Islam, Karimul

Importance The role and safety of transcranial electrical stimulation (tES) for treating depressive disorders remain under evaluation. Objective To evaluate tES treatment in patients with major depressive disorder (MDD) and comorbid depressive conditions. Data Sources A search of MEDLINE, Embase, Cochrane, APA PsycINFO, and Scopus databases was conducted from inception to September 17, 2024. Study Selection Randomized clinical trials (RCTs) of adults with MDD, depression with psychiatric comorbidities (DPC), or depression with medical comorbidities (DMC), treated with transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or transcranial random noise stimulation (tRNS), compared with sham or other treatments were included. Data Extraction and Synthesis Independent reviewers extracted data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, with random-effects meta-analysis used for pooling. Main Outcomes and Measures Primary outcomes were depression severity, response and remission rates, and adverse events. Standardized mean differences (SMDs) were reported for continuous outcomes, and odds ratios (ORs) were reported for categorical outcomes. Quality of evidence (QOE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Results The meta-analysis included 5522 participants from 114 study groups from 88 RCTs (3198 female [58.9%]; mean [range] age, 43.1 [19.4-76.9] years). Most studies (104 study groups from 79 RCTs [91.2%]) evaluated tDCS, while 7 study groups from 6 RCTs (6.1%) evaluated tACS, and 3 study groups from 3 RCTs (2.7%) evaluated tRNS. tES was associated with reduced depressive symptoms (SMD = −0.59; 95% CI, −0.83 to −0.35; low QOE) and improvement in DMC (SMD = −1.05; 95% CI, −1.67 to −0.43; low QOE) and DPC (SMD = −0.78; 95% CI, −1.27 to −0.29; low QOE) compared with MDD (SMD = −0.22; 95% CI, −0.44 to 0.01; low QOE). tDCS was associated with reduced depression in DMC (SMD = −1.05; 95% CI, −1.70 to −0.40; very low QOE) and DPC (SMD = −0.88; 95% CI, −1.40 to −0.36; low QOE) but not MDD. tACS was associated with improved MDD symptoms (SMD = −0.58; 95% CI, −0.96 to −0.20; high QOE) and response rates (OR, 2.07; 95% CI, 1.34 to 3.19; high QOE). Combined tDCS and medication was associated with reduced symptoms (SMD = −0.51; 95% CI, −0.90 to −0.13; moderate QOE) and increased response (OR, 2.25; 95% CI, 1.08 to 4.65; high QOE) in MDD. tDCS combined with psychotherapy was not associated with improvement. Subgroup analysis showed that anodal left dorsolateral prefrontal cortex DCS was associated with improved outcomes. Mild to moderate adverse events were more frequent in tES groups. Conclusions and Relevance In this systematic review and meta-analysis, tDCS was associated with improvement in depression among patients with DMC and DPC (with smaller benefits in MDD), tACS was associated with improved MDD outcomes (while tRNS had insufficient evidence) in smaller samples, and combined tDCS and medication was associated with improvement in depression. These findings suggest that tES is well-tolerated overall, with only mild to moderate adverse events, and that future research should optimize stimulation parameters and individualize tES interventions.

Abstract Objective Noninvasive brain stimulation (NIBS) provides a treatment option for patients not eligible for surgical intervention or who seek low‐risk approaches and may be used in the hospital, clinic, and at home. Our objective is to summarize our single‐center experience with multiple NIBS approaches for the treatment of focal epilepsy. Methods A retrospective chart review identified drug‐resistant focal epilepsy patients who received NIBS as an epilepsy treatment at Mayo Clinic in Rochester, MN. Patients were typically treated as follows: (1) for TMS, 1 Hz stimulation was applied for five consecutive days in the neuromodulation clinic, (2) for outpatient tDCS, stimulation was applied for five consecutive days in the clinic, followed by optional treatment at home, and (3) for inpatient tDCS, stimulation was applied for three consecutive days. We analyzed continuous EEG data for the inpatient tDCS cohort and available HD‐EEG data for outpatient cohorts to quantify changes in interictal epileptiform discharges (IEDs) as a result of stimulation. Outcomes were assessed at 1 month for TMS and outpatient tDCS and 1 week for inpatient tDCS. Results Twenty‐four patients were treated with TMS ( n = 10) and tDCS ( n = 14, 9 as outpatients). The median age was 40 years (range 15–73). The median seizure reduction following stimulation was 50%. Fourteen patients (58%) were responders to treatment (TMS = 4/10, tDCS Outpatient = 7/9, tDCS Inpatient = 3/5). Five outpatient tDCS participants elected to continue treatment at home. Four TMS and four outpatient tDCS patients underwent high‐density EEG before and after 5 days of therapy. Following stimulation, IED rate was reduced in 4/5 inpatient tDCS patients, 4/4 outpatient tDCS patients, and 4/4 TMS patients. Two patients experienced an increase in seizure frequency (1 following TMS and 1 following outpatient tDCS), which returned to baseline 4–6 weeks after stimulation treatments were discontinued. Significance TMS and tDCS are potential treatment approaches for drug‐resistant focal epilepsy patients in the hospital, clinic, and home. They have a favorable safety profile and can lead to a reduction in IED rates and seizures. These results suggest further studies are needed to examine NIBS as a treatment for epilepsy. Plain Language Summary Noninvasive brain stimulation, such as transcranial magnetic stimulation and transcranial direct current stimulation, offers new treatment options for patients with focal seizures. This study reviewed the experience at Mayo Clinic using noninvasive brain stimulation in the hospital, clinic, and at‐home settings to treat seizures. The results showed an overall 50% median seizure reduction, and 58% of patients had at least a 50% reduction in seizures. Noninvasive brain stimulation is a promising treatment approach with a favorable safety profile.

AbstractObjectiveNeuromodulation for pediatric refractory epilepsy (PRE) is preferred when the seizure onset zone is not amenable to surgical resection, due to multifocal onset or involvement of eloquent cortex. Given its rapidly evolving landscape, we describe our institutional experience with neurostimulation therapies including deep brain stimulation (DBS) of the anterior nucleus (DBS‐ANT), the centromedian nucleus (DBS‐CM), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS) to treat PRE.MethodsA retrospective chart review was conducted to identify pediatric patients (≤18 years of age) who presented to our institution with PRE. Patients were included who had at least 1 year of follow‐up after neurostimulation was started. Patients with ≥50% seizure frequency reduction at last follow‐up compared to baseline were classified as responders.ResultsA total of 35 patients (21 females) were included in the series. Nine patients underwent DBS‐ANT, 9 underwent DBS‐CM (+ ANT in 7 patients), 5 underwent RNS, and 12 underwent CSS. The median age at seizure onset and surgery was 8 and 16 years, respectively. Structural lesions were the most common etiology of epilepsy (54%). Eighteen patients had prior interventions and 13 received invasive EEG. Post‐operative complications following neurostimulation implantation were noted in three patients (9%). However, no permanent deficits were noted. Median follow‐up time was 46 months (range 13–162 months). Twenty‐three patients (59%) were responders (3/9 DBS‐ANT; 7/9 DBS‐CM; 4/5 RNS; 9/12 CSS). Further, median seizure reduction was 25% (DBS‐ANT), 89% (DBS‐CM), 87% (RNS), and 88% (CSS) across the cohort. Six patients (17%) had improved subjective neurocognitive outcomes while the other 29 had stable neurocognitive outcomes.SignificanceDBS, RNS, and CSS are safe and effective options for PRE. An understanding of treatment approaches can optimize results by tailoring therapy to individual patients.Plain Language SummaryThis study investigates the use of various neurostimulation therapies for treating pediatric refractory epilepsy (PRE) including deep brain stimulation (DBS), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS). Overall, neuromodulation was found to be effective in reducing seizures in most patients, with 59% of patients showing at least a 50% reduction in seizure frequency. Additionally, the treatments were generally safe, with few complications and no instances of permanent deficits.

AbstractObjectiveStereoelectroencephalography‐guided radiofrequency thermocoagulation (SEEG‐guided RFTC) has been increasingly used as diagnostic and therapeutic approach for drug‐resistant focal epilepsies (DREs). We aimed to describe seizure outcomes of RFTC before and after further neurosurgical intervention.MethodsRetrospective single‐institution case series of patients who underwent SEEG‐RFTC. The primary outcome was Engel class I–IV classification ([responders Engel I–III and non‐responders Engel IV]) at last follow‐up after RFTC and prior to further neurosurgical intervention (open surgical resection, laser ablation, and neuromodulation).ResultsTwenty‐five patients (median age 18.9 years) with DRE were included. The median follow‐up time after RFTC was 7.2 months, including 20 patients who underwent further intervention (median follow‐up time of 7.3 months) and 5 without intervention (median of 3.5 months). From the patients who had further intervention, 17 (85%) underwent surgical procedure (laser ablation 53%, open surgical resection 47%) (median 4.4 months) and 3 (15%) had responsive neurostimulators placed (median 6.9 months). Prior to further intervention (median follow‐up 3.5 months after RFTC), 12 (48%) patients were classified as responders (12% Engel class I, 16% class II, and 20% class III) and 13 (52%) as non‐responders. Following neurosurgical intervention, 17 (68%) patients were followed for a median time of 2.7 months and 3 were lost to follow‐up. Of eight initial RFTC responders, 87.5% and 12.5% had Engel classes I and III, respectively. Of nine who were non‐responders, 33% had Engel class I, 22% II and III, and 44% IV outcomes following further intervention. No neurologic complications were reported.SignificanceSEEG‐guided RFTC is a well‐tolerated procedure and a beneficial diagnostic approach prior to further neurosurgical interventions in patients with DRE.Plain Language SummarySEEG‐guided RFTC is a well‐tolerated procedure and in the patients who experienced initial seizure reduction (n = 8), subsequent neurosurgical intervention (surgery or neuromodulation) led to favorable seizure outcomes (87.5% seizure freedom and 12.5% worthwhile seizure improvement).