should be considered an alternative therapy for pediatric patients with previous failed surgeries.

Editors' note: SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy

In “ SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy,” Vlaskamp et al. reviewed the phenotype of 57 patients with SYNGAP1 mutations/microdeletions and found that this disorder is characterized by generalized epilepsy (often eyelid myoclonia with absences) particularly after eating, developmental delay, moderate to severe intellectual disability, behavioral impairment, sleeping problems, hypotonia, and gait abnormalities. Wolf et al. emphasized that in their experience, chewing and biting were the characteristic triggers for seizures during eating. They also noted these patients to be sensitive to eyelid closure. Vlaskamp et al. replied that eyelid closure sensitivity was very common in their cohort. They proposed that the limited photosensitivity observed may be attributed to EEG timing (because photosensitivity is age dependent), technical difficulties, or behavioral problems interfering with the assessment. Vlaskamp et al. found that 18% of patients with SYNGAP1 encephalopathy became seizure-free after age 7, most of whom were on valproate or lamotrigine. Fung described a patient with SYNGAP1 mutation who had improved seizure frequency and development on a ketogenic diet, but this was complicated by pneumonia due to lipid aspiration. Vlaskamp et al. responded that they had seen one patient with SYNGAP1 encephalopathy improve markedly on the ketogenic diet and that although less than 10% of patients on the diet develop lipoid pneumonia, Fung's case serves as an important reminder of the potential for aspiration in patients with developmental and epileptic encephalopathies. In “ SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy,” Vlaskamp et al. reviewed the phenotype of 57 patients with SYNGAP1 mutations/microdeletions and found that this disorder is characterized by generalized epilepsy (often eyelid myoclonia with absences) particularly after eating, developmental delay, moderate to severe intellectual disability, behavioral impairment, sleeping problems, hypotonia, and gait abnormalities. Wolf et al. emphasized that in their experience, chewing and biting were the characteristic triggers for seizures during eating. They also noted these patients to be sensitive to eyelid closure. Vlaskamp et al. replied that eyelid closure sensitivity was very common in their cohort. They proposed that the limited photosensitivity observed may be attributed to EEG timing (because photosensitivity is age dependent), technical difficulties, or behavioral problems interfering with the assessment. Vlaskamp et al. found that 18% of patients with SYNGAP1 encephalopathy became seizure-free after age 7, most of whom were on valproate or lamotrigine. Fung described a patient with SYNGAP1 mutation who had improved seizure frequency and development on a ketogenic diet, but this was complicated by pneumonia due to lipid aspiration. Vlaskamp et al. responded that they had seen one patient with SYNGAP1 encephalopathy improve markedly on the ketogenic diet and that although less than 10% of patients on the diet develop lipoid pneumonia, Fung's case serves as an important reminder of the potential for aspiration in patients with developmental and epileptic encephalopathies.

Effectiveness, retention, and safety of modified ketogenic diet in adults with epilepsy at a tertiary-care centre in the UK

With the rising demand for ketogenic diet therapy in adult epilepsy, there is a need for research describing the real-life effectiveness, retention, and safety of relevant services. In this 1-year prospective cohort study we present outcomes of the first 100 referrals for modified ketogenic diet (MKD) at the UK’s largest tertiary-care epilepsy centre, where patients received dietetic review up to twice per week. Of the first 100 referrals, 42 (31 females, 11 males; mean age 36.8 [SD ± 11.4 years]) commenced MKD, having used a mean of 4 (SD ± 3) previous antiepileptic drugs. Retention rates were: 60% at 3 months, 43% at 6 months, and 29% at 12 months. 60% of patients reported an improvement in seizure frequency, 38% reported a > 50% reduction, and 13% reported a period of seizure freedom; 30% reported a worsening in seizure frequency at some point during MKD therapy. The most common reasons for discontinuing MKD were side effects and diet restrictiveness. The most common side effects were weight loss, gastrointestinal symptoms and low mood. The likelihood of discontinuing MKD was significantly decreased by experiencing an improvement in seizure frequency (p ≤ 0.001). This study demonstrates that MKD can be effective in adults, although, even with regular dietetic support, retention rates remain low, and periods of worsening seizure frequency are common.

Effect of low glycaemic diet and structured exercise on quality of life and psychosocial functions in children with epilepsy.

ObjectiveThe study aimed to investigate the combined effects of structured exercise therapy and a low glycaemic diet on quality of life and psychosocial functions in children with epilepsy.MethodsForty-two subjects aged 11 to 17 years and diagnosed with refractory epilepsy were recruited. Structured home-based exercise and a low glycaemic diet designed by exercise and diet specialists were administered for 6 months. The Children’s Depression Inventory (CDI) and the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) were administrated to compare the effects of the combined treatment after 6 months.ResultsParticipants’ mean (±standard deviation) age was 13.1 ± 2.3 years and mean epilepsy duration was 8.9 ± 4.2 years. The seizure frequency was approximately two to four/day per week in 28 cases and five per day/week in 8 cases. After the study period, there was a significant improvement in seizure frequency and in scores on the CDI and QOLCE-55 scales.ConclusionCombined therapy demonstrated a promising improvement in seizure frequency, depression level and quality of life in children with epilepsy.

Seizure control after radiosurgery for cerebral arteriovenous malformations: a 25-year experience.

Seizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control. Patients with AVM who presented with a history of seizure and underwent SRS at the authors' institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6-295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up. Seizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0-27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4-23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15-0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16-0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test). This study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

Analysis of pharmacotherapy regimen and costs in patients with drug-resistant epilepsy following vagus nerve stimulation therapy: a single-center study (Poland).

Approximately 30-40% of patients with drug-resistant epilepsy (DRE) who underwent vagus nerve stimulator (VNS) implantation achieve above 50% reduction in seizure frequency. VNS proves effective in reducing frequency of seizures in DRE patients, when combined with antiepileptic drugs (AEDs). This raises a question whether improvement of clinical parameters is achieved with VNS only or relies on combined therapy with AEDs. The aim of the study was the analysis of impact of VNS on clinical recovery of patients with DRE and the analysis of pharmacotherapy costs and drug regimen following VNS implantation in DRE patients. The study included all the patients who had VNS implanted at our department in the years 2014-2018. The patients would be followed up for 2years after the VNS implantation date. The most commonly used drugs included levetiracetam, lacosamide, valproate, oxcarbazepine, and topiramate. Average cost of AEDs in year 1 following VNS implantation was between EUR 15.53 (CLB) and EUR 545.52 (TGB) and in year 2 between EUR 13.51 (NTZ) and EUR 779.44 (LAC). The greatest number of seizures affected the group of patients treated with three drugs. A statistically significant improvement in seizure frequency was observed in the group of patients treated with two and three drugs. With the rising costs of healthcare, the importance of economic efficiency is becoming increasingly relevant. VNS is a reasonable option for saving money in the healthcare system while ensuring measurable clinical and therapeutic outcomes over the long term.

Oxcarbazepine effectiveness as add-on therapy in Bulgarian patients with drug-resistant epilepsy

The study purpose was to perform an open, prospective study on various aspects of oxcarbazepine (OCBZ) effectiveness in Bulgarian patients with drug-resistant epilepsy. The study was performed with the participation of patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. Patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with OCBZ and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. OCBZ was applied as add-on treatment in 82 patients (44 males, mean age 40 years). There was a relatively mild and stable dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 25.6% of participants, a stable mean seizure frequency reduction (40-38.55%) from the 6th to the 24th month of treatment and a stable responder rate (39-48.6%) during the same period. There were adverse events (generalized rash, dizziness, nausea, vomiting, edemas of the extremities, memory problems) in 8.54% of patients. In conclusion, OCBZ treatment is associated with: a low and stable improvement of seizure severity, a good and stable improvement of seizure frequency, a possible worsening of seizure control, a good safety and tolerability.

Lamotrigine: how effective is it as add-on therapy in Bulgarian patients with drug-resistant epilepsy

The study purpose was to perform an open, prospective study on various aspects of Lamotrigine (LTG) effectiveness in Bulgarian patients with drug-resistant epilepsy. The study was performed with the participation of patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LTG and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. LTG was applied as add-on treatment in 73 patients (47 males, mean age 36 years). There was a relatively mild and stable dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 39.7% of participants, a stable mean seizure frequency reduction (43-59%) from the 6th to the 36th month of treatment and a stable responder rate (55.7-59.4%) during the same period. There were adverse events (dizziness/vertigo, generalized edema, irritability, aggressiveness, speech disturbances, visual hallucinations, sleepiness, insomnia, headache, diplopia, nystagmus, impaired balance, muscle cramps, gastrointestinal discomfort, generalized rash, fatigue, nausea) in 12.3% of patients. In conclusion, LTG treatment is associated with: a low and stable improvement of seizure severity, a good and stable improvement of seizure frequency, a possible worsening of seizure control, a good safety and tolerability.

SEEG-guided radiofrequency thermocoagulation of epileptic foci in the paediatric population: Feasibility, safety and efficacy

PurposeFocal epilepsy in children may be refractory to pharmacological treatment and surgical resection may be an appropriate option. When invasive electroencephalogram is required in the presurgical evaluation, depth electrodes can be used to create focal lesions in the epileptogenic zone using radiofrequency thermocoagulation (RFTC), to disrupt the epileptogenic zone. MethodsThis study aimed to assess the efficacy and safety of RFTC in a paediatric population of 46 patients. ResultsThe mean age of onset was 3.3 years and the mean age at SEEG was 8.2 years. MRI lesions were identified in 71.7% of the series, among them 60% of malformation of cortical development. 43.5% of the patients were seizure free at 1 month, 26.1% were responders. The mean duration of improvement was 6.8 months. 8 children were seizure free for >8 months and among them, 6 are currently seizure free for 8–24 months. 5 patients had functional deficits post-procedures, transient in 4 patients and prolonged in one of whom. 3/5 were anticipated following the results of cortical stimulation. Multivariate analysis found 3 independent criteria linked to RFTC efficiency one month after RFTC: frequency of the seizures before RFTC, age and number of contacts used. ConclusionRFTC is a safe method for the paediatric population providing important predictive information for surgical resection. An improvement in seizure frequency, often transient, is seen in 2/3 of our patients. RTFC could be useful as a palliative technique for children with an epileptogenic zone overlapping with eloquent areas, with minimal risk of sequelae.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study.Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified.Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication.Conclusion: The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.

Predominantly nocturnal seizures post temporal lobectomy: Characteristics of an unusual outcome group

PurposeTo describe the characteristics of a patient group who, after temporal lobectomy for predominantly diurnal seizures, experience a postoperative conversion from diurnal to predominantly nocturnal seizures, and compare this group to those who continue to have a diurnal seizure pattern postoperatively. MethodsFrom a cohort of 470 surgical cases with long-term follow-up, we retrospectively identified 16 patients with a predominantly nocturnal seizure pattern, including five with nocturnal seizures only (median follow-up 21 years) and compared them with 20 predominantly diurnal seizure patients. ResultsSustained postoperative improvement in seizure frequency was observed in 14/16 cases. Seizure recurrence after surgery occurred within the first postoperative year in 13/16 cases. In all but 3 cases the seizures were all predominantly nocturnal from the time of recurrence, whereas in 3 there was a period of diurnal seizures during the early postoperative years. One patient lapsed back to diurnal seizures after 16 years of predominantly nocturnal seizures. Compared to the predominantly diurnal group, these patients had a significantly later age at seizure onset and were older at the time of surgery. ConclusionPatients with predominantly nocturnal seizures comprise a small but distinct post-operative outcome category. Although not formally assessed, this outcome appears associated with improved quality of life, such as with eligibility to drive, with 50% of the sample confirmed as driving. This finding may help with providing prognostic information and counseling to these patients when they are identified postoperatively.