Dystonia syndromes are diverse movement disorders characterized by disabling, painful,
and sustained involuntary muscle contraction.[1] It's classified by body distribution (focal, segmental, multifocal, hemidystonia,
and generalized) and etiology (heritable, secondary to nervous system pathology, or
idiopathic).[1] The pathophysiology is poorly understood but lesion studies,[2] functional imaging,[3] and electrophysiological studies[4] provide evidence for the involvement of the basal ganglia, specifically the globus
pallidus. Symptoms result from impaired sensory-motor inhibition resulting in increased
basal ganglia excitability and decreased spatial and temporal somatosensory discrimination.[5] Treatment is aimed at reducing pain and functional impairment, with pharmacological
approaches as the first line. Despite multiple options, many patients with generalized
and some focal dystonias remain refractory to pharmacological treatments.[6]
Various neurosurgical interventions have been trialled for the treatment of dystonia,
including peripheral denervation, intrathecal baclofen infusion, and ablating the
basal ganglia or thalamus. However, deep brain stimulation (DBS) primarily targeting
the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has evolved as
a covetable option with the ability to provide personalized, reversible, and titratable
neuromodulation. The available literature has recently been reviewed[7] and demonstrates the safe and efficacious use of DBS in dystonia for both GPi or
STN, resulting in excellent and equivalent improvement in patients' movement and disability
scores. Efficacy was also assessed relative to the body distribution with focal dystonia
exhibiting better improvement in motor symptoms scores but less enhancement in quality
of life compared with segmental dystonia. However, all dystonia distributions studied
showed significant postoperative improvement. Also, it is well established that those
with primary dystonias also respond better to DBS than those with secondary dystonias.
Moreover, those with motor improvement from DBS will likely also demonstrate significant
improvement in disability symptoms. As such, the current state of the literature supports
the use of DBS, however, still fails to explain outcome variability and does not allow
for a tailored patient-specific approach to management with DBS. Advances in neuroimaging
may provide insights into this through patient-specific treatment selection, surgical
targeting, and DBS programming.
In the current edition of the Arquivos de Neuro-Psiquiatria, Listik et al.[8] present work aimed at better understanding factors that predict individual patient
responsiveness to DBS therapy. They hypothesize that connectivity of the stimulation
site may be responsible for some of the DBS response. Motor impairment and disability
scores (Burke-Fahn-Marsden Dystonia Rating Scale) were prospectively acquired in 5
patients with generalized dystonia of inherited/idiopathic etiology and undergoing
bilateral STN-DBS for refractory motor symptoms. Using a combination of stimulation-outcome
mapping and normative connectivity analysis, the authors show that stimulation location
within the STN target does not explain the variability in clinical outcomes seen.
However, the pattern of connectivity between the stimulated region and the left pre
and postcentral gyrus and right cerebellar lobule III and vermis IX were significantly
correlated with improved motor response to DBS. This supports other recent evidence
that states the ideal DBS target relies not only on the anatomical position but also
on its structural connectivity.[9] This work presents a step toward individualized target selection based on preoperative
patient characteristics, including structural connectivity.
Similarly, intraoperative target selection has been further refined by studies employing
stimulation-outcome mapping in large cohorts. Elias et al.[10] examined the motor outcome in 64 dystonia subjects (11 idiopathic/genetic, 53 acquired)
who underwent bilateral GPi-DBS. They showed the greatest symptomatic improvement
with stimulation in the ventroposterior GPi gray matter, located 3mm posterior, 1mm
superior, and 1mm medial to the typical target location. They also localized areas
of stimulation associated with poorer response to the superior parts of the external
globus pallidus. These maps can predict clinical variance in outcomes following DBS
therapy and provide preliminary blueprints for refined surgical targeting and postoperative
DBS programming.
Insights into outcome variation in DBS therapy have also come from the functional
magnetic resonance imaging literature. Loh et al. demonstrate that optimal DBS programming
engages a functional network resulting in sensorimotor cortex deactivation in 15 cervical
dystonia patients with GPi-DBS.[11] This pattern of functional changes was also shown to be intimately related to clinical
improvement. This work highlights the potential for imaging biomarkers in DBS programming.
There is growing scientific evidence demonstrating the safety and efficacy of DBS
for the treatment of medically refractory dystonia, however, optimal patient and surgical
target selection remains unclear. Here multiple examples are presented that demonstrate
how advances in neuroimaging are contributing to the understanding of DBS therapy
in dystonia. These advances may lead to improved patient and target selection and
DBS programming.
