Dipankar Nandi

Globus pallidus internus deep brain stimulation for dystonic conditions: A prospective audit

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 target in the treatment of patients with dystonia. The results of 25 consecutive patients with medically intractable dystonia (12 with generalised dystonia, 7 with spasmodic torticollis, and 6 with other types of dystonia) treated with GPi stimulation are reported. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS benefited all groups, resulting in clear and progressive improvements in their condition. This study clearly demonstrates that DBS of the GPi provides amelioration of intractable dystonia.

Hardware-Related problems of deep brain stimulation

Deep brain stimulation for the alleviation of movement disorders and pain is now an established therapy. However, very little has been published on the topic of hardware failure in the treatment of such conditions irrespective of clinical outcome. Such device‐related problems lead to significant patient morbidity and increased cost of therapy in the form of prolonged antibiotics, in‐patient hospitalization, repeat surgery, and device replacement. We report a prospective review of our experience at the Radcliffe Infirmary Oxford from the period of April 1998 to March 2001. Overall there is a 20% rate of hardware‐related problems in this series, which falls between the 7% and 65% rates reported by other groups. The majority of these failures occurred early on in the series, and numbers declined with experience. Some of the problems may be idiosyncratic to the methodology of individual groups.

Deep brain stimulation for generalised dystonia and spasmodic torticollis.

Dystonia appears distinct from the other tremulous disorders in that improvement following deep brain stimulation frequently appears in a delayed and progressive manner. The rate of this improvement and the point at which no further progress can be expected are presently unknown. The establishment of these parameters is important in the provision of accurate and relevant prognostic information to these patients, their carers, and their treating physicians. We studied 12 consecutive patients with generalised dystonia (n=6) and spasmodic torticollis (n=6) who underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed up for a minimum of 2 years postoperatively. Standard rating scales were used to quantify their neurological improvement. Both groups experienced a statistically significant improvement in their rating scores at both one and two years following surgery. At 2 years follow-up, the spasmodic torticollis group exhibited a 59% improvement in their total Toronto Western Spasmodic Torticoilis Rating Scale (TWSTRS) rating score and the generalised dystonia group attained a 46% improvement in their overall Burke, Fahn and Marsden Dystonia Rating Scale (BFMDRS) evaluation. Ninety-five percent of the final improvement was attained by 6.4 months in the generalised dystonia group and by 6.6 months in those with spasmodic torticollis. There was no significant improvement after one year postoperatively. These findings add further support to GPi DBS as an effective treatment for generalised dystonia and spasmodic torticollis, and furnish important information as to the expected rate of improvement and the point at which no further gains can be reasonably anticipated.

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.

Deep brain stimulation of the pedunculopontine region in the normal non-human primate.

Lesions in the pedunculopontine nucleus (PPN) cause akinesia. The PPN degenerates in Parkinsons disease. Stimulation of the PPN region induces stepping movements in rats and cats. These findings suggest that the PPN may play an important role in akines ia and that stimulating it may alleviate akinesia.Therefore, we have stereotactically implanted a macroelectrode in the left PPN region in a normal macaque to investigate the effects of deep brain stimulation at different frequencies. Motor activity was recorded with an infra-red counter and behaviour videotaped. At frequencies above 45 Hz there was significantly more severe akinesia than at lower frequencies (paired t -test, n=15, P<0.005). At 100 Hz, there was gross impairment of postural control. At low frequencies (5-30 Hz), stimulation induced a 5-Hz tremor in the right arm. We conclude that stimulating the PPN region at high frequency causes akinesia, whereas low frequencies induce some positive motor effects.

Deep brain stimulation: indications and evidence.

Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson’s disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive–compulsive disorder and Tourette’s syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research augurs for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson’s disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested.

The sensory and motor representation of synchronized oscillations in the globus pallidus in patients with primary dystonia

In 15 patients with primary dystonia (six cervical and nine generalized dystonias) who were treated with bilateral chronic pallidal stimulation, we investigated the sensorimotor modulation of the oscillatory local field potentials (LFPs) recorded from the pallidal electrodes. We correlated these with the surface electromyograms in the affected muscles. The effects of involuntary, passive and voluntary movement and muscle-tendon vibration on frequency ranges of 0-3 Hz, theta (3-8 Hz), alpha (8-12 Hz), low (12-20 Hz) and high beta (20-30 Hz), and low (30-60 Hz) and high gamma (60-90 Hz) power were recorded and compared between cervical and generalized dystonia groups. Significant decreases in LFP synchronization at 8-20 Hz occurred during the sensory modulation produced by voluntary or passive movement or vibration. Voluntary movement also caused increased gamma band activity (30-90 Hz). Dystonic involuntary muscle spasms were specifically associated with increased theta, alpha and low beta (3-18 Hz). Furthermore, the increase in the frequency range of 3-20 Hz correlated with the strength of the muscle spasms and preceded them by approximately 320 ms. Differences in modulation of pallidal oscillation between cervical and generalized dystonias were also revealed. This study yields new insights into the pathophysiological mechanisms of primary dystonias and their treatment using pallidal deep brain stimulation.

The oscillatory activity in the Parkinsonian subthalamic nucleus investigated using the macro-electrodes for deep brain stimulation

OBJECTIVES To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation. METHODS During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinsons disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN. RESULTS Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity. CONCLUSIONS We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Deep brain stimulation in the management of neuropathic pain and multiple sclerosis tremor.

Abstract: Deep brain stimulation (DBS) of the central gray matter was an important component of the surgical management of chronic, drug-refractory, central neuropathic pain until only a decade ago. However, in the recent past, this technique has been increasingly neglected and has been largely replaced by motor cortex stimulation (MCS). The results of MCS, however, are far from uniform, and the best reports quote a range of 50% to 75% success in providing satisfactory pain relief. In recent years, there has been considerable success in treating various movement disorders, particularly in Parkinson’s disease (PD) and dystonia, by chronic high-frequency DBS of nuclear structures in the basal ganglia. This technique has also been shown to be relatively effective in some selected cases of tremulous conditions like essential tremor and posttraumatic tremor. However, when the same techniques have been applied to patients with multiple sclerosis tremor (MST), the results have been mixed. As a result, DBS for MST has often been perceived as an unreliable and inconsistent therapeutic intervention. The authors present their experience with the application of DBS in these two relatively unpopular areas for neuromodulation in the current practice of functional stereotactic neurosurgery. The results demonstrate that with careful patient selection, DBS can offer significant functional benefit in both of these difficult clinical conditions.

Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases.

&NA; Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been used for the treatment of chronic central pain for decades. In recent years motor cortex stimulation (MCS) has largely supplanted DBS in the surgical management of intractable neuropathic pain of central origin. However, MCS provides satisfactory pain relief in about 50–75% of cases, a range comparable to that reported for DBS (none of the reports are in placebo‐controlled studies and hence the further need for caution in evaluating and comparing these results). Our experience also suggests that there is still a role for DBS in the control of central pain. Here we present a series of eight consecutive cases of intractable chronic pain of central origin treated with PVG DBS with an average follow‐up of 9 months. In each case, two electrodes were implanted in the PVG and the ventroposterolateral thalamic nucleus, respectively, under guidance of corneal topography/magnetic resonance imaging image fusion. The PVG was stimulated in the frequency range of 2–100 Hz in alert patients while pain was assessed using the McGill‐Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5–35 Hz stimulation while 50–100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency thalamic FPs at 0.2–0.4 Hz closely associated with the pain. During 5–35 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50–100 Hz), however, there was no reduction in the FPs and no pain suppression. We have found an interesting and consistent correlation between thalamic electrical activity and chronic pain. This low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation. It may be possible to use the presence of these slow FPs and the effect of trial PVG DBS on both the clinical status and the FPs to predict the probable success of future pain control in individual patients.