Concurrent inflammation-related brain reorganization in multiple sclerosis and depression.

BACKGROUND: Neuroinflammation affects brain tissue integrity in multiple sclerosis (MS) and may have a role in major depressive disorder (MDD). Whether advanced magnetic resonance imaging characteristics of the gray-to-white matter border serve as proxy of neuroinflammatory activity in MDD and MS remain unknown. METHODS: We included 684 participants (132 MDD patients with recurrent depressive episodes (RDE), 70 MDD patients with a single depressive episode (SDE), 222 MS patients without depressive symptoms (nMS), 58 MS patients with depressive symptoms (dMS), and 202 healthy controls (HC)). 3 T-T1w MRI-derived gray-to-white matter contrast (GWc) was used to reconstruct and characterize connectivity alterations of GWc-covariance networks by means of modularity, clustering coefficient, and degree. A cross-validated support vector machine was used to test the ability of GWc to stratify groups according to their depression symptoms, measured with BDI, at the single-subject level in MS and MDD independently. FINDINGS: MS and MDD patients showed increased modularity (ANOVA partial-η2 = 0.3) and clustering (partial-η2 = 0.1) compared to HC. In the subgroups, a linear trend analysis attested a gradient of modularity increases in the form: HC, dMS, nMS, SDE, and RDE (ANOVA partial-η2 = 0.28, p < 0.001) while this trend was less evident for clustering coefficient. Reduced morphological integrity (GWc) was seen in patients with increased depressive symptoms (partial-η2 = 0.42, P < 0.001) and was associated with depression scores across patient groups (r = -0.2, P < 0.001). Depressive symptoms in MS were robustly classified (88 %). CONCLUSIONS: Similar structural network alterations in MDD and MS exist, suggesting possible common inflammatory events like demyelination, neuroinflammation that are caught by GWc analyses. These alterations may vary depending on the severity of symptoms and in the case of MS may elucidate the occurrence of comorbid depression.

Favorable combinations of antiseizure medication with vagus nerve stimulation to improve health-related quality of life in patients with epilepsy.

BACKGROUND: Vagus nerve stimulation (VNS) is a non-pharmacological treatment of refractory epilepsy, which also has an antidepressive effect. The favorable combinations of VNS with specific mechanisms of action of antiseizure medication (ASM) on mood and health-related quality of life (HrQol) have not yet been studied. The objective was to identify favourable combinations of specific ASMs with VNS for the HrQoL and depression in refractory epilepsy. METHODS: We performed an observational study including patients with refractory epilepsy and an implanted VNS (N = 151). In the first 24 months after VNS implantation, all patients were on stable ASM therapy. We used the standardized questionnaires QOLIE10, EQVAS and EQ5D to evaluate HrQoL as well as the Beck Depression Inventory (BDI). Multiple regression analysis was performed to evaluate the synergistic combinations of ASM with VNS for HrQoL. RESULTS: At the year-two follow-up (N = 151, age 45.2 ± 17.0 years), significant improvement (p < 0.05) in BDI scores was found for combination of VNS with SV2A modulators (58.4 %) or AMPA antagonists (44.4 %). A significant increase of HrQoL by at least 30 % (p < 0.05) was measured for a combination of VNS with SV2A modulators (brivaracetam, levetiracetam) or slow sodium channel inhibitors (eslicarbazepine, lacosamide). CONCLUSION: The results of our study suggests a favorable effect of the combination of SV2A modulators or slow sodium channel inhibitors with VNS on the HrQoL in comparison to other ASMs. Besides the possible synergistic effects on the seizure frequency, the amelioration of behavioral side effects of SV2A modulators by VNS is an important factor of HrQoL-improvement in these combinations.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Dynamic flexibility and controllability of network communities in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most common syndrome within the idiopathic generalized epilepsy spectrum, manifested by myoclonic and generalized tonic-clonic seizures and spike-and-wave discharges (SWDs) on electroencephalography (EEG). Currently, the pathophysiological concepts addressing SWD generation in JME are still incomplete. In this work, we characterize the temporal and spatial organization of functional networks and their dynamic properties as derived from high-density EEG (hdEEG) recordings and MRI in 40 JME patients (25.4 ± 7.6 years, 25 females). The adopted approach allows for the construction of a precise dynamic model of ictal transformation in JME at the cortical and deep brain nuclei source levels. We implement Louvain algorithm to attribute brain regions with similar topological properties to modules during separate time windows before and during SWD generation. Afterwards, we quantify how modular assignments evolve and steer through different states towards the ictal state by measuring characteristics of flexibility and controllability. We find antagonistic dynamics of flexibility and controllability within network modules as they evolve towards and undergo ictal transformation. Prior to SWD generation, we observe concomitantly increasing flexibility (F(1,39) = 25.3, corrected p < 0.001) and decreasing controllability (F(1,39) = 55.3, p < 0.001) within the fronto-parietal module in γ-band. On a step further, during interictal SWDs as compared to preceding time windows, we notice decreasing flexibility (F(1,39) = 11.9, p < 0.001) and increasing controllability (F(1,39) = 10.1, p < 0.001) within the fronto-temporal module in γ-band. During ictal SWDs as compared to prior time windows, we demonstrate significantly decreasing flexibility (F(1,14) = 31.6; p < 0.001) and increasing controllability (F(1,14) = 44.7, p < 0.001) within the basal ganglia module. Furthermore, we show that flexibility and controllability within the fronto-temporal module of the interictal SWDs relate to seizure frequency and cognitive performance in JME patients. Our results demonstrate that detection of network modules and quantification of their dynamic properties is relevant to track the generation of SWDs. The observed flexibility and controllability dynamics reflect the reorganization of de-/synchronized connections and the ability of evolving network modules to reach a seizure-free state, respectively. These findings may advance the elaboration of network-based biomarkers and more targeted therapeutic neuromodulatory approaches in JME.

Screening for health-related quality of life and its determinants in Fabry disease: A cross-sectional multicenter study.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. In order to improve health care of FD-patients, knowledge of its predictors is important. The aim of our study was to evaluate health-related quality of life (HrQol) in FD and to identify its independent determinants by exploring a wide range of demographic, social and clinical parameters. RESULTS: In this cross-sectional multicenter study, 135 adult patients with FD were recruited at three specialized European centers in Germany and Switzerland. Demographics, social status and clinical parameters as well as data on HrQol (EQ5D, EQ VAS) and depression were collected by means of self-reporting questionnaires and confirmed by medical records. HrQol and its predictors were evaluated by univariate and multivariate regression analyses. The study population consisted of 78 female and 57 male FD patients (median age 48 yrs) of whom 80.7% (N = 109) were on enzyme replacement therapy (ERT) and 10.4% (N = 14) were on chaperone treatment. Univariate analysis revealed various factors reducing HrQol such as age > 40 years, classic phenotype, organ involvement (kidney and heart disease, stroke/transient ischemic attack (TIA), gastrointestinal disturbances), depression, and burning limb pain. However, only the following factors were identified as independent predictors of decreased HrQol: classic phenotype, kidney and heart disease, stroke/TIA, depression, and burning limb pain. ERT and chaperone therapy were independent determinants of increased HrQol. CONCLUSIONS: Modifiable factors, such as burning limb pain and depression, identified as independent predictors of HrQol-deterioration should be addressed in programs aiming to improve HrQol in FD. A multidisciplinary approach is essential in FD-patients since diverse organ involvement prominently compromises HrQol in affected patients. Our findings showed that the classic phenotype is a strong predictor of worsening HrQol.

Characterizing the individual course of health-related quality of life after subarachnoid haemorrhage: Latent growth mixture modelling.

BACKGROUND: Survivors of aneurysmal subarachnoid haemorrhage (SAH) show heterogeneous profiles of health-related quality of life (HrQoL). The aim of this study was to characterize individual differences in the course of HrQoL following SAH using latent growth mixture modelling (LGMM). METHODS: A longitudinal study with 113 incident cases of aneurysmal SAH was performed in order to evaluate clinical outcome (Hunt and Hess scale, Barthel-Index, Beck Depression Inventory) and HrQoL data (EQ-5D) at baseline, 6 and 12 months. The heterogeneity in HrQoL courses after SAH was analysed using LGMM. RESULTS: Four subgroups (classes) of different patterns of HrQoL course after SAH were identified. Two of these classes (1 and 3) comprised patients with considerably reduced initial HrQoL, which was associated with more severe symptoms of SAH. Class 1 showing the worst EQ5D-index values during the entire study period. Class 3 experiencing a considerable improvement in HrQoL values. In comparison to classes 1 and 3, class 2 and 4 were characterized by less severe SAH and better functional outcome. An important difference in the disease course between classes 2 and 4 was a temporary increase in depression scores at the 6-month time point in class 4, which was associated with a considerable reduction in HrQoL.The specific clinical parameters characterizing differences between classes, such as severity of SAH, functional outcome, cognitive impairment and post-stroke depression, were identified and the influence of their potential improvement on HrQoL was estimated. CONCLUSION: By means of LGMM we could classify the course of HrQoL after SAH in four different patterns, which are relevant for the clinical decisions. Clinical parameters, which can be modified in order to improve the course of HrQoL were identified and could help to develop individual therapeutic strategies for the rehabilitation after SAH.

Relative importance of clinical outcomes and safety risks of antiseizure medication monotherapy for patients and physicians: Discrete choice experiment eliciting preferences in real-world study "VOTE".

OBJECTIVE: This study was undertaken to elicit patients' preferences for attributes characterizing antiseizure medication (ASM) monotherapy options before treatment consultation, and to explore the trade-offs patients consider between treatment efficacy and risks of side effects. Further objectives were to explore how treatment consultation may affect patient preferences, to elicit physicians' preferences in selecting treatment, and to compare patient and physician preferences for treatment. METHODS: This prospective, observational study (EP0076; VOTE) included adults with focal seizures requiring a change in their ASM monotherapy. Patients completed a discrete choice experiment (DCE) survey before and after treatment consultation. Physicians completed a similar survey after the consultation. The DCE comprised 12 choices between two hypothetical treatments defined by seven attributes. The conditional relative importance of each attribute was calculated. RESULTS: Three hundred ten patients (mean [SD] age = 46.8 [18.3] years, 52.3% female) were enrolled from eight European countries, of whom 305 completed the survey before consultation and 273 completed the survey before and after consultation. Overall, this preference study in patients who intended to receive a new ASM monotherapy suggests that patient preferences were ordered as expected, with better outcomes being preferred to worse outcomes; patients preferred a higher chance of seizure freedom, lower risk of developing clinical depression, and fewer severe adverse events; avoiding moderate-to-severe "trouble thinking clearly" was more important than avoiding any other side effect. There were qualitative differences in what patients and physicians considered to be the most important aspects of treatment for patients; compared with patients, physicians had a qualitatively stronger preference for greater chance of seizure freedom and avoiding personality changes. Patients' preference weights were qualitatively similar before and after treatment consultation. SIGNIFICANCE: For patients, seizure freedom and avoiding trouble thinking clearly were the most important treatment attributes. Physicians and patients may differ in the emphasis they place on specific attributes.

Altered grey matter integrity and network vulnerability relate to epilepsy occurrence in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the relevance of compartmentalized grey matter (GM) pathology and network reorganization in multiple sclerosis (MS) patients with concomitant epilepsy. METHODS: From 3-T magnetic resonance imaging scans of 30 MS patients with epilepsy (MSE group; age 41 ± 15 years, 21 females, disease duration 8 ± 6 years, median Expanded Disability Status Scale [EDSS] score 3), 60 MS patients without epilepsy (MS group; age 41 ± 12 years, 35 females, disease duration 6 ± 4 years, EDSS score 2), and 60 healthy subjects (HS group; age 40 ± 13 years, 27 females) the regional volumes of GM lesions and of cortical, subcortical and hippocampal structures were quantified. Network topology and vulnerability were modelled within the graph theoretical framework. Receiver-operating characteristic (ROC) curve analysis was applied to assess the accuracy of GM pathology measures to discriminate between MSE and MS patients. RESULTS: Higher lesion volumes within the hippocampus, mesiotemporal cortex and amygdala were detected in the MSE compared to the MS group (all p < 0.05). The MSE group had lower cortical volumes mainly in temporal and parietal areas compared to the MS and HS groups (all p < 0.05). Lower hippocampal tail and presubiculum volumes were identified in both the MSE and MS groups compared to the HS group (all p < 0.05). Network topology in the MSE group was characterized by higher transitivity and assortativity, and higher vulnerability compared to the MS and HS groups (all p < 0.05). Hippocampal lesion volume yielded the highest accuracy (area under the ROC curve 0.80 [0.67-0.91]) in discriminating between MSE and MS patients. CONCLUSIONS: High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with a greater propensity for epilepsy occurrence in people with MS.

Quality of Life and Resilience of Patients With Juvenile Stroke: A Systematic Review.

BACKGROUND: The incidence of juvenile stroke is increasing. Considering younger age of patients and the potential long-lasting disability, the consequences of juvenile stroke may have a greater societal impact than those of stroke in elder population. METHODS: A systematic review was performed in order to evaluate quality of life in juvenile stroke. All studies on quality of life in juvenile stroke published in PUBMED before March 1st, 2020. The search terms were "stroke", "juvenile", "young", "adult", "quality of life" and "resilience" were considered. After the abstract evaluation of 748 hits only six studies we identified as appropriate for the review. The age criterion for juvenile stroke was set as 55 years and younger. RESULTS: The studies have shown a decline of quality of life in at least 46% of patients with juvenile stroke. On average, quality of life was reduced by 37%. The following domains as measured on SF-36 were particularly impaired: physical role, physical functioning and emotional role. The factors influencing the quality of life in juvenile stroke were ability to return to work, post-stroke depression, functional outcome, level of education and age of stroke onset. CONCLUSIONS: This systematic review shows a decline of quality of life in patients with juvenile stroke. Rehabilitation programs should consider the factors influencing quality of life in these patients in order to improve outcome of juvenile stroke. Patients who are unable to return to work should receive necessary social support. In addition, our data underline the importance of screening procedures for post-stroke depression in this population.

Effectiveness of eslicarbazepine acetate in dependency of baseline anticonvulsant therapy: Results from a German prospective multicenter clinical practice study.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.

Health-related quality of life in patients with poststroke epilepsy.

BACKGROUND: Lesional epilepsy is an important long-term sequela of stroke. Data on health-related quality of life (HrQoL) in patients with poststroke epilepsy are limited. We investigated HrQoL in patients with epilepsy after ischemic stroke and identified independent HrQoL-determinants. METHODS AND PATIENTS: All patients with acute ischemic stroke, who were permanent residents in the district Marburg-Biedenkopf (Hessia, Germany, reference population 240,000 inhabitants) were recruited within 12months in the population-based Marburg Stroke Register (MARSTREG). Follow-up visits were performed after 6, 12, and 24months, and patients who developed poststroke epilepsy were identified. Data on demographics, antiepileptic drugs (AEDs), stroke severity (National Institute of Heath Stroke Scale (NIHSS), Barthel-Index, modified Rankin Scale), depression (Geriatric Depression Scale), and HrQoL (EQ-5D and EQ VAS) were collected. A multiple regression analysis was performed to identify HrQoL-determinants. RESULTS: Among the study participants (n=374), 23 (6.1%) developed poststroke epilepsy. The HrQoL of patients with poststroke epilepsy was reduced in comparison with patients without seizures (24-month follow-up: EuroQol Visual Analogue Scale (EuroQol-VAS): 55.3±10.7 versus 64.2±11.4, p=0.03). Seizure frequency, depression, and functional impairment (Barthel-Index) were identified as independent determinants of HrQoL. The adjustment of AEDs between 6-month and 24-month follow-ups resulted in decrease of seizure frequency by 40% and reduction of complications (dizziness by 27.8%, nausea by 52.2%, fatigue by 84.2%). CONCLUSION: Lesional epilepsy is associated with decreased HrQoL in patients with stroke. We identified HrQoL-determinants, which would improve the management of patients with poststroke epilepsy. These determinants include proper adjustment of AEDs with reduction of seizure frequency, treatment of depression, and focused rehabilitation programs for poststroke epilepsy.

Obesity and Abdominal Fat Markers in Patients with a History of Stroke and Transient Ischemic Attacks.

BACKGROUND: Abdominal obesity is a well-recognized cardiovascular risk factor. Conflicting data concerning its significance with respect to stroke have been discussed in recent years. The objective of this study was to analyze the association between anthropometric parameters and the risk of stroke and transient ischemic attacks (TIAs) in German primary care. METHODS: Patient recruitment in this large-scale epidemiological study was performed in 3188 representative primary care offices in Germany. Among 6980 study participants, 1745 patients with a history of stroke or TIA were identified and matched for age and gender with 5235 regional controls. Associations between standard anthropometric measures such as body mass index (BMI), waist-to-hip ratio, waist circumference, waist-to-height ratio, and cerebrovascular risk were investigated using logistic regression analysis with adjustment for age, gender, and vascular risk factors. RESULTS: BMI showed no significant associations with the risk of stroke or TIA in any of the applied mathematical models. Markers of abdominal obesity were associated with an increased risk of stroke or TIA in the unadjusted model (waist circumference: odds ratio [OR] 1.15; 95% confidence interval [CI], 1.00-1.32; waist-to-hip ratio: OR 1.21; 95% CI, 1.05-1.38; waist-to-height ratio: OR 1.25; 95% CI, 1.09-1.44, comparisons between top and bottom tertiles). After adjustment for vascular risk factors, all associations were insignificant. CONCLUSIONS: Abdominal obesity is a stronger predictor of risk of stroke or TIA than BMI. However, the association between abdominal obesity and the risk of stroke or TIA is not independent of other vascular risk factors. Stroke-related weight changes should be considered in longitudinal studies examining the role of obesity in cerebrovascular disease.

Measurement of costs and scales for outcome evaluation in health economic studies of Parkinson's disease.

Health economic studies in Parkinson's disease (PD) have become increasingly common in recent years. Because several methodologies and instruments have been used to assess cost and outcomes in PD, the Movement Disorder Society (MDS) commissioned a Task Force to assess their properties and make recommendations regarding their use. A systematic literature review was conducted to explore the use of those instruments in PD and to determine which should be selected for this review. We assessed approaches to evaluate cost of illness (COI), cost effectiveness, and cost utilities, which include the use of direct (standard gamble, time trade-off. and visual analogue scales) and indirect instruments to measure health status and utilities. No validated instruments/models were identified for the evaluation of COI or cost-effectiveness in patients with PD; therefore, no instruments in this group are recommended. Among utility instruments, only a few of these outcome instruments have been used in the PD population, and only limited psychometric data are available for these instruments with respect to PD. Because psychometric data for further utility instruments in conditions other than PD already exist, the standard gamble and time trade-off methods and the EQ-5D (a European quality-of-life health states instrument) and Health Utility Index instruments met the criteria for scales that are "recommended (with limitations)," but only the EQ-5D has been assessed in detail in PD patients. The MDS Task Force recommends further study of these instruments in the PD population to establish core psychometric properties. For the assessment of COI, the Task Force considers the development of a COI instrument specifically for PD, like that available for Alzheimer's disease.

Cerebral vasculitis as a clinical manifestation of neurosarcoidosis: A scoping review.

The occurrence of cerebral vasculitis in individuals with neurosarcoidosis (NS) is considered to be rare. Although the number of relevant publications has increased in recent years, evidence is mostly limited to case reports. To obtain a better understanding of this rare and severe manifestation of disease, we carried out a scoping review on cerebral vasculitis in patients diagnosed with NS. The results of the review indicate that the diagnosis of cerebral vasculitis in patients with NS is made especially in patients with systemic sarcoidosis. However, recurrent strokes in patients with NS remains the main indicator of cerebral vasculitis. A tissue biopsy is considered the gold standard to confirm the diagnosis despite occasional false-negative results. Glucocorticoids and steroid-sparing agents are the most successful current treatments. Favorable outcomes were observed with strategies targeting TNFα and B cells. The goal of this review is to summarize the current literature and treatment options for cerebral vasculitis in patients with NS.

Vagus nerve stimulation for the treatment of narcolepsy.

BACKGROUND AND OBJECTIVE: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. METHODS: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. RESULTS: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. CONCLUSION: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Deep Learning Accelerated Brain Diffusion-Weighted MRI with Super Resolution Processing.

OBJECTIVES: To investigate the clinical feasibility and image quality of accelerated brain diffusion-weighted imaging (DWI) with deep learning image reconstruction and super resolution. METHODS: 85 consecutive patients with clinically indicated MRI at a 3 T scanner were prospectively included. Conventional diffusion-weighted data (c-DWI) with four averages were obtained. Reconstructions of one and two averages, as well as deep learning diffusion-weighted imaging (DL-DWI), were accomplished. Three experienced readers evaluated the acquired data using a 5-point Likert scale regarding overall image quality, overall contrast, diagnostic confidence, occurrence of artefacts and evaluation of the central region, basal ganglia, brainstem, and cerebellum. To assess interrater agreement, Fleiss' kappa (Ï°) was determined. Signal intensity (SI) levels for basal ganglia and the central region were estimated via automated segmentation, and SI values of detected pathologies were measured. RESULTS: Intracranial pathologies were identified in 35 patients. DL-DWI was significantly superior for all defined parameters, independently from applied averages (p-value <0.001). Optimum image quality was achieved with DL-DWI by utilizing a single average (p-value <0.001), demonstrating very good (80.9%) to excellent image quality (14.5%) in nearly all cases, compared to 12.5% with very good and 0% with excellent image quality for c-MRI (p-value <0.001). Comparable results could be shown for diagnostic confidence. Inter-rater Fleiss' Kappa demonstrated moderate to substantial agreement for virtually all defined parameters, with good accordance, particularly for the assessment of pathologies (p = 0.74). Regarding SI values, no significant difference was found. CONCLUSION: Ultra-fast diffusion-weighted imaging with super resolution is feasible, resulting in highly accelerated brain imaging while increasing diagnostic image quality.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study.

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson's disease.

BACKGROUND: Clinical studies employ the Unified Parkinson's Disease Rating Scale (UPDRS) to measure the severity of Parkinson's disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. METHODS: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson's disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson's disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R(2), the root mean square error (RMS), the Bayesian information criterion, and Pregibon's link test. Three independent data sets validated the models. RESULTS: The regression analyses resulted in a single best prediction model (R(2): 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. CONCLUSION: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.

PERPRISE: A prospective non-interventional study of PERampanel as only adjunctive treatment in patients with PRImary or SEcondarily generalized tonic-clonic seizures: First interim analysis.

OBJECTIVE: To report the interim results of the PERPRISE study (Study 509; NCT04202159), which is evaluating perampanel as the only adjunctive anti-seizure medication (ASM) in adults with focal to bilateral tonic-clonic seizures (FBTCS) or primary generalized tonic-clonic seizures (GTCS). METHODS: PERPRISE is an ongoing 12-month multicenter, prospective, observational, non-interventional study of perampanel in a real-world setting in Germany. Patients are aged ≥18 years with FBTCS or GTCS due to focal or idiopathic generalized epilepsy. Perampanel, as an adjunctive therapy to ASM monotherapy ('add-on therapy') or as a substitute for one ASM in dual therapy ('substitution therapy'), is prescribed in line with its SmPC. The Interim Analysis Set comprises the first 100 patients who received ≥1 dose of perampanel and attended or discontinued prior to the ~6-month visit. Interim endpoints include retention rate, measures of effects on seizure frequency, and treatment-emergent adverse events (TEAEs). RESULTS: One hundred patients were included in the Interim Analysis Set (add-on, n = 43 [43.0%]; substitution, n = 55 [55.0%]; unknown, n = 2). The 6-month retention rate was 78.0% (add-on, 83.7%; substitution, 72.7%). For the overall population with GTCS and/or FBTCS, seizure-freedom rate at 6 months was 58.8% (add-on, 72.2%; substitution, 47.9%) and 50% responder rate at 6 months was 82.6% (add-on, 89.2%; substitution, 76.6%). Retention rates and seizure outcomes were better with perampanel as an early-line treatment than as a late-line treatment. TEAEs were reported by 48 patients (48.0%), most commonly dizziness (n = 9), fatigue (n = 7), and irritability (n = 7). Sixteen patients (16.0%) withdrew from perampanel treatment due to TEAEs. SIGNIFICANCE: The interim analysis of PERPRISE offers insight into the real-world use of perampanel in Germany, including for the first time, clinical practice data from patients with GTCS and switching ASMs within a dual therapy. Further data from PERPRISE will be of value to inform clinical decision-making in this patient cohort. PLAIN LANGUAGE SUMMARY: Patients with epilepsy often take more than one medication for seizure control. This 12month study looked at patients in Germany receiving perampanel as only add-on medication. The interim analysis shows, that at 6 months, over 70% of the 100 patients continued to use perampanel; 59% experienced no seizures during treatment with perampanel, and in 83%, seizure frequency was reduced by half. Side effects occurred in 48% of patients (most commonly dizziness, fatigue, and irritability) and caused 16% to withdraw from the study. Overall, perampanel was a suitable as only add-on medication for patients with epilepsy.

Eslicarbazepine acetate for the treatment of status epilepticus.

OBJECTIVE: Due to the high mortality of patients with refractory status epilepticus (SE), new antiseizure medications (ASMs) are needed to improve long-term outcomes. In this study, we evaluated the efficacy and safety of eslicarbazepine acetate (ESL), a new sodium channel blocker, based on the data from a large epilepsy register. METHODS: Data on the efficacy and safety of ESL for the treatment of refractory SE were gathered from the Mainz Epilepsy Registry (MAINZ-EPIREG). Logistic regression was applied to identify predictors of status interruption. RESULTS: In total, 64 patients with remote symptomatic refractory SE were treated with ESL. No cases of idiopathic generalized epilepsy were included. The average age was 61.4 ± 11.0 years. The median number of administered ASMs before the start of ESL was three. On average, 2 days had elapsed since the onset of SE before the administration of ESL. The initial dose of 800 mg/day was increased up to a maximum daily dose of 1600 mg in case of nonresponse. In 29 of 64 patients (45.3%), the SE could be interrupted within 48 h of ESL therapy. In patients with poststroke epilepsy, the control of SE was achieved in 62% of patients (15/23). The earlier initiation of ESL therapy was an independent predictor of control of SE. Hyponatraemia occurred in five patients (7.8%). Other side effects were not observed. SIGNIFICANCE: Based on these data, ESL may be used as an adjunct therapy for the treatment of refractory SE. The best response was found in patients with poststroke epilepsy. In addition, early initiation of ESL therapy appears to result in better control of SE. Besides a few cases of hyponatraemia, no other adverse events were detected.