Transcranial laser therapy for acute ischaemic stroke.

Rationale: Ischaemic stroke is a leading cause of disability and death worldwide, but limited treatment options are available to improve its outcomes. Some studies have explored transcranial laser therapy in people with acute ischaemic stroke, but the benefits and harms of this treatment are unclear.

Objectives: The primary objective was to assess the benefits and harms of transcranial laser therapy for improving functional outcomes after acute ischaemic stroke. The secondary objective was to assess the equity of transcranial laser therapy in people with acute ischaemic stroke.

Search methods: We searched CENTRAL, MEDLINE, Embase, ISI Science Citation Index, CINAHL, PEDro (Physiotherapy Evidence Database), REHABDATA, and four ongoing trials registries. We also searched reference lists and databases of conference abstracts for other studies, including any that are ongoing or unpublished. The latest search date was 3 August 2024 for all databases except CenterWatch, which we searched on 1 November 2024.

Eligibility criteria: We included randomised controlled trials (RCTs) comparing transcranial laser therapy with sham treatment or no treatment in people with acute ischaemic stroke, with or without standard treatment in both groups.

Outcomes: The critical outcomes were unfavourable functional outcome, defined as a score of 3 to 6 on the modified Rankin Scale (mRS), and all-cause mortality. The important outcomes were improvement of stroke severity measured on the National Institutes of Health Stroke Scale (NIHSS), serious adverse events, and adverse events.

Risk of bias: We used the Cochrane risk of bias tool (RoB 2) to assess the risk of bias for all outcomes in all RCTs.

Synthesis methods: We planned to use risk ratios (RRs) with 95% confidence intervals (CIs) to compare all outcomes. However, for improvement of stroke severity, we extracted odds ratios (ORs) and 95% CIs from the original studies because the raw data were unavailable. Our meta-analyses used fixed-effect modelling. To assess statistical heterogeneity, we used the I² statistic. We used the GRADE approach to assess the certainty of the evidence.

Included studies: We included four RCTs enrolling a total of 1420 people with acute ischaemic stroke. The studies were published between 2007 and 2014. All were multicentre studies, based in Europe, North America, South America, Asia, or more than one of these continents. All studies included people older than 40 years (mean age 68.3 years), and 59.6% of participants were men. All studies enrolled participants within 24 hours after onset of stroke symptoms, all used a transcranial laser of 808-nm wavelength, and all compared transcranial laser therapy with sham treatment.

Synthesis of results: Critical outcomes Transcranial laser therapy results in little to no difference in unfavourable functional outcome at 90 days compared with sham treatment (RR 0.93, 95% CI 0.85 to 1.02; I² = 10%; 3 studies, 1408 participants; high-certainty evidence). Transcranial laser therapy may result in little to no difference in all-cause mortality at 90 days compared with sham treatment (RR 0.96, 95% CI 0.72 to 1.28; I² = 0%; 4 studies, 1420 participants; low-certainty evidence). Important outcomes Transcranial laser therapy may result in little to no difference in improvement of stroke severity at 90 days compared with sham treatment (OR 1.14, 95% CI 0.92 to 1.42; I² = 73%; 3 studies, 1408 participants; low-certainty evidence). Transcranial laser therapy may lead to a slight reduction in serious adverse events at 90 days compared with sham treatment (RR 0.83, 95% CI 0.71 to 0.96; I² = 0%; 4 studies, 1420 participants; low-certainty evidence). Transcranial laser therapy likely results in little to no difference in adverse events at 90 days compared with sham treatment (RR 1.01, 95% CI 0.97 to 1.06; I² = 8%; 3 studies, 1300 participants; moderate-certainty evidence). After excluding the only study with high risk of bias judgements, the findings of sensitivity analyses for unfavourable functional outcome, improvement of stroke severity, and serious adverse events were consistent with the findings of the main analyses. For serious adverse events, we excluded the only study (630 participants) with positive findings, and the pooled effect estimate of the remaining three studies indicated little or no difference between the intervention and control groups.

Authors' conclusions: The current evidence shows no clear benefit or harm associated with transcranial laser therapy in people with acute ischaemic stroke. Our results suggest transcranial laser therapy compared with sham treatment results in little to no difference in unfavourable functional outcome and may result in little to no difference in all-cause mortality at 90 days. The evidence regarding adverse events was of low-to-moderate certainty. More high-quality trials are needed to further evaluate the role of transcranial laser therapy in people with acute ischaemic stroke, to inform the optimal treatment regimen, and to identify people who might benefit most from the therapy.

Funding: This review was supported by the National Natural Science Foundation of China (grant numbers 82171285; 82371323); the Science and Technology Department of Sichuan Province (grant numbers 2024YFHZ0330; 2023NSFSC1558); the 1·3·5 project for disciplines of excellence-Clinical Research Fund, West China Hospital, Sichuan University (grant numbers 2024HXFH022; 2024HXFH023); and the Postdoctor Research Fund of West China Hospital, Sichuan University (grant number 2024HXBH139).

Registration: Protocol available via DOI: 10.1002/14651858.CD012426.