Induction of Bradykinesia with Pallidal Deep Brain Stimulation in Patients with Cranial-Cervical Dystonia

Department of Neurology, University of California, San Francisco, Calif., USA.
Stereotactic and Functional Neurosurgery (Impact Factor: 2.02). 02/2009; 87(1):37-44. DOI: 10.1159/000195718
Source: PubMed


Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and well-tolerated treatment for idiopathic generalized dystonia. More recently, it has been applied as a treatment for focal and segmental dystonias. This patient population offers an opportunity to study the effects of alteration of pallidal outflow on previously normal limb function.
We sought to retrospectively characterize the extent of novel GPi DBS-induced adverse motor effects in patients with adult-onset cervical and cranial-cervical dystonia using a questionnaire, and compared the findings to dystonia improvement as measured by standard scales.
Despite significant improvement in dystonia (65% in mean Burke-Fahn-MarsdenDystonia Rating Scale motor score, p < 0.005, and 59% in mean Toronto Western Spasmodic Torticollis Rating Scale score, p < 0.008), slowing and difficulty with normal motor function was reported in previously nondystonic extremities in 10 of 11 patients. Symptoms were common in both upper and lower extremities and included new difficulties with handwriting (82%), getting up from a chair or in/out of a car (73%), and walking (45%), and were not associated with aberrant lead placement near the internal capsule.
Although GPi DBS was shown to be effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.


Available from: Brian D Berman, Jan 20, 2014
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    • "It has also been observed that chronic ventral GPi DBS can provoke features of parkinsonism in patients with cervical dystonia [20]. Furthermore, the effects of GPi DBS in patients with dystonia are known to evolve over days, weeks or even months suggesting downstream effects on synaptic plasticity as one mechanism of action of this therapy. "
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    ABSTRACT: Deep brain stimulation of the globus pallidus can be a highly effective treatment for patients with Parkinson's disease (PD), experiencing Levodopa-induced-dyskinesia (LID). Stimulation programming can focus simply on eliminating dyskinesia, or can also attempt to relieve the rigidity, tremor or akinesia of PD itself. In this study, we explored whether additional benefit on the "off" symptoms and signs of PD, could be achieved in post-operative PD patients with good LID control, by making further adjustment to existing stimulation parameters directed towards the more superior electrode contacts, located in the Globus Pallidus pars externa (GPe). Acutely, GPe-DBS led to clear improvement in the akinesia, rigidity and tremor of PD in the off-medication state compared with Globus Pallidus pars interna (GPi) DBS (p = 0.003), however this was accompanied by the development of off-medication dyskinesia. Combined GPi-GPe DBS allowed maintained improvement but without dyskinesia. Follow up of patients over the subsequent 6-12 weeks showed gradual loss of this initial improvement. Switching back to GPi-DBS alone provided greater improvement in off medication symptoms than had been observed using the same GPi-DBS setting, 6-12 weeks previously. Benefits on the off-medication symptoms of PD obtained acutely with GPe-DBS are in general not sustained. Similarly, the effects of GPi-DBS on the off medication symptoms of PD, can evolve over short periods of time presumably as a result of changes in network-wide neuronal plasticity. These clinical observations provide further insight into DBS mechanism of action, and can also help inform optimal methods of GPi-DBS programming. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 03/2015; 21(6). DOI:10.1016/j.parkreldis.2015.03.019 · 3.97 Impact Factor
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    • "). Equally, patients with dystonia who have no disturbance of limb function may develop motor impairment in the upper limbs or gait disturbance during pallidal high-frequency stimulation that otherwise improves their dystonia (Ostrem et al., 2007; Berman et al., 2009; Schrader et al., 2011). Under these circumstances, high-frequency stimulation may be reducing beta activity to an inappropriate level for the tasks undertaken. "
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    ABSTRACT: Oscillatory activity in the beta (13–30 Hz) frequency band is widespread in cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information-coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance.
    European Journal of Neuroscience 04/2014; 39(11). DOI:10.1111/ejn.12574 · 3.18 Impact Factor
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    • "However, problems of speech and swallowing may be more difficult to manage with DBS as assessed by BFMDRS [7,8,34]. Worsening of handwriting and stimulation induced parkinsonism have also been reported in DBS patients with cervical dystonia [23,35-37]. "
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    ABSTRACT: Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory movement disorders, and has been approved by the United States Food and Drug Administration for treatment of dystonia. The success of DBS in the treatment of dystonia depends on our understanding of the anatomy and physiology of this disorder and close collaboration between neurosurgeons, neurologists, clinical neurophysiologists, neuroradiologists and neuropsychologists. Currently, pallidal DBS is an established treatment option for medically refractive dystonia. This review is intended to provide a comprehensive review of the use of DBS for dystonia, focusing mainly on the surgical aspects, clinical outcome, MRI findings and side effects of DBS.
    Translational Neurodegeneration 01/2014; 3(1):2. DOI:10.1186/2047-9158-3-2
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