Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage

Spontaneous subarachnoid hemorrhage (SAH), often resulting from intracerebral aneurysm rupture is a relatively uncommon but impactful form of stroke predominantly affecting middle-aged individuals. Aneurysmal SAH (aSAH) presents a high risk of post-stroke cognitive impairment (PSCI) compared to other stroke types, with an occurrence rate ranging from 26% to 43%. Cognitive impairments, particularly in executive function, attention, memory, and language abilities, are prevalent among aSAH survivors, with notable differences observed in cognitive outcomes based on medical interventions such as clipping or coiling. Additionally, cerebral changes following aSAH, including delayed onset cerebral infraction, white matter hyperintensities and focal encephalomalacia, contribute to cognitive deficits. In clinical settings, patients with aSAH often demonstrate notable improvements in motor function recovery, however, cognitive issues, such as executive function and complex attention, are closely linked to patients' inability to perform the activities of daily living (ADL) independently and return to work, even after disease recovery. While physical therapy interventions, including early mobilization, show promise in enhancing functional outcomes, there is a dearth of research specifically addressing cognitive rehabilitation in aSAH patients. Integration of motor-cognitive training approaches, such as motor-cognitive integrative training (MCIT), may hold potential for improving cognitive and motor recovery in SAH patients, akin to their application in other neurological disorders like Parkinson's disease and stroke. Understanding the intricate relationship between cognitive deficits and functional outcomes is crucial for developing targeted rehabilitation strategies to improve the quality of life for aSAH survivors.

The present study aims to examine the impact of early intervention with MCIT (e-MCIT) on cognitive function, motor recovery, functional abilities, and ADL in acute SAH patients upon discharge from the ICU and during the post-intervention assessment. Additionally, we investigate whether SAH patients who receive e-MCIT achieve better long-term workplace reintegration.

This is a randomized, controlled, assessor-blinded clinical trial. The intervention commences during the acute setting in the ICU period and extends through the subacute phase in the hospital's general ward. Evaluation will be conducted at five assessment time points including baseline assessment (following initial medical intervention), assessment at the time of discharge from the intensive care center (ICU), discharge from the hospital, 3-month follow up and 1-year follow up. After recruiting in this study, participants will be randomized into traditional group (early mobilization group) or e-MCIT group.

Eighteen patients with aSAH will be recruited, which Inclusion criteria for enrolment are as follows: (1) Diagnosis of spontaneous SAH resulting from aneurysm rupture confirmed by either CT scan or angiography. (2) Onset of stroke occurring in the acute phase, specifically 2-7 days after medical intervention. (3) Participants must be over 18 years old. (4) WFNS: 1-5. (5) Able to stand above 30 seconds. (6) Montreal Cognitive Assessment (MoCA)\<26. Patients who present unstable vital sign (e.g., heart rate (HR): 40-100bpm, mean arterial pressure (MAP)\> 80mmHg, respiratory rate (RR): 12-20, oxygen saturation (SpO2) \> 95%, intracranial pressure (ICP) \< 20mmHg and cerebral perfusion pressure (CPP) \> 70mmHg) according to the criteria in previous study\[1\] or evaluated as unsuitable by their attending physician will be excluded. Participants who are with other neurological disease might interfere the experiment and their education years less than 12 years will be excluded in this study.

Early motor-cognitive integrative training (e-MCIT) is an approach where motor and cognitive training are conducted simultaneously. Traditional group receive the same motor-only program in e-MCIT. The intervention consists of 30-minute sessions, conducted 4-5 times per week, until discharging from the hospital.

Outcome measurements includes side-effect events record, Montreal Cognitive Assessment (MoCA), Trail Making Test part A(TMT-A), Trail Making Test part B(TMT-B), Stroop color and word test (SCWT), digit span (DS) test, Go and no-go (GNG) test, Verbal Fluency test (VFT), Fugl-Meyer Assessment for upper extremity (FMA-UE) and lower extremity (FMA-LE), Medical Research Council (MRC), Functional ambulatory category (FAC), kinematics performance in single and dual task ability, brain activity by functional Near-Infrared Spectroscopy (fNIRS) during all cognition assessment and in single and dual task, Functional independence measure (FIM), Modified Rankin Scale (mRS), Perme ICU mobility score, and National Institutes of Health Stroke Scale (NIHSS), Instrumental Activity of Daily Living scale, Hospital anxiety and depression scale (HADS), 36-item short form health survey (SF-36) and 1-year follow-up telephone interview .

Statistical analysis was conducted using SPSS version 26.0. Categorical variables in the descriptive data of the participants were presented as numbers and percentages, while continuous variables were expressed as mean ± standard deviation. Nominal variables would be analyzed by X2 test. Analyzed using either a two-way ANOVA or Wilcoxon Signed-Rank Test will be used to test the differences between pre-test and post-intervention time points due to small sample size. A two-tailed significance level (α) was set at 0.05. Thus, p\< 0.05 revealed significant difference.

• Kinematics performance [Срок оценки: T0(baseline), T1(discharge from ICU, an average of 2 weeks), T2(discharge from hospital, an average of 4weeks), T3(3-month follow up)]
• Brain activity [Срок оценки: T1(discharge from ICU, an average of 2 weeks), T2(discharge from hospital, an average of 4weeks), T3(3-month follow up)]
• Functional independence measure (FIM) [Срок оценки: T0(baseline), T1(discharge from ICU, an average of 2 weeks), T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]
• Modified Rankin Scale (mRS) [Срок оценки: T0(baseline), T1(discharge from ICU, an average of 2 weeks), T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]
• Perme ICU mobility score [Срок оценки: T0(baseline), T1(discharge from ICU, an average of 2 weeks)]
• National Institutes of Health Stroke Scale (NIHSS) [Срок оценки: T0(baseline), T1(discharge from ICU, an average of 2 weeks), T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]
• Instrumental Activity of Daily Living scale [Срок оценки: T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]
• Hospital anxiety and depression scale (HADS) [Срок оценки: T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]
• 36-item short form health survey (SF-36) [Срок оценки: T2(discharge from hospital, an average of 4weeks), T3(3-month follow up) and T4(1-year follow up).]