Use Of Antiepileptic Drugs Research Articles

Effect of the combined use of vagus nerve stimulation and antiepileptic drugs in an experimental model of audiogenic epilepsy, the GASH/Sal

Effect of the combined use of vagus nerve stimulation and antiepileptic drugs in an experimental model of audiogenic epilepsy, the GASH/Sal

Effectiveness, safety and assessing the results of drug therapy in patients with epilepsy

On June 26, 2021, a meeting of the experts of the Russian League Against Epilepsy (RLAE) was held, dedicated to the effectiveness, safety and assessing the results of drug therapy in patients with epilepsy. Having considered the history of the issue and guided by domestic and foreign experience, the participants discussed the problems associated with the use of various antiepileptic drugs for different forms of epilepsy in patients of different sex and age. Special attention was paid to psychiatric comorbidity in patients with epilepsy, increasing their compliance with treatment and quality of life. The article presents the Resolution of RLAE experts meeting adopted as a result of the discussion.

Treatment of epilepsy associated with primary and metastatic brain tumors

There is a number of unsolved issues in management of epilepsy associated with primary and metastatic brain tumors (BTs). In particular, no consensus approaches to treatment of patients with epilepsy associated with BTs have been proposed regarding use of current anti-epileptic drugs (AEDs). The review presents the relevant data on epidemiology, features of clinically manifested epilepsy at varying stages of BTs, aspects of drug-drug interaction between AEDs and anti-tumor agents, AED-related effects on cognitive functions as well as quality of life in patients with epilepsy associated with BTs. Levetiracetam and valproic acid comprise the first-line drugs for treating seizures in patients with BTs. It is unreasonable to use AEDs acting as hepatic microsomal enzyme inducers for therapy of epileptic seizures in BTs, because it may decrease efficacy of chemotherapy agents and glucocorticoids along with elevated rate of side effects. Perampanel acting as a selective noncompetitive AMPA receptor antagonist, may be one of the drugs of choice for the adjunctive therapy of epileptic seizures associated with BTs.

Developing guidelines for the management of brain tumour related epilepsy

Abstract Aims Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment and social and domestic activities. Management of BTRE is complex due to the higher incidence of pharmacoresistance and the potential for interaction between anti-cancer therapy and anti-epileptic drugs (AEDs). Neurologists, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current evidence to adapt current NICE guidelines for Epilepsy and to outline specific recommendations for the optimal treatment of BTRE, encompassing both primary and metastatic brain tumours. Method A comprehensive search of the literature from the past 20 years on BTRE was carried out in three databases: Embase, Medline and EMCARE. A broad search strategy was used and the evidence was evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Results All patients with BTRE should be treated with AEDs. There is no proven benefit for the use of prophylactic AEDs, although there are no randomised trials testing newer agents. Seizure frequency varies between 10-40% (Class 2a evidence) in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) (Class 2a evidence) in patients with Primary Brain Tumours (PBT). In patients with BM, risk factors include number of BM and melanoma histology (Class 2b evidence). In patients with PBT, risk factors include frontal and temporal location, oligodendroglial histology, IDH mutation and cortical infiltration (Class 2b evidence). There is a low incidence of seizures (13%) after stereotactic radiosurgery for BM (Class 2b evidence). Non-enzyme inducing AEDs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant (Class 2b evidence). Conclusion The review has highlighted the relative dearth of high quality evidence for the management of BTRE, and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for AEDs.

CARDIAC CONVULSIONS-POLYMORPHIC VENTRICULAR TACHYCARDIA MASQUERADING AS SEIZURES

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cardiac arrhythmias can occasionally precipitate convulsions through decreased cardiac output resulting in cerebral hypoxia and epileptiform-like activity. Differentiating a seizure from ventricular arrhythmia is crucial for accurate and timely management. CASE PRESENTATION: A 46-year-old female with a history of breast adenocarcinoma with metastasis to the brain presented with staring and unresponsive episodes. These episodes lasted for a few minutes and were accompanied by jerking of all extremities. Physical examination and laboratory investigations were unremarkable, except for mild hypokalemia of 3.2 mmol/L. She underwent a computerized tomography scan and magnetic resonance imaging of the head that redemonstrated multiple hypodense lesions within the internal capsule and caudate nucleus. The patient subsequently underwent an electroencephalogram (EEG) that did not reveal any epileptiform discharges. She was initiated on anti-epileptic drugs (AEDS). Her hospital course was complicated by recurrent unresponsive episodes similar to presentation despite the use of AEDS. She was lethargic during the episodes, without any post-ictal confusion. She was also tachycardic with a heart rate of 150 beats/min. Review of telemetry showed premature ventricular conduction dependent polymorphic ventricular tachycardia (PMVT), concerning for torsade de pointes. Her baseline EKG revealed a prolonged QTc of 550 msec. Further, it was noted that her recurrent episodes of unresponsiveness coincided with the PMVT events on telemetry. Her PMVT were managed with aggressive electrolyte repletion as well as a lidocaine infusion. DISCUSSION: While the brain metastasis and hypodense lesions on the MRI were a confounder to the patient's true diagnosis, the misdiagnosis of cardiac arrhythmias as convulsions is not uncommon. Since cardiac arrhythmia and convulsive seizures share many common characteristics, identifying the true cause of the patient's presentation is of paramount importance. CONCLUSIONS: All patients who present with neurological symptoms should have a baseline EKG and echo to evaluate for underlying cardiac pathology and ideally should be monitored on telemetry until a clear neurological diagnosis is established. Although torsades de pointe episodes can be short lasting and transient, they have the potential to cause cardiac arrest and death. REFERENCE #1: Sabu J, Regeti K, Mallappallil M, et al. Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review. J Clin Med Res. 2016;8(8):610-615. doi:10.14740/jocmr2583w DISCLOSURES: No relevant relationships by Naga Vaishnavi Gadela, source=Web Response No relevant relationships by Nino Nozadze, source=Web Response No relevant relationships by Mahati Paravathaneni, source=Web Response No relevant relationships by Naveen Sablani, source=Web Response No relevant relationships by Evan Wasserman, source=Web Response

A rare cause of drug induced mononeuropathy

Drug-induced mononeuropathy is a common and painful condition seen with use of chemotherapeutic agents, antimicrobials and anticonvulsants. It takes weeks to months to set in. Churg Strauss Syndrome (CSS) is primarily a disease of middle age and its presentation in childhood is rare. We hereby present a rare case of an adolescent female presenting with mononeuropathy which later turned out to be a part of eosinophilic granulomatosis with polyangiitis or CSS precipitated by prolonged use of leukotriene receptor antagonist.

Clinical Characteristics, Treatment Effectiveness, and Predictors of Response to Pharmacotherapeutic Interventions Among Patients with Herpetic-Related Neuralgia: A Retrospective Analysis.

BackgroundThe treatment for herpetic-related neuralgia focuses on symptom control by use of antiviral drugs, anticonvulsants, and tricyclic antidepressants. We aimed to explore the clinical characteristics associated with medication responsiveness, and to build a classifier for identification of patients who have risk of inadequate pain management.MethodsWe recruited herpetic-related neuralgia patients during a 3-year period. Patients were stratified into a medication-resistant pain (MRP) group when the pain decrease in the visual analogue scale (VAS) is < 3 points, and otherwise a medication-sensitive pain (MSP) group. Multivariate logistic regression was performed to determine the factors associated with MRP. We fitted four machine learning (ML) models, namely logistic regression, random forest, supporting vector machines (SVM), and naïve Bayes with clinical characteristics gathered at admission to identify patients with MRP.ResultsA total of 213 patients were recruited, and 132 (61.97%) patients were diagnosed with MRP. Subacute herpes zoster (HZ) (vs. acute, OR 8.95, 95% CI 3.15–29.48, p = 0.0001), severe lesion (vs. mild lesion, OR 3.84, 95% CI 1.44–10.81, p = 0.0084), depressed mood (unit increase OR 1.10, 95% CI 1.00–1.20, p = 0.0447), and hypertension (hypertension, vs. no hypertension, OR 0.36, 95% CI 0.14–0.87, p = 0.0266) were significantly associated with MRP. Among four ML models, SVM had the highest accuracy (0.917) and receiver operating characteristic-area under the curve (0.918) to discriminate MRP from MSP. Phase of disease is the most important feature when fitting ML models.ConclusionsClinical characteristics collected before treatment could be adopted to identify patients with MRP.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00303-7.

OS09.7.A Quality of life outcomes in patients with incidental and operated meningiomas: the QUALMS study

Abstract BACKGROUND Long-term Health-Related Quality of Life (HRQoL) is an important measure of patient wellbeing. There is a paucity of studies evaluating HRQoL in meningioma patients. MATERIAL AND METHODS Cross-sectional study of adult patients with an incidental or symptomatic intracranial meningioma. Patients with less than 5 years of follow-up, a history of craniospinal radiation or neurofibromatosis type 2 were excluded. HRQoL was evaluated with SF-36, EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Outcome determinants were evaluated using a multi-variable linear regression analysis, adjusted for patient, tumour and treatment characteristics, and duration of follow-up. RESULTS 699 patients were invited to participate and 246 responded: 118 (48%) had an incidental meningioma. Mean age at diagnosis was 56.8 years (SD=13) and 81% were female. Median time from diagnosis to completion of questionnaire was 8.5 years (IQR 6.8–11.5). During follow-up, 158 patients (64.2%) had at least one operation for their meningioma and 47 patients (19.1%) had radiotherapy. Of those operated, 126 (79.7%) had WHO grade 1 and 24 (15.2%) had grade 2 meningiomas. Compared to normative population values, meningioma patients reported a worse SF-36 general health score (mean 61.9 vs 56.5, P=0.003) but a similar QLQ-C30 global health score (mean 62.3 vs 65.8, P=0.039), worse SF-36 and QLQ-C30 physical functioning scores (mean 74.1 vs 64.6, P&amp;lt;0.001 and mean 81.8 vs 76.5, P=0.007) and similar SF-36 and QLQ-C30 emotional health scores (mean 72.2 vs 70.9, P=0.367 and mean 71.0 vs 71.9, P=0.960). QLQ-C30 cognitive functioning was worse (mean 80.5 vs 71.4, P&amp;lt;0.001). Compared to the meningioma literature, QLQ-BN20 seizure burden was similar (mean 2.0 vs 1.6, P=0.760). A worse performance status at diagnosis was associated with an inferior QLQ-C30 global health score (β-coefficient=-4.9 [95% CI -9.1-(-)0.6] P=0.024). Number of surgeries was significantly associated with a worse QLQ-C30 cognitive functioning score (β-coefficient=-7.0 [95% CI -13.2-(-)0.9], P=0.025). Anti-epileptic drug use was associated with a significantly worse QLQ-C30 emotional health score (β-coefficient=-10.9 [95% CI -21.7-(-)0.01], P=0.050). CONCLUSION Meningioma patients have long-term HRQoL impairments affecting their physical and cognitive functions. An understanding that multiple surgeries affects cognitive function, and the need for anti-epileptic drugs equate to poorer emotional health, could help target appropriate therapies and support in the future.

Patterns of prophylactic anticonvulsant use in spontaneous intracerebral and subarachnoid hemorrhage: results of a practitioner survey.

The use of prophylactic anti-seizure medications (ASMs) in the management of patients with spontaneous intracerebral hemorrhage (sICH) and aneurysmal subarachnoid hemorrhage (aSAH) is controversial. The purpose of this survey was to better characterize the current state of prophylactic ASM use in sICH and aSAH in North America. US and Canadian neurosurgeons, neurologists, and interventional neuroradiologists with an interest in or expertise in the management of neurovascular disease were surveyed using an electronic survey tool. Seven hundred ninety-four survey requests were sent; responses were received from 103 (13%). The majority of respondents were neurosurgeons (84%). Thirty-eight percent of respondents self-identified as vascular neurosurgeons and 10% self-identified as neurocritical care specialists. Seventy-two percent were in academic practice. When asked their preference for ASM prophylaxis (aSAH, sICH, or both), the most common response was to use prophylaxis in both aSAH and sICH (43, 45%). Twenty-one (22%) did not use routine prophylaxis, while 22 (23%) used prophylaxis only in aSAH and 9 (9%) only in sICH. The majority of practitioners (35, 67%) who answered that they used ASM prophylaxis in sICH, used ASMs selectively. For aSAH, the vast majority (53, 82%) used prophylaxis for all patients. Respondents felt that they were more likely to use ASMs for sICH patients if the sICH was in a cortical location, supratentorial location, or was related to a structural abnormality (e.g., tumor, arteriovenous malformation) Levetiracetam (Keppra) was the most commonly used ASM (73, 99%). When asked whether the statement "Current AHA/ASA Guidelines recommend against the use of prophylactic anticonvulsants in spontaneous ICH" was true or false, 78 (83%) responded correctly that the recommendation is true. Only 24 respondents answered the question as to whether they would be willing to randomize sICH and/or aSAH patients to management with or without ASM prophylaxis. Of these, 13 (54%) said they would be willing to randomize sICH patients, while only 6 (25%) were willing to randomize aSAH patients. There were no statistically significant differences in responses to survey questions when analyzed by practice type (academic versus non-academic) or physician specialty (critical care versus non-critical care, or vascular neurology/neurosurgery versus other). The use of ASMs for seizure prophylaxis after sICH and aSAH remains widespread despite the lack of any specific evidence-based guideline to support the practice. A large-scale randomized controlled trial is needed to add clarity to the practice of prophylactic ASM use in patients with spontaneous intracranial hemorrhage.

Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China

BackgroundThe relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China.MethodsWe enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test.ResultsWe found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found.ConclusionsIn northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Clinical and genomic factors associated with seizures in meningiomas.

The association of seizures with meningiomas is poorly understood. Moreover, any relationship between seizures and the underlying meningioma genomic subgroup has not been studied. Herein, the authors report on their experience with identifying clinical and genomic factors associated with preoperative and postoperative seizure presentation in meningioma patients. Clinical and genomic sequencing data on 394 patients surgically treated for meningioma at Yale New Haven Hospital were reviewed. Correlations between clinical, histological, or genomic variables and the occurrence of preoperative and postoperative seizures were analyzed. Logistic regression models were developed for assessing multiple risk factors for pre- and postoperative seizures. Mediation analyses were also conducted to investigate the causal pathways between genomic subgroups and seizures. Seventeen percent of the cohort had presented with preoperative seizures. In a univariate analysis, patients with preoperative seizures were more likely to have tumors with a somatic NF2 mutation (p = 0.020), WHO grade II or III tumor (p = 0.029), atypical histology (p = 0.004), edema (p < 0.001), brain invasion (p = 0.009), and worse progression-free survival (HR 2.68, 95% CI 1.30-5.50). In a multivariate analysis, edema (OR 3.11, 95% CI 1.46-6.65, p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03-3.90, p = 0.041) were positive predictors of preoperative seizures, while genomic subgroup was not, such that the effect of an NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort, and only 20.8% of the seizure-free patients, who were more likely to have undergone gross-total resection (p = 0.031), were able to discontinue antiepileptic drug use postoperatively. Preoperative seizures (OR 3.54, 95% CI 1.37-9.12, p = 0.009), recurrent tumors (OR 2.89, 95% CI 1.08-7.74, p = 0.035), and tumors requiring postoperative radiation (OR 2.82, 95% CI 1.09-7.33, p = 0.033) were significant predictors of postoperative seizures in a multivariate analysis. Seizures are relatively common at meningioma presentation. While NF2-mutated tumors are significantly associated with preoperative seizures, the association appears to be mediated through edema and atypical histology. Patients who undergo radiation and/or have a recurrence are at risk for postoperative seizures, regardless of the extent of resection. Preoperative seizures may indeed portend a more potentially aggressive molecular entity and challenging clinical course with a higher risk of recurrence.

The effect of antiepileptic drugs on re-myelinization of axons: Phenytoin, levetiracetam, carbamazepine, and valproic acid, used following traumatic brain injury

ObjectiveTraumatic brain injury is a major health and socioeconomic problem and the first cause of young death worldwide. For this reason, the prevention of post-traumatic brain injury and the research of new methods for it are important today. In this study, we aimed to determine whether the use of antiepileptic drugs contributed to axonal healing after traumatic brain injury. MethodsThirty-six Long-Evans rats, each weighing 300–350 g, were used in this study. A total of 6 groups, including the sham, control, and 4 study groups, were determined. A 1.5 mm-sized trauma was created in the biparietal area with a blunt-tipped dissector. Carbamazepine phenytoin valproic acid and levetiracetam (phenytoin: 30 mg/kg, valproic acid: 60 mg/kg, levetiracetam: 80 mg/kg, and carbamazepine: 36 mg/kg) were intraperitoneally administered to the study groups, and the control group intraperitoneally received a physiological saline solution (15 ml/kg) twice daily for 3 days. After 72 h, hemispheres of the sacrificed subjects were taken for examination in biochemistry and histology. Glutathione, malondialdehyde, and NG2 levels in the samples were determined. ResultsNo significant difference was found in biochemical measurements. Histopathological examination revealed that the NG2 expression was more intense in the group treated with phenytoin and levetiracetam (phenytoin was partly higher) and the amount of edema decreased. The NG2 expression increased and the edema decreased, though lower in the group treated with carbamazepine and valproic acid, compared with phenytoin and levetiracetam. An increase in the NG2 expression and edema intensity were determined in the control and sham groups. ConclusionAntiepileptic drug selection after traumatic brain injury is an important medical matter. Although the patient-oriented selection is essential, the study suggests that the choice of phenytoin, levetiracetam carbamazepine, and valproic acid will, respectively, have an accelerating effect for axonal healing.

PCDH19 interplay with GABA(A) receptors: a window to DEE9 pathogenetic mechanisms.

PCDH19 interplay with GABA(A) receptors: a window to DEE9 pathogenetic mechanisms.

Children with idiopathic generalized epilepsy those underwent at least two years seizure remission: a retrospective analysis

Background: The aim of the retrospective study was to evaluate the effectiveness of the index antiepileptic drugs in children with idiopathic generalized epilepsy who underwent at least 2 years remission.Methods: A total of 52 children with idiopathic generalized epilepsy who underwent at least 2 years remission were identified retrospectively from the records of the paediatric and neurology care clinic from April 2017 to December 2020.Results: The seizure patterns of 52 cases were tonic-clonic seizures alone (73%), a combination of tonic-clonic seizures and absences (13.5%), and combined tonic-clonic seizures and myoclonus (13.5%). The total number of seizures at enrolment in all (age at seizure onset 7.44±5.12 years, male-female ratio (31:21) was 651 (mean 12.52±26.60). The total number of follow-up visits in all was 6.62±14.44 consisting of 1177.5±772.86 days of follow-up periods. All patients continued index antiepileptic drugs with initial target doses varies from low to moderate ranges. Add-on therapy was initiated in 43% of cases around the titration phase of index antiepileptic drugs (i.e. very early add-on). Treatment trends reveal increased use of 1st generation antiepileptic drugs than 2nd and 3rd generation. 2 years seizure remission rates were 55.77% by index antiepileptic drugs only therapy and 44.23% by very early add-on therapy. The seizure remission period was mean±SD 858.71±209.08 days.Conclusions: Index antiepileptic drugs with low to moderate initial target doses lead to achieving 2 years or more seizure remission. Very early add-on therapy is the novelty and leads to achieving the goal.

Risk Factors and Characteristics of Intraoperative Seizures During Awake Craniotomy: A Retrospective Cohort Study of 562 Consecutive Patients With a Space-occupying Brain Lesion.

Intraoperative seizures (IOSs) during awake craniotomy (AC) are associated with significant morbidity. The reported incidence of IOS is between 3% and 30%. The aim of this study was to identify risk factors for IOS during AC for elective resection or biopsy of a space-occupying brain lesion. In this retrospective study, we reviewed the records of all awake craniotomies performed by a single neurosurgeon at a single university hospital between July 2006 and December 2018. IOS was defined as a clinically apparent seizure that occurred in the operating room and was documented in the medical records. Explanatory variables were chosen based on previously published literature on risk factors for IOS. Five hundred and sixty-two patients had a total of 607 AC procedures during the study period; 581 cases with complete anesthesia records were included in analysis. Twenty-nine (5.0%) IOS events were reported during 29 (5%) awake craniotomies. Most seizures (27/29; 93%) were focal in nature and did not limit planned intraoperative stimulation mapping. Variables associated with IOS at a univariate P -value <0.1 (frontal location of tumor, preoperative radiotherapy, preoperative use of antiepileptic drugs, intraoperative use of dexmedetomidine, and intraoperative stimulation mapping) were included in a multivariable logistic regression. Frontal location of tumor (adjusted odds ratio: 5.68, 95% confidence interval: 2.11-15.30) and intraoperative dexmedetomidine use (adjusted odds ratio: 2.724, 95% confidence interval: 1.24-6.00) were independently associated with IOS in the multivariable analysis. This study identified a low incidence (5%) of IOS during AC. The association between dexmedetomidine and IOS should be further studied in randomized trials as this is a modifiable risk factor.

Efficacy and Safety of Anticonvulsants for the Inpatient Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis.

To examine the efficacy and safety of antiepileptic drugs (AED) for the inpatient treatment of patients with moderate to severe alcohol withdrawal syndrome (AWS). We searched in databases and gray literature to include randomized controlled clinical trials in adults that compare the use of AED versus placebo or any other medication. Studies that did not specify severity or were performed on an outpatient basis were excluded. The outcomes were improvement of symptoms, delirium tremens, seizures and adverse events. Two researchers independently selected the references, extracted the data and assessed the risk of bias. A qualitative synthesis was made and, when the heterogeneity was mild or moderate, a meta-analysis was performed. The quality of the evidence obtained was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. In total, 26 studies with 1709 patients were included. No benefit is described in withdrawal syndrome severity measured by scales or in the development of delirium tremens. The only possible meta-analysis showed that there are no differences in the incidence of seizures (risk ratio [RR] = 1.0; confidence interval (CI) 95% 0.76-1.33), even when compared with placebo (RR = 0.95; CI95% 0.57-1.57). There were also no differences in adverse events, although a higher proportion of some mild cases were described with the use of carbamazepine and valproic acid. The routine use of AED is not suggested in the treatment of patients with moderate or severe AWS unless indicated for comorbidity (weak recommendation against using moderate quality of evidence).

The Impact of Non-dopaminergic Medication on Quality of Life in Parkinson's Disease.

Quality of life (QoL) in Parkinson's disease (PD) depends on multiple factors. Due to PD treatment and accompanying, age-related or independent comorbidities, pill burden is often high. The relation of QoL and pharmacotherapy for comorbidities in PD has not been widely studied. This study investigated if and to what extent non-dopaminergic drugs are related to QoL in PD. Second, the impact of demographics and non-motor symptoms were evaluated. A better understanding of the impact of different non-dopaminergic drugs and polypharmacy on QoL will have added value in selecting appropriate (medication) interventions. In a cross-sectional analysis, medication prescription data of 209 PD patients were analyzed and grouped according to the Rx-Risk comorbidity index. QoL was measured using the PDQ-39 questionnaire. Non-motor symptoms were analyzed with the Non-Motor Symptoms questionnaire. Independent factors associated with a reduced QoL were identified with a multivariate linear regression analysis. Non-dopaminergic drugs, subdivided into Rx-Risk comorbidity categories, were not associated with reduced QoL, except for the use of anti-epileptic drugs. However, using more daily non-dopaminergic drugs was also negatively associated with QoL, as well as female sex, increased PD severity, and more non-motor symptoms. Contraindicated non-dopaminergic medication was barely prescribed (0.4%). Non-dopaminergic drugs are frequently prescribed, and higher numbers are associated with impaired QoL in PD. However, when divided in drug types, only anti-epileptic drugs were negatively associated with QoL. In these patients, physicians might improve QoL by further optimizing the condition it was prescribed for (e.g., pain or anxiety), or managing of side effects. Netherlands Trial Register; NL4360.

Resistance to Neuromuscular Blockade by Rocuronium in Surgical Patients with Spastic Cerebral Palsy.

Individuals with spastic cerebral palsy (CP) often exhibit altered sensitivities to neuromuscular blocking agents (NMBAs) used for surgical intubation. We assessed usage of the NMBA rocuronium in patients with spastic CP and evaluated potential modifiers of dosing including gross motor function classification system (GMFCS) level, birthweight, gestational age, and the use of anticonvulsant therapy. In a case-control study, surgical patients with spastic CP (n = 64) or with idiopathic or non-neuromuscular conditions (n = 73) were enrolled after informed consent/assent. Patient data, GMFCS level, anticonvulsant use, and rocuronium dosing for intubation and post-intubation neuromuscular blockade were obtained from medical records. Findings reveal participants with CP required more rocuronium per body weight for intubation than controls (1.00 ± 0.08 versus 0.64 ± 0.03 mg/kg; p < 0.0001). Dosing increased with GMFCS level (Spearman’s rho = 0.323; p = 0.005), and participants with moderate to severe disability (GMFCS III-V) had elevated rocuronium with (1.21 ± 0.13 mg/kg) or without (0.86 ± 0.09 mg/kg) concurrent anticonvulsant therapy. Children born full-term or with birthweight >2.5 kg in the CP cohort required more rocuronium than preterm and low birthweight counterparts. Individuals with CP exhibited highly varied and significant resistance to neuromuscular blockade with rocuronium that was related to GMFCS and gestational age and weight at birth.

Comparison of Medication Prescribing Before and After the COVID-19 Pandemic Among Nursing Home Residents in Ontario, Canada

COVID-19 has had devastating effects on the health and well-being of older adult residents and health care professionals in nursing homes. Uncertainty about the associated consequences of these adverse effects on the use of medications common to this care setting remains. To examine the association between the COVID-19 pandemic and prescription medication changes among nursing home residents. This population-based cohort study with an interrupted time-series analysis used linked health administrative data bases for residents of all nursing homes (N = 630) in Ontario, Canada. During the observation period, residents were divided into consecutive weekly cohorts. The first observation week was March 5 to 11, 2017; the last observation week was September 20 to 26, 2020. Onset of the COVID-19 pandemic on March 1, 2020. Weekly proportion of residents dispensed antipsychotics, benzodiazepines, antidepressants, anticonvulsants, opioids, antibiotics, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors. Autoregressive integrated moving average models with step and ramp intervention functions tested for level and slope changes in weekly medication use after the onset of the pandemic and were fit on prepandemic data for projected trends. Across study years, the annual cohort size ranged from 75 850 to 76 549 residents (mean [SD] age, 83.4 [10.8] years; mean proportion of women, 68.9%). A significant increased slope change in the weekly proportion of residents who were dispensed antipsychotics (parameter estimate [β] = 0.051; standard error [SE] = 0.010; P < .001), benzodiazepines (β = 0.026; SE = 0.003; P < .001), antidepressants (β = 0.046; SE = 0.013; P < .001), trazodone hydrochloride (β = 0.033; SE = 0.010; P < .001), anticonvulsants (β = 0.014; SE = 0.006; P = .03), and opioids (β = 0.038; SE = 0.007; P < .001) was observed. The absolute difference in observed vs estimated use in the last week of the pandemic period ranged from 0.48% (for anticonvulsants) to 1.52% (for antipsychotics). No significant level or slope changes were found for antibiotics, ARBs, or ACE inhibitors. In this population-based cohort study, statistically significant increases in the use of antipsychotics, benzodiazepines, antidepressants, anticonvulsants, and opioids followed the onset of the COVID-19 pandemic, although absolute differences were small. There were no significant changes for antibiotics, ARBs, or ACE inhibitors. Studies are needed to monitor whether changes in pharmacotherapy persist, regress, or accelerate during the course of the pandemic and how these changes affect resident-level outcomes.

An integrative prediction algorithm of drug-refractory epilepsy based on combined clinical-EEG functional connectivity features

Although the use of antiepileptic drugs (AEDs) is routine, 30-40% of patients with epilepsy (PWEs) experience drug resistance. Thus, early identification of AED resistance will help optimize treatment regimens and improve patients' prognoses. However, there have been few studies on this topic to date. Here, we try to establish an integrative prediction model of AED resistance for drug-naive PWEs, and to identify the clinical and Electroencephalogram (EEG) factors that affect their outcomes. One hundred sixty-four PWEs naive to AEDs treated at a tertiary care center from January 2014 to June 2020 were retrospectively analyzed. A total of 113 of these patients were well controlled and 53 were drug refractory with regular AED treatment for more than oneyear. Eighty clinical characteristics and 684 EEG functional connectivity variables based on phase lag index before drug initiation were identified. Overall, 80% of each group was chosen to establish a support vector machine (SVM) model with ten-fold cross validation, and the other 20% were used to evaluate the model's performance. Absolute weight value was used to rank the features that had impacts on classification. An integrative algorithm was modeled to predict AED resistance for drug-naive PWEs by SVM based on clinical characteristics and EEG functional connectivity values. The model had an accuracy of 94% [95% confidence interval (CI) 0.85-1.0], sensitivity of 95% [95% CI 0.82-1.0], specificity of 93% [95% CI 0.77-1.0], and an area under the curve (AUC) of 0.98 [95% CI 0.91-1.0]. The p values of accuracy, sensitivity specificity and AUC were calculated as 0.001, 0.001, 0.01 and 0.001, respectively. The δ band fromT4-FZ and T3-PZ, α band from T3-T6 and β band from F7-CZ and FP2-F3 were the top five EEG features that impacted the SVM classifier. We constructed an integrative prediction algorithm of AED resistance for drug-naive PWEs. Its utility in clinical settings should be evaluated in the future.