Subcortical evoked activity and motor enhancement in Parkinson's disease.

Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease.

Implementing novel trial methods to evaluate surgery for essential tremor.

INTRODUCTION: Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. MATERIALS AND METHODS: Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. RESULTS: I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0.0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0.001), 20% had 11 correct perceptions (p = 0.013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. CONCLUSIONS: DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. CLASSIFICATION OF EVIDENCE: This study is the first to provide Class I evidence for the efficacy of DBS for ET.

High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma.

We investigate the clinical outcome from stimulation of the mamillothalamic tract in two patients with intractable epilepsy secondary to hypothalamic hamartomas. One patient has a left-sided and the other a right-sided tumor. Both patients presented with a history of gelastic and complex partial seizures resistant to multiple antiepileptic drugs. Both patients underwent insertion of a single deep brain-stimulating electrode ipsilateral to the site of the tumor, lying adjacent to the mamillothalamic tract. Postoperatively they both had a significant reduction in seizure frequency, with one patient being seizure free for the last 10 months. An improvement in mood was reported by the patient's primary carers and demonstrated on quality of life questionnaires.