Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

BACKGROUND: The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. METHODS: A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. RESULTS: Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. CONCLUSIONS: Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

Externalising deep brain electrodes: an increased risk of infection?

It is the practice in many centres to externalise deep brain electrodes in functional neurosurgery to confirm efficacy of therapy prior to full implantation of the pacemaker. It has been a concern that such practice might lead to an increased rate of infection. We report a retrospective study of the rates of infection in two major centres where all electrodes are externalised in one centre and directly implanted in the other. We have not found an increased rate of infection as a result of externalisation and feel, particularly in pain patients, that doing so can lead to significant cost savings by avoiding ineffective implantations.

Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured intervention for patients with dystonia. Here we report our results in 20 patients with medically intractable dystonia treated with GPi stimulation. The series comprised 14 patients with generalized dystonia and six with spasmodic torticollis. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS clearly benefited both patient groups. Data conveying the rate of change in neurological function following intervention are also presented, demonstrating the gradual but progressive and sustained nature of improvement following stimulation of the GPi in dystonic patients.

Electrophysiological confirmation of the zona incerta as a target for surgical treatment of disabling involuntary arm movements in multiple sclerosis: use of local field potentials.

Lesioning or chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius results in abolition of tremor in the contralateral limbs in Parkinson's disease (PD) and also in essential tremor. Recently, chronic DBS of the subthalamic nucleus has also proved to be very effective in reducing contralateral limb tremor in PD. These targets have been less effective in controlling the complex limb tremor often seen in multiple sclerosis (MS). Consequently, other targets have been sought in cases of MS with tremor. We describe a patient with MS with disabling proximal and distal involuntary arm movements in whom we were able to obtain sustained control of contralateral arm tremor and achieve functional improvement of the affected arm by chronic DBS of the region of the zona incerta. We also highlight the important role played by local field potentials recorded from the brain, with simultaneous recording of corresponding EMGs, in target localisation.

Targeting the subthalamic nucleus.

The small size and surrounding neuronal structures and fibre tracts make the STN a difficult stereotactic target. In this article we present the technique used by us to target the STN. Our combined experience from two centres comprises 18 lesions and 27 stimulator implants in the STN. Our criteria for patient selection and the use of MRI, frame-on CT and volumetric image fusion are presented. The role of a movement disorder specialist neurologist in the operating theatre, local field potential recording, impedance monitoring, macrostimulation, post-operative CT/MRI and test stimulation are detailed.

Motor cortex stimulation for neuropathic pain.

Motor cortex stimulation is increasingly reported in the literature as a surgical option for the alleviation of neuropathic pain. The authors review the published literature and present their results including those demonstrated in a randomized controlled trial that confirmed the efficacy of the procedure. Patient selection and prediction of outcomes, however, remain difficult issues.

Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases.

There is growing evidence to support the use of motor cortex stimulation (MCS) in the management of patients with chronic neuropathic pain. A prospective audit of ten patients using a modified staged technique for motor cortex implantation provides further evidence for the analgesic effectiveness of this technique. Ten patients suffering from phantom limb pain (n=3), post stroke pain (n=5), post traumatic neuralgia secondary to gunshot injury to the brain stem (n=1) and brachyalgia secondary to neuro-fibromatosis (n=150% pain relief) and long-term benefit in 4/5 of patients who initially responded to intermittent cortical stimulation (longest follow up 31 months after implantation). Of those patients who benefited two had post stroke pain, two phantom limb pain and one post-traumatic neuralgia. We conclude that motor cortex stimulation is an effective analgesic intervention in some patients with chronic neuropathic pain, but it is difficult if not impossible to predict those patients who may respond to treatment prior to implantation. Randomised controlled trials are now urgently needed to test the effectiveness of motor cortex stimulation under double-blind conditions.