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International Journal of Molecular... Jun 2024A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory... (Review)
Review
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
Topics: Humans; Biomarkers; Neuroinflammatory Diseases; HMGB1 Protein; Epilepsy; Cytokines; Toll-Like Receptor 4; Drug Resistant Epilepsy
PubMed: 38928193
DOI: 10.3390/ijms25126488 -
Neurologia I Neurochirurgia Polska 2024Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for... (Review)
Review
INTRODUCTION
Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for resective surgery. For these patients, deep brain stimulation (DBS) may constitute the last resort in the treatment of DRE.
STATE OF THE ART
We undertook a systematic review of the current literature on DBS efficacy and the safety of two thalamic nuclei-anterior nucleus of the thalamus (ANT) and the centromedian nucleus of the thalamus in the management of patients with DRE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL) was conducted.
CLINICAL IMPLICATIONS
We found 30 articles related to ANT DBS and 13 articles related to CMN DBS which were further analysed. Based on the clinical research articles, we found a mean seizure frequency reduction for both thalamic nuclei. For ANT DBS, the mean seizure frequency reduction ranged from 48% to 75%, and for CMN DBS from 46.7% to 91%. The responder rate (defined as at least 50% reduction in seizure frequency) was reported to be 53.2-75% for patients after ANT DBS and 50-90% for patients after CMN DBS.
FUTURE DIRECTIONS
ANT and CMN DBS appear to be safe and efficacious treatments, particularly in patients with refractory partial seizures and primary generalised seizures. ANT DBS reduces most effectively seizures originating in the temporal and frontal lobes. CMN DBS reduces mostly primary generalised tonic-clonic and atypical absences and atonic seizures. Seizures related to Lennox-Gastaut syndrome respond very favourably to CMN DBS.
Topics: Humans; Deep Brain Stimulation; Drug Resistant Epilepsy; Anterior Thalamic Nuclei; Intralaminar Thalamic Nuclei; Treatment Outcome
PubMed: 38864766
DOI: 10.5603/pjnns.98258 -
Frontiers in Neurology 2024Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a...
BACKGROUND
Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE.
METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up.
RESULTS
A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance ( = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified.
CONCLUSION
Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.
PubMed: 38863514
DOI: 10.3389/fneur.2024.1403266 -
Seizure Jul 2024Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their effectiveness on seizure outcomes.
METHODS
This systematic review and meta-analysis synthesises the available data. In February 2023, we completed a systematic search of four electronic databases. We described the range of seizure-related outcomes captured, used meta-analytic methods to analyse data collected during treatment and follow-up; and explored sources of heterogeneity between outcomes.
RESULTS
Overall, 44 relevant studies were identified involving 1,300 patients. Most were categorised as being at high (39.5 %) or medium (41.9 %) risk of bias. Seizure frequency was examined in all but one study; seizure intensity, severity or bothersomeness in ten; and seizure duration and cluster in one study each. Meta-analyses could be performed on seizure freedom and seizure reduction. A pooled estimate for seizure freedom at the end of treatment was 40 %, while for follow-up it was 36 %. Pooled rates for ≥50 % improvement in seizure frequency were 66 % and 75 %. None of the included moderator variables for seizure freedom were significant. At the group level, seizure frequency improved during the treatment phase with a moderate pooled effect size (d = 0.53). FDS frequency reduced by a median of 6.5 seizures per month. There was also evidence of improvement of the other (non-frequency) seizure-related measures with psychological therapy, but data were insufficient for meta-analysis.
CONCLUSIONS
The findings of this study complement a previous meta-analysis describing psychological treatment-associated improvements in non-seizure-related outcomes. Further research on the most appropriate FDS-severity measure is needed.
Topics: Adult; Humans; Dissociative Disorders; Psychotherapy; Seizures; Treatment Outcome
PubMed: 38824867
DOI: 10.1016/j.seizure.2024.05.016 -
The Archives of Bone and Joint Surgery 2024To compile the existing literature on bilateral anterior shoulder dislocation (BASD) and analyze patient demographics, mechanisms of injury, injury characteristics,... (Review)
Review
OBJECTIVES
To compile the existing literature on bilateral anterior shoulder dislocation (BASD) and analyze patient demographics, mechanisms of injury, injury characteristics, management, and outcome.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) guidelines. Online databases, including Ovid Medline 1946-, Embase.com 1947-, Scopus 1960-, Cochrane Central, and Clinicaltrials.gov were systematically queried. Studies eligible for inclusion were case reports or case-series, documenting BASD. Two reviewers independently screened and applied a set of a priori exclusion criteria to each returned study. Data were extracted, compiled, and synthesized from each reported case of BASD. Contingency tables/Chi-Square Analyses, T-tests, and univariate regression analyses were conducted to assess relationships between different variables.
RESULTS
Eighty-one studies (87 cases of BASD) were included. Patients were 41.1 (SD± 19.5) years old and most were male (n=63; 72.4%). Around a quarter of patients (28.7%) had a history of epilepsy/seizures or were being worked-up for such. Younger males were more likely to have BASD due to a seizure or electrocution (P<0.05). Close to a third of cases (n=27; 31.0%) were delayed in presentation. Those sustaining seizures or electrocutions were more likely to be delayed in presentation (P=0.013). Most events resulted in simple dislocations that were closed reduced successfully. BASD resulting from seizures or electrocutions were more likely to be fracture-dislocations (P=0.018); and in younger patients with fracture-dislocations, closed reduction was more often to fail or not be attempted (P<0.05). Median follow-up was 6 months (IQR: 3 months - 12 months). Seven patients (10.6%) had complications and 4 (2.3%) demonstrated recurrent instability.
CONCLUSION
In young males presenting with BASD without known trauma, suspicion should be high for a convulsant event. In patients with a known seizure disorder who present with chronic bilateral shoulder or arm pain, BASD should be considered and work-up should be expedited to avoid misdiagnosis.
PubMed: 38817413
DOI: 10.22038/ABJS.2024.67743.3211 -
Epilepsia Open May 2024To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). (Review)
Review
OBJECTIVE
To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE).
METHODS
We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis.
RESULTS
Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD.
SIGNIFICANCE
The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment.
PLAIN LANGUAGE SUMMARY
This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.
PubMed: 38798030
DOI: 10.1002/epi4.12939 -
Epilepsy & Behavior Reports 2024Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the... (Review)
Review
Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the effectiveness of exercise in improving sleep in epilepsy is less clear. The purpose of this report is to identify the published literature regarding exercise interventions in people with epilepsy to determine 1) what proportion of published clinical trials assess sleep as an outcome, and 2) what benefits of exercise interventions on sleep have been observed. We searched the PubMed, PsycINFO, and SCOPUS electronic databases using the search terms "epilepsy AND [exercise OR physical activity]" and identified 23 articles reporting on 18 unique clinical trials. Nine studies were conducted in adults, five in children, and four in adults and children with active seizures, controlled seizures, or both. Exercise modalities included aerobic exercise, strength training, walking, and yoga, among others, and some also included educational and motivational components. Exercise effects on sleep were tested in four studies, two of which only included indirect measures of sleep- and rest-related fatigue, with mixed results. Of the two reports assessing sleep directly, one reported marginal non-significant improvements in subjective sleep quality and no improvements in objective sleep quality in children after twelve weeks of walking, and the other reported no benefits in subjective sleep quality after twelve weeks of combined aerobic, strength, and flexibility training in adults. Given the health benefits of sleep and detrimental effects of sleep deprivation in epilepsy, epilepsy researchers need to assess the effects of exercise interventions on sleep.
PubMed: 38779424
DOI: 10.1016/j.ebr.2024.100675 -
Neurology Jun 2024Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome.
METHODS
PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
RESULTS
Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87).
DISCUSSION
Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.
Topics: Humans; Electrocorticography; Epilepsy; Intraoperative Neurophysiological Monitoring; Seizures; Treatment Outcome; Neurosurgical Procedures
PubMed: 38768406
DOI: 10.1212/WNL.0000000000209430 -
Seizure Jul 2024The epidemiology of psychogenic non-epileptic seizures (PNES) is still unclear. Although approximately 14 million people need neurosurgical care annually, there is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The epidemiology of psychogenic non-epileptic seizures (PNES) is still unclear. Although approximately 14 million people need neurosurgical care annually, there is a dearth of thorough analysis on PNES occurrence following surgery. This study seeks to estimate the proportion of newly diagnosed PNES.
METHODS
We conducted a literature search of the PubMed, Ovid, CINAHL, and Cochrane Library databases up to December 2023. We identified studies using an observational design on the occurrence of PNES in patients who underwent intracranial surgery, and confirmed diagnosis using video-EEG. Estimates are reported as proportions using random effects models. We reported both 95 % CIs and prediction intervals (PI). We assessed the risk of bias and identified the pooled odds ratio (OR) for mutually exclusive groups. The heterogeneity was investigated using the I² statistic and significance determined using Cochran's Q-test. Post-hoc Egger's regression test, and several sensitivity analyses were performed. This study was registered in PROSPERO (CRD42023488611).
RESULTS
Of the 1766 unique studies identified, 86 were selected for full-text review. Eight studies (n = 3,699) were eligible for inclusion. Studies, spanning from 1995 to 2017, primarily focused on epilepsy surgeries. The pooled proportion was 3 % (95 % CI 2 %-5 %; 95 % PI 0 %-11 %). Temporal resections indicated twofold increase of PNES comparing to either resections (OR 2.05, 95 %CI 0.81-5.19). The risk of bias assessment indicated satisfactory quality for included studies, and heterogeneity in estimates was mainly explained by publication year of studies and their rounded sample size.
CONCLUSIONS
Given the estimations, there is expected impact of intracranial procedures on functional seizures epidemiology. Further efforts need to understand the contribution of brain resections to PNES incidence.
Topics: Humans; Seizures; Neurosurgical Procedures; Postoperative Complications; Psychophysiologic Disorders
PubMed: 38761671
DOI: 10.1016/j.seizure.2024.04.023 -
Journal of Psychiatric Research May 2024Deep transcranial magnetic stimulation (dTMS) has gained attention as an enhanced form of traditional TMS, targeting broader and deeper regions of the brain. However, a... (Review)
Review
Deep transcranial magnetic stimulation (dTMS) has gained attention as an enhanced form of traditional TMS, targeting broader and deeper regions of the brain. However, a fulsome synthesis of dTMS efficacy across psychiatric and cognitive disorders using sham-controlled trials is lacking. We systematically reviewed 28 clinical trials comparing active dTMS to a sham/controlled condition to characterize dTMS efficacy across diverse psychiatric and cognitive disorders. A comprehensive search of APA PsycINFO, Cochrane, Embase, Medline, and PubMed databases was conducted. Predominant evidence supports dTMS efficacy in patients with obsessive-compulsive disorder (OCD; n = 2), substance use disorders (SUDs; n = 8), and in those experiencing depressive episodes with major depressive disorder (MDD) or bipolar disorder (BD; n = 6). However, the clinical efficacy of dTMS in psychiatric disorders characterized by hyperactivity or hyperarousal (i.e., attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and schizophrenia) was heterogeneous. Common side effects included headaches and pain/discomfort, with rare but serious adverse events such as seizures and suicidal ideation/attempts. Risk of bias ratings indicated a collectively low risk according to the Grading of Recommendations, Assessment, Development, and Evaluations checklist (Meader et al., 2014). Literature suggests promise for dTMS as a beneficial alternative or add-on treatment for patients who do not respond well to traditional treatment, particularly for depressive episodes, OCD, and SUDs. Mixed evidence and limited clinical trials for other psychiatric and cognitive disorders suggest more extensive research is warranted. Future research should examine the durability of dTMS interventions and identify moderators of clinical efficacy.
PubMed: 38759496
DOI: 10.1016/j.jpsychires.2024.05.011