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Palliative Medicine Apr 2024Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish...
BACKGROUND
Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy.
AIM
To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability.
DESIGN
A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines.
DATA SOURCES
The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023.
RESULTS
The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site.
CONCLUSIONS
There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.
Topics: Humans; Valproic Acid; Palliative Care; Seizures; Neuralgia
PubMed: 38444061
DOI: 10.1177/02692163241234597 -
Frontiers in Psychiatry 2024Autism is a multifaceted developmental disorder of the nervous system, that necessitates novel therapeutic approaches beyond traditional medications and psychosomatic...
AIMS
Autism is a multifaceted developmental disorder of the nervous system, that necessitates novel therapeutic approaches beyond traditional medications and psychosomatic therapy, such as appropriate sensory integration training. This systematic mapping review aims to synthesize existing knowledge on enriching environmental interventions as an alternative avenue for improving autism, guiding future research and practice.
METHOD
A comprehensive search using the terms ASD and Enriched Environment was conducted across PubMed, EMBASE, ISI, Cochrane, and OVID databases. Most of the literature included in this review was derived from animal model experiments, with a particular focus on assessing the effect of EE on autism-like behavior, along with related pathways and molecular mechanisms. Following extensive group discussion and screening, a total of 19 studies were included for analysis.
RESULTS
Enriched environmental interventions exhibited the potential to induce both behavioral and biochemical changes, ameliorating autism-like behaviors in animal models. These improvements were attributed to the targeting of BDNF-related pathways, enhanced neurogenesis, and the regulation of glial inflammation.
CONCLUSION
This paper underscores the positive impact of enriched environmental interventions on autism through a review of existing literature. The findings contribute to a deeper understanding of the underlying brain mechanisms associated with this intervention.
PubMed: 38362032
DOI: 10.3389/fpsyt.2024.1328240 -
Seizure Jan 2024Epilepsy is one of the most frequent neurological comorbidities in patients with Down Syndrome (DS). Young patients and adults are the most affected, the latter mostly... (Review)
Review
INTRODUCTION
Epilepsy is one of the most frequent neurological comorbidities in patients with Down Syndrome (DS). Young patients and adults are the most affected, the latter mostly showing a phenotype labeled as "Late-onset myoclonic epilepsy" (LOMEDS). Status epilepticus (SE) is a life-threatening complication in patients with epilepsy. In this study, we described a non-convulsive SE (NCSE) case in a patient diagnosed with LOMEDS. We also performed a systematic review of the literature on SE diagnosis and treatment in patients with Down Syndrome.
METHODS
Clinical and demographic characteristics of a DS patient diagnosed with NCSE were described. The systematic literature search dissected the diagnostic and therapeutic management of SE in patients with DS. The following databases were used: PubMed, EMBASE, and Google Scholar.
RESULTS
5 DS individuals (4 from the past literature + 1 novel case report) with SE have been identified. The median age at SE onset was 42 years (IQR: 21-60.5 years). The most common SE type was myoclonic SE (MSE), followed by NCSE. Two cases of acute symptomatic etiology were described, whereas a progressive symptomatic etiology was otherwise reported. Ictal EEG recording information was available in two patients who showed generalized spike waves and polyspike and wave discharges. In 3 cases, SE was treated with intravenous antiseizure medications that produced a complete resolution.
CONCLUSION
SE may represent a rare complication in patients with DS. Although no definitive conclusions may be achieved due to the lack of evidence, treatment with valproic acid seems effective, especially in MSE. NCSE management is more challenging. It requires low doses of anesthetics, which should be used cautiously due to the high rate of complications.
Topics: Adult; Humans; Middle Aged; Young Adult; Down Syndrome; Electroencephalography; Epilepsy; Status Epilepticus; Valproic Acid
PubMed: 38101201
DOI: 10.1016/j.seizure.2023.11.009 -
European Journal of Clinical... Jan 2024This study intends to assess the reference range of lamotrigine concentration for treating childhood epilepsy. (Review)
Review
PURPOSE
This study intends to assess the reference range of lamotrigine concentration for treating childhood epilepsy.
METHODS
PubMed, Ovid-Embase, The Cochrane Library, CNKI, WanFang data and VIP databases were searched from database inception to January 2022. RCT, cohort study, case-control study, cross-sectional study that estimated the reference range of lamotrigine for children epilepsy treatment were included. The data extracted included basic information, statistical methods, data type, and results of reference range. Descriptive analysis was performed for them.
RESULTS
8 studies were included and estimated the reference range, and all of them were calculated based on efficacy data and/or concentration data. Statistical methods including ROC curve, concentration-effect curve, mean ± standard deviation, 95% confidence interval and percentile interval were utilized. For lamotrigine monotherapy, the lower limits ranged from 2.06 mg/L to 3.99 mg/L, and the upper limits ranged from 8.43 mg/L to 9.08 mg/L, showing basic consistency. However, for lamotrigine concomitant with valproate, the lower limits ranged from 2.00 mg/L to 8.00 mg/L, and the upper limit was 11.50 mg/L, for lamotrigine concomitant with other antiepileptics, the lower limits ranged from 1.00 mg/L to 3.09 mg/L, and the upper limits varied from 5.90 mg/L to 16.24 mg/L, indicating inconsistency.
CONCLUSION
Several studies have estimated the reference range of lamotrigine for childhood epilepsy, while controversy exist and no studies have determined the upper limit of the range based on safety data. To establish the optimal reference range, further high-quality studies are necessary that consider both efficacy and safety data.
Topics: Child; Humans; Anticonvulsants; Lamotrigine; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Reference Values; Triazines; Epilepsy; Valproic Acid
PubMed: 37906300
DOI: 10.1007/s00228-023-03562-9 -
Journal of Clinical Medicine Sep 2023Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this... (Review)
Review
Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.
PubMed: 37762984
DOI: 10.3390/jcm12186044 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
European Journal of Investigation in... Aug 2023This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact... (Review)
Review
This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.
PubMed: 37623307
DOI: 10.3390/ejihpe13080110 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8 -
Seizure Jul 2023The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS),... (Review)
Review
INTRODUCTION
The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.
METHODS
We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).
RESULTS
Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.
CONCLUSIONS
AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Topics: Humans; Down Syndrome; Epilepsy; Epilepsies, Myoclonic; Levetiracetam; Seizures; Alzheimer Disease; Electroencephalography; Anticonvulsants; Epilepsy, Generalized
PubMed: 37267668
DOI: 10.1016/j.seizure.2023.05.017