Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia.

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs.

Differential effect of dopa and subthalamic stimulation on vestibular activity in Parkinson's disease.

Postural disturbances in advanced Parkinson's disease are less responsive to therapy than other cardinal motor signs. The vestibulocollic reflex represents one brain-stem neuronal circuit involved in postural adjustments. The objective of this study was to investigate the vestibulocollic reflex in parkinsonian patients and the effects of subthalamic stimulation and dopa by recording vestibular-evoked myogenic potentials. After overnight withdrawal of medication, 20 patients with Parkinson's disease with (6 men, 4 women; mean age, 64.4 ± 2.2 years) or without (8 men, 2 women; mean age, 62.7 ± 3.9 years) implanted subthalamic electrodes in different treatment conditions were compared with 10 age-matched controls (5 men, 5 women; mean age, 59.6 ± 2.4 years). Vestibular-evoked myogenic potentials were recorded by electromyographic surface electrodes applied to both sternocleidomastoid muscles (band-pass filter, 8-1600 Hz; sampling rate, 5 kHz) and averaged in response to bilateral auditory tone bursts (120 dB SPL; sine waves, 7 ms; 1000 Hz) applied through earphones. Adjusted vestibular-evoked myogenic potential amplitudes were significantly smaller in parkinsonian patients than in controls, in particular in patients without surgery. Administration of dopa, but not subthalamic stimulation, significantly increased amplitudes. Onset latencies were similar for all groups and treatment conditions. Decreased vestibular-evoked myogenic potential amplitudes in parkinsonian patients suggest reduced vestibular nuclei excitability within the brain stem, which is modulated by dopa but not by subthalamic stimulation. This suggests different pathways for the action of both treatment modalities in Parkinson's disease and may explain clinical differences in terms of postural disturbances. © 2012 Movement Disorder Society.