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

Despite its lower incidence rate within the stroke population and tendency to affect younger individuals, SAH carries the highest risk of PSCI. The neural mechanisms underlying these cognitive deficits remain poorly understood, but potential factors include treatment approaches, underlying disease pathophysiology, post-disease complications, or alterations in neural connectivity. Previous literature indicates that cognitive deficits in SAH primarily manifest in areas such as visuospatial skill, verbal memory language abilities (including verbal comprehension, verbal fluency, abstract language), executive function (working memory) and attention. These impairments significantly impact patients' ability to perform ADL independently and return to work, despite motor function recovery. This pilot study tests the feasibility, logistics, and methodology of the research project, as well as to identify any potential problems or challenges that may arise. In the future, the investigators plan 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. The hypothesis of this study is that there is feasibility and safety in early intervention with MCIT (e-MCIT) in aSAH patients. Otherwise, e-MCIT will result in significant improvements in cognitive function, motor recovery, functional abilities, and ADL among SAH patients upon discharge from the ICU and the post-intervention assessment (in future work will identify by comparing with early mobilization group only).

Background and literature review: 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.

Purpose: This pilot study tests the feasibility, logistics, and methodology of the research project, as well as to identify any potential problems or challenges that may arise. In the future, the investigators plan 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.

Study design: This is a pilot study to testify the feasibility, logistics, and methodology of evaluation and early motor-cognitive integrative training (e- MCIT) on cognitive function, motor recovery, functional ability and abilities in ADL in patients with aSAH in acute phase. 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 three assessment time points including baseline assessment (following initial medical intervention), assessment at the time of discharge from the intensive care center (ICU), and discharge from the hospital. After recruiting in this study, participants all receive the intervention of e-MCIT. If the subjects can complete the tasks, the results and completion times will be recorded. If the tasks cannot be completed, this situation and its probability will be documented as well. Due to the large number of measurement items in this study, it is expected to take a longer time. Breaks will be taken as needed according to each subject's tolerance. If the tasks cannot be completed in one session, they will be carried over to the next day. Our future study will be well-designed according to the result from this study.

Method: 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: 1-3. (5) Able to stand without support 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 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. The e-MCIT consists of early mobilization and early cognitive training. Intervention will be 30 minutes per session, 4-5 sessions 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), forward and reverse digit span (DS) test, Go and no-go (GNG) test, Semantic Verbal Fluency test (SVFT), 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) . 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. 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.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of spontaneous SAH resulting from aneurysm rupture confirmed by either CT scan or angiography.
* Onset of stroke occurring in the acute phase, specifically 2-7 days after medical intervention.
* Participants must be over 18 years old.
* WFNS: 1-3.
* Able to stand without support above 30 seconds.
* Montreal Cognitive Assessment (MoCA)\<26.

Exclusion Criteria:

* 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)
* patients evaluated as unsuitable by their attending physician
* those with other neurological diseases that might interfere with the experiment
* with less than 12 years of education