Cerebellar Deep Brain Stimulation for Acquired Hemidystonia

Abstract

Background Background: The cerebellum's role in dystonia is increasingly recognized. Dystonia can be a disabling and refractory condition; deep brain stimulation can help many patients, but it is traditionally less effective in acquired dystonia. New surgical targets would be instrumental in providing treatment options and understanding dystonia further. Objective Objective: To evaluate the efficacy of deep brain stimulation of the cerebellum in acquired dystonia. Methods Methods: We report our management of a 37-year-old woman with severe left arm and leg dystonia, a complication of an ischemic stroke in childhood. She had already had 2 thalamotomies with only transient benefit. These procedures, in addition to her initial stroke that had damaged the basal ganglia, left traditional deep brain stimulation targets unavailable. ResultsResults: After implantation of bilateral deep cerebellar nuclei, dystonia improved with a 40% reduction in severity on scales and subjective reports of improved posturing, gait, and pain. This improvement has been maintained for almost 2 years after implantation. Conclusion Conclusion: Cerebellar stimulation has potential for therapeutic benefit in acquired dystonia and should be further explored.Although dystonia was classically thought to arise from basal ganglia pathology, increasing evidence supports a critical role of the cerebellum in its pathophysiology as well. 1 Through pharmacologic or genetic alteration of cerebellar output pathways, irregular cerebellar activity leads to high-frequency burst firing of the basal ganglia and is associated with dystonic posturing in mice. 2-4 Subsequent inhibition of cerebellar outflow, either electrically or pharmacologically, reduces the abnormal basal ganglia activity and improves dystonia. 3,4 Whereas classically the cerebellum and basal ganglia communicate through rubro-thalamo-cortical connections, rapid modulation may occur through a more direct, disynaptic pathway, with 1 relay in the thalamus. This pathway has recently been identified in rodents and nonhuman primates 5-8 and, in animal models, conveys the aberrant activity that underlies dystonic posturing. 3 In humans, structural abnormalities in the cerebellum or its afferent pathways have been implicated as the cause of dystonia in several cases. 9,10 Similarly, in a small autopsy study, a reduced density of cerebellar Purkinje cells was found in patients with cervical dystonia when compared with healthy controls. 11 The role of the cerebellum in dystonia indicates its potential as a therapeutic target for deep brain stimulation (DBS). In mouse models of dystonia, DBS of cerebellar output nuclei improved dystonic posturing and general mobility. 4 In humans, the invasive stimulation of the cerebellar hemispheres has been described previously for spasticity and dystonia with variable effect. 12,13 Recently, stimulation of the deep cerebellar nuclei has been employed for spasticity and dystonia as a result of cerebral palsy. 14,15 Identifying a new target would be clinically very use...

Neuromodulation of the cerebellum rescues movement in a mouse model of ataxia

“…If prolonged muscle contractions are a prerequisite for DBS working, then cerebellar stimulation could also be beneficial for different forms of dystonia, a heterogeneous disorder in which specific abnormalities, such as widened EMG signals and muscle co-contractions, tend to occur as consistent features 43 . Preliminary studies in humans 78 and mice 26 indeed support the utility of cerebellar stimulation for dystonia. How effective therapeutic cerebellar DBS would be for neurodegenerative ataxias depends on which circuit properties change and how they might mediate the positive effects of stimulation because Purkinje cell loss alone does not block cerebellar DBS effectiveness 18 .…”

High Frequency Deep Brain Stimulation of Superior Cerebellar Peduncles in a Patient with Cerebral Palsy

“…The deviation of electrode placement in DN stimulation due to the large size of the DN may account for the variable effects observed in those reported cases and in our case. The stimulation parameters (1.85~2.45 V, 50 µs, 130 Hz) used in this study were lower than most previously reported stimulation parameters of cerebellar DBS studies (Table 4) [ [13][14][15][16][17][18]. The selection of the electrode lead and correct lead placement may be the key step for the low parameter in our study.…”

“…Shiro Horisawa et al also reported a patient with generalized dystonia who responded well to SCP DBS than DN DBS [16]. The study reported by Brown et al showed the validity of DN DBS in treating hemidystonia; however, it is worth noting that the active contacts were in close proximity to or within SCP [17].…”

“…DBS is conducted by a cylinder lead that can be precisely inserted into deep brain targets such as the DN and SCP using a stereotactic technique. Recently, case reports have demonstrated the efficacy of DN or SCP DBS in patients with dystonia [16][17][18]. However, there is limited clinical evidence for the efficacy of cerebellar DBS, and consensus on the selection of appropriate stimulation targets for patients with CP has yet to be reached.…”

Case Report: Deep Cerebellar Stimulation for Tremor and Dystonia

“…However, this procedure was abandoned for unknown reasons. To date, there have been few reports on deep cerebellar stimulation (8)(9)(10)(11). Sokal et al reported the treatment of secondary dystonia by anterior cerebellar DBS, which resulted in a 42.8% improvement according to the Unified Dystonia Rating Scale (10).…”