Implementing clinical guidelines.

Clinical guidelines that support practice and improve care are essential in this era of evidence-based medicine. However, implementing this guidance often falls short in practice. Sharing knowledge and auditing practice are important, but not sufficient to implement change. This article brings together evidence from the study of behaviour, education and clinical practice and offers practical tips on how practising neurologists might bring about change in the healthcare environment. Common themes include the importance of team working, multidisciplinary engagement, taking time to identify who and what needs changing, and selecting the most appropriate tool(s) for the job. Engaging with the challenge is generally more rewarding than resisting and is important for the effective provision of care

Non-Hyperammonaemic Valproate encephalopathy after 20 years of treatment.

Sodium valproate is a commonly used antiseizure drug with broad indications for different seizuretypes and epilepsy syndromes. Well-recognised side effects include weight gain, tremor, dizziness, and unsteadiness. Non-hyperammonaemic parkinsonism, with or without cognitive impairment, is a rare adverse effect of sodium valproate. We present the case of a sixty year-old lady with a generalized seizure disorder, treated with phenytoin, valproate, lamotrigine and clonazepam. Following withdrawal of phenytoin she developed an akinetic-rigid syndrome, with ataxia and marked cognitive impairment. Extensive investigation failed to identify a cause. Serum ammonia and valproate levels were normal. Hypothesizing this might be valproate encephalopathy, valproate was rapidly substituted with levetiracetam. Her severe motor symptoms resolved within two weeks and cognitive impairment markedly improved. Valproate-induced encephalopathy, with or without hyperammonaemia and liver toxicity are typically recognizable for their temporal relation between the start of therapy with valproate and emergence of the clinical syndrome. Reversible disorders of motor function and cognition attributable to valproate are well described, but few cases have been reported presenting years after starting treatment. Given the insidious progression, delayed onset, lack of association with drug levels or presence of hyperammonaemia, a high index of suspicion is needed to make the diagnosis

Clinical correlates of memory complaints during AED treatment.

OBJECTIVES: To investigate clinical correlates of memory complaints (MC) during anti-epileptic drug (AEDs) treatment in adults with epilepsy with special attention to the role of depression, using user-friendly standardized clinical instruments which can be adopted in any outpatient setting. MATERIALS & METHODS: Data from a consecutive sample of adult outpatients with epilepsy assessed with the Neurological Disorder Depression Inventory for Epilepsy (NDDIE), the Adverse Event Profile (AEP) and the Emotional Thermometer (ET) were analysed. RESULTS: From a total sample of 443 patients, 28.4% reported MC as 'always' a problem. These patients were less likely to be seizure free (18.3% vs 34.3%; P < 0.001), had a high number of previous AED trials (4 vs 3; P < 0.001) and high AEP total scores (49 vs 34.2; P < 0.001). There was no correlation with specific AED type or combination. Depression was the major determinant with a 2-fold increased risk (95%CI 1.15-3.86; P = 0.016). When depression was already known and under treatment, patients with MC were less likely to be in remission from depression despite antidepressant treatment (11.9% vs 1.6% P < 0.001). Among patients without depression, those reporting MC presented with significantly high scores for depression (3.3 vs 2; t = 3.07; P = 0.003), anxiety (4.5 vs 2.7; t = 4.43; P < 0.001), anger (3 vs 2; t = 2.623; P = 0.009) and distress (3.8 vs 2.2; t = 4.027; P < 0.001) than those without MC. CONCLUSIONS: Depression has to be appropriately treated and full remission from depression should represent the ultimate goal as subthreshold or residual mood and anxiety symptoms can contribute to MC

Subspecialty preferences among Neurologists of the future.

INTRODUCTION: In the era of neurological subspecialization, most neurologists will have a field of specialist interest. The aim of this cross-sectional multi-national study was to identify the key areas of interest among trainees or junior specialists, assess the potential influence of an interest in research, and consider the results in light of population needs. METHODS: A total of 300 residents and junior neurologists who received a bursary to attend the European Academy of Neurology conference were invited to participate in this study. Demographic and work-related characteristics, as well as main subspecialty of choice were examined via an anonymous electronic questionnaire. Participants holding a higher degree (PhD/MD) or working in research posts were considered research oriented. RESULTS: In total, 191 Neurologists in training or junior specialists responded (response rate 63.7%). Full data were available for 187 participants (59.4% females). The study sample had a mean age of 30.5±3.4 years (range 25 - 45). The most popular subspecialty was movement disorders (18.2%), followed by multiple sclerosis (11.2%) and epilepsy (10.2%). This did not differ significantly between the participants who were or were not research-oriented. CONCLUSIONS: There is a potential mismatch between the interests of trainees, and the future needs of the populations they serve, which it is important to identify for workforce planning

Screening of anxiety and quality of life in people with epilepsy.

PURPOSE: Up to 60% of people with epilepsy (PwE) have psychiatric comorbidity including anxiety. Anxiety remains under recognized in PwE. This study investigates if screening tools validated for depression could be used to detect anxiety disorders in PWE. Additionally it analyses the effect of anxiety on QoL. METHOD: 261 participants with a confirmed diagnosis of epilepsy were included. Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Emotional Thermometers (ET), both validated to screen for depression were used. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) with a cut off for moderate and severe anxiety was used as the reference standard. QoL was measured with EQ5-D. Sensitivity, specificity, positive and negative predictive value and ROC analysis as well as multivariate regression analysis were performed. RESULTS: Patients with depression (n=46) were excluded as multivariate regression analysis showed that depression was the only significant determinant of having anxiety in the group. Against HADS-A, NDDI-E and ET-7 showed highest level of accuracy in recognizing anxiety with ET7 being the most effective tool. QoL was significantly reduced in PwE and anxiety. CONCLUSION: Our study showed that reliable screening for moderate to severe anxiety in PwE without co-morbid depression is feasible with screening tools for depression. The cut off values for anxiety are different from those for depression in ET7 but very similar in NDDI-E. ET7 can be applied to screen simultaneously for depression and "pure" anxiety. Anxiety reduces significantly QoL. We recommend screening as an initial first step to rule out patients who are unlikely to have anxiety

Fatigue during treatment with antiepileptic drugs: a levetiracetam specific adverse event?

Purpose To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Methods Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Results Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square = 16.762; df = 3; p = 0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square = 11.462; df = 3; p = 0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square = 11.547; df = 3; p = 0.009). Conclusions One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood

Testing blood and CSF in people with epilepsy: a practical guide.

Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy. Some, such as hypoglycaemia or severe hyponatraemia, can be fatal without prompt identification and treatment. Failure to identify seizures associated with recreational drug or alcohol misuse can lead to inappropriate AED treatment, as well as a missed opportunity for more appropriate intervention. In individuals with established epilepsy on treatment, some laboratory monitoring is desirable at least occasionally, in particular, in relation to bone health, as well as in situations where changes in AED clearance or metabolism are likely (extremes of age, pregnancy, comorbid disorders of renal or hepatic function). For any clinician managing people with epilepsy, awareness of the commoner derangements associated with individual AEDs is essential to guide practice. In this article, we review indications for tests on blood, urine and/or cerebrospinal fluid in patients presenting with new-onset seizures and status epilepticus and in people with established epilepsy presenting acutely or as part of planned monitoring. Important, but rare, neurometabolic and genetic disorders associated with epilepsy are also mentioned

Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6.

OBJECTIVE: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). METHODS: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. RESULTS: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1-56.8) years. Patients had discontinued a median (range) of 4 (0-15) antiseizure medications and were currently taking 3 (0-5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p < .049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. SIGNIFICANCE: Onset of treatment effect occurred within 6-10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16-week trial in most patients

The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus

The Established Status Epilepticus Treatment Trial was a blinded, comparative‐effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine‐refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight‐based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight‐normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54‐1.51) or >90 kg (OR = 0.85, 95% CI = 0.42‐1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings