Cenobamate: real-world data from a retrospective multicenter study.

BACKGROUND: Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs. METHODS: We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs. RESULTS: 116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged. CONCLUSIONS: CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy.

Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis - A German multicenter experience.

OBJECTIVE: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics. METHODS: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics. RESULTS: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service. CONCLUSION: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management. SIGNIFICANCE: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.

Tetraparesis and sensorimotor axonal polyneuropathy due to co-occurrence of Pompe disease and hereditary ATTR amyloidosis.

INTRODUCTION/AIMS: Hereditary transthyretin amyloidosis with polyneuropathy (hATTRPN) is an autosomal dominant multi-organ disorder manifesting in the third to fifth decade with the key clinical features of distal and painful sensory loss of the lower limbs and autonomic dysregulation. Motor neuropathy and cardiomyopathy evolve in the course of the disease. Pompe disease is an autosomal recessive disease leading to decreased levels of lysosomal enzyme acid α-glucosidase and proximal muscle weakness. We report the clinical features and diagnostic workup in the rare case of a patient with ATTR amyloidosis and late-onset Pompe disease, both genetically confirmed. METHODS: We performed a detailed clinical assessment, exome sequencing, and biochemical measurements. RESULTS: The patient presented with a distal, painful hypaesthesia of both legs, a cardiomyopathy, and a muscle weakness in the form of a girdle-type pattern of the arms and legs at the beginning and a spreading to distal muscle groups in the course of disease. DISCUSSION: This study highlights the importance of searching for co-occurrence of rare monogenetic neuromuscular diseases, especially in cases in which all clinical features can be readily explained by a single gene defect.

Continuous tissue microarray based identification of cancers with homogeneous target expression for successful targeted therapy in clinical routine practice.

In cancer therapy, the number of drugs targeting cells with characteristic molecular aberrations is continuously rising. However, application of these new drugs still is limited to a few tumor entities. The aim of this study was to test the concept of routinely identifying all possible cancer patients who might eventually benefit from targeted therapy. Therefore, all malignant tumors routinely submitted to our Institute of Pathology over a period of 4 months were brought into a tissue microarray format. Using "in situ" methods, tumors were analyzed for HER2, EGFR, and KIT status as examples for potential therapeutic target genes. In positive cases, target heterogeneity was excluded by analyzing all available large sections. Outside of tumor entities for which targeted drugs are already approved, the study revealed six tumors with homogeneously distributed HER2 overexpression/amplification (bladder, esophageal and colorectal) and seven tumors with homogeneous EGFR amplification (vulvar, ovarian, breast, esophageal and laryngeal, and adenocarcinoma of unknown primary). A total of 151 tumors showed KIT overexpression but none of seven sequenced cases showed KIT mutations. We furthermore report on a 69-year-old patient with homogeneously HER2-amplified metastatic colorectal cancer who is successfully treated by trastuzumab monotherapy. This study demonstrates that tissue microarray based screening for therapeutic target genes in tumors outside established indications represents a feasible approach suitable for routine application. The successful treatment of one patient with homogeneously HER2 positive metastatic colorectal cancer argues for the clinical utility of this approach at least in carefully selected, homogeneous cancers.

Speeding up older adults: age-effects on error processing in speed and accuracy conditions.

Behavioral performance in older adults is often characterized by normal error rates but longer response latencies compared to younger adults. The slowing of reaction times might reflect a compensatory strategy to avoid errors and might be associated with performance monitoring alterations. The present study investigated whether the ability to compensate for potential deficits influences age-related differences in performance monitoring. A modified flanker task was used with either accuracy or speed instruction. Both groups showed reliable differences between conditions: accuracy, reaction times and error-related negativities were reduced in the speed compared with the accuracy condition. Older adults showed smaller error-related negativities compared with younger adults and the reduction was more pronounced in the speed condition. Further, similar-sized error-related and correct-related negativities were found in older adults. Results indicate that performance monitoring deficits in older adults are related to deficits in behavioral performance, at least if they are forced to respond quickly.

ERP correlates of performance monitoring in elderly.

Previous studies on performance monitoring repeatedly found attenuated error-related negativities (Ne/ERN) in elderly, while findings for the correct-related negativity (Nc/CRN) are inconsistent. The present study aimed at clarifying inconsistent Nc/CRN results in elderly. Therefore, a refined design was employed to control for potential influences on the Nc/CRN, namely decision uncertainty and partial error processing. Further, we intended to study Nc/CRN variations with trial compatibility that were found in previous studies for younger but not for older adults. Results revealed increased Nc/CRN and decreased Ne/ERN amplitudes in older compared to younger adults. While the Ne/ERN was larger than the Nc/CRN in younger adults, both components were similar-sized in older adults. Further, a modulation of Nc/CRN amplitudes between compatible and incompatible trials was observed in younger adults, but was absent in older adults. Reduced differentiation of response-related negativities with response accuracy or stimulus compatibility in elderly suggests a reduced adaptation of associated processes to changing demands. Further, this might also point to different processes reflected by Nc/CRN and Ne/ERN and to reduced error-specific monitoring but increased general or strategic monitoring in elderly.