A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Teaching distinguishing semiological features improves diagnostic accuracy of seizure-like events by emergency physicians.

BACKGROUND: Misdiagnosis of seizure-like events (SLE) in emergency situations is common. Here, we evaluate whether a single, video-based lesson highlighting distinguishing semiological features can improve the diagnostic accuracy of emergency physicians for epileptic seizures (ES), psychogenic non-epileptic seizures (PNES) and syncopes (SY). METHODS: 40 emergency physicians (24 anesthetists, nine surgeons and seven internal medicine specialists by primary specialty) participated in a prospective trial on the diagnostic accuracy of SLE. They assessed video-displayed SLE at two time points: before and after a lecture on distinguishing semiological features. In the lecture, semiological features were demonstrated using patient videos, some were acted by the instructor in addition. The increase in correct diagnoses and recognition of distinguishing semiological features were analyzed. RESULTS: Before the lesson, 45% of 200 SLE-ratings were correct: 15% of SY (n = 40), 30% of PNES (n = 40), 59% of ES (n = 120, focal to bilateral tonic-clonic seizures (FBTCS) 87.5% (n = 40), focal impaired aware seizures (FIAS) 45% (n = 80)). Semiology teaching increased both the rate of correct diagnoses of SLE to overall 79% (p < 0.001) (ES 91% (p < 0.001), FBCTS 98% (n.s.), FIAS 88% (p < 0.001), PNES 88% (p < 0.001), SY 35% (p < 0.001)), and the number of recognized distinguishing semiological features. We identified several semiological features with high entity specific positive predictive values (> 0.8). CONCLUSIONS: A single 45-min video-based lesson highlighting distinguishing semiological features improves the diagnostic accuracy of ES, PNES and SY by emergency physicians. We expect that including this aspect into the curriculum of emergency physicians will lead to better individual patient treatment in pre-hospital medicine and more appropriate subsequent use of clinical resources.

Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication.

BACKGROUND: Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence is highly dependent on the type of tumor, ranging from 10-15% in brain metastases to > 80% in low grade gliomas. Clinical management is challenging and has to take into account aspects beyond the treatment of non-tumoral epilepsy. MAIN BODY: Increasing knowledge about the pathophysiology of BTRE, particularly on glutamatergic mechanisms of oncogenesis and epileptogenesis, might influence management of anti-tumor and BTRE treatment in the future. The first seizure implies the diagnosis of epilepsy in patients with brain tumors. Due to the lack of prospective randomized trials in BTRE, general recommendations for focal epilepsies currently apply concerning the initiation of antiseizure medication (ASM). Non-enzyme inducing ASM is preferable. Prospective trials are needed to evaluate, if AMPA inhibitors like perampanel possess anti-tumor effects. ASM withdrawal has to be weighed very carefully against the risk of seizure recurrence, but can be achievable in selected patients. Permission to drive is possible for some patients with BTRE under well-defined conditions, but requires thorough neurological, radiological, ophthalmological and neuropsychological examination. CONCLUSION: An evolving knowledge on pathophysiology of BTRE might influence future therapy. Randomized trials on ASM in BTRE with reliable endpoints are needed. Management of withdrawal of ASMs and permission to drive demands thorough diagnostic as well as neurooncological and epileptological expertise.

German translation and validation of the brief Epilepsy Anxiety Survey Instrument (brEASI).

BACKGROUND: Anxiety disorders remain undiagnosed in routine clinical practice in up to two thirds of affected patients with epilepsy despite their significant impact on medical and psychosocial outcomes. The study objective was to translate and validate the German 8-item "brief Epilepsy Anxiety Survey Instrument" (brEASI) to facilitate effective screening for the presence of anxiety disorders in German-speaking patients. METHODS: After expert translation into German, the brEASI was completed by consecutive adult inpatients with epilepsy hospitalized for seizures at an academic reference epilepsy center. Patients also completed the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Generalized Anxiety Disorder scale (GAD-7) for external validity, and underwent a standardized interview (Mini-DIPS-OA) as a gold standard to determine the presence of an ICD-10 anxiety disorder (generalized anxiety disorder (GAD), panic disorder, agoraphobia, and social phobia). Receiver operating characteristics (ROC) were calculated to determine the diagnostic accuracy of the brEASI, including the associated area under the curve (AUC) statistics to determine the potential of the brEASI to identify ICD-10 anxiety disorders diagnosed by interview. For comparative purposes, these analyses were also conducted for the GAD-7. RESULTS: Of 80 recruited adult inpatients with epilepsy, 18 (23 %) were found to have a current anxiety disorder through standardized interview. In this study, both brEASI and GAD-7 showed a better diagnostic performance at a cutoff of >5 than at the previously reported cutoff values of >6 and >9, respectively. The AUC of the German brEASI was outstanding (AUC = 0.90, 95 % confidence interval (CI) = 0.82-0.96) for detecting all anxiety disorders and excellent for detecting non-GAD disorders (AUC = 0.85, CI = 0.76-0.92) at a cutoff of >5. At this optimal cutoff of >5 the brEASI demonstrated better sensitivity and specificity (89 % and 84 %) for identifying anxiety disorders than the GAD-7 (83 % and 74 %). The final German version of the brEASI is free to download at https://www.v-neuro.de/veroeffentlichungen/. CONCLUSION: The German version of the brEASI represents a valid and reliable epilepsy-specific anxiety screening instrument. A positive screening result should be followed by further diagnostic procedures. Appropriate therapeutic steps should be initiated if the presence of an anxiety disorder or other psychiatric disorders is confirmed.

Screening for Psychiatric Comorbidities and Psychotherapeutic Assessment in Inpatient Epilepsy Care: Preliminary Results of an Implementation Study.

Background: Anxiety and depression remain underdiagnosed in routine clinical practice in up to two thirds of epilepsy patients despite significant impact on medical and psychosocial outcome. Barriers to adequate mental health care for epilepsy and/or psychogenic non-epileptic seizures (PNES) include a lack of integrated mental health specialists and standardized procedures. This naturalistic study outlines the procedures and outcome of a recently established psychotherapeutic service. Methods: Routine screening included the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, cut-off value > 13) and Generalized Anxiety Disorder scale (GAD-7, cut-off value > 5). Positively (above cut-off in at least one questionnaire) screened patients were seen for a standardized interview for mental health disorders and the development of a personalized treatment plan. PNES patients were seen irrespective of their screening score. Resources were provided to support self-help and access to psychotherapy. Patients were contacted 1 month after discharge to evaluate adherence to therapeutic recommendations. Results: 120 patients were screened. Overall, 56 of 77 positively screened patients (77%) were found to have a psychiatric diagnosis through standardized interview. More epilepsy patients with an anxiety disorder had previously been undiagnosed compared to those with a depressive episode (63% vs. 30%); 24 epilepsy patients (62%) with a psychiatric comorbidity and 10 PNES patients (59%) were not receiving any mental health care. At follow-up, 16/17 (94%) epilepsy patients and 7/7 PNES patients without prior psychiatric treatment were adhering to therapeutic recommendations. Conclusion: Integrating mental health specialists and establishing standardized screening and follow-up procedures improve adherence to mental health care recommendations in epilepsy and PNES patients.

Suggestive seizure induction for inpatients with suspected psychogenic nonepileptic seizures.

OBJECTIVE: To determine the utility of suggestive seizure induction for inpatient work-up of suspected psychogenic nonepileptic seizures (PNES). METHODS: Prospective study of epilepsy center inpatient admissions with suspected PNES. Patients were randomized to undergo suggestive induction first (group A) and then, if necessary, long-term video-electroencephalography (EEG) monitoring, or vice versa (group B). Diagnostic pathways were compared. Potential clinical predictors for diagnostic success were evaluated. RESULTS: Length of in-hospital stay did not significantly differ between groups. Suspicion of PNES was confirmed in 43 of 77 (56%) patients, evenly distributed between group A (22 of 39) and group B (21 of 38). In nine patients, recorded habitual seizures were epileptic and in 25 cases, no diagnostic event could be recorded. Diagnosis of PNES was ascertained primarily by recording a typical seizure through suggestive induction in 24 patients and through long-term monitoring in 19 patients. In group A (induction first), monitoring was not deemed necessary in 21% of cases. In group B (monitoring first), 13% would have remained inconclusive without suggestive induction. Patients who reported triggers to their habitual seizures were not more likely to have spontaneous or provoked PNES during monitoring or suggestive inducion, respectively. Patients with subjective seizure prodromes (auras) were significantly more likely to have a PNES during suggestive induction than those without (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.1-10.4). There was no significant difference in seizure frequency between patients with spontaneous PNES during long-term monitoring and those with nondiagnostic monitoring sessions. SIGNIFICANCE: Our results support the notion that suggestive seizure induction can reduce the number of inconclusive inpatient workups, and can obviate resource-intensive long-term monitoring in one fifth of cases. Patients who are aware of prodromes might have a higher chance of having seizures induced through suggestion.

Practical Management of Epileptic Seizures and Status Epilepticus in Adult Palliative Care Patients.

In terminally ill patients, paroxysmal or episodic changes of consciousness, movements and behavior are frequent. Due to ambiguous appearance, the correct diagnosis of epileptic seizures (ES) and non-epileptic events (NEE) is often difficult. Treatment is frequently complicated by the underlying condition, and an approach indicated in healthier patients may not always be appropriate in the palliative care setting. This article provides recommendations for diagnosis of ES and NEE and treatment options for ES in adult palliative care patients, including aspects of alternative administration routes for antiepileptic drugs such as intranasal, subcutaneous, or rectal application.

Progressive hippocampal sclerosis after viral encephalitis: Potential role of NMDA receptor antibodies.

PURPOSE: Survivors of viral encephalitis can develop refractory epilepsy and hippocampal sclerosis. Both the initial infectious insult and the secondary effects of recurrent seizures have been implicated in chronic disease progression. Recently, post-infectious autoimmunity, involved in acute relapses, has also been proposed as a pathomechanism for chronic disease progression. Our case series suggests a potential role of antibodies against the N-methyl-d-aspartate receptor (NMDAR) in chronic inflammatory disease beyond acute manifestations. METHODS: Retrospective chart review of four patients with epilepsy, hippocampal sclerosis following viral encephalitis and NMDAR-antibodies in CSF. RESULTS: The four patients were female, developed hippocampal sclerosis (in 3/4 in a step-wise progression) after Herpes simplex or Varicella zoster virus encephalitis and harboured immunoglobulin G antibodies against the NMDAR in their CSF. Two patients were treated with short-term immunosuppression but did not benefit. CONCLUSION: This case series presents the first tentative evidence in support of chronic autoimmune inflammation driving disease progression after viral encephalitis beyond the known acute immune-mediated relapses. The anecdotal nature of the data does not, however, permit conclusive judgement on causality. Should our findings be replicated in larger cohorts, the treatment of post-infectious epilepsy could potentially be expanded to include immunosuppressive strategies in antibody-positive cases.

Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty.

Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0±12.9years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force report's utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic ("negative") VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency.

Paroxysmal belching: Epileptic or nonepileptic?

The prevalence and localizing value of ictal belching are yet unknown. We present the case of a patient with medically refractory focal epilepsy with simple and complex partial seizures, as well as generalized seizures. One presumed seizure type comprised frequent episodes of repetitive belching. Video-EEG monitoring during these attacks showed no ictal changes. The belching episodes were inducible and terminable through suggestion. The diagnosis of excessive supragastric belching, a previously described psychogenic condition, was made.

Two different phenomena in basic motor speech performance in premanifest Huntington disease.

OBJECTIVE: Dysarthria is a common feature in Huntington disease (HD). The aim of this cross-sectional pilot study was the description and objective analysis of different speech parameters with special emphasis on the aspect of speech timing of connected speech and nonspeech verbal utterances in premanifest HD (preHD). METHODS: A total of 28 preHD mutation carriers and 28 age- and sex-matched healthy speakers had to perform a reading task and several syllable repetition tasks. Results of computerized acoustic analysis of different variables for the measurement of speech rate and regularity were correlated with clinical measures and MRI-based brain atrophy assessment by voxel-based morphometry. RESULTS: An impaired capacity to steadily repeat single syllables with higher variations in preHD compared to healthy controls was found (variance 1: Cohen d = 1.46). Notably, speech rate was increased compared to controls and showed correlations to the volume of certain brain areas known to be involved in the sensory-motor speech networks (net speech rate: Cohen d = 1.19). Furthermore, speech rate showed correlations to disease burden score, probability of disease onset, the estimated years to onset, and clinical measures like the cognitive score. CONCLUSIONS: Measurement of speech rate and regularity might be helpful additional tools for the monitoring of subclinical functional disability in preHD. As one of the possible causes for higher performance in preHD, we discuss huntingtin-dependent temporarily advantageous development processes of the brain.

A systematic review of suggestive seizure induction for the diagnosis of psychogenic nonepileptic seizures.

Suggestive seizure induction is a widely used method for diagnosing psychogenic nonepileptic seizures (PNES). Despite seven decades of multidisciplinary research, however, there is still no unified protocol, no definitive agreement on the ethical framework and no consensus on diagnostic utility. This systematic review surveys the evidence at hand and addresses clinically relevant aspects of suggestive seizure induction. In addition to its use for facilitating the diagnostic process, its mechanism of action and utility in elucidating the psychopathology of PNES will be discussed.

Hyperventilation and photic stimulation are useful additions to a placebo-based suggestive seizure induction protocol in patients with psychogenic nonepileptic seizures.

The early and definitive diagnosis of psychogenic nonepileptic seizures is a common challenge in epileptology practice. Suggestive seizure induction is a valuable tool to aid the differentiation between epileptic and psychogenic nonepileptic seizures, especially when long-term video-EEG monitoring is inconclusive or unavailable. In this retrospective analysis, we compared the diagnostic yield of a classical, placebo-based induction protocol with that of an extended protocol that includes hyperventilation and photic stimulation as means of suggestion while also implementing more open, standardized patient information. We investigated whether the diversification of suggestive seizure induction has an effect on diagnostic yield and whether it preempts the administration of placebo. Data from 52 patients with confirmed psychogenic nonepileptic seizures were analyzed. While suggestive seizure induction using only placebo-based suggestion provoked a typical event in 13 of 20 patients (65%), the extended protocol was positive in 27 of 34 cases (84%); this improvement was not significant (p=0.11). Noninvasive suggestion techniques accounted for 78% of inductions, avoiding placebo administration in a majority of patients. Still, placebo remains an important part of suggestive seizure induction, responsible for 22% (6 out of 27) of successful inductions using our extended protocol. Our study demonstrates that the diversification of suggestive seizure induction is feasible and beneficial for both patients and diagnosticians.

Effect of subthalamic stimulation on voice and speech in Parkinson's disease: for the better or worse?

BACKGROUND: Deep brain stimulation of the subthalamic nucleus, although highly effective for the treatment of motor impairment in Parkinson's disease (PD), can induce speech deterioration in a subgroup of patients. The aim of the current study was to survey (1) if there are distinctive stimulation effects on the different parameters of voice and speech and (2) if there is a special pattern of preexisting speech abnormalities indicating a risk for further worsening under stimulation. METHODS: N = 38 patients with PD had to perform a speech test without medication with stimulation ON (StimON) and stimulation OFF (StimOFF). Speech samples were analyzed: (1) according to a four-dimensional perceptual speech score and (2) by acoustic analysis to obtain quantifiable measures of distinctive speech parameters. RESULTS: Quality of voice was ameliorated with StimON, and there were trends of increased loudness and better pitch variability. N = 8 patients featured a deterioration of speech with StimON, caused by worsening of articulation or/and fluency. These patients already had more severe overall speech impairment with characteristic features of articulatory slurring and articulatory acceleration under StimOFF condition. CONCLUSION: The influence of subthalamic StimON Parkinsonian speech differs considerably between individual patients, however, there is a trend to amelioration of voice quality and prosody. Patients with stimulation-associated speech deterioration featured higher overall speech impairment and showed a distinctive pattern of articulatory abnormalities at baseline. Further investigations to confirm these preliminary findings are necessary to allow neurologists to pre-surgically estimate the individual risk of deterioration of speech under stimulation.

Impairment of vowel articulation as a possible marker of disease progression in Parkinson's disease.

PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD) shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male) and 40 healthy speakers (20 male) were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA) and vowel articulation index (VAI). Measurement of tVSA and VAI were based upon analysis of the first and second formant of the vowels /α/, /i/and /u/ extracted from defined words within the text. RESULTS: At first visit, VAI values were reduced in male and female PD patients as compared to the control group, and showed a further decrease at the second visit. Only in female Parkinsonian speakers, VAI was correlated to overall speech impairment based upon perceptual impression. VAI and tVSA were correlated to gait impairment, but no correlations were seen between VAI and global motor impairment or overall disease duration. tVSA showed a similar reduction in the PD as compared to the control group and was also found to further decline between first and second examination in female, but not in male speakers with PD. CONCLUSIONS: Measurement of VAI seems to be superior to tVSA in the description of impaired vowel articulation and its further decline in the course of the disease in PD. Since impairment of vowel articulation was found to be independent from global motor function but correlated to gait dysfunction, measurement of vowel articulation might have a potential to serve as a marker of axial disease progression.

Instability of syllable repetition in progressive supranuclear palsy.

Dysarthria is a prominent feature of progressive supranuclear palsy (PSP) and consists--amongst other features--of impaired speech fluency. Since in Parkinson's disease (PD) steadiness of syllable repetition in the course of the performance has been shown to be impaired, the aim of the present study was to investigate if measurement of syllable repetition shows similar or even more pronounced abnormalities in PSP. Thirty six patients with the clinical diagnosis of PSP (16 PSP-Richardson syndrome/PSP-RS and 20 PSP-parkinsonism/PSP-P), 60 patients with PD and 32 healthy speakers were tested. Participants had to repeat a single syllable in a self chosen isochronous pace. Percental coefficient of variance (COV) of interval length was measured for description of pace stability throughout the performance. All patients were tested according to Unified Parkinson's Disease Rating Scale (UPDRS III). Patients with PSP were additionally scored according to PSP rating scale (PSPRS). In the PSP group, COV was significantly worse not only when compared with healthy speakers but also when compared with PD patients of similar disease duration and similar global motor impairment. COV showed only a trend to higher values in the subgroup with PSP-RS as compared to PSP-P. In the PSP-P, but not in the PSP-RS subgroup, there was a positive correlation between COV and PSPRS/UPDRS III. PSP patients feature more pronounced difficulties in the steady syllable repetition than patients with PD and healthy controls as a hint for a more profound dysfunction of basal motor speech performance in PSP than in PD.

Intonation and speech rate in Parkinson's disease: general and dynamic aspects and responsiveness to levodopa admission.

OBJECTIVE: The aim of our study was the analysis of fundamental frequency (F(0)) variability (fundamental frequency standard deviation [F(0)SD]) and net speech rate (NSR) in the course of reading in Parkinsonian patients' speech, with special emphasis on the changes of F(0)SD and NSR from the first to the last sentence of the task. PATIENTS AND METHODS: We examined 138 patients with Parkinson's disease (PD) and 50 age-matched control persons using a standardized reading task with subsequent acoustical analysis of F(0)SD and NSR. A subgroup of 20 PD patients underwent a standardized levodopa challenge. RESULTS: F(0)SD in PD patients was significantly reduced compared with the control group when based on the measurement of the entire reading task. Furthermore, in the PD group, NSR and F(0)SD showed significant changes from the first to the last sentence of the reading task, but no correlation was seen between NSR and F(0)SD. Standardized levodopa administration had no effect on NSR and F(0)SD when related to the entire reading passage, but the aforementioned decline of F(0) variability in the course of reading seemed to be counterbalanced by levodopa administration. CONCLUSIONS: In this large series of PD patients, previous findings of reduced F(0)SD in PD were confirmed. Additionally, this is the first analysis to show an increasing reduction of F(0) variability in the course of reading mirroring abnormalities in the dynamical aspects of speech in PD. According to the results of the levodopa challenge, dopaminergic stimulation seems to ameliorate dynamic intonation changes over time, whereas overall intonation variability might be a PD symptom independent of dopaminergic control.