Abstract, published in Epilepsia

Objective: It has been known that West syndrome (WS) patients with an unknown etiology have better clinical outcomes than patients with an identified etiology of any kind. However, after the exponential discovery of genes with mutations responsible for developmental and epileptic encephalopathy (DEE), a significant proportion of patients with a previously unknown etiology have been reclassified as having a genetic etiology, requiring reinvestigation of this concept. Therefore, this study investigated clinical outcomes of WS patients with genetic and unknown etiologies.

Methods: Patients diagnosed with WS without structural or metabolic abnormalities were included in this study. The DEE gene panel, comprising 172 genes, was performed for all patients. All patients were treated using the same treatment protocol for vigabatrin and high-dose prednisolone add-on therapy. Favorable responders were defined as patients who were seizure-free and whose electroencephalogram showed Burden of Amplitudes and Epileptiform Discharges scores of 2 or less.

Results: Of the 58 patients included in the study, 17 (29.3%) patients had an identified genetic etiology. There was no significant difference in rates of favorable response at 1 and 3 months after treatment, but significantly higher proportions of patients exhibited favorable responses among those with an unknown etiology at long-term follow-up (41.2% vs. 78.0%, p = .006 at 6 months; 29.4% vs. 65.9%, p = .011 at 1 year; 23.5 vs. 65.9%, p = .003 at 2 years). Moreover, the mental, psychomotor, and social age quotients of the patients with an identified genetic etiology were reduced to a significantly greater degree since diagnosis compared with those of the patients with an unknown etiology.

Significance: WS patients with genetic and unknown etiologies did not initially exhibit significantly different response rates to the vigabatrin and high-dose prednisolone add-on treatment. However, patients with a genetic etiology exhibited significantly higher relapse rates and significantly poorer long-term responses.

Summary, originally published on medicalxpress.com

An advanced imaging approach developed at the University of Virginia School of Medicine could let surgeons determine the best target in the brain to stop epilepsy seizures, new research suggests.

UVA’s approach could improve patient outcomes and open underused surgical options to patients who are now ineligible, the research team reports.

“This imaging approach is significant, as it creates 4D brain maps that offer additional sensitivity over standard-of-care imaging by revealing rates of glucose uptake rather than final absolute glucose uptake,” said imaging expert Bijoy Kundu of UVA’s Department of Radiology and Medical Imaging and UVA’s Department of Biomedical Engineering. “This imaging approach might be beneficial, as it may offer non-invasive localization of potential epileptic foci.”

UVA’s new approach uses an enhanced form of positron-emission tomography, or PET, to measure glucose use in the brain. This allows doctors to pinpoint the trouble spot in the brain that is triggering seizures. Once that spot is identified, it can be removed surgically, stopping the seizures.

Abstract, originally published in Epilepsy & Behavior

Objective: This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy.

Methods: A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs.

Results: Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome.

Conclusions: The results of this study indicate that treatment with sodium channel blockers might be effective and safe in a subset of patients with CDKL5 deficiency disorder-related epilepsy.

Summary, originally published in MedPageToday

Valproate (Depakene) emerged as the best first-line choice for generalized epilepsy in a pragmatic study and lamotrigine (Lamictal) as the best first-line treatment for focal epilepsy, British researchers said.

The conclusions came from the phase IV open-label Standard and New Antiepileptic Drugs (SANAD II) study with two parts: a randomized trial of levetiracetam (Keppra) and valproate in newly diagnosed generalized epilepsy patients, and a randomized trial of levetiracetam, lamotrigine, and zonisamide (Zonegran) in newly diagnosed focal epilepsy patients. Results were published in separate papers in The Lancet.

In new patients with generalized or unclassified epilepsy, levetiracetam did not meet non-inferiority criteria compared with valproate in intention-to-treat analysis of time to 12-month remission (HR 1.19, 95% CI 0.96-1.47; non-inferiority margin 1.329), reported Anthony Marson, MD, of University of Liverpool in England, and co-authors. Treatment failure due to inadequate seizure control was more likely with levetiracetam, and a per-protocol analysis that took treatment failure into account found valproate to be superior (HR 1.68, 95% CI 1.30–2.15). Cost-effectiveness based on differences in costs and quality-adjusted life years found valproate to be superior.

“The available evidence now identifies valproate as more clinically and cost effective than both lamotrigine and levetiracetam,” Marson said in a statement. “Levetiracetam has been widely adopted in the U.K. and worldwide as a first-line treatment for focal epilepsy, but this should no longer be the case as it is neither clinically nor cost effective compared to lamotrigine,” he added.

Abstract, originally published in Seizure

Objectives: The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy.

Methods: Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)).

Results: Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy.

Conclusion: Stiripentol seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of stiripentol in adult patients with pharmacoresistant focal epilepsy.

Abstract, originally published in Epilepsia

Objective: This study was undertaken to improve understanding of late relapse following epilepsy surgery in pharmacoresistant epilepsy.

Methods: Retrospective comparison was made of 99 of 1278 patients undergoing surgery during 1999–2015 with seizure relapses after at least 2 years of complete seizure freedom with matched controls experiencing continued long?term seizure freedom. Univariate and multivariate analyses were performed.

Results: With a mean follow-up of 9.7 years, mean time to seizure relapse was 56.6 months. In multivariate analysis, incomplete resection based on magnetic resonance imaging (MRI), bilateral lesions on preoperative MRI, and epilepsy onset in the first year of life carried a significantly higher risk of late relapse. In patients with late relapse, additional functional imaging with positron emission tomography had been performed significantly more often. Although the differences were not significant in multivariate analysis, doses of antiepileptic drugs were higher in the relapse group preoperatively and in the first 24 months and complete withdrawal was more frequent in the control group (68% vs. 51%). Regarding seizure frequency, most patients had mild seizure relapse (single relapse seizure or <1/month).

Significance: In our predominantly lesional cohort, complete resection of the MRI lesion is the most important factor to maintain long-term seizure freedom. Two patterns of recurrence were identified: (1) incomplete resected lesions with seizure generation in proximity to the initial resection and (2) epileptogenic networks not detected preoperatively or evolving in the postoperative interval and manifesting with new clinical and diagnostic features.

Summary, originally published in Epilepsia

Objective: This is an audit of the use of valproate (VPA) during pregnancy in women with epilepsy (WWE).

Methods: We identified all pregnancies exposed to VPA in the Kerala Registry of Epilepsy and Pregnancy between January 2010 and December 2019. Subjects’ past usage of antiepileptic drugs (AEDs), seizure count before and during pregnancy, fetal outcome, and major congenital malformations (MCMs) were abstracted from the registry records. The presumed reason for usage of VPA was deducted from the clinical records.

Results: There were 221 pregnancies (17.75%) exposed to VPA (monotherapy, n = 149) during the audit period. The MCM rate for the completed pregnancies exposed to VPA was higher (n = 20, 10.36%) than that of VPA?unexposed pregnancies (n = 39, 4.96%). The relative risk for MCM with VPA exposure was 2.1 (95% confidence interval = 1.24–3.48, number needed to treat with VPA to result in MCM = 19). Reasons for using VPA during pregnancy (some women had more than one reason) were (1) VPA was the first AED prescribed and was effective (68, 29.06%), (2) other AEDs were ineffective (128, 54.70%), and (3) other AEDs were discontinued due to adverse effects (17, 7.28%). Other reasons (21, 8.97%) were (1) VPA was selected after the epilepsy classification was revised (3, 1.28%), (2) other AEDs were expensive (2, .85%), and (3) patient switched to VPA from other AEDs for unspecified reason (16, 6.83%). VPA was discontinued during pregnancy for 6 (2.71%) persons. Less than 10% of women were tried on lamotrigine or levetiracetam before switching to VPA.

Significance: Nine major congenital malformations per thousand pregnancies can be avoided if valproate is not used in women with epilepsy. Safe and effective antiepileptic drugs as alternatives to valproate are the need of the hour. Professional bodies and regulatory authorities need to implement updated guidelines on antiepileptic drug usage in girls and women.