Cognitive phenotype of childhood myotonic dystrophy type 1: A multicenter pooled analysis.

INTRODUCTION/AIMS: There is clear evidence for brain involvement in childhood myotonic dystrophy type 1 (DM1) from imaging studies and the prevalence of intellectual impairment and neurodevelopmental disorders. The cognitive profile of children with DM1 however is poorly understood. The aim of this study was to assess the cognitive profile of children with DM1. METHODS: Neuropsychological examination reports of 45 children aged 2-17 y were analyzed. All cognitive subtests used in this cohort were pooled in 10 cognitive domains. For every patient a composite z-score was calculated for every assessed domain. Composite scores were classified as average (z > -1), mild cognitive impairment (-1 ≥ z > -2), or major cognitive impairment (z ≤ -2). RESULTS: The nature and extent of neuropsychological examinations differed between centers and patients. The domains with the highest frequency of major cognitive impairment were social cognition (4/9 children tested; 44%), attention (13/32; 41%), and fine motor skills (3/10; 30%). Combining mild and major cognitive impairment, working memory (20/28; 71%), attention (21/32; 66%), and visuospatial functions (16/28; 57%) were the most frequently affected domains. Long-term memory was least affected, with mild impairment only in 5/29 (17%). DISCUSSION: Children with DM1 may have specific cognitive deficits, most frequently affecting working memory, attention, and visuospatial functions, in addition to the previously described global intellectual impairments. We recommend including a standardized neuropsychological examination in the standards of care for DM1 children. Early recognition of cognitive deficits and behavioral disorders in children with DM1 can improve their management.

Assessment of Quality of Life 8-Dimension (AQoL-8D): translation, validation, and application in two Dutch trials in patients with epilepsy and schizophrenia.

BACKGROUND: To translate and linguistically validate the Assessment of Quality of Life 8-dimensions (AQoL-8D) for use in the Netherlands and to compare the psychometric properties of AQoL-8D with the EuroQol 5-dimensions 5-levels (EQ-5D-5L) in two patient samples. METHODS: AQoL-8D was translated from English into Dutch. The translated AQoL-8D was then administered alongside the EQ-5D-5L at baseline and follow-up of two Dutch randomized controlled trials among patients with epilepsy and schizophrenia. These data were subjected to a post-hoc analysis assessing the psychometric properties of AQol-8D vis-à-vis EQ-5D-5L in terms of known-groups construct validity, responsiveness, and floor/ceiling effects. RESULTS: In total, 103 epilepsy patients and 99 schizophrenia patients were included in this study. In both datasets, the two instruments discriminated between known-groups, but in schizophrenia, AQoL-8D showed higher responsiveness than EQ-5D-5L, while both instruments showed equal responsiveness in epilepsy. Ceiling effects were only found for EQ-5D-5L in both epilepsy (26.6%) and schizophrenia (6.1%). CONCLUSION: Our results have shown that, among other things, AQoL-8D presents better ability to discriminate between known-groups and shows no ceiling effect. Based on our results, we would recommend the use of AQoL-8D in addition to EQ-5D-5L in trials assessing patient's quality of life in patients with epilepsy or schizophrenia.

ZMILE, a multicomponent self-management intervention for adults with epilepsy: Rationale and description of the intervention.

OBJECTIVE: In this paper, we aim to provide a comprehensive description of the multicomponent self-management intervention for adults with epilepsy, ZMILE. RATIONALE OR THEORY: Acquiring self-management skills has been shown to play a vital role in enabling patients with epilepsy overcoming (health-related) struggles in daily life and coping with limitations their condition poses on them. ZMILE is a course consisting of education (to increase concordance to treatment), goal-setting (proactive coping), and self-monitoring. RESOURCES NEEDED: The course is guided by two nurse practitioners and each patient is allowed to bring one family member or friend. Self-monitoring plays an important role and can be done through e-Health tools or written diaries. PROCESSES INVOLVED: During and after the course, patients are required to work toward a personally defined goal using a five-step approach by means of pro-active coping. Moreover, patients are expected to use self-monitoring tools to reflect on their own behavior and identify ways to optimize medication intake when required. QUANTIFICATION: ZMILE is provided in an outpatient setting over five weekly group sessions and one booster session. From the start, patients are encouraged to set individual goals. Each group session will have a different theme but part of every session is reflecting on personal goals and to learn from eachother. CONCLUSIONS: The ZMILE-intervention has been evaluated and may be a promising intervention in terms of effectiveness and feasibility for adults with epilepsy, relatives, and professionals. We present the adapted version which can be implemented in clinical practice.

Effectiveness of a multicomponent self-management intervention for adults with epilepsy (ZMILE study): A randomized controlled trial.

BACKGROUND: The objective of the ZMILE study was to compare the effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy (PWE) over a six-month period. METHODS: Participants (PWE & relative) were randomized into intervention or CAU groups. Self-report questionnaires were used to measure disease-specific self-efficacy as the primary outcome measure and general self-efficacy, adherence, seizure severity, emotional functioning, quality of life, proactive coping, and side-effects of antiepileptic drugs (AED) as secondary outcome measures. Instruments used at baseline and during a six-month follow-up period were the following: disease-specific self-efficacy (Epilepsy Self-Efficacy Scale [ESES], General Self-Efficacy Scale [GSES]); adherence (Medication Adherence Scale [MARS] and Medication Event Monitoring System [MEMS]); seizure severity (National Hospital Seizure Severity Scale [NHS3]); emotional well-being (Hospital Anxiety and Depression Scale [HADS]); quality of life (Quality of Life in Epilepsy [QOLIE-31P]); proactive coping (Utrecht Proactive Coping Competence [UPCC]); and side-effects of antiepileptic drugs [SIDAED]. Multilevel analyses were performed, and baseline differences were corrected by inclusion of covariates in the analyses. RESULTS: In total, 102 PWE were included in the study, 52 of whom were in the intervention group. On the SIDAED and on three of the quality of life subscales QOLIE-31P, a significant difference was found (p<0.05) in the intervention group. Self-efficacy, however, showed no significant differences between the MCI and the CAU groups. None of the other outcome measures showed any significant difference between the two groups. SIGNIFICANCE: Although we found no statistically significant difference in the primary outcome measure, disease-specific self-efficacy, this MCI could prove promising, since we found improvement in some domains of quality of life in epilepsy scale and a decrease in AED side-effects in the MCI group compared with the CAU group.

Process evaluation of a multi-component self-management intervention for adults with epilepsy (ZMILE study).

BACKGROUND: People with epilepsy need to monitor and manage their symptoms. They, as well as their relatives, have to deal with the psychological burden, reflected in a reduced quality of life. Support in self-management can be of importance. We have developed a multi-component self-management intervention for patients and their relatives (MCI). This eight-week group intervention is conducted by nurse practitioners and consists of six two-hour sessions. The main components are: 1) providing self-management education, 2) stimulating proactive coping and goal-setting and 3) facilitating peer and social support. This study is a process evaluation to establish the feasibility, fidelity and acceptability of the intervention by assessing performance according to protocol, attendance and adherence, and the opinion of patients, relatives and facilitators about the intervention. METHOD: Study population consists of 52 patients with epilepsy living in the community (e.g. at home), 37 relatives and six facilitators. In this prospective mixed methods study, data were gathered using questionnaires for patients and relatives, registration forms for facilitators and by carrying out semi-structured group interviews with patients, relatives and facilitators. RESULTS: Patients and relatives attended a mean of 5.2 sessions. Forty-seven (90%) patients and 32 (86.5%) relatives attended at least five sessions. The mean group size was 8.1 (SD=1.3; range 6-10). All elements of the intervention were offered to participants, except for one e-Health tool which was only available at the start of the study. Overall, the sessions were considered useful by patients, their relatives and facilitators. The participation of a relative (social support) and sharing ideas and feelings about having epilepsy with peers (peer support) were rated as important aspects. CONCLUSION: This process evaluation revealed that the MCI was largely performed according to protocol, attendance rate was high, and participants and facilitators had, on the whole, a favourable opinion about the MCI, and would recommend it to others with epilepsy and their relatives. Overall, the adherence of patients and relatives was high. The MCI is considered feasible according to patients, relatives and facilitators. Implementation is recommended if the intervention proves to be effective.

An economic evaluation of a multicomponent self-management intervention for adults with epilepsy (ZMILE study).

OBJECTIVE: The objective of this (trial-based) economic evaluation was, from a societal perspective, to compare the cost-effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy over a 12-month period. METHODS: In a randomized-controlled trial, participants were randomized into intervention or CAU group. Adherence, self-efficacy (Epilepsy Self-Efficacy Scale [ESES]), quality-adjusted life years (QALYs), healthcare costs, production losses, and patient and family costs were assessed at baseline and during the 12-month study period. Incremental cost-effectiveness ratios (ICERs) (i.e., cost per increased adherence, self-efficacy, or QALY), and cost-effectiveness acceptability curves were calculated. RESULTS: In total, 102 patients were included in the study, of whom 52 were in the intervention group. Adherence rates over 6 months were 63.7% for the CAU group and 75.9% for the intervention group. Adherence, ESES, and quality of life did not differ significantly between groups. An ICER of €54 per point increase in ESES score at 6 months and €1,105 per point increase at 12-month follow-up was found. The intervention resulted in an ICER of €88 per percentage of adherence increase at 6 months. ICERs of €8,272 and €15,144 per QALY gained were found at 6- and 12-month follow-up, respectively. SIGNIFICANCE: Although no statistically significant difference was found after baseline adjustments, cost-effectiveness estimates for MCI appear promising. As rules of inference are arbitrary, it has been argued that decisions should be based only on the net benefits, irrespective of whether differences are statistically significant. Hence, the MCI may be a cost-effective addition to the current standard care for adults with epilepsy.

Are people with epilepsy using eHealth-tools?

INTRODUCTION: Self-management for people with epilepsy (PWE) should lead to shared decision-making and thus to adherence to the treatment plan. eHealth is an important way of supporting PWE in their self-management. METHOD: In this survey, we used a mixed method to explore the following: 1) which factors were monitored by PWE and how (using pen and paper or eHealth-tools), 2) how many PWE own a computer or smartphone, and 3) how do they perceive the use of eHealth. A consecutive series of 1000 PWE attending the outpatient clinic of a tertiary epilepsy center were asked to fill in a questionnaire. RESULTS: In comparison with the general population, fewer PWE owned a computer or smartphone. They were, however, more likely to self-monitor their health than other patients suffering from a chronic condition. Although PWE did not use eHealth-tools often, they perceived it as a user-friendly tool, promoting health behavior as well as adherence. On the other hand, problems with privacy and the perception that not everyone is able to use eHealth were considered as disadvantages by PWE. Promoting self-care was perceived as both an advantage and a disadvantage. It was seen as an advantage when PWE mentioned the option of eHealth-tools in order to gain insight into one's epilepsy. At the same time, it was seen as a disadvantage because it confronts PWE with their disease, which causes emotional stress. CONCLUSION: The high level of self-monitoring combined with a low usage of eHealth-tools seems to indicate that there is a need for a more tailored approach to stimulate the use of eHealth-tools by PWE. Further research should focus on this aspect, e.g., what PWE need in order to make more use of eHealth-tools in their self-care.

(Cost)-effectiveness of a multi-component intervention for adults with epilepsy: study protocol of a Dutch randomized controlled trial (ZMILE study).

BACKGROUND: In patients with epilepsy, poor adherence to anti-epileptic drugs has been shown to be the most important cause of poorly controlled epilepsy. Furthermore, it has been noted that the quality of life among patients with epilepsy can be improved by counseling and treatments aimed at increasing their self-efficacy and concordance, thus stimulating self-management skills. However, there is a need for evidence on the effectiveness of such programs, especially within epilepsy care. Therefore, we have developed a multi-component intervention (MCI) which combines a self-management/education program with e-Health interventions. Accordingly, the overall objective of this study is to assess the (cost)-effectiveness and feasibility of the MCI, aiming to improve self-efficacy and concordance in patients with epilepsy. METHODS: A RCT in two parallel groups will be conducted to compare the MCI with a control condition in epilepsy patients. One hundred eligible epilepsy patients will be recruited and allocated to either the intervention or control group. The intervention group will receive the MCI consisting of a self-management/education program of six meetings, including e-Health interventions, and will be followed for 12 months. The control group will receive care as usual and will be followed for 6 months, after which patients will be offered the possibility of participating in the MCI. The study will consist of three parts: 1) a clinical effectiveness study, 2) a cost-effectiveness study, and 3) process evaluation. The primary outcome will be self-efficacy. Secondary outcomes include adherence, side effects, change in seizure severity & frequency, improved quality of life, proactive coping, and societal costs. Outcome assessments will be done using questionnaires at baseline and after 3, 6, 9, and 12 months (last two applicable only for intervention group). DISCUSSION: In times of budget constraints, MCI could be a valuable addition to the current healthcare provision for epilepsy, as it is expected that higher concordance and self-efficacy will result in reduced use of healthcare resources and an increased QOL. Accordingly, this study is aimed helping patients to be their own provider of health care, shifting epilepsy management from professionals to self-care by patients equipped with appropriate skills and tools. TRIAL REGISTRATION NUMBER: NTR4484 .

Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity.

BACKGROUND: Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. METHODS AND FINDINGS: Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2)) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV(Mean); 0.55 ± 0.25 versus 0.67 ± 0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). CONCLUSIONS: VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. TRIAL REGISTRATION: The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

Behavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy - a randomized controlled trial.

BACKGROUND/AIMS: In addition to effects on seizure frequency in intractable epilepsy, multiple studies report benefits of vagus nerve stimulation (VNS) on behavioural outcomes and quality of life. The present study aims to investigate the effects of VNS on cognition, mood in general, depression, epilepsy-related restrictions and psychosocial adjustment in children with intractable epilepsy, as well as the relation between these effects and seizure reduction. METHODS: We conducted a randomized, active-controlled, double-blinded, add-on study in 41 children (age 4-18) with medically refractory epilepsy. We performed cognitive and behavioural testing at baseline (12 weeks), at the end of the blinded phase (20 weeks) in children receiving either high-output or low-output (active control) stimulation, and at the end of the open label phase (19 weeks) with all children receiving high-output stimulation. Seizure frequency was recorded using seizure diaries. RESULTS: VNS did not have a negative effect on cognition nor on psychosocial adjustment. At the end of the follow-up phase we noted an improvement of mood in general and the depression subscale for the entire group, unrelated to a reduction of seizure frequency. At the end of the blinded phase a ≥50% reduction of seizure frequency occurred in 16% of the high-stimulation group and 21% of the low-stimulation group. At the end of the open-label follow-up phase, 26% of the children experienced a seizure frequency reduction of 50% or more (responders). CONCLUSIONS: VNS has additional beneficial effects in children with intractable epilepsy. As opposed to anti-epileptic drugs, there are no negative effects on cognition. Moreover, we observed an improvement of mood in general and depressed feelings in particular, irrespective of a reduction in seizure frequency. These beneficial effects should be taken into account when deciding whether to initiate or continue VNS treatment in these children.

Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial.

AIM: The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety. METHOD: In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews. RESULTS: At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001). INTERPRETATION: VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children. Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.

The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice.

INTRODUCTION: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure. METHOD: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment. RESULTS: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant. CONCLUSION: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.