Stroke is a leading cause of disability, with over half of stroke survivors being dependent on others for activities of daily living. Two-thirds of strokes are ischemic strokes with over 12 million incident cases annually. Globally, strokes account for over seven million deaths each year.  Modifiable risk factors include blood pressure management, blood glucose and cholesterol control, physical activity, weight management and environmental exposures.

Acute Stroke Therapies

For patients with strokes, tissue plasminogen activator, or alteplase, is the gold standard thrombolytic agent given within 4.5 hours of stroke symptom onset.  It is absolutely contraindicated in active internal bleeding within 21 days, intracranial or subarachnoid hemorrhage, suspected aortic dissection, recent cranial or spinal surgery within 3 months, recent head trauma or stroke, bleeding diathesis, blood thinner use, intracranial vascular malformation or neoplasm, severe uncontrolled hypertension, suspected or confirmed endocarditis, abnormal blood glucose and extensive stroke on cranial imaging.

Evidence-based review of randomised controlled trials of treatment of anterior circulation strokes demonstrates significant improvement in functional independence at 90 days after endovascular thrombectomy plus medical therapy.  Between 2015 and 2023, 15 randomised controlled trials pooling 3897 patients demonstrated efficacy of endovascular thrombectomy and medical treatment for anterior circulation strokes in patients with symptom onset up to 24 hours.

Blood pressure regulation is essential after endovascular thrombectomy to ensure collateral flow to the ischemic penumbra.  Meta-analysis of randomised controlled trials pooling 1516 patients revealed that intensive blood pressure lowering with systolic blood pressures lower than 140 mmHg after successful thrombectomy with modified TICI > 2b (≥50% perfusion) is associated with harm and more functional disability at 90 days.

Neurorehabilitation for Patients with Stroke

Neuroplasticity is key for motor improvement and recovery post stroke, whereby neural circuits may reorganise in perilesional tissue and non-lesional hemisphere to compensate for lost motor function.  Neural networks and circuits develop to facilitate communication between motor and sensory pathways.  Intensive and repetitive training is crucial.

A systematic review of 28 randomised controlled trials (1251 participants) showed that robot-assisted gait training using exoskeleton and end-effector robots within 3 months of stroke significantly improved lower extremity function in terms of gait balance, speed, walking distance and cadence.  A systematic review summarising the most frequently used neurorehabilitation upper extremity interventions of 1307 randomised controlled trials comprising 56,879 subjects included robotics, virtual reality, neuromuscular electrical stimulation, repetitive transcranial magnetic stimulation, therapist-guided task-specific training and botulinum toxin injections for treatment of focal spasticity.

Repetitive transcranial magnetic stimulation can modulate neuronal networks with increased cortical excitability using high-frequency rTMS and decreased cortical excitability using low-frequency rTMS.  In patients with right middle cerebral artery territory strokes, the intact left hemisphere increases inhibition of the injured right hemisphere, depressing its neuronal network activity.  Affected patients may exhibit improved left hemineglect after repetitive transcranial magnetic stimulation with improved detection of stimuli of the contralesional hemisphere, improved usage of contralesional limbs and decreased bidirectional hypokinesis of unaffected limbs into the contralesional space.

Brain-computer interface (BCI) technology in post-stroke upper extremity rehabilitation was demonstrated to be efficacious in a systematic review of 12 randomised controlled trials comprising 298 patients, whereby BCI coupled with existing therapies enhanced both short- and long-term upper limb motor functional recovery.  In motor imagery-based BCI, patients imagine moving the impaired extremity, which produces movement-related cortical potentials and event-related desynchronization on electroencephalography (EEG).  EEG band powers, for instance beta rhythms, decrease over sensorimotor regions before motor tasks, followed by event-related desynchronization to a minimum during the imagined task, with recovery resynchronisation after the task.  These signals are acquired, processed, extracted and sent to wearable robots to provide assistive forces to complete desired movements of the affected limbs toward the imagined task.

Conclusion

Ongoing clinical studies should continue to find ways of activating the brain-body interface, including medical modulation of the altered autonomic nervous system after central nervous system injury, together with wireless biocompatible polymer implants harnessing the benefits of brain-computer interface technology, optogenetic activation, acupuncture and end-effector robots to promote improvement and recovery in patients with strokes and other types of central nervous system injuries.
 
References
 
1. Makkawi S, Bukhari JI, Salamatullah HK, et al. Endovascular thrombectomy after anterior circulation large vessel ischemic stroke: an updated meta-analysis. Syst Rev. 2024;13(1):255.
2. da Silva Neto EP, Ferreira LF, de Cardozo Hernandez ALC, Figueiredo EG, Mota Telles JP. Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomised clinical trials. Neurol Sci. 2024;45(8):3879–86.
3. Calabrò RS. Re-Evaluating the Role of Robotic Gait Training in Post-Stroke Balance Rehabilitation. Brain Sci. 2025 Apr 22;15(5):427.
4. Hofmeijer J, Ham F, Kwakkel G. Evidence of rTMS for Motor or Cognitive Stroke Recovery: Hype or Hope? Stroke. 2023 Oct;54(10):2500-2511.
5. Mansour S, Ang KK, Nair KPS, Phua KS, Arvaneh M. Efficacy of Brain-Computer Interface and the Impact of Its Design Characteristics on Poststroke Upper-limb Rehabilitation: A Systematic Review and Meta-analysis of Randomised Controlled Trials. Clin EEG Neurosci. 2022 Jan;53(1):79-90.
 
--AHHM Issue 71--