The role of evidence-based guidelines in the diagnosis and treatment of functional neurological disorder

Evidence-based clinical practice guidelines, based on systematic reviews of existing evidence, play an important role in improving and standardizing the quality of patient care in many medical and psychiatric disorders, and could play an important role in the diagnosis and treatment of functional seizures and other functional neurological disorder (FND) subtypes. There are several reasons to think that evidence-based guidelines might be especially beneficial for the management of FND. In particular, the interdisciplinary and multidisciplinary teamwork necessary for the care of people with FND, the current lack of formal clinical training in FND, and the rapidly expanding body of evidence relating to FND all make guidelines based on systematic literature reviews especially valuable. In this perspective piece, we review clinical practice guidelines, their advantages and limitations, the reasons why evidence-based guidelines might be especially beneficial in the diagnosis and treatment of FND, and the steps that must be taken to create such guidelines for FND. We propose that professional organizations such as the American Academy of Neurology and the American Psychiatric Association undertake guideline development, ideally to create a co-authored or jointly endorsed set of guidelines that can set standards for interdisciplinary care for neurologists and mental health clinicians alike

Driving a motor vehicle and psychogenic nonepileptic seizures: ILAE Report by the Task Force on Psychogenic Nonepileptic Seizures

Objectives This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about “driving and psychogenic nonepileptic seizures (PNES)”; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. Methods Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. Results Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES‐related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty‐six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as “active” if the last psychogenic seizure had occurred within 6 months. Significance Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice

Effectiveness and tolerability of 12-Month Brivaracetam in the real world: EXPERIENCE, an international pooled analysis of individual patient records

Background and Objective Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. Methods EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. Results Analyses included 1644 adults. At baseline, 72.0% were 16–49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. Conclusions This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population

Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis

Background: People with language problems following stroke (aphasia) benefit from speech and language therapy. Optimising speech and language therapy for aphasia recovery is a research priority. Objectives: The objectives were to explore patterns and predictors of language and communication recovery, optimum speech and language therapy intervention provision, and whether or not effectiveness varies by participant subgroup or language domain. Design: This research comprised a systematic review, a meta-analysis and a network meta-analysis of individual participant data. Setting: Participant data were collected in research and clinical settings. Interventions: The intervention under investigation was speech and language therapy for aphasia after stroke. Main outcome measures: The main outcome measures were absolute changes in language scores from baseline on overall language ability, auditory comprehension, spoken language, reading comprehension, writing and functional communication. Data sources and participants: Electronic databases were systematically searched, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Linguistic and Language Behavior Abstracts and SpeechBITE (searched from inception to 2015). The results were screened for eligibility, and published and unpublished data sets (randomised controlled trials, non-randomised controlled trials, cohort studies, case series, registries) with at least 10 individual participant data reporting aphasia duration and severity were identified. Existing collaborators and primary researchers named in identified records were invited to contribute electronic data sets. Individual participant data in the public domain were extracted. Review methods: Data on demographics, speech and language therapy interventions, outcomes and quality criteria were independently extracted by two reviewers, or available as individual participant data data sets. Meta-analysis and network meta-analysis were used to generate hypotheses. Results: We retrieved 5928 individual participant data from 174 data sets across 28 countries, comprising 75 electronic (3940 individual participant data), 47 randomised controlled trial (1778 individual participant data) and 91 speech and language therapy intervention (2746 individual participant data) data sets. The median participant age was 63 years (interquartile range 53–72 years). We identified 53 unavailable, but potentially eligible, randomised controlled trials (46 of these appeared to include speech and language therapy). Relevant individual participant data were filtered into each analysis. Statistically significant predictors of recovery included age (functional communication, individual participant data: 532, n = 14 randomised controlled trials) and sex (overall language ability, individual participant data: 482, n = 11 randomised controlled trials; functional communication, individual participant data: 532, n = 14 randomised controlled trials). Older age and being a longer time since aphasia onset predicted poorer recovery. A negative relationship between baseline severity score and change from baseline (p < 0.0001) may reflect the reduced improvement possible from high baseline scores. The frequency, duration, intensity and dosage of speech and language therapy were variously associated with auditory comprehension, naming and functional communication recovery. There were insufficient data to examine spontaneous recovery. The greatest overall gains in language ability [14.95 points (95% confidence interval 8.7 to 21.2 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.78 points (95% confidence interval 0.48 to 1.1 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with receiving speech and language therapy 4 to 5 days weekly; for auditory comprehension [5.86 points (95% confidence interval 1.6 to 10.0 points) on the Aachen Aphasia Test-Token Test], the greatest gains were associated with receiving speech and language therapy 3 to 4 days weekly. The greatest overall gains in language ability [15.9 points (95% confidence interval 8.0 to 23.6 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.77 points (95% confidence interval 0.36 to 1.2 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with speech and language therapy participation from 2 to 4 (and more than 9) hours weekly, whereas the highest auditory comprehension gains [7.3 points (95% confidence interval 4.1 to 10.5 points) on the Aachen Aphasia Test-Token Test] were associated with speech and language therapy participation in excess of 9 hours weekly (with similar gains notes for 4 hours weekly). While clinically similar gains were made alongside different speech and language therapy intensities, the greatest overall gains in language ability [18.37 points (95% confidence interval 10.58 to 26.16 points) on the Western Aphasia Battery-Aphasia Quotient] and auditory comprehension [5.23 points (95% confidence interval 1.51 to 8.95 points) on the Aachen Aphasia Test-Token Test] were associated with 20–50 hours of speech and language therapy. Network meta-analyses on naming and the duration of speech and language therapy interventions across language outcomes were unstable. Relative variance was acceptable (< 30%). Subgroups may benefit from specific interventions. Limitations: Data sets were graded as being at a low risk of bias but were predominantly based on highly selected research participants, assessments and interventions, thereby limiting generalisability. Conclusions: Frequency, intensity and dosage were associated with language gains from baseline, but varied by domain and subgroup. Future work: These exploratory findings require confirmatory study designs to test the hypotheses generated and to develop more tailored speech and language therapy interventions. Study registration: This study is registered as PROSPERO CRD42018110947. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 28. See the NIHR Journals Library website for further project information. Funding was also provided by The Tavistock Trust for Aphasia

Bilateral independent periodic discharges are associated with electrographic seizures and poor outcome: A case-control study

Objective: To determine the clinical correlates bilateral independent periodic discharges (BIPDs) and their association with electrographic seizures and outcome. Methods: Retrospective case-control study of patients with BIPDs compared to patients without periodic discharges (“No PDs”) and patients with lateralized periodic discharges (“LPDs”), matched for age, etiology and level of alertness. Results: We included 85 cases and 85 controls in each group. The most frequent etiologies of BIPDs were stroke, CNS infections, and anoxic brain injury. Acute bilateral cerebral injury was more common in the BIPDs group than in the No PDs and LPDs groups (70% vs. 37% vs. 35%). Electrographic seizures were more common with BIPDs than in the absence of PDs (45% vs. 8%), but not than with LPDs (52%). Mortality was higher in the BIPDs group (36%) than in the No PDs group (18%), with fewer patients with BIPDs achieving good outcome (moderate disability or better; 18% vs. 36%), but not than in the LPDs group (24% mortality, 26% good outcome). In multivariate analyses, BIPDs remained associated with mortality (OR: 3.0 [1.4–6.4]) and poor outcome (OR: 2.9 [1.4–6.2]). Conclusion: BIPDs are caused by bilateral acute brain injury and are associated with a high risk of electrographic seizures and of poor outcome. Significance: BIPDs are uncommon but their identification in critically ill patients has potential important implications, both in terms of clinical management and prognostication.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Generalized periodic discharges and 'triphasic waves': A blinded evaluation of inter-rater agreement and clinical significance

Objectives: Generalized periodic discharges (GPDs) are associated with nonconvulsive seizures. Triphasic waves (TWs), a subtype of GPDs, have been described in relation to metabolic encephalopathy and not felt to be associated with seizures. We sought to establish the consistency of use of this descriptive term and its association with seizures. Methods: 11 experts in continuous EEG monitoring scored 20 cEEG samples containing GPDs using Standardized Critical Care EEG Terminology. In the absence of patient information, the inter-rater agreement (IRA) for EEG descriptors including TWs was assessed along with raters' clinical EEG interpretation and compared with actual patient information. Results: The IRA for 'generalized' and 'periodic' was near-perfect (kappa = 0.81), but fair for 'triphasic' (kappa = 0.33). Patients with TWs were as likely to develop seizures as those without (25% vs 26%, N.S.) and surprisingly, patients with TWs were less likely to have toxic-metabolic encephalopathy than those without TWs (55% vs 79%, p < 0.01). Conclusions: While IRA for the terms "generalized" and "periodic" is high, it is only fair for TWs. EEG interpreted as TWs presents similar risk for seizures as GPDs without triphasic appearance. GPDs are commonly associated with metabolic encephalopathy, but 'triphasic' appearance is not predictive. Significance: Conventional association of 'triphasic waves' with specific clinical conditions may lead to inaccurate EEG interpretation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study

Purpose To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key Findings Permanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control ("possible" or "likely" responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9 mg/kg/h, when ketamine was introduced at least 8 days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24 h of ketamine initiation (16% vs. 56%, p = 0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE. © 2013 International League Against Epilepsy.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe