title: Risk of surgical delivery to deep nuclei: a meta-analysis.
abstract: Many novel strategies aimed at neuroprotection or neurorestoration involve surgical delivery of agents to deep nuclei along multiple trajectories. Using intracerebral hemorrhage on a per-trajectory basis as our primary end point, we quantified the level of surgical risk associated with agent delivery to deep nuclei. Secondarily, we quantified other event rates and examined relationships between intracerebral hemorrhage and 8 variables related to patient and practice characteristics. Meta-analytic techniques were used to pool complication rates reported in published articles involving deep brain stimulator electrode implantation or infusion of vectors, tissues, or trophic factors. One hundred nine studies were included in our analysis, comprising 6237 patients and 9890 trajectories to deep nuclei. The estimated per-trajectory intracerebral hemorrhage rate was 1.57% (95% confidence interval, 1.26%-1.95%). The proportion of trajectories leading to permanent or serious neurological deficits was 0.41% (0.28%-0.60%). The estimated mortality rate per trajectory was 0.14% (0.07%-0.29%). No relationship between intracerebral hemorrhage and sex, age, duration of disease, or exclusion of patients with surgical complications was observed; a significant positive relationship was observed with the use of microelectrode recording and a significant negative relationship with putamenal delivery. Our results show a significant difference in intracerebral hemorrhage rates between inoculations and electrode implantation. Our findings suggest that studies involving multiple trajectories to deep nuclei involve a high level of risk. However, inoculations may be significantly safer than electrode implantation. Our analysis has implications for the ethics of preclinical research, independent review of risk, subject selection, and adverse event reporting.
authors.affiliation: Biomedical Ethics Unit, Department of Social Studies of Medicine, McGill University, Montreal, Quebec, Canada. jonathan.kimmelman@mcgill.ca
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kimmelman
authors.forename: Katherine
authors.initials: K
authors.lastname: Duckworth
authors.forename: Tim
authors.initials: T
authors.lastname: Ramsay
authors.forename: Tiffini
authors.initials: T
authors.lastname: Voss
authors.forename: Bernard
authors.initials: B
authors.lastname: Ravina
authors.forename: Marina Elena
authors.initials: ME
authors.lastname: Emborg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000209:etiology*; D002648:Child; D016208:Databases, Factual / Q000706:statistics & numerical data; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004567:Electrodes, Implanted / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology*; D055815:Young Adult