Reduced Gastric Contraction in Rapid-Eye-Movement Sleep Behavior Disorder and De Novo Parkinson's Disease.

BACKGROUND: Reduced gastric motility in Parkinson's disease (PD) has been reported, but hardly any study exists in subjects with isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD), a specific prodrome of α-synucleinopathies. OBJECTIVES: We compared the gastric motility of 17 iRBD subjects with that of 18 PD subjects (15 drug naive, 3 early treated in defined off) and 15 healthy controls (HC) with real-time magnetic resonance imaging (rtMRI). METHODS: After overnight fasting, participants consumed a standardized breakfast and underwent a 3-T rtMRI of the stomach. Amplitude and velocity of the peristaltic waves were analyzed under blinded conditions. Gastric motility index (GMI) was calculated. The procedure was repeated in 12 of 17 iRBD subjects ~2.5 years later. Nine of these 12 iRBD subjects were hyposmic. RESULTS: In iRBD and PD subjects the amplitude of the peristaltic waves was significantly reduced compared with HCs (iRBD vs. HC: 8.7 ± 3.7 vs. 11.9 ± 4.1 mm, P = 0.0097; PD vs. HC: 6.8 ± 2.2 vs. 11.9 ± 4.1 mm, P = 0.0001). The amplitude in iRBD and PD subjects was decreased to the same extent. The GMI was reduced in only PD subjects (PD vs. HC: P = 0.0027; PD vs. iRBD: P = 0.0203). After ~2.5 years the amplitude in iRBD subjects did not significantly decrease further. CONCLUSION: The amplitude of the peristaltic waves was markedly reduced in iRBD, a prodrome of α-synucleinopathies. This reduction was similar to the extent observed already in manifest early PD. This finding implies that the α-synuclein pathology affects the innervation of the stomach already in the prodromal stage. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Lacosamide in status epilepticus: Systematic review of current evidence.

OBJECTIVE: The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE. METHODS: We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported. RESULTS: In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug-drug interactions. SIGNIFICANCE: The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany.

OBJECTIVE: To evaluate factors predicting efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. METHODS: A multicenter, retrospective cohort study recruiting all patients who started BRV between February and November 2016 with observation time between 3 and 12 months. RESULTS: Of a total of 262 patients (mean age 40, range 5-81 years, 129 male) treated with BRV, 227 (87%) were diagnosed to have focal, 19 (7%) idiopathic generalized and 8 (3%) symptomatic generalized epilepsy, whereas 8 (3%) were unclassified. The length of exposure to BRV ranged from 1 day to 12 months, with a median retention time of 6.1 months, resulting in a total exposure time to BRV of 1,504 months. The retention rate was 79.4% at 3 months and 75.8% at 6 months. Efficacy at 3 months was 41.2% (50% responder rate) with 14.9% seizure-free for 3 months and, at 6 months, 40.5% with 15.3% seizure-free. Treatment-emergent adverse events were observed in 37.8% of the patients, with the most common being somnolence, dizziness, and behavioral adverse events (BAEs). BAE that presented under previous levetiracetam (LEV) treatment improved upon switch to BRV in 57.1% (20/35) and LEV-induced somnolence improved in 70.8% (17/24). Patients with BAE on LEV were more likely to develop BAE on BRV (odds ratio [OR] 3.48, 95% confidence interval [CI] 1.53-7.95). SIGNIFICANCE: BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.

Fractures in Parkinson's Disease: injury patterns, hospitalization, and therapeutic aspects.

AIM: The primary aim of this study was to analyze the frequency and characteristic patterns of fall-related fractures as well as consecutive hospitalization and management relating to such fractures. In addition, important pathognomonic and therapeutic aspects are discussed. METHODS: This retrospective mono-center study was conducted at the University Hospital Frankfurt am Main, Germany. Between 2007 and 2017, a total of 145 PD patients with fall-related fractures were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G20.0-G20.9. Patients with unclear or falsely coded PD were strictly excluded. RESULTS: The mean age of the cohort was 77.7 years (± 7.5, median 77.) and 57.9% of the cohort were females (n = 84). A total number of 151 fractures were reported, with 140 patients (96.6%) suffering from one, four patients from two (2.8%), and one patient from three fractures (0.6%) at a time. For 43.9% (n = 65) of the cohort, fractures concerned lower extremities (LE) followed by trunk (38.1%, n = 58) and upper extremities (UE, 17.9%, n = 27). Most common fracture types in LE were femoral neck fractures (52.3%, n = 34). Mean length of hospital stay (LOS) was 13.6 days (95% CI 12.4-14.7). In 43.4% (n = 63) of cases, an interim admission to an intensive-care unit (ICU) was necessary. Mean ICU LOS was 2.3 days (95% CI 1.5-3.0), and mean LOS for normal care unit was 10.5 days (95% CI 10.3-12.4). Surgical treatment was necessary in 75.9% of the cases (n = 110). Patients undergoing surgical treatment showed significantly longer LOS compared to conservatively treated patients (p < 0.001). Moreover, fractures of the LE (p = 0.018) and UE (p = 0.010) were associated with a significant longer LOS. CONCLUSION: Fall-related fractures are a common and relevant complication in PD patients leading to increased immobility, frequent hospitalization, and immediate surgical care. Fractures of the lower extremities and trunk were the most common in the cohort for this study. A PD patient presenting to the emergency room or at the general practitioner with a fracture should always be checked for osteoporosis and a fall-related injury should be seen as a red flag for reviewing a patient's individual therapeutic regime.

Prevalence, risk factors and therapeutic aspects of injuries and accidents in women with epilepsy.

BACKGROUND: Epilepsy-related injuries and accidents (ERIA) are a frequent cause of hospitalisation and represent a relevant burden for patients with epilepsy. In particular, osteoporosis and other gender-specific aspects may increase the risk of seizure-related fractures and injuries in women with epilepsy. AIM AND SCOPE: The aim of this analysis is to determine the prevalence and clinical nature of ERIA in a cohort of women with epilepsy, to identify possible determinants including osteoporosis and to give an overview of the current knowledge of clinically important prophylactic and therapeutic aspects. RESULTS: In total, 167 women (mean age 39.0 years, range 18-67 years) with established diagnosis of epilepsy (mean disease duration 18.2 years, range 0-64) were analysed for the occurrence of ERIA. Overall, 22 patients (13.2%) reported at least one ERIA (mean number 3.4, ± 3.1) during the last three months prior to enrollment. The most frequent types of ERIA were lacerations (n = 7/22; 31.8%), abrasions, cuts, bruises or hematoma (n = 6/22, 27.3%), burns (n = 3/22, 13.6%), and fractures (n = 3/22, 13.6%). Moreover, one seizure-related road traffic accident with consecutive trauma (4.5%) was reported. Ictal falls, periictal abnormalities of behaviour and missing seizure freedom were associated with ERIA. Furthermore, female patients with ERIA had a significantly reduced quality of life (QoL, p = 0.002) and increased anxiety (p = 0.008) compared to patients without ERIA. A review of the pertinent literature suggests decreased bone mineral density and use of enzyme-inducing AEDs to be risk factors for ERIA in women with epilepsy. CONCLUSION: ERIA represent relevant complications for women with epilepsy and are associated with a lower QoL and anxiety compared with non-affected controls. Improvement of anticonvulsive treatment and therapy for osteoporosis or osteomalacia may help to decrease ERIA and the associated burden.

Characteristics of bilateral versus unilateral temporal encephalocele-associated epilepsy.

PURPOSE: To characterise bilateral temporal encephalocele (BTE)-associated epilepsy relative to unilateral temporal encephalocele (UTE)-associated epilepsy as a rare but curable cause of structural epilepsy using demographics, epilepsy status and imaging findings. METHOD: In this single-centre retrospective study we included all patients from June 2015 to August 2018, who suffered from epilepsy and were diagnosed with a temporal encephalocele. Data were systematically collected and analysed for differences between BTE and UTE. RESULTS: Seventeen epilepsy patients diagnosed with temporal encephaloceles (TE) were identified. One-third exhibited BTE. The age of epilepsy onset was higher in patients with BTE compared to UTE (median 51 vs. 37 years, p = 0.074). Latency between epilepsy diagnosis and definitive TE diagnosis differed considerably with a median five-fold shorter duration for the BTE-group when compared to the UTE-group (2-10 years, p = 0.02). Five of seven (81%) patients with BTE were pharmacoresistant, while this applied to only five out of ten (50%) patients with a UTE. CONCLUSION: When compared to UTE-associated epilepsy, BTE-associated epilepsy is characterised by a later age at onset, shorter delay in TE diagnosis and more frequent drug-resistance. As epilepsy surgery is a valid treatment option for both syndromes, a standardised diagnostic workup should be implemented for temporal lobe epilepsy (TLE) patients with unknown aetiology to facilitate early detection of UTE and BTE.

Improved synthetic T1-weighted images for cerebral tissue segmentation in neurological diseases.

Structural cerebral MRI analysis in patients with neurological diseases usually requires T1-weighted datasets for tissue segmentation. For this purpose, synthetic T1-weighted images which are constructed from quantitative maps of the underlying tissue parameters such as the T1 relaxation time and the proton density (PD) may provide advantages over conventional datasets. However, in some cases synthetic images may suffer from specific artifacts, hampering accurate tissue segmentation. The goal was to improve a previously described method for the calculation of synthetic magnetization-prepared rapid gradient-echo (MP-RAGE) datasets from quantitative T1 and PD maps. Improvements comprise a B0-correction for the water-selective excitation pulses employed in T1-mapping and the use of T1-based pseudo-PD maps. Synthetic T1-weighted MP-RAGE datasets were calculated, using the standard and the improved algorithm, for 10 patients with focal epilepsy (caused by focal cortical dysplasia in 9), 10 patients with multiple sclerosis and 10 healthy control subjects and segmented with the Freesurfer toolbox. Visual inspection disclosed that segmentation of the standard synthetic datasets was inaccurate in 6 out of 10 patients with epilepsy, 7 out of 10 patients with multiple sclerosis and 7 out of 10 healthy control subjects, while the improved synthetic datasets resulted in adequate segmentation outcomes in the majority of cases. Only for one patient with multiple sclerosis and one with epilepsy, segmentation in basal temporal regions was not sufficient. Furthermore, data based on the standard algorithm showed strong signal non-uniformities in basal regions. This effect was not present in the improved synthetic datasets.

Eslicarbazepine acetate in epilepsies with focal and secondary generalised seizures: systematic review of current evidence.

INTRODUCTION: Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved for adjunctive treatment in adults, children, and adolescents with focal-onset seizures. Recently ESL was approved for initial monotherapy in adults. The intention of this article is to review current evidence for ESL and to summarise its pharmacological profile in comparison to other AEDs of the dibenzazepine group. Areas covered: We performed a systematic literature search in electronic databases (MEDLINE database, Cochrane Central Register of Controlled Trials, Excerpta Medica dataBASE) using a combined search strategy including the following keywords: eslicarbazepine, epilepsy and seizure. The search was performed from 2000 until December 2017. Using a standardised assessment form, information on the study design, methodological framework, data sources and efficacy and adverse events attributed to ESL were extracted from each publication and systematically reported. Expert commentary: ESL is an effective, safe and well tolerated third-generation AED for the treatment of focal epilepsies. During therapy, especially serum sodium levels and possible interactions with other substances have to be monitored. As of yet, long-term experience is still needed to make severe late-occurring adverse events unlikely and to obtain data regarding its use in pregnancy.

The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience.

Lacosamide (LCM) is approved for anticonvulsive treatment in focal epilepsy and exhibits its function through the slow inactivation of voltage-gated sodium channels (VGSCs). LCM shows comparable efficacy with other antiepileptic drugs (AEDs) licensed in the last decade: in three randomized placebo-controlled trials, significant median seizure reduction rates of 35.2% for 200 mg/day, 36.4-39% for 400 mg/day and 37.8-40% for 600 mg/day were reported. Likewise, 50% responder rates were 38.3-41.1% for 400 mg/day and 38.1-41.2% for 600 mg/day. Similar rates were reported in post-marketing studies. The main adverse events (AEs) are dizziness, abnormal vision, diplopia and ataxia. Overall, LCM is well tolerated and has no clinically-relevant drug-drug interactions. Due to the drug's intravenous availability, its use in status epilepticus (SE) is increasing, and the available data are promising.

Molecular and antigenic characterization of a Streptococcus oralis coaggregation receptor polysaccharide by carbohydrate engineering in Streptococcus gordonii.

The coaggregation receptor polysaccharides (RPS) of Streptococcus oralis and related species are recognized by lectin-like adhesins on other members of the oral biofilm community and by RPS-specific antibodies. The former interactions involve beta-GalNAc or beta-Gal containing host-like motifs in the oligosaccharide repeating units of these polysaccharides, whereas the latter involves features of these molecules that are immunogenic. In the present investigation, the molecular and corresponding structural basis for the serotype specificity of S. oralis ATCC 10557 RPS was determined by engineering the production of this polysaccharide in transformable Streptococcus gordonii 38. This involved the systematic replacement of genes in the rps cluster of strain 38 with different but related genes from S. oralis 10557 and structural characterization of the resulting polysaccharides. The results identify four unique genes in the rps cluster of strain 10557. These include wefI for an alpha-Gal transferase, wefJ for a GalNAc-1-phosphotransferase that has a unique acceptor specificity, wefK for an acetyl transferase that acts at two positions in the hexasaccharide repeating unit, and a novel wzy associated with the beta1-3 linkage between these units. The serotype specificity of engineered polysaccharides correlated with the wefI-dependent presence of alpha-Gal in these molecules rather than with partial O-acetylation or with the linkage between repeating units. The findings illustrate a direct approach for defining the molecular basis of polysaccharide structure and antigenicity.