Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy

Trail Making Test Part A (TMT-A) assesses visual scanning speed and psychomotor speed. Participants connect numbered circles in ascending order (1-2-3-4-5...-25). Completion time is measured in seconds, with typical ranges from 15-300 seconds depending on age and education. Lower completion times indicate better performance. The outcome is calculated as: (TMT-A time at assessment point) - (TMT-A time at baseline). A negative change indicates improvement.

Trail Making Test Part B (TMT-B) assesses executive function including cognitive flexibility and attention switching. Participants alternate between numbers and letters (1-A-2-B-3-C...). Completion time is measured in seconds, with typical ranges from 30-600 seconds depending on age and education. Lower completion times indicate better performance. The outcome is calculated as: (TMT-B time at assessment point) - (TMT-B time at baseline). A negative change indicates improvement.

Digit Span Forward Test assesses attention and short-term memory capacity. Participants repeat number sequences in the same order as presented. Scores range from 0 to 9 points, with higher scores indicating better attention and short-term memory performance. The outcome is calculated as: (Digit Span Forward score at assessment point) - (Digit Span Forward score at baseline). A positive change indicates improvement.

Digit Span Backward Test assesses working memory and mental manipulation abilities. Participants repeat number sequences in reverse order. Scores range from 0 to 8 points, with higher scores indicating better working memory performance. The outcome is calculated as: (Digit Span Backward score at assessment point) - (Digit Span Backward score at baseline). A positive change indicates improvement.

Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall assesses verbal learning and immediate memory capacity. Participants recall a 15-word list immediately after the fifth presentation. Scores range from 0 to 15 words correctly recalled, with higher scores indicating better immediate verbal memory performance. The outcome is calculated as: (RAVLT immediate recall score at assessment point) - (RAVLT immediate recall score at baseline). A positive change indicates improvement.

Rey Auditory Verbal Learning Test (RAVLT) Delayed Recall assesses long-term verbal memory retention. Participants recall the 15-word list after a 30-minute delay. Scores range from 0 to 15 words correctly recalled, with higher scores indicating better long-term verbal memory performance. The outcome is calculated as: (RAVLT delayed recall score at assessment point) - (RAVLT delayed recall score at baseline). A positive change indicates improvement.

Percentage change in average monthly seizure frequency from baseline to each assessment timepoint. Seizure frequency is recorded daily through seizure diary maintained by patients and caregivers, verified during clinical visits. The outcome is calculated as: [(Average monthly frequency at assessment point) - (Average monthly frequency at baseline)] / (Average monthly frequency at baseline) × 100%. A negative percentage indicates reduction in seizure frequency (improvement).

Percentage of participants achieving at least 50% reduction in average monthly seizure frequency compared to baseline. Response is defined as: (Baseline monthly frequency - Average monthly frequency during weeks 45-48) / Baseline monthly frequency ≥ 50%. Seizure data collected through daily seizure diary and verified by caregivers.

Activities of Daily Living (ADL) Scale is a 14-item assessment tool that evaluates both basic activities of daily living (BADL) including feeding, bathing, grooming, dressing, bowel control, and bladder control, and instrumental activities of daily living (IADL) including using telephone, shopping, food preparation, housekeeping, laundry, transportation, medication responsibility, and financial management. Each item is scored from 1 to 4 points, with total scores ranging from 14 to 56 points. Higher scores indicate greater functional impairment (worse outcome). The outcome is calculated as: (ADL score at assessment point) - (ADL score at baseline). A negative change indicates functional improvement.

Quality of Life in Epilepsy Inventory-31-Patient weighted (QOLIE-31-P) evaluates epilepsy-specific quality of life across 7 domains: seizure worry, overall quality of life, emotional well-being, energy/fatigue, cognitive functioning, medication effects, and social function. Total scores range from 0 to 100 points, with higher scores indicating better quality of life. The outcome is calculated as: (QOLIE-31-P score at assessment point) - (QOLIE-31-P score at baseline). A positive change indicates improvement.

Safety and tolerability assessed by incidence of treatment-related adverse events classified and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All adverse events will be recorded and their relationship to study drug will be assessed by investigators as unrelated, unlikely, possible, probable, or definite.

Incidence of serious adverse events (SAEs) defined according to International Conference on Harmonisation (ICH) guidelines as events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability/incapacity, are congenital anomaly/birth defect, or are medically important events.

Incidence of clinically significant hepatic function abnormalities defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2 times the upper limit of normal (ULN), or total bilirubin greater than 1.5 times ULN as measured by standard laboratory methods.

Incidence of clinically significant renal function abnormalities defined as serum creatinine levels greater than 1.5 times the upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) decrease by ≥25% from baseline as measured by standard laboratory methods.

Incidence of clinically significant hematological abnormalities including hemoglobin decrease to less than 11 g/dL, white blood cell count less than 3,000/μL or greater than 11,000/μL, or platelet count less than 100,000/μL or greater than 450,000/μL as measured by standard hematology laboratory methods.