Literature Review on Lesion-Symptom Mapping and Deep Brain Stimulation for Poststroke Spasticity: Restoring a...

The present study aimed to define a structural network of stroke-induced and spasticity-related lesions and to relate this network to target sites and reported effects of deep brain stimulation (DBS) to treat poststroke spasticity.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed (online suppl. Table 2). We performed two separate systematic literature reviews, collecting data from previously published voxel-based lesion-symptom mapping (VLSM) studies for poststroke spasticity patients searching the Medline database on Pubmed using the keywords "stroke," "spasticity," and "lesion mapping" as well as data from previously published cohorts undergoing DBS for poststroke spasticity using the keywords "brain stimulation" and "spasticity." Data collected from each study included patient demographic characteristics, stroke diagnosis, movement disorder, DBS target, stimulation parameters, complications, and outcomes. Data from VLSM studies were used to calculate coordinate-based activation likelihood clusters, which were then used as seeds for enhanced fiber tracking to analyze affected networks.

Data from five studies on voxel-based lesion-symptom mapping for stroke-induced spasticity were included in the analysis. Meta-analytical mapping of stroke-related lesions identified significant clusters located in the basal ganglia-thalamo-cortical network which were predominantly connected to the sensorimotor cortex. We identified eight studies (four retrospective case series, two prospective open-label non-randomized trials, and two prospective double-blind trials) fulfilling our inclusion and exclusion criteria on DBS for spasticity reporting on 107 patients in total. Most studies reported outcomes in patients with cerebral palsy, a condition associated with both stroke-related spasticity and hypertonia-related dystonia, which are difficult to differentiate clinically. Target sites included different parts of the cerebellum and the motor thalamus with overall mixed results.

Because all reported effective DBS target sites are situated along the cerebello-thalamo-cortical network, we hypothesize that the therapeutic effect of DBS on spasticity might be induced by resetting a functional imbalance between the basal ganglia-thalamo-cortical and the cerebello-thalamo-cortical networks in patients with a supraspinal etiology of spasticity. However, the results need to be interpreted cautiously due to the inevitable inclusion of stroke-related dystonia.