Cerebrolysin does not improve global functional performance of patients with aneurysmal subarachnoid haemorrhage
A prospective, randomized, double-blind, placebo-controlled, parallel-group pilot study shows that use of cerebrolysin in addition to standard-of-care management of aneurysmal subarachnoid haemorrhage (SAH) is well tolerated and feasible, but does not improve the 6-month global functional performance of patients.
Patients diagnosed with a ruptured intracranial aneurysm were treated at Kwong Wah Hospital in Hong Kong according to the latest 2012 American Heart Association/American Stroke Association guidelines for the management of aneurysmal SAH, with 25 patients receiving additional intravenous cerebrolysin (10–50 mL per day) and 25 control patients receiving normal saline infusions. The mean time from ictus to cerebrolysin or placebo infusion was 29 hours. The patients’ mean age was 53 years, with a male:female ratio of 1:2. Patients in both groups had relatively few comorbidities, with comparable Charlson Comorbidity Index score. [BMC Neurol 2020;20:401]
There was no significant difference in favourable 6-month Extended Glasgow Outcome Scale (GOSE) outcome among patients who received cerebrolysin compared with those who received saline. “Although a higher proportion of cerebrolysin recipients had favourable 6-month modified Rankin Scale [mRS] scores [88 percent] vs the saline group [68 percent], the difference was not significant,” reported the researchers.
A higher incidence of 3-month and 6-month mortality was observed in patients in the saline group than those in the cerebrolysin group. Four out of 25 patients receiving saline alongside the standard-of-care treatment died at these times points, while all patients in the cerebrolysin group survived.
“However, the trial’s sample size was not adequately powered to assess mortality, and our findings could have been coincidental,” noted the researchers.
Nevertheless, in an earlier study in patients with poor-grade SAH, cerebrolysin demonstrated significantly lower 3-month and 6-month mortality rates vs the control group. [Adv Ther 2018;35:2224-2235]
Neurocognitive and quality of life assessments at 6 months were feasible in 80 percent of patients, while the remaining patients were noncommunicable. The mean Montreal Cognitive Assessment scores and neurobehavioral cognitive state examination findings were similar between the cerebrolysin and the placebo groups, but patients in the cerebrolysin group performed notably better in naming (odds ratio [OR], 4.71; 95 percent confidence interval [CI], 1.10 to 20.00) and in reasoning (OR, 2.83; 95 percent CI, 1.01 to 9.61).
Cerebrolysin-related severe adverse effects (AEs) are rare. They are defined as hypersensitivity reactions such as anaphylactic shock, seizures and acute renal failure. Other AEs are generally infrequent, transient and mild, and include agitation, headache, vertigo, as well as gastrointestinal symptoms such dyspepsia, diarrhoea, constipation, nausea and vomiting. [J Med Life 2009;2:350-360] No serious AEs or mortality attributable to cerebrolysin were observed in the current study, and its administration did not interfere with standard-of-care management.
“An earlier intervention time window, a longer duration of drug administration, a larger trial to assess 6-month GOSE or mRS, along with the recruitment of a more homogeneous cohort of moderate-to-severe World Federation of Neurosurgical Societies grade SAH patients may impart greater insight into cerebrolysin’s potential therapeutic role,” concluded the researchers.