Cerebrolysin in Patients with TBI: Systematic Review and Meta-Analysis. — VialBase Research

Summary

Traumatic brain injury is among the most common causes of death and of failure to return to society, and Cerebrolysin — a mixture of neuropeptides derived from purified porcine brain proteins, with neuroprotective and neurorestorative properties demonstrated in multiple experimental studies both in vitro and in vivo — is an approved treatment for TBI patients in some jurisdictions. This meta-analysis searched PubMed, CINAHL, Web of Science, and Embase from database inception until 11 July 2022 and identified ten eligible clinical studies, both retrospective and prospective, comprising 8749 patients. The pooled analysis found that treatment with Cerebrolysin was associated with a statistically significant change in the Glasgow Coma Scale and the Glasgow Outcome Scale — the two standard measures of consciousness level and functional recovery after brain injury. Two harder endpoints did not move: mortality from any cause was not affected by treatment, and neither was length of hospital stay. The authors concluded that their findings support and confirm the beneficial effects of Cerebrolysin treatment on clinical outcome after TBI, and called for further multi-centre studies to optimise dosing and the timing of administration. The design point that matters for weighing this result is that the included evidence was not restricted to randomised controlled trials; retrospective studies were pooled alongside prospective ones, which is a materially weaker basis than the RCT-only inclusion criteria used by the Cochrane reviews of Cerebrolysin in stroke and vascular dementia.

Key Findings

• Ten clinical studies with 8749 patients, identified by searching PubMed, CINAHL, Web of Science, and Embase from inception to 11 July 2022
• Cerebrolysin treatment was associated with a statistically significant change in Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS)
• Mortality of any cause was not affected by treatment
• Length of hospital stay was not affected by treatment
• The pool combined retrospective and prospective studies rather than randomised controlled trials alone; the authors call for further multi-centre studies to optimise dosing and administration timing

Relevance to Cerebrolysin

This is the most favourable of the clinical syntheses on Cerebrolysin, and it is worth reporting alongside a clear statement of where it sits in the evidence hierarchy. On the positive side, it is the largest patient pool in the file — 8749 patients across ten studies — and it found statistically significant improvement on both GCS and GOS, which are the conventional functional endpoints in traumatic brain injury. On the qualifying side, the pool mixes retrospective with prospective studies rather than restricting to randomised controlled trials, so confounding by indication and selection effects cannot be excluded; the review was published in Brain Sciences rather than through the Cochrane process, so it carries no formal GRADE certainty ratings or systematic risk-of-bias assessment of the kind Cochrane applies; and the two endpoints least vulnerable to observer bias — all-cause mortality and length of stay — showed no effect at all. That pattern, benefit on rated scales without movement on hard outcomes, is exactly the pattern a systematic review is designed to scrutinise. TBI is therefore the indication where Cerebrolysin’s case is strongest, but the case is built on a lower grade of evidence than the unfavourable Cochrane findings in acute ischaemic stroke and vascular dementia, and it should never be presented as though it outranks them.

Citation

Jarosz K, Kojder K, Andrzejewska A, et al. Cerebrolysin in Patients with TBI: Systematic Review and Meta-Analysis. Brain sciences. 2023;13(3). doi:10.3390/brainsci13030507.

See Also

• Parent compound: Cerebrolysin