Long-term cenobamate retention, efficacy, and safety: outcomes from Expanded Access Programme.

AIM OF THE STUDY: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). CLINICAL RATIONALE FOR THE STUDY: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. MATERIAL AND METHODS: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. RESULTS: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.

The Utility of BDNF Detection in Assessing Severity of Huntington's Disease.

Brain-derived neurotrophic factor (BDNF) is involved in the survival and maturation of neurons, and also promotes and controls neurogenesis. Its levels are lowered in many neurodegenerative diseases, including Huntington's disease (HD). Clinical pictures of HD can be very diverse, which makes it difficult to assess its severity; however, molecular markers may be helpful. The aim of the study was to determine the relationship between HD severity and the plasma BDNF concentration in HD patients. The study recruited 42 patients with diagnosed and genetically confirmed HD and 40 healthy volunteers. BDNF levels were determined in plasma with the enzyme-linked immunosorbent assay (ELISA). Correlations between BDNF levels and clinical profiles and HD severity were also investigated. The BDNF level was significantly lower in HD patients compared to the control. There was no correlation between the BDNF level and motor symptoms and cognitive impairment. In the early disease stages, BDNF levels were associated with a better neurological examination, independence, and functional evaluation, in contrast to later HD stages, where the correlations were inverse. Multidirectional correlations between parameters of saccadic disorders and the BDNF level do not allow for drawing a conclusion, whether or not there is a relationship between the severity of saccadic disorders and the BDNF concentration.

Adequate Knowledge of Stroke Symptoms, Risk Factors, and Necessary Actions in the General Population of Southern Poland.

BACKGROUND AND OBJECTIVES: Stroke is the third most common cause of mortality in developed countries and the primary cause of neurological disability in adults. Recombinant tissue plasminogen activator administered intravenously within 4.5 h from the onset of symptoms constitutes a gold standard in the treatment of acute ischemic stroke. Prompt hospital admission is the prerequisite of effective thrombolysis. Therefore, stroke awareness in the general population is the key factor in timely recognition of the acute stroke victims and determines proper actions. Therefore, the purpose of this study was to determine the awareness of stroke in the general population of the Silesian voivodeship, the most populated region of Poland. We assessed also the "adequate knowledge of stroke", a combined measure of the optimal level of stroke awareness, as a prerequisite for effective stroke management, and aimed to identify most impacting factor for adequate stoke knowledge, to help shaping education strategies. MATERIALS AND METHODS: A proprietary anonymous questionnaire consisting of 15 items related to stroke was used in this research. A total of 1134 individuals were surveyed. Additionally to the knowledge of individual aspects of stroke, we assessed "adequate knowledge of stroke", which was combined measure of risk factors, symptoms, and actions in the case of acute stroke. RESULTS: The accurate definition of stroke was selected by 834 participants (73.5%). The vast majority of them indicated that a stroke is an emergency (92.8%) and medical assistance is required (97.5%). However, 42.4% of respondents did not know any specific symptom of stroke and only 38.6% participants were able to list two or more risk factors, which resulted in only 36.3% of individuals with adequate knowledge of stroke. Education duration, previous occurrence of stroke in relatives or friends, gender and place of residence were identified as independent predictors of adequate knowledge of stroke. CONCLUSIONS: 1. Knowledge of stroke in the population of southern Poland is low and may be considered insufficient to address the needs of timely management in the action chain. 2. Previous occurrence of stroke in the relatives or friends is the most impacting factor for adequate knowledge of stroke.

Transitional Locomotor Tasks in People With Mild to Moderate Parkinson's Disease.

Background: People with Parkinson's disease (PD) exhibit deficits in maintaining balance both during quiet standing and during walking, turning, standing up from sitting, and step initiation. Objective: The purpose of this study was to examine balance disorders during a transitional task under different conditions in participants with PD. Methods: The research was conducted on 15 PD-II (mild) and 15 PD-III (moderate) individuals (H&Y II-III stage) and 30 healthy elderly. The transitional task was measured on two force platforms (A and B). The procedure consisted of three phases: (1) quiet standing on platform A, (2) crossing to platform B, and (3) quiet standing on platform B, each until measurements were completed. There were four conditions: crossing without an obstacle, crossing with an obstacle, and walking up and down the step. Results: There were no significant differences between mild PD individuals and healthy elderly during quiet standing before the transitional task and after completing the task. The temporal aspects describing the different transitional tasks were comparable between mild PD and healthy subjects. Moderate PD participants presented a significantly higher COP velocity after the transitional task compared to the healthy older adults (p < 0.05). Additionally, the moderate PD group showed significantly higher values for transit time relative to healthy subjects during the transitional task in all conditions (p < 0.05). Conclusions: Disease severity affects the temporal aspects of different transitional tasks in people with PD. The procedure of completing a transitional task under different conditions allowed differences between moderate and mild PD stages and healthy subjects to be observed.

Eye movement abnormalities in essential tremor.

Essential tremor (ET) is the most prevalent movement disorder, characterized mainly by an action tremor of the arms. Only a few studies published as yet have assessed oculomotor abnormalities in ET and their results are unequivocal. The aim of this study was to assess the oculomotor abnormalities in ET patients compared with the control group and to find the relationship between oculomotor abnormalities and clinical features of ET patients. We studied 50 ET patients and 42 matched by age and gender healthy controls. Saccadometer Advanced (Ober Consulting, Poland) was used to investigate reflexive, pace-induced and cued saccades and conventional electrooculography for evaluation of smooth pursuit and fixation. The severity of the tremor was assessed by the Clinical Rating Scale for Tremor. Significant differences between ET patients and controls were found for the incidence of reflexive saccades dysmetria and deficit of smooth pursuit. Reflexive saccades dysmetria was more frequent in patients in the second and third phase of ET compared to the first phase. The reflexive saccades latency increase was correlated with severity of the tremor. In conclusion, oculomotor abnormalities were significantly more common in ET patients than in healthy subjects. The most common oculomotor disturbances in ET were reflexive saccades dysmetria and slowing of smooth pursuit. The frequency of reflexive saccades dysmetria increased with progression of ET. The reflexive saccades latency increase was related to the severity of tremor.