Focal Impaired Awareness Seizures Research Articles

Optimizing deep brain stimulation for the treatment of drug-resistant temporal lobe epilepsy: a pilot study.

The authors sought to determine the antiseizure effects of deep brain stimulation (DBS) of the parahippocampal cortex (PHC) for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE). After a 3-month baseline period, 6 adult patients with drug-resistant MTLE and hippocampal sclerosis (HS) had stereoelectroencephalography (SEEG)-DBS electrodes implanted at the PHC for identification of the seizure onset zone (SOZ). Patients entered an 8-month, randomized, double-blind protocol for DBS, followed by a 12-month open-phase study. Monthly reports of seizure frequency were collected, with separate counting of focal seizures with or without awareness impairment (focal impaired awareness seizures [FIAS] or focal aware seizures [FAS], respectively) and focal evolving to bilateral generalized tonic clonic seizures (GTCS). Stimulation parameters were 130 Hz, 450 μsec, 2.5-3 V, and cyclic stimulation 1 minute on/4 minutes off. The total seizure rate decrement during follow-up was 41% (CI 25%-56%), with better seizure control for GTCS (IQR 19%-20%) and FIAS (IQR 0%-16%), with FAS being less responsive (IQR 67%-236%). No neuropsychological deterioration was observed. PHC DBS induced important antiseizure effects in patients with incapacitating FIAS and GTCS, most likely through blocking the propagation of hippocampal-onset seizures. The PHC target can be easily and safely approached due to positioning away from vascular structures, and there was no evidence of DBS-induced cognitive deterioration.

Emerging evidence of genotype-phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G.

Developmental and epileptic encephalopathies (DEEs) have high genetic heterogeneity, and DEE due to the potassium voltage-gated channel subfamily C member 2 (KCNC2) variant remains poorly understood, given the scarcity of related case studies. We report on two unrelated Chinese patients, an 11-year-old boy and a 5-year-old girl, diagnosed with global developmental delay (GDD), intellectual disability (ID), and focal impaired awareness seizure characterized by generalized spike and wave complexes on electroencephalogram (EEG) in the absence of significant brain lesions. Whole-exome sequencing (WES) and electrophysiological analysis were performed to detect genetic variants and evaluate functional changes of the mutant KCNC2, respectively. Importantly, we identified a novel gain-of-function KCNC2 variant, R405G, in both patients. Previously reported variants, V471L, R351K, T437A, and T437N, and novel R405G were found in multiple unrelated patients with DEE, showing consistent genotype–phenotype associations. These findings emphasize that the KCNC2 gene is causative for DEE and facilitates treatment and prognosis in patients with DEE due to KCNC2 mutations.

Non-lesional late-onset epilepsy in the elderly Japanese patients: Presenting characteristics and seizure outcomes with regard to comorbid dementia

The objective of the present retrospective study was analysis of clinical, radiological, and electrophysiological characteristics of the non-lesional late-onset epilepsy (NLLOE) in the elderly Japanese patients, and comparison of the seizure outcomes in this population with regard to presence of comorbid dementia. The study cohort comprised 89 consecutive patients with NLLOE aged ≥ 65 years. In 49 cases (55%), NLLOE manifested with a single type of seizure. Focal impaired awareness seizures (FIAS) were encountered most often (in 69 patients; 78%). Ten patients (11%) had a history of the status epilepticus. Comorbid dementia was diagnosed in 31 patients (35%). Localized or diffuse white matter hyperintensity was the most common imaging finding (66 cases). Epileptiform discharges in the temporal area represented the most frequent abnormality on interictal EEG (24 cases). Seizure-free status for ≥ 12 months was attained in 46 out of 64 patients (72%), who were followed for ≥ 12 months (range, 12 – 110 months), and 42 of them received monotherapy, mainly with levetiracetam (21 patients), carbamazepine (10 patients), or lacosamide (8 patients). In comparison to their counterparts, the rate of seizure-free status for ≥ 12 months was significantly lower in patients with comorbid dementia (81% vs. 52%; P = 0.0205). In conclusion, the NLLOE among Japanese patients aged ≥ 65 years has variable presenting characteristics, and comorbid dementia is diagnosed in one-third of cases. Seizure-free status for ≥ 12 months may be attained in more than two-thirds of treated patients, but comorbid dementia is associated with significantly worse response to antiseizure therapy.

Epidemiological and clinical features of epileptic patients in Goma, Democratic Republic of the Congo

Introduction: Epilepsy is one of the most common neurological conditions but the majority of epileptic patients in sub-Saharan African countries do not receive appropriate treatment. In the Democratic Republic of the Congo (DRC), very few epidemiological studies have been conducted on epilepsy. The objective of this study was to describe socio-demographic characteristics, the type of epileptic seizures, and etiological factors of these seizures in a hospital cohort of epileptic patients followed at the Neuropsychiatric Hospital Center in Goma (in the DRC). Materials and methods: This was a cross-sectional study of 917 epileptic patients received in neurology consultation at the Neuropsychiatric Hospital Center in Goma (in the DRC) from January 1st, 2017 to December 31st, 2021. Results: The median age of patients was 16 years, the median age of the patients at onset of seizures was 13 years and the median time between onset of seizures and consultation was 8.0 months; 14.2% of had a family history of epilepsy. Generalized tonic-clonic seizures were the most frequent (76.7%), followed by motor focal impaired awareness seizures (5.2%) and non-motor focal aware seizures (3.6%). The etiologic factor was found in 444 (48.4%) patients and was dominated by chronic alcoholism (20.9%), neurocysticercosis (17.6%), meningitis (14.6%), malnutrition (11.3%), cerebral malaria (8.3%), and head injury (7.7%). Conclusion: This study provides an epidemiological overview of epilepsy in Goma city. The etiological factors and types of seizures will dictate the best possible treatment options.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n=15; CASPR2, n=5) of 32 patients with LGI1 (n=24) and CASPR2 (n=8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Seizures and COVID-19: Results from the Spanish Society of Neurology’s COVID-19 registry

We describea series of patients with COVID-19 who presented with seizures, reported in the Spanish Society of Neurology’s COVID-19 Registry.This observational, descriptive,multicentre, registry-based study includes patients with confirmed COVID-19 who experienced seizures during active infection.Wedescribe theclinicalpresentation of COVID-19,seizures,and resultsof complementary tests.Wealsodescribe the suspectedaetiologyof the seizures.Of 232 reported cases, 26 (11.2%) presented with seizures;7 of these patients (26.9%) had prior history of epilepsy, whereas the remaining 19 (73.1%) had no history of seizures.In most cases, seizures presented on days 0 and 7 after onset of COVID-19. By seizure type, 8 patients (30.7%) presentedgeneralised tonic-clonic seizures, 7 (26.9%) status epilepticus, 8 (30.7%) focal impaired-awareness seizures, and 4 (11.7%) secondary generalised seizures.Six patients (23.1%) also presented other neurological symptoms, includingaltered mental status and decreased level of consciousness. Predisposing factors for seizures (eg, dementia, tumour, cerebrovascular disease) were observed in 10 of the 19 patients with no prior history of epilepsy (52.6%).Patients with COVID-19 may present with seizures over the course of the disease,either alone or in the context of encephalopathy.Seizures may present in patients with no prior history of epilepsy; however, most of these patients present predisposing factors.

Right Peri-insular Hemispherotomy: 2-dimensional operative video

This is a surgical technique video of a right peri-insular hemispherotomy in a child with Rasmussen’s encephalitis. The patient is a 5-year-old boy with focal onset impaired awareness seizures started 6 months before surgery, developing different subtypes of focal seizures and evolving to drug-resistant epilepsy. In neurological examination, he already had a left-sided hemiparesis with pyramidal signs. Magnetic resonance imaging showed right-sided cortical atrophy and fronto-insular subcortical hyperintensity signal areas. The preoperative electroencephalogram revealed frequent right-sided central mid temporal spikes. The history and complementary exams raised a hypothesis of Rasmussen’s encephalitis, a rare neurological condition, characterized by unilateral chronic inflammation of the cerebral cortex, causing drug-resistant epilepsy, and evolving to progressive neurological decline1. The hemispherotomy is an effective procedure aimed to isolate the entire hemisphere functionally with minimal removal of brain tissue, and remains the only cure for seizures caused by Rasmussen’s encephalitis2,3. Long-term seizure freedom may be achieved in around 80% of patients and improves quality of life4. It’s already accepted that briefer duration of epilepsy preceding the surgery is associated to better adaptive functioning postoperatively due to the high neuroplasticity of young patients4. Three years after surgery, the patient remains seizure free, walking without help.

An Open-Label Pilot Trial Assessing the Safety and Efficacy of SPN-817 (Huperzine A Extended-Release) in Adults with Treatment-Resistant Focal Impaired Awareness Seizures (P12-8.003)

An Open-Label Pilot Trial Assessing the Safety and Efficacy of SPN-817 (Huperzine A Extended-Release) in Adults with Treatment-Resistant Focal Impaired Awareness Seizures (P12-8.003)

Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging

PurposeArterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. MethodsOverall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. ResultsOf the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). ConclusionA diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.

Evaluation of real‐world effectiveness of perampanel in Japanese adults and older adults with epilepsy

While previous studies have demonstrated the safety and effectiveness of perampanel (PER) in combination with other anti-seizure medications in adult patients, data for older patients are limited. This study aimed to confirm real-world safety and effectiveness of combination treatment with PER in Japanese patients with focal seizures with or without focal to bilateral tonic-clonic seizures (FBTCS) or generalised tonic-clonic seizures (GTCS) according to age subgroups (<65 and ≥65 years of age). This large-sample prospective post-marketing observational study included a 24-52-week observation period after the first PER treatment. Safety was assessed according to adverse drug reactions (ADRs) and efficacy was evaluated based on the 50% responder rate and rates of overall symptom improvement. Among the 3,808 patients who were enrolled, 3,716 (3,026 patients aged <65 years and 690 patients aged ≥65 years) and 3,272 were included in the safety and efficacy analysis datasets, respectively. ADRs were reported for 1,247 patients (33.6%) in the safety analysis dataset. Of these, 36.2% and 22.2% were aged <65 years and ≥65 years, respectively, and the most common ADRs were somnolence (11.6%, 5.5%) and dizziness (9.7%, 5.4%). The 50% responder rates in patients aged <65 years and those ≥65 years were 60.1% and 89.0% for those with focal aware seizures (FAS) with motor signs; 48.0% and 60.0% for FAS without motor signs; 47.4% and 80.2% for focal impaired awareness seizures; 70.8% and 93.4% for FBTCS; and 63.6% and 88.9% for GTCS, respectively. The improvement rates of symptoms/conditions were also higher in patients aged ≥65 years than those <65 years. PER was effective in reducing seizure frequency and was safe, especially in older patients. PER may be a clinical treatment option for older patients with seizure disorders.

Expert Perspective: Who May Benefit Most From the New Ultra Long-Term Subcutaneous EEG Monitoring?

Today's modalities for short-term monitoring of EEG are primarily meant for supporting clinical diagnosis of epilepsy or classifying seizures and interictal epileptiform discharges while long-term EEG adds the value of differential diagnosis investigation or pre-surgical evaluation. However, longitudinal epilepsy care relies on patient diaries, which is known to be unreliable for most patients and especially those with focal impaired awareness or nocturnal seizures. The subcutaneous ultra long-term EEG (ULT-EEG) systems alleviate those issue by enabling objective, continuous EEG monitoring for days, weeks, months, or years. Albeit a great advance in continuous EEG over extended periods, it comes with the caveat of limited spatial resolution of two channels. Therefore, the new subcutaneous EEG modality may be especially suited for a selected group of patients. We convened a panel of experienced epileptologists to consider the utility of a subcutaneous, two-channel ULT-EEG device with the goal of developing a consensus-based expert recommendation on selecting the optimal patient types for this investigative technique. The ideal patients to select for this type of monitoring would have focal impaired awareness seizures without predominant motor features and seizures with medium to high voltage patterns. As this technology matures and we learn more about its limitations and benefits we might find a wider array of use case scenarios as it is believed that the benefits for many patients are most likely to outweigh the risks and cost.

The prevalence and major determinants of non-compliance with anti-seizure medication among children

Background: A wide range of adherence to the use of anti-seizure medications has been reported among children with the disease, and accordingly, various factors on the degree of adherence to the drug have been reported. But in our society, there is no clear picture of drug adherence and related factors among children with seizures. We evaluated the frequency of adherence to anti-seizure medication as well as related factors. Methods: This cross-sectional study was conducted on 120 children with epilepsy who referred to Ali Asghar Hospital in Tehran, Iran, during 2019 and 2020. Along with demographic characteristics, adherence to antiepileptic medications was assessed by the Modified Morisky Scale (MMS). Results: The overall frequency of adherence to anti-seizure medications among children was reported to be about 41.7%. Among all baseline characteristics, much higher adherence was revealed in patients with educated parents. The rate of drug adherence in children with a history of perinatal morbidities was much lower than in other patients. The type of seizure could also affect the rate of drug adherence as the highest and the lowest adherence was found concerning focal impaired awareness seizure (57.1%) and atonic seizures (11.1%) indicating a significant difference (P = 0.022). The most common causes of non-adherence to treatment were expressing inability to treat the patient (23.0%), parents’ forgetfulness to give medicine to the child (18.3%), and not taking medication when traveling or leaving home (16.7%). Conclusion: The lower level of education of the parents, type of seizure, as well as the presence ofunderlying perinatal morbidity in the child can predict non-compliance with anticonvulsant medication regimens among affected children.

Epilepsy surgery in patient with monogenic epilepsy related to SCN8A mutation.

Epilepsy surgery is superior to prolonged medical therapy in patients with drug-resistant focal epilepsy, but reports on epilepsy surgery outcomes for patients with a genetic etiology are limited, especially in adults. This is the first documented report of a stereoelectroencephalography (SEEG) evaluation and resective surgery outcome in an adult patient with epilepsy related to SCN8A mutation. We describe a patient with epilepsy related to SCN8A mutation which was reported as a variant of uncertain significance at time of his pre-surgical evaluation and reclassified as likely pathogenic about 3years after resective epilepsy surgery. Most of his pre-surgical evaluation results suggested right temporal lobe epilepsy, but few reported semiological symptoms, ictal SPECT, and neuropsychology results were discordant, and brain MRI was non-lesional. Therefore, SEEG was recommended; ultimately, seizures were localized to the right hippocampus. He was seizure-free for 1.5years after right anterior temporal lobectomy, then reported three focal to bilateral tonic-clonic (FBTC) seizures in the subsequent 12months (preoperatively, 6 focal impaired awareness seizures and 4-6 FBTC per year). This case demonstrates that epilepsy surgery reduced seizure burden in a patient with SCN8A-related epilepsy granting him short-term seizure freedom after resection, and then decreased seizure frequency after relapse compared to the preoperative baseline.

Knowledge gap exists among caregivers of adults compared to caregivers of children with epilepsy: A comparative analysis from a low resource setting

Caregivers of adults (CG-A) and caregivers of children (CG-C) may differ in their knowledge, attitude and behavior and hence their education requirements during epilepsy counseling could vary. This study compares the current knowledge, attitudes, behavior during a seizure, presence of myths surrounding epilepsy and ability to recognize seizures among a sample of CG-A and CG-C. Caregivers of children and adult patients with minimum 6months history of epilepsy were enrolled. Information was collected using a questionnaire about clinical and demographic details and five domains (KAP-plus); knowledge, attitude, behavior, presence of myths and a video data for identification of focal impaired awareness seizures (FIAS) and generalized tonic-clonic seizures (GTCS). There were 132 CG-A and 127 CG-C. CG-C were younger and better educated compared to CG-A (formal education of 64.6% vs 44.7% p=0.001). CG-A and CG-C were comparable in the knowledge and attitude domains. CG-A scored less than CG-C in the domains of behavior (15.5 vs 16.8 p=<0.001), myths (15.4 vs 16.2 p=0.002), video recognition of FIAS and GTCS (0.7 vs 0.94 p=0.001) and KAP-plus score (22.9 vs 24.6 p=0.017). The knowledge-behavior or knowing-doing gap, knowledge-faith gap and knowledge-recognition gaps existed more among CG-A compared to CG-C. Focused education strategies are required to bridge the gap among CG-A.

A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy

ObjectivePerampanel is a once-daily oral anti-seizure medication for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures (FBTCS), and generalized tonic-clonic seizures. Study 402 (NCT02033902) collected safety information on clinically important treatment-emergent adverse events (TEAEs) from real-world clinical practice in patients aged ≥12 years with refractory epilepsy who were receiving perampanel as an add-on therapy. MethodsStudy 402 was a multicenter, observational, 52-week cohort study conducted in Austria, Belgium, Czech Republic, Denmark, France, Israel, Sweden, and the United Kingdom. Safety data were gathered prospectively from patients at clinic visits. The primary endpoint was the incidence of clinically important TEAEs defined as dizziness; blurred vision; somnolence; aggression; balance disorders (including ataxia and falls); weight gain; suicidality; drug abuse, misuse, dependence, and withdrawal; skin photosensitivity; and unintended pregnancy while taking levonorgestrel-containing contraceptives. Off-label use of perampanel and outcomes associated with any suspected drug–drug interaction were also monitored and recorded. Secondary endpoints included the Hospital Anxiety and Depression Scale (HADS) and Clinical Global Impression of Change. ResultsOf 483 patients in the Safety Analysis Set, mean (standard deviation [SD]) age was 38.3 (15.1) years, 48.4% were female, mean (SD) time since diagnosis was 23 (14.8) years, 56.5% had focal impaired awareness seizures, and 48.7% had FBTCS. Overall, 243 (49.3%) patients treated with perampanel completed the study and 227 (46.0%) patients discontinued. The most common primary reason for discontinuation was adverse events (n = 130 [26.4%]).A total of 301 (62.3%) patients reported at least one TEAE, of which 45 (15.0%) patients had severe TEAEs and 256 (85.0%) patients had TEAEs judged as mild to moderate in severity. Overall, 51 (10.6%) patients had serious TEAEs, including two deaths that were judged as not related to perampanel, and 136 (28.2%) patients experienced a TEAE that led to treatment discontinuation. Clinically important TEAEs were reported by 153 (31.7%) patients, with the most common being dizziness (13.9%), balance disorders (5.6%), aggression (5.4%), and weight gain (5.4%). In general, the frequencies of clinically important TEAEs were lower in this study compared with previous interventional clinical studies, except for the incidence of suicidality (2.1% vs 1.0%) and aggression (5.4% vs 5.1%). Mean total HADS scores were similar at the end of the study compared with baseline; at the end of treatment, most (>60%) patients had no shift in HADS score category; ∼15% of patients moved to a worse category vs baseline and ∼20% of patients moved to an improved category vs baseline for both anxiety and depression. Based on investigator assessment, disease severity was improved in 185/415 (44.6%) patients. A subanalysis in elderly patients aged ≥65 years showed similar results to the overall population. ConclusionsThe data from this observational study are consistent with the known safety profile of perampanel derived from previous interventional phase II and III clinical studies. No unusual or unexpected TEAEs were observed in this real-world clinical practice setting.

Focal impaired awareness seizures in a rodent model: A functional anatomy.

ObjectivePatients with temporal lobe epilepsy (TLE) frequently report debilitating comorbidities such as memory impairments, anxiety, and depression. An extensive neuronal network generates epileptic seizures and associated comorbidities, but a detailed description of this network is unavailable, which requires the generation of neuronal activation maps in experimental animals.MethodsWe recorded electrographic seizures from the hippocampi during a kindling‐evoked focal impaired awareness seizure with observed freezing, facial twitching, and involuntary head bobbing. We mapped seizure circuits activated during these seizures by permanently tagging neurons through activity‐induced immediate early genes, combined with immunohistochemical approaches.ResultsThere was bilateral activation of circuits necessary for memory consolidation, including the hippocampal complex, entorhinal cortex, cingulate gyrus, retrosplenial cortex, piriform cortex, and septohippocampal complex in kindled animals compared with unstimulated awake behaving mice. Neuronal circuits in the ventral hippocampus, amygdala, and anterior cingulate cortex, which regulate the stress response of hypothalamic‐pituitary‐adrenal axis, were also markedly activated during a focal impaired awareness seizure.SignificanceThis study highlights neuronal circuits preferentially activated during a focal awareness impaired seizure in a rodent model. Many of the seizure‐activated neuronal circuits are critical modulators of memory consolidation and long‐term stress/depression response. The hijack of these memory and depression regulatory systems by a focal seizure could account for the frequent reports of comorbidities such as memory impairment and depression in many TLE patients.

Cluster analysis: Predicting the seizure outcome in temporal lobe epilepsy

ObjectivesWe applied the Two-Step cluster analysis on a large cohort of patients with temporal lobe epilepsy (TLE). We hypothesized that there are distinct clusters of patients with TLE based on their clinical characteristics and these clusters may predict their seizure outcome. MethodsThis was a longitudinal study of a prospectively developed database. All patients with a diagnosis of TLE were studied at the outpatient epilepsy clinic, Shiraz, Iran, from 2008 until 2021. The Two-Step cluster analysis (Schwarz’s Bayesian Criterion: BIC) was applied to the whole dataset considering the demographic data, clinical characteristics, imaging, and electroencephalography data. The seizure outcome was compared between the clusters of patients. ResultsThree hundred and seventy-four patients had the inclusion criteria and were studied. The Two-Step cluster analysis showed that there were two distinct clusters of patients with TLE. The most important clinical predictors were the presence (or absence) of focal impaired awareness seizures or focal to bilateral tonic-clonic seizures, aura with seizures, and the brain imaging findings. The seizure outcomes were significantly different between these two clusters (p = 0.008). ConclusionThe Two-Step cluster analysis could identify two distinct clusters of patients with TLE; these data are helpful in providing prognosis and counseling for patients and their care-givers. These data may also be used to develop a practical outcome prediction tool for patients with TLE.

Reader Response: Clinical Reasoning: A 70-Year-Old Man With Right Arm and Leg Shaking.

The authors describe a case of a 70-year-old man presenting with increased right arm flexion, right leg extension, and limb shaking ischemic events because of an atypical anterior cerebral artery (ACA) stroke in concurrence with normal vital signs.1 We agree with the concluded localization of the stroke. However, serial focal motor seizures, focal-impaired awareness seizures, or status epilepticus with acute stroke may be more likely explanations of the event than limb shaking ischemic events and an akinetic mutism resulting in seizure mimicry.

Endoscopic Transcortical Selective Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy: 2-Dimensional Operative Video.

This surgical video shows a 19-yr-old woman with focal impaired awareness seizures. Seizure semiology showed no lateralizing signs. Ictal electroencephalography (EEG) failed to determine the seizure origin. Interictal EEG showed bilateral spike-and-waves at the temporal electrodes. Magnetic resonance imaging (MRI) showed suspected hippocampal sclerosis on the right side. To determine the side of the focus, depth electrodes were implanted in both hippocampi. Invasive video EEG identified the seizure origin on the right. The decision was made to perform selective amygdalohippocampectomy (SelAH) via the middle temporal gyrus (MTG). An endoscope was used to minimize the craniotomy and shorten the skin incision. A 5-cm linear skin incision and 2.5-cm craniotomy were made. A thin tube was inserted to the inferior horn of the lateral ventricle (Inf-H) under neuronavigation to guide the route to the Inf-H. The endoscope was introduced. A 1.5-cm corticotomy was made at the MTG, and white matter was aspirated until opening the Inf-H. The hippocampus and parahippocampal gyrus were removed with the usual steps in microsurgical SelAH. The surgical time was 4 h 20 min. The patient was discharged without complications and has remained seizure free. In addition to the preoperative objectives, using an endoscope widens the surgical view in the Inf-H compared with microsurgical procedures. Although seizure and cognitive outcomes are expected to be comparable to those from other methods of SelAH, invasiveness might be reduced. This appears to represent the first video report of endoscopic SelAH. The patient consented to the procedure and publication of her images and surgical video.

Safety and Tolerability of Transdermal Cannabidiol Gel in Children With Developmental and Epileptic Encephalopathies

Developmental and epileptic encephalopathies (DEEs) are the most severe group of drug-resistant epilepsies. Alternatives to oral therapies are urgently needed to reduce seizures and improve developmental outcomes and comorbidities in this medically complex population. To assess the safety and tolerability of cannabidiol (CBD) transdermal gel in children with DEEs and to evaluate seizure frequency, sleep, and quality of life. This nonrandomized controlled trial was conducted in 2 centers in Australia and New Zealand from April 2018 to July 2019. Children and adolescents aged 3 to 18 years with DEEs who were receiving a stable regimen of 1 to 4 antiseizure medications were eligible for this study. After 1-month baseline and titration periods, patients entered a 5.5-month flexible-dosing maintenance period for a total of 6.5 months of treatment. Data were analyzed throughout the 6.5-month treatment period. Twice-daily applications of CBD transdermal gel at doses of 125 to 500 mg for 6.5 months. Safety and tolerability assessments included adverse events (AEs) and examination of skin. The outcome for seizures was the median percentage change from baseline in monthly (28-day) seizure frequency of focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) over 6.5 months. Of 48 patients (mean [SD] age, 10.5 [3.8] years; 26 [54%] boys), 29 (60%) had at least 1 treatment-related AE over 6.5 months; 44 of 46 treatment-related AEs (96%) were mild or moderate. Treatment-related AEs that occurred in at least 5% of patients were application-site dryness, application-site pain, and somnolence (each reported by 4 patients [8%]). The only treatment-related gastrointestinal AE was diarrhea, reported in a single patient. CBD treatment was associated with reductions in FIAS and TCS frequency. Analysis of the 33 patients with FIAS and TCS showed a median (interquartile range) monthly reduction in seizures of 58% (-5.3% to 81.8%) at 5 months and 43.5% (-23.8% to 57.5%) over the entire 6.5-month study period. Parents and caregivers noted improvements in social or interpersonal engagement and irritability (33 of 43 [77%] participants); alertness, energy, and sleep (23 of 43 [53%]); and cognition or concentration (20 of 43 [47%]). In this study, CBD transdermal gel was safe, well tolerated, and was associated with reductions in FIAS and TCS frequency and disease burden. ClinicalTrials.gov Identifier: ACTRN12618000516280.