What EXACT treatments is your doctor doing during your recovery? Anything out of the ordinary? My previous doctor knew nothing and did nothing. I'm having my new doctor go thru my blog and throw the kitchen sink at my next stroke. If my doctors don't know of most of these treatments I'M FIRING THEM ALL.
A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke
Tsong-Hai Lee1
Shinichiro Uchiyama2
Yohanna Kusuma3
Hou Chang Chiu4
Jose C. Navarro5
Kay Sin Tan6Jeyaraj Pandian7Liang Guo8Yoko Wong8†
Narayanaswamy Venketasubramanian9* 
for the Asian Stroke Advisory Panel- 1Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- 2Clinical Research Center for Medicine, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Medical Center, Tokyo, Japan
- 3National Brain Center Hospital, Jakarta, Indonesia
- 4Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
- 5Jose R. Reyes Memorial Medical Center, Manila, Philippines
- 6University of Malaya Medical Center, Kuala Lumpur, Malaysia
- 7Christian Medical College and Hospital, Ludhiana, India
- 8Singapore Clinical Research Institute, Consortium for Clinical Research and Innovation, Singapore, Singapore
- 9Raffles Hospital, Singapore, Singapore
Background: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities.
Methods: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. “The best available studies” based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus.
Results: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as “the best studies” across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects.
Conclusion: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence.
Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.
Introduction
Stroke is a major cause of death and disability with only a limited number of treatment options to improve functional outcomes or reduce death and disability after a stroke, including thrombolytic therapy, thrombectomy, early use of anti-platelets, decompression craniectomy for “malignant” infarcts, organized stroke care, and constraint-induced movement therapy (1). However, many patients do not receive time-sensitive acute stroke therapies for various reasons (2, 3). Alternative strategies using neuroprotectants have failed to live up to their earlier promise (4). Drug interventions that mediate recovery beyond the acute windows are, therefore, clinically important research targets.
As much as three-quarters of all stroke patients suffer impairments and disabilities, the most common of which are motor weakness (77.4%), urinary incontinence (48.2%), impaired consciousness (44.7%), dysphagia (44.7%), and impaired cognition (43.9%) (5). Transition from independence in activities of daily living to dependency between 3 and 12 months after a stroke may be observed in a high proportion of patients (6). At 5 years, functional and motor outcomes may deteriorate to the status at 2 months post-stroke (7). In a large multi-center clinical trial of stroke patients with one-third of participants coming from Asia, at a median follow-up of 4 years, 19–22% were disabled and 12–14% were dependent, requiring regular help with everyday activities (8).
Stroke burden is largely due to long-term impairments suffered after a stroke, requiring long-term care and loss of productivity (9–14). Improving the degree and chances of recovery will translate to an overall reduction in the burden and cost of stroke care. Apart from standard rehabilitation strategies, however, there is currently no common recommendation on pharmacological treatment for stroke recovery.
With the aging of the global population, the number of disabled stroke survivors is likely to rise. Clearly, treatments are needed to enhance recovery after stroke. Prematurely judging a treatment as ineffective may mean lost opportunities in moving stroke recovery research forward to benefit stroke sufferers. It is entirely possible that the apparent “lack” of the efficacy of neuro-recovery interventions thus far may not only be due to small sample sizes or varying severity of study subjects but also because of premature summative assessments and that following up at an extended time frame might show positive effects. Conversely, claiming a treatment as effective, when there is a lack of evidence, can be problematic as patients may be exposed unnecessarily to possible side effects or miss the opportunity of receiving a more appropriate treatment, in addition to incurring the costs of an ineffective intervention. A review of registered pharmacological therapies that have been investigated for improving post-stroke outcomes will help identify the types of available evidence, information on how research was conducted on them, key characteristics or factors related to treatment effects, and knowledge gaps in the pharmacological treatment of post-stroke patients that will be helpful in both clinical decision-making and planning future studies.
We, therefore, aimed to identify and assess studies of different registered pharmacological therapies investigated for improving post-stroke impairments and/or disabilities. The research questions we sought to answer are:
1. What is the best available evidence based on study design for different registered pharmacological therapies investigated for improving recovery after a stroke?
2. What stroke sub-populations and post-stroke outcomes are improved by these treatments, if any.
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