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Frontiers in Neurology 2023The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD...
BACKGROUND/OBJECTIVES
The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have?
METHODS
A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established.
RESULTS
The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD.
CONCLUSION
ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156.
PubMed: 37560457
DOI: 10.3389/fneur.2023.1206106 -
Frontiers in Neurology 2023Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying...
BACKGROUND
Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying brief electrical stimulation to induce a seizure, and anesthesia is used to ensure sedation and muscle relaxation. Finding the right anesthetic agent with minimal side effects, especially on seizure duration, is crucial for optimal outcomes because seizure duration is an important factor in the effectiveness of ECT, but the anesthetic agents used can affect it.
OBJECTIVE
This systematic review and meta-analysis aimed to pool the results of all relevant studies comparing the two induction agents, etomidate and propofol, for motor and electroencephalogram (EEG) seizure duration outcomes.
METHODS
A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases to identify the relevant articles. The primary outcome measures were motor and EEG seizure durations. Statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Standard mean difference and 95% confidence intervals were calculated for continuous outcomes, and a random-effects model was used.
RESULTS
A total of 16 studies were included in this meta-analysis, comprising 7 randomized control trials (RCTs), 7 crossover trials, and 2 cohorts. The overall motor seizure duration was statistically significantly longer with etomidate than with propofol. The overall result for EEG seizure duration was also longer with the use of etomidate over propofol and was statistically significant. In addition, subgrouping was performed based on the study design for both outcomes, which showed insignificant results in the cohort's subgroup for both outcomes, while the RCTs and crossover subgroups supported the overall results. Heterogeneity was assessed through subgrouping and sensitivity analysis.
CONCLUSION
Our meta-analysis found that etomidate is superior to propofol in terms of motor and EEG seizure duration in ECT, implying potentially better efficacy. Hence, etomidate should be considered the preferred induction agent in ECT, but larger studies are needed to further validate our findings.
PubMed: 37915381
DOI: 10.3389/fneur.2023.1251882 -
Cureus Feb 2024Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population.... (Review)
Review
Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.
PubMed: 38533170
DOI: 10.7759/cureus.54863 -
Orphanet Journal of Rare Diseases Jan 2024Combined methylmalonic acidemia and homocystinuria, cblC type is an inborn error of intracellular cobalamin metabolism and the most common one. The age of onset ranges... (Review)
Review
INTRODUCTION
Combined methylmalonic acidemia and homocystinuria, cblC type is an inborn error of intracellular cobalamin metabolism and the most common one. The age of onset ranges from prenatal to adult. The disease is characterised by an elevation of methylmalonic acid (MMA) and homocysteine and a decreased production of methionine. The aim is to review existing scientific literature of all late onset cblC patients in terms of clinical symptoms, diagnosis, and outcome.
METHODS
A bibliographic database search was undertaken in PubMed (MEDLINE) complemented by a reference list search. We combined search terms regarding cblC disease and late onset. Two review authors performed the study selection, data extraction and quality assessment.
RESULTS
Of the sixty-five articles included in this systematic review, we collected a total of 199 patients. The most frequent clinical symptoms were neuropathy/myelopathy, encephalopathy, psychiatric symptoms, thrombotic microangiopathy, seizures, kidney disease, mild to severe pulmonary hypertension with heart failure and thrombotic phenomena. There were different forms of supplementation used in the different studies collected and, within these studies, some patients received several treatments sequentially and/or concomitantly. The general outcome was: 64 patients recovered, 78 patients improved, 4 patients did not improve, or the disease progressed, and 12 patients died.
CONCLUSIONS
Most scientific literature regarding the late onset cblC disease comes from case reports and case series. In most cases treatment initiation led to an improvement and even recovery of some patients. The lack of complete recovery underlines the necessity for increased vigilance in unclear clinical symptoms for cblC disease.
Topics: Adult; Female; Pregnancy; Humans; Amino Acid Metabolism, Inborn Errors; Hyperhomocysteinemia; Homocystinuria; Methylmalonic Acid; Vitamin B 12
PubMed: 38245797
DOI: 10.1186/s13023-024-03021-3 -
Frontiers in Neuroscience 2023Although more and more clinical studies have shown that acupuncture as an auxiliary combined with Western medicine is effective in the treatment of patients with... (Review)
Review
BACKGROUND
Although more and more clinical studies have shown that acupuncture as an auxiliary combined with Western medicine is effective in the treatment of patients with epilepsy, no systematic reviews of acupuncture as a treatment for epilepsy have been published. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on patients with epilepsy.
METHODS
This study retrieved randomized controlled trials (RCTs) of acupuncture treatment for epilepsy from various electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, and Wangfang database. These studies evaluated the effectiveness of acupuncture as an auxiliary treatment combined with Western medicine for patients with epilepsy. The methodological quality of the studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS
A total of 17 RCTs involving a total of 1,389 participants were included. The results showed that acupuncture combined with Western medicine improved the effective rates of treatment (OR: 4.28; 95% CI: 3.04-6.02; < 0.001), and reduced the seizure frequency of patients (SMD: -3.29; 95% CI: -3.51 to -3.07; < 0.001) and the EEG discharge frequency (SMD: -5.58; 95% CI: -7.02 to -4.14; < 0.001). Regarding the quality of life and adverse events, the acupuncture group was superior to the control group in improving the overall quality of life of patients with epilepsy (SMD: 14.41; 95% CI: 12.51-16.32; < 0.001) and decreased adverse events (OR: 0.38; 95% CI: 0.23-0.63, < 0.001).
CONCLUSION
The results of the analysis suggested that acupuncture combined with Western medicine is probably helpful in patients with epilepsy, but strong supportive data are not yet available. Given that this study is based on a low to moderate evidence-based analysis, the conclusions should be viewed with caution.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier no. CRD42023409923.
PubMed: 37547148
DOI: 10.3389/fnins.2023.1203231 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930 -
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 -
Irish Journal of Medical Science Apr 2024Gastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Gastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many studies report conflicting results.
METHODS
The aim of the study was to perform the first systematic review and meta-analysis of RCTs to evaluate the efficacy TXA for both upper and lower gastrointestinal bleeding. This was performed per PRISMA guidelines. PubMed, EMBASE, Cochrane and Scopus databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) with 95% confidence intervals (CI) using the MH method with random effects modelling.
RESULTS
Fourteen RCTs were identified with 14,338 patients and mean age of 58.4 years. 34.9% (n = 5008) were female and 65.1% (n = 9330) male. There was no significant difference in mortality between TXA and placebo (RR 0.86 95% CI (0.74 to 1.00), P: 0.05). The secondary outcomes, similarly, did not yield significant results. These included rebleeding, need for surgical intervention (RR: 0.75 95% CI (0.53, 1.07)), endoscopic intervention (RR: 0.92 95% CI (0.70, 1.22)), transfusion requirement (RR: 1.01 95% CI (0.94, 10.7)) and length of stay (RR: 0.03 95% CI (- 0.03, 0.08)). There was no increased risk of VTE, RR: 1.29 95% CI (0.53, 3.16). One trial (n = 12,009) reported an increased risk of seizure in the TXA group, RR: 1.73 95% CI (1.03-2.93).
CONCLUSION
TXA does not reduce mortality in patients with acute upper or lower gastrointestinal bleeding and may confer an increased risk of seizures. The authors do not recommend the use of TXA in acute gastrointestinal bleeding.
Topics: Humans; Male; Female; Middle Aged; Tranexamic Acid; Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Blood Transfusion; Blood Loss, Surgical
PubMed: 37794272
DOI: 10.1007/s11845-023-03517-0 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
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