Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. prolonged effects at high and low levels of stimulation.

PURPOSE: To measure vagus nerve stimulation (VNS)-induced cerebral blood flow (CBF) effects after prolonged VNS and to compare these effects with immediate VNS effects on CBF. METHODS: Ten consenting partial epilepsy patients had positron emission tomography (PET) with intravenous [15O]H2O. Each had three control scans without VNS and three scans during 30 s of VNS, within 20 h after VNS began (immediate-effect study), and repeated after 3 months of VNS (prolonged study). After intrasubject subtraction of control from stimulation scans, images were anatomically transformed for intersubject averaging and superimposed on magnetic resonance imaging (MRI) for anatomic localization. Changes on t-statistical maps were considered significant at p < 0.05 (corrected for multiple comparisons). RESULTS: During prolonged studies, CBF changes were not observed in any regions that did not have CBF changes during immediate-effect studies. During both types of studies, VNS-induced CBF increases were similarly located in the bilateral thalami, hypothalami, inferior cerebellar hemispheres, and right postcentral gyrus. During immediate-effect studies, VNS decreased bilateral hippocampal, amygdalar, and cingulate CBF and increased bilateral insular CBF; no significant CBF changes were observed in these regions during prolonged studies. Mean seizure frequency decreased by 25% over a 3-month period between immediate and prolonged PET studies, compared with 3 months before VNS began. CONCLUSIONS: Seizure control improved during a period over which some immediate VNS-induced CBF changes declined (mainly over cortical regions), whereas other VNS-induced CBF changes persisted (mainly over subcortical regions). Altered synaptic activities at sites of persisting VNS-induced CBF changes may reflect antiseizure actions.

Acute stimulation in the external segment of the globus pallidus improves parkinsonian motor signs.

High frequency (>100Hz) electrical stimulation in both the external (GPe) and internal (GPi) segments of the globus pallidus was effective in improving parkinsonian motor signs. Improvement generally occurred at short latency (<5-10 seconds) in both GPe and GPi but was often (50% of the time) delayed in GPi. Dyskinetic movements were observed during stimulation within GPe and GPi but were more frequent in GPe (20% vs. 9%). These findings suggest that electrical stimulation in both GPe and GPi may ameliorate parkinsonian motor signs. The mechanisms responsible for these observations, however, may differ. The tendency for delayed responses with GPi stimulation suggests a more complex spatial-temporal profile of stimulation on the electrical activity of GPi neurons and/or its effect on network activity in pallido-thalamo-cortical circuitry. The rarity of delayed effects with GPe stimulation suggests a more direct role of synaptic inhibition or normalization of neuronal activity of GPi either directly by means of activation of striatopallidal fibers passing through GPe (direct pathway), by means of activation of GPe-->GPi or GPe-->subthalamic nucleus projections (indirect pathway) or indirectly by means of the tonic activation of adjacent fiber pathways. These data provide a rationale for the exploration of electrical stimulation in GPe in patients with medically intractable Parkinson's disease and provide a basis on which to develop further investigations into the use of chronic electrical stimulation for the treatment of Parkinson's disease and other movement disorders.

Effects of subthalamic nucleus stimulation and medication on resting and postural tremor in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and antiparkinsonian medication have proved to be effective treatments for tremor in Parkinson's disease. To date it is not known how and to what extent STN DBS alone and in combination with antiparkinsonian medication alters the pathophysiology of resting and postural tremor in idiopathic Parkinson's disease. The purpose of this study was to examine the effects of STN DBS and antiparkinsonian medication on the neurophysiological characteristics of resting and postural hand tremor in Parkinson's disease. Resting and postural hand tremor were recorded using accelerometry and surface electromyography (EMG) from 10 Parkinson's disease patients and 10 matched control subjects. The Parkinson's disease subjects were examined under four treatment conditions: (i) off treatment; (ii) STN DBS; (iii) medication; and (iv) medication plus STN DBS. The amplitude, EMG frequency, regularity, and 1-8 Hz tremor-EMG coherence were analysed. Both STN DBS and medication reduced the amplitude, regularity and tremor-EMG coherence, and increased the EMG frequency of resting and postural tremor in Parkinson's disease. STN DBS was more effective than medication in reducing the amplitude and increasing the frequency of resting and postural tremor to healthy physiological levels. These findings provide strong evidence that effective STN DBS normalizes the amplitude and frequency of tremor. The findings suggest that neural activity in the STN is an important modulator of the neural network(s) responsible for both resting and postural tremor genesis in Parkinson's disease.