Epilepsy surgery as a treatment option for select patients with PCDH19-related epilepsy.

PCDH19 is a common epilepsy gene causing medication resistant epilepsy with fever-related seizures. Traditionally, patients with PCDH19-related epilepsy have not been considered surgical candidates. This retrospective review evaluated three patients with pathogenic variants in PCDH19 who presented with seizures in childhood, had one seizure semiology, became medication resistant, and had concordant imaging, seizure semiology and electrographic findings. All three patients ultimately underwent temporal lobectomy, resulting in seizure freedom. These findings suggest epilepsy surgery can be an effective treatment option for select patients with PCDH19-related epilepsy and a single seizure semiology.

Role of optically pumped magnetometers in presurgical epilepsy evaluation: Commentary of the American Clinical Magnetoencephalography Society.

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis.

OBJECTIVE: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy. METHODS: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS. Clinical, neuropsychological, electrophysiologic, and surgical data were abstracted through chart review. RESULTS: In comparison with MTS, ATE patients were more often female, had significantly later onset of epilepsy, and did not have prior febrile seizures. In addition, ATE patients were more likely to have chronic headaches and other historical features consistent with idiopathic intracranial hypertension (IIH). Failure to identify ATE on initial imaging was common. Most patients had limited temporal cortical resections sparing mesial structures. Of the twenty ATE patients who had a long-term postsurgical follow-up, seventeen (85%) had International League Against Epilepsy (ILAE) Class 1 or 2 outcomes. SIGNIFICANCE: A shorter duration of epilepsy, female gender, and lack of history of febrile seizures may suggest ATE as an etiology of refractory TLE in adults. Targeted encephalocele resections can result in seizure freedom, underscoring the importance of encephalocele identification.

The effect of ketogenic diet on serum lipid concentrations in children with medication resistant epilepsy.

BACKGROUND: Ketogenic diet (KD) is a valuable treatment option for patients with medication-resistant epilepsy. It is associated with a number of side effects. However limited data are available for the long-term effects of KD on serum lipid levels. PURPOSE: The aim of this study was to investigate the long-term effects of KD on serum lipid concentrations in children with medication-resistant epilepsy in daily clinical practice. METHOD: A total of 73 children (40 girls) aged 3 to 193 months (median, 53 months) with medication-resistant epilepsy who received a KD treatment for at least 12 months between 2014 and 2019 years were enrolled in the study. All children were started on a KD with 3:1 ratio which was then adjusted between 2:1 to 4:1 after the onset of KD as clinically necessary. Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride concentrations and body mass index-standard deviation scores (BMI-SDS) were measured at onset and at 1, 6 and 12 months of treatment, and also in 40 of these patients they were measured at 18 and 24 months of treatment. RESULTS: Dyslipidemia was observed in 71.2, 63, 63, 50, and 52.5% of the patients, at 1, 6, 12, 18, and 24 months, respectively. Median total cholesterol and triglyceride concentrations increased significantly at month-1, and although these high levels persisted for 24 months, the increase did not continue and showed a downward trend. However, this increase did not occur in the subset of patients with pre-existing dyslipidemia. Compared to baseline values, total cholesterol and triglyceride concentrations were higher at all time points, except 24-month cholesterol values. During the 24-month treatment period, BMI-SDS increased and the number of antiepileptic drugs decreased significantly. CONCLUSION: Total cholesterol and triglyceride concentrations appear to increase during the first month of KD treatment, and although these high values persist for 24 months, the increase does not continue, on the contrary, it approaches the normal values by drawing a downward trend. However, cholesterol and triglyceride concentrations do not increase in the subset of patients with pre-existing dyslipidemia.

Surgical Outcomes and EEG Prognostic Factors After Stereotactic Laser Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy.

Objective: To assess the seizure outcomes of stereotactic laser amygdalohippocampectomy (SLAH) in consecutive patients with mesial temporal lobe epilepsy (mTLE) in a single center and identify scalp EEG and imaging factors in the presurgical evaluation that correlate with post-surgical seizure recurrence. Methods: We retrospectively reviewed the medical and EEG records of 30 patients with drug-resistant mTLE who underwent SLAH and had at least 1 year of follow-up. Surgical outcomes were classified using the Engel scale. Univariate hazard ratios were used to evaluate the risk factors associated with seizure recurrence after SLAH. Results: The overall Engel class I outcome after SLAH was 13/30 (43%), with a mean postoperative follow-up of 48.9 ± 17.6 months. Scalp EEG findings of interictal regional slow activity (IRSA) on the side of surgery (HR = 4.05, p = 0.005) and non-lateralizing or contra-lateralizing seizure onset (HR = 4.31, p = 0.006) were negatively correlated with postsurgical seizure freedom. Scalp EEG with either one of the above features strongly predicted seizure recurrence after surgery (HR = 7.13, p < 0.001) with 100% sensitivity and 71% specificity. Significance: Understanding the factors associated with good or poor surgical outcomes can help choose the best candidates for SLAH. Of the variables assessed, scalp EEG findings were the most clearly associated with seizure outcomes after SLAH.

Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis.

BACKGROUND AND PURPOSE: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE. METHODS: A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size. RESULTS: The random-effects model analysis revealed a pooled effect size of -5.96 (95% CI= -8.98 to -2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p<0.0001), with an overall effect size of -9.36 (95% CI=-13.24 to -5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect. CONCLUSIONS: This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis

Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

OBJECTIVE: Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. METHODS: Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. RESULTS: Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. SIGNIFICANCE: Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.