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Epilepsy Research May 2024Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term... (Meta-Analysis)
Meta-Analysis
Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.
Topics: Humans; Deep Brain Stimulation; Electrodes, Implanted; Electroencephalography; Seizures
PubMed: 38564925
DOI: 10.1016/j.eplepsyres.2024.107356 -
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 -
BMC Neurology Apr 2024Spasticity can significantly affect a patient's quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Spasticity can significantly affect a patient's quality of life, caregiver satisfaction, and the financial burden on the healthcare system. Baclofen is one of only a few options for treating spasticity. The purpose of this study is to investigate the impact of intrathecal baclofen (ITB) therapy on severe40.23 spasticity and motor function in patients with cerebral palsy.
METHODS
We conducted a systematic review in PubMed, Scopus, Ovid, and the Cochrane Library in accordance with the PRISMA guidelines. We included studies based on eligibility criteria that included desired participants (cerebral palsy patients with spasticity), interventions (intrathecal baclofen), and outcomes (the Ashworth scales and the Gross Motor Function Measure [GMFM]). The within-group Cohen's d standardized mean differences (SMD) were analyzed using the random effect model.
RESULTS
We screened 768 papers and included 19 in the severity of spasticity section and 6 in the motor function section. The pre-intervention average spasticity score (SD) was 3.2 (0.78), and the post-intervention average score (SD) was 1.9 (0.72), showing a 40.25% reduction. The SMD for spasticity reduction was - 1.7000 (95% CI [-2.1546; -1.2454], p-value < 0.0001), involving 343 patients with a weighted average age of 15.78 years and a weighted average baclofen dose of 289 µg/day. The SMD for the MAS and Ashworth Scale subgroups were - 1.7845 (95% CI [-2.8704; -0.6986]) and - 1.4837 (95% CI [-1.8585; -1.1088]), respectively. We found no relationship between the participants' mean age, baclofen dose, measurement time, and the results. The pre-intervention average GMFM (SD) was 40.03 (26.01), and the post-intervention average score (SD) was 43.88 (26.18), showing a 9.62% increase. The SMD for motor function using GMFM was 0.1503 (95% CI [0.0784; 0.2223], p-value = 0.0030), involving 117 patients with a weighted average age of 13.63 and a weighted average baclofen dose of 203 µg/day. In 501 ITB implantations, 203 medical complications were reported, including six new-onset seizures (2.96% of medical complications), seven increased seizure frequency (3.45%), 33 infections (16.26%), eight meningitis (3.94%), and 16 cerebrospinal fluid leaks (7.88%). Delivery system complications, including 75 catheter and pump complications, were also reported.
CONCLUSION
Despite the risk of complications, ITB has a significant impact on the reduction of spasticity. A small but statistically significant improvement in motor function was also noted in a group of patients.
Topics: Baclofen; Humans; Muscle Spasticity; Cerebral Palsy; Injections, Spinal; Muscle Relaxants, Central; Treatment Outcome; Severity of Illness Index; Motor Activity
PubMed: 38678195
DOI: 10.1186/s12883-024-03647-7 -
BMC Medicine Mar 2024Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy.
METHODS
The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights.
RESULTS
We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56).
CONCLUSIONS
While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy.
SYSTEMATIC REVIEW REGISTRATION
CRD42022342510.
Topics: Humans; Cross-Sectional Studies; Epilepsy; Smokers; Risk Factors; Smoking
PubMed: 38433201
DOI: 10.1186/s12916-024-03307-0 -
European Journal of Paediatric... Mar 2024To conduct a systematic review of post-neonatal neurological outcomes and mortality following neonatal seizures with electroencephalographical verification.
AIM
To conduct a systematic review of post-neonatal neurological outcomes and mortality following neonatal seizures with electroencephalographical verification.
METHODS
The databases Medline, Embase and Web of Science were searched for eligible studies. All abstracts were screened in a blinded fashion between research team members and reports found eligible were obtained and screened in full text by two members each. From studies included, outcome results for post-neonatal epilepsy, cerebral palsy, intellectual disability, developmental delay, mortality during and after the neonatal period and composite outcomes were extracted. A quality assessment of each study was performed.
RESULTS
In total, 5518 records were screened and 260 read in full text. Subsequently, 31 studies were included, containing cohorts of either mixed or homogenous etiologies. Follow-up time and gestational ages varied between studies. No meta-analysis could be performed due to the low number of studies with comparable outcomes and effect measures. Reported cumulative incidences of outcomes varied greatly between studies. For post-neonatal epilepsy the reported incidence was 5-84%, for cerebral palsy 9-78%, for intellectual disability 24-67%, for developmental delay 10-67% and for mortality 1-62%. Subgroup analysis had more coherent results and in cohorts with status epilepticus a higher incidence of post-neonatal epilepsy from 46 to 84% was shown.
CONCLUSION
The large variation of reported incidences for neurological outcomes and mortality found even when restricting to cohorts with electroencephalographically verified neonatal seizures indicates selection bias as a significant confounder in existing studies. Population-based approaches are thus warranted to correctly predict outcomes in this group.
Topics: Humans; Infant, Newborn; Cerebral Palsy; Developmental Disabilities; Electroencephalography; Seizures
PubMed: 38367369
DOI: 10.1016/j.ejpn.2024.02.005 -
Frontiers in Neurology 2024Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS)....
OBJECTIVE
Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). However, the exploration of its optimal target dose is ongoing. This study aimed to summarize the best evidence to inform this clinical issue.
MATERIALS AND METHODS
We searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).
RESULTS
Six hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction ( < 0.001, < 0.001, < 0.001) and at least 75% reduction ( < 0.001, = 0.007, < 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators ( < 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure ( = 0.006) but not on at least 50% reduction. Weight loss ( = 0.002), decreased appetite ( = 0.04), and all-cause withdrawal ( = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.
CONCLUSION
The higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.
CLINICAL TRIAL REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454.
PubMed: 38590719
DOI: 10.3389/fneur.2024.1371704 -
Frontiers in Neurology 2023There is mounting evidence suggesting that autoimmune encephalitis (AE) can be observed as a neurological complication in patients with COVID-19. This review aimed to...
BACKGROUND
There is mounting evidence suggesting that autoimmune encephalitis (AE) can be observed as a neurological complication in patients with COVID-19. This review aimed to summarize the clinical manifestations, types, and outcomes of COVID-19-associated AE.
METHODS
A systematic search was conducted in the PubMed, Embase, and Web of Science databases to identify case reports and case series related to COVID-19-associated AE from 1 January 2020 to 31 March 2023. After a thorough screening and evaluation, irrelevant articles were excluded. Relevant information concerning types, clinical manifestations, and outcomes was extracted and synthesized.
RESULTS
A total of 37 studies, comprising 34 case reports and 3 case series, were included in this review. Among the 42 COVID-19-associated AE patients, 21 (50%) cases were classified as an unknown antibodies (Ab) type of COVID-19-associated AE, 10 (23.80%) cases as anti-N-methyl-D-aspartate (NMDA) encephalitis, 4 (9.5%) cases as limbic encephalitis, and 3 (7.1%) cases as anti-myelin-oligodendrocyte-glycoprotein encephalitis, along with other rare types of AE. Disturbance of consciousness, seizures, and psychiatric symptoms were identified as the main clinical manifestations of COVID-19-associated AE. While the symptoms of AE displayed variation, most patients achieved full recovery although a few experienced residual symptoms of neurological damage.
CONCLUSION
This systematic review comprehensively describes the characteristics of COVID-19-associated AE. The main type of COVID-19-associated AE identified in this study is an unknown Ab type of COVID-19-associated AE. Despite the potentially life-threatening risks of COVID-19-associated AE, the majority of patients survived, with some patients reporting residual neurological symptoms.
PubMed: 37771454
DOI: 10.3389/fneur.2023.1207883 -
International Journal of Infectious... Jan 2024Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but...
OBJECTIVES
Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children.
METHODS
A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients.
RESULTS
A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis.
CONCLUSION
Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.
Topics: Adult; Humans; Child; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Posterior Leukoencephalopathy Syndrome; Neuroimaging; Systemic Inflammatory Response Syndrome
PubMed: 37944584
DOI: 10.1016/j.ijid.2023.11.006 -
Eculizumab in Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: a systematic review.Pediatric Nephrology (Berlin, Germany) May 2024Infection-associated hemolytic uremic syndrome (IA-HUS), most often due to infection with Shiga toxin-producing bacteria, mainly affects young children. It can be... (Review)
Review
BACKGROUND
Infection-associated hemolytic uremic syndrome (IA-HUS), most often due to infection with Shiga toxin-producing bacteria, mainly affects young children. It can be acutely life-threatening, as well as cause long-term kidney and neurological morbidity. Specific treatment with proven efficacy is lacking. Since activation of the alternative complement pathway occurs in HUS, the monoclonal C5 antibody eculizumab is often used off-label once complications, e.g., seizures, occur. Eculizumab is prohibitively expensive and carries risk of infection. Its utility in IA-HUS has not been systematically studied. This systematic review aims to present, summarize, and evaluate all currently available data regarding the effect of eculizumab administration on medium- to long-term outcomes (i.e., outcomes after the acute phase, with a permanent character) in IA-HUS.
METHODS
PubMed, Embase, and Web of Science were systematically searched for studies reporting the impact of eculizumab on medium- to long-term outcomes in IA-HUS. The final search occurred on March 2, 2022. Studies providing original data regarding medium- to long-term outcomes in at least 5 patients with IA-HUS, treated with at least one dose of eculizumab during the acute illness, were included. No other restrictions were imposed regarding patient population. Studies were excluded if data overlapped substantially with other studies, or if outcomes of IA-HUS patients were not reported separately. Study quality was assessed using the ROBINS-I tool for risk of bias in non-randomized studies of interventions. Data were analyzed descriptively.
RESULTS
A total of 2944 studies were identified. Of these, 14 studies including 386 eculizumab-treated patients met inclusion criteria. All studies were observational. Shiga toxin-producing E. coli (STEC) was identified as the infectious agent in 381 of 386 patients (98.7%), effectively limiting the interpretation of the data to STEC-HUS patients. Pooling of data across studies was not possible. No study reported a statistically significant positive effect of eculizumab on any medium- to long-term outcome. Most studies were, however, subject to critical risk of bias due to confounding, as more severely ill patients received eculizumab. Three studies attempted to control for confounding through patient matching, although residual bias persisted due to matching limitations.
DISCUSSION
Current observational evidence does not permit any conclusion regarding the impact of eculizumab in IA-HUS given critical risk of bias. Results of randomized clinical trials are eagerly awaited, as new therapeutic strategies are urgently needed to prevent long-term morbidity in these severely ill patients.
SYSTEMATIC REVIEW REGISTRATION NUMBER
OSF Registries, MSZY4, Registration DOI https://doi.org/10.17605/OSF.IO/MSZY4 .
Topics: Child; Humans; Child, Preschool; Shiga-Toxigenic Escherichia coli; Hemolytic-Uremic Syndrome; Kidney; Escherichia coli Infections; Shiga Toxins; Antibodies, Monoclonal, Humanized
PubMed: 38057431
DOI: 10.1007/s00467-023-06216-1 -
Computational and Structural... Dec 2024Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic... (Review)
Review
BACKGROUND
Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic performances of computed biomarkers for epilepsy in individuals undergoing rEEG.
METHODS
We searched MEDLINE, EMBASE, EBM reviews, IEEE Explore and the grey literature for studies published between January 1961 and December 2022. We included studies reporting a computational method to diagnose epilepsy based on rEEG without relying on the identification of interictal epileptiform discharges or seizures. Diagnosis of epilepsy as per a treating physician was the reference standard. We assessed the risk of bias using an adapted QUADAS-2 tool.
RESULTS
We screened 10 166 studies, and 37 were included. The sample size ranged from 8 to 192 (mean=54). The computed biomarkers were based on linear (43%), non-linear (27%), connectivity (38%), and convolutional neural networks (10%) models. The risk of bias was high or unclear in all studies, more commonly from spectrum effect and data leakage. Diagnostic accuracy ranged between 64% and 100%. We observed high methodological heterogeneity, preventing pooling of accuracy measures.
CONCLUSION
The current literature provides insufficient evidence to reliably assess the diagnostic yield of computational analysis of rEEG.
SIGNIFICANCE
We provide guidelines regarding patient selection, reference standard, algorithms, and performance validation.
PubMed: 38204455
DOI: 10.1016/j.csbj.2023.12.006