Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Epilepsy surgery in adults older than 50 years: A systematic review and meta-analysis.

OBJECTIVE: Despite the general safety and efficacy of epilepsy surgery, there is evidence that epilepsy surgery remains underutilized. Although there are an increasing number of studies reporting epilepsy surgery in older adults, there is no consensus on whether epilepsy surgery is efficacious or safe for this population. Our objective was to systematically assess the efficacy as well as safety of resective surgery in people aged 50 years or older with drug-resistant epilepsy. METHODS: We considered studies that examine the efficacy and safety of epilepsy surgery in adults aged 50 years and older. Study eligibility was limited to studies carried out after 1990, with a minimum of 10 participants and 6 months of follow-up. We searched the following databases for published studies: Ovid MEDLINE, Ovid Embase, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, and Web of Science Conference Proceedings Citation Index - Science. The risk of bias of each included study was independently assessed by two reviewers using the MINORS (Methodological Index for Non-Randomized Studies) instrument. RESULTS: Eleven case series and 14 cohort studies met the criteria for inclusion, for a total of 1111 older adults who underwent epilepsy surgery along with 4111 adults younger than 50 years as control groups. The pooled cumulative incidence of older adults achieving seizure freedom after resective surgery was 70.1% (95% confidence interval [CI] = 65.3-74.7). There was no evident difference in the incidence of seizure freedom among older adults as compared to younger adults (risk ratio [RR] = 1.05, 95% CI = .97-1.14) in cohort studies. The pooled cumulative incidence of perioperative complications in older adults was 26.2% (95% CI = 21.3-31.7). Among them, 7.5% (95% CI = 5.8-9.5) experienced major complications. Older adults were significantly more at risk of experiencing any complication than younger adults (RR = 2.8, 95% CI = 1.5-5.4). SIGNIFICANCE: Despite important considerations, epilepsy surgery may be considered appropriate among carefully selected individuals older than 50 years.

Comparison of three frailty measures for predicting hospitalization and mortality in the Canadian Longitudinal Study on Aging.

BACKGROUND: Few studies have compared different measures of frailty for predicting adverse outcomes. It remains unknown which frailty measurement approach best predicts healthcare utilization such as hospitalization and mortality. AIMS: This study aims to compare three approaches to measuring frailty-grip strength, frailty phenotype, and frailty index-in predicting hospitalization and mortality among middle-aged and older Canadians. METHODS: We analyzed baseline and the first 3-year follow-up data for 30,097 participants aged 45 to 85 years from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA). Using separate logistic regression models adjusted for multimorbidity, age and biological sex, we predicted participants' risks for overnight hospitalization in the past 12 months and mortality, at the first 3-year follow-up, using each of the three frailty measurements at baseline. Model discrimination was assessed using Harrell's c-statistic and calibration assessed using calibration plots. RESULTS: The predictive performance of all three measures of frailty were roughly similar when predicting overnight hospitalization and mortality risk among CLSA participants. Model discrimination measured using c-statistics ranged from 0.67 to 0.69 for hospitalization and 0.79 to 0.80 for mortality. All measures of frailty yielded strong model calibration. DISCUSSION AND CONCLUSION: All three measures of frailty had similar predictive performance. Discrimination was modest for predicting hospitalization and superior in predicting mortality. This likely reflects the objective nature of mortality as an outcome and the challenges in reducing the complex concept of healthcare utilization to a single variable such as any overnight hospitalization.

The association between grip strength and carotid intima media thickness: A Mendelian randomization analysis of the Canadian Longitudinal Study on Aging.

BACKGROUND: Several two-sample Mendelian randomization studies have reported discordant results concerning the association between grip strength and cardiovascular disease, possibly due to the number of instrumental variables used, pleiotropic bias, and/ or effect modification by age and sex. METHODS: We conducted a sex- and age-stratified one-sample Mendelian randomization study in the Canadian Longitudinal Study on Aging. We investigated whether grip strength is associated with carotid intima media thickness (cIMT), a marker of vascular atherosclerosis event risk, using eighteen single nucleotide polymorphisms (SNP) identified as specifically associated with grip strength. RESULTS: A total of 20,258 participants of self-reported European ancestry were included in the analytic sample. Our Mendelian randomization findings suggest a statistically significant association between grip strength and cIMT (MR coefficient of 0.02 (95% CI: 0.01, 0.04)). We found no statistically significant differences between sexes (p-value = 0.201), or age groups [(≤ 60 years old versus >60 years old); p-value = 0.421]. CONCLUSION: This study provides evidence that grip strength is inversely associated with cIMT. Our one-sample MR study design allowed us to demonstrate that there is no evidence of heterogeneity of effects according to age group or biological sex.

Inter-rater reliability of risk of bias tools for non-randomized studies.

PURPOSE: There is limited knowledge on the reliability of risk of bias (ROB) tools for assessing internal validity in systematic reviews of exposure and frequency studies. We aimed to identify and then compare the inter-rater reliability (IRR) of six commonly used tools for frequency (Loney scale, Gyorkos checklist, American Academy of Neurology [AAN] tool) and exposure (Newcastle-Ottawa scale, SIGN50 checklist, AAN tool) studies. METHODS: Six raters independently assessed the ROB of 30 frequency and 30 exposure studies using the three respective ROB tools. Articles were rated as low, intermediate, or high ROB. We calculated an intraclass correlation coefficient (ICC) for each tool and category of ROB tool. We compared the IRR between ROB tools and tool type by inspection of overlapping ICC 95% CIs and by comparing their coefficients after transformation to Fisher's Z values. We assessed the criterion validity of the AAN ROB tools by calculating an ICC for each rater in comparison with the original ratings from the AAN. RESULTS: All individual ROB tools had an IRR in the substantial range or higher (ICC point estimates between 0.61 and 0.80). The IRR was almost perfect (ICC point estimate > 0.80) for the AAN frequency tool and the SIGN50 checklist. All tools were comparable in IRR, except for the AAN frequency tool which had a significantly higher ICC than the Gyorkos checklist (p = 0.021) and trended towards a higher ICC when compared to the Loney scale (p = 0.085). When examined by category of ROB tool, scales, and checklists had a substantial IRR, whereas the AAN tools had an almost perfect IRR. For the criterion validity of the AAN ROB tools, the average agreement between our raters and the original AAN ratings was moderate. CONCLUSION: All tools had substantial IRRs except for the AAN frequency tool and the SIGN50 checklist, which both had an almost perfect IRR. The AAN ROB tools were the only category of ROB tools to demonstrate an almost perfect IRR. This category of ROB tools had fewer and simpler criteria. Overall, parsimonious tools with clear instructions, such as those from the AAN, may provide more reliable ROB assessments.

Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.

BACKGROUND AND OBJECTIVES: Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality. METHODS: We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster. RESULTS: From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters. SIGNIFICANCE: Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Medical and surgical treatment of epilepsy in older adults: A national survey.

OBJECTIVE: There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists). METHODS: We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings. RESULTS: One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults). SIGNIFICANCE: Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Association Between Frailty and Antiseizure Medication Tolerability in Older Adults With Epilepsy.

BACKGROUND AND OBJECTIVE: Frailty is an important aspect of biological aging, referring to the increased vulnerability of individuals with frailty to physical and psychological stressors. While older adults with epilepsy are an important and distinct clinical group, there are no data on frailty in this population. We hypothesize that frailty will correlate with the seizure frequency and especially the tolerability of antiseizure medications (ASMs) in older adults with epilepsy. METHODS: We recruited individuals aged 60 years or older with active epilepsy from 4 Canadian hospital centers. We reported the seizure frequency in the 3 months preceding the interview, while ASM tolerability was quantified using the Liverpool Adverse Events Profile (LAEP). We applied 3 measures of frailty: grip strength as a measure of physical frailty, 1 self-reported score (Edmonton frail score [EFS]), and 1 scale completed by a healthcare professional (clinical frailty scale [CFS]). We also administered standardized questionnaires measuring levels of anxiety, depression, functional disability, and quality of life and obtained relevant clinical and demographic data. RESULTS: Forty-three women and 43 men aged 60-93 years were recruited, 87% of whom had focal epilepsy, with an average frequency of 3.4 seizures per month. Multiple linear regression and zero-inflated negative binomial regression models showed that EFS and CFS scores were associated with decreased ASM tolerability, each point increase leading to 1.83 (95% CI: 0.67-4.30) and 2.49 (95% CI: 1.27-2.39) point increases on the LAEP scale, respectively. Neither the EFS and CFS scores nor grip strength were significantly associated with seizure frequency. The EFS was moderately correlated with depression, anxiety, quality of life, and functional disability, demonstrating the best construct validity among the 3 tested measures of frailty. DISCUSSION: The EFS was significantly, both statistically and clinically, associated with ASM tolerability. It also showed multiple advantages in performance while assessing for frailty in older adults with epilepsy, when compared with the 2 other measures of frailty that we tested. Future studies must focus on what role the EFS during epilepsy diagnosis may play in ASM selection among older adults with epilepsy.

Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: There is a paucity of data on the frequency and prognosis of infratentorial brain injury among patients suspected of death by neurologic criteria (DNC), which likely contributes to scientific uncertainty regarding the role of isolated brainstem death in DNC determination. Our aim was to synthesize the prevalence, characteristics, and evolution of infratentorial brain injury, including isolated brainstem death, among patients suspected of DNC. METHODS: We conducted a systematic review by searching Medline, Embase, EBM Reviews, CINAHL Complete, and the gray literature from inception to March 26, 2021. We selected cohort and cross-sectional studies, case reports, and case series that included patients suspected of DNC. Two study investigators independently performed study selection, data collection, and risk of bias assessment. Our primary outcomes were the respective prevalence of infratentorial brain injury and isolated brainstem death, which we meta-analyzed using mixed-effects Bayesian hierarchical models with diffuse priors. Our secondary outcomes were the characteristics and evolution of patients with infratentorial brain injury and isolated brainstem death. RESULTS: Twenty-one studies met the selection criteria, most of which were of moderate to high risk of bias. Among patients suspected of DNC, the prevalence of infratentorial brain injury ranged from 2% to 16% (n = 3,602, mean prevalence: 6.3%, 95% highest density interval [2.4%-14.2%]), whereas the prevalence of isolated brainstem death ranged from 1% to 4% (n = 3,692, mean prevalence: 1.5%, 95% highest density interval [0.5%-3.9%]). A total of 38 isolated brainstem death cases with data on clinical characteristics and/or evolution were included. All had infratentorial strokes. Twenty patients had EEG background activity in the α or θ frequencies, 19 had preserved cerebral blood flow, 2 had preserved supratentorial cerebral perfusion, 2 had cortical responses to visual evoked potentials, and 1 had cortical responses to somatosensory evoked potentials. At the latest follow-up, 28 had progressed to whole-brain death. DISCUSSION: Studies with moderate to high risk of bias suggest that infratentorial brain injury is relatively uncommon among patients suspected of DNC. Isolated brainstem death is rarer and seems to carry a high risk of progression to whole-brain death. These findings require further high-quality investigation.

The treatment of epilepsy in younger and older adults: Demographic differences and prescribing patterns of anti-seizure medications in Canada.

OBJECTIVE: Our study describes adults in Canada between 2009 and 2013 receiving at least one antiseizure medication (ASM) at the end of a hospitalization for newly-diagnosed epilepsy, with a focus on the type of ASM prescribed, changes in drug prescriptions after one year, and how this differs between younger and older adults. METHODS: Canada-wide data from the Discharge Abstract Database and the National Prescription Drug Utilization Information System database from 2009 to 2013 were used to identify individuals hospitalized with newly-diagnosed epilepsy and prescribed an ASM at the end of this hospitalization. We classified ASMs into enzyme inducing (EIASM) and non-enzyme inducing (non-EIASM). Confidence intervals and p-values were generated using an exact binomial distribution. RESULTS: Our study sample included 10,568 adults. 61.3% (95% CI: 60.3, 62.2) of all prescriptions were for EIASMs. Among EIASMs, phenytoin was the most frequently prescribed drug in both younger (aged 18-59 years) and older subjects. Among older adults prescribed EIASMs, 53.1% (95% CI: 51.5, 54.7) were men; and for non-EIASMs, 45.2% (95% CI: 43.0%, 47.4) were men. Among the 3847 older adults initially prescribed EIASMs, 7.1% (95% CI: 6.4, 8.0) switched to non-EIASMs at one year following their hospital discharge. CONCLUSION: Non-EIASM have been available to clinicians since the 1990's but suboptimal ASMs such as phenytoin remained frequently prescribed during the period of this study. This is an especially pressing issue among older adults due to the greater risk of drug intolerability, related to metabolic changes that occur with greater age, increasing comorbidity burden, and frailty. Men were disproportionately prescribed EIASM, as compared to women who were more often prescribed non-EIASM.

Sudden Death and Cardiac Arrythmia With Lamotrigine: A Rapid Systematic Review.

BACKGROUND AND OBJECTIVES: A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or ECG abnormalities. METHODS: We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. RESULTS: We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions. DISCUSSION: There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results.

Neurostimulation in people with drug-resistant epilepsy: Systematic review and meta-analysis from the ILAE Surgical Therapies Commission.

OBJECTIVE: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta-analysis. METHODS: We followed the Preferred Reporting Items of Systematic reviews and Meta-Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open-label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow-up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. RESULTS: We identified 30 eligible studies, six of which were RCTs. At long-term follow-up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: -5.1, 74.5). In the open-label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow-up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow-up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. SIGNIFICANCE: Neurostimulation modalities are an effective treatment option for drug-resistant epilepsy, with improving outcomes over time and few major complications. Seizure-reduction rates among the three therapies were similar during the initial blinded phase. Recent long-term follow-up studies are encouraging for RNS and DBS but are lacking for VNS.

Validity and reliability of global ratings of satisfaction with epilepsy surgery.

OBJECTIVE: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery. METHODS: We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1 year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4-6 weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19 summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups. RESULTS: Median age and time since surgery were 42 years (IQR 32-54) and 5 years (IQR 2-8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC = 0.76; 95% CI 0.67-0.84) and criterion validity (0.85; 95% CI 0.81-0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51-0.63), health utilities (0.55; 95% CI 0.45-0.65), disability (-0.51; 95% CI -0.41, -0.61), depression (-0.48; 95% CI -0.38, -0.58), and epilepsy severity (-0.48; 95% CI -0.38, -0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28-0.52) and medical treatment satisfaction (0.33; 95% CI 0.21-0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67-0.82), depressed (AUC 0.75; 95% CI 0.67-0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71-0.85) and being more disabled (AUC 0.82; 95% CI 0.74-0.90). SIGNIFICANCE: The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research.

Adults with tuberous sclerosis complex: A distinct patient population.

OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.

The Impact of Stroke Public Awareness Campaigns Differs Between Sociodemographic Groups.

BACKGROUND: Prehospital delays are a major obstacle to timely reperfusion therapy in acute ischemic stroke. Stroke sign recognition, however, remains poor in the community. We present an analysis of repeated surveys to assess the impact of Face, Arm, Speech, Time (FAST) public awareness campaigns on stroke knowledge. METHODS: Four cross-sectional surveys were conducted between July 2016 and January 2019 in the province of Quebec, Canada (n = 2,451). Knowledge of FAST stroke signs (face drooping, arm weakness and speech difficulties) was assessed with open-ended questions. A bilingual English/French FAST public awareness campaign preceded survey waves 1-3 and two campaigns preceded wave 4. We used multivariable ordinal regression models weighted for age and sex to assess FAST stroke sign knowledge. RESULTS: We observed an overall significant improvement of 26% in FAST stroke sign knowledge between survey waves 1 and 4 (odds ratio [OR] = 1.26; 95% CI: 1.02, 1.55; p = 0.035). After the last campaign, however, 30.5% (95% CI: 27.5, 33.6) of people were still unable to name a single FAST sign. Factors associated with worse performance were male sex (OR = 0.68; 95% CI: 0.53, 0.86; p = 0.002) and retirement (OR = 0.54; 95% CI: 0.35, 0.83; p = 0.005). People with lower household income and education had a tendency towards worse stroke sign knowledge and were significantly less aware of the FAST campaigns. CONCLUSIONS: Knowledge of FAST stroke signs in the general population improved after multiple public awareness campaigns, although it remained low overall. Future FAST campaigns should especially target men, retired people and individuals with a lower socioeconomic status.