Management and Outcome of Pallidal Deep Brain Stimulation in Severe Huntington's Disease

Abstract

Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS.

Behavioral Neurobiology of Huntington's Disease and Parkinson's Disease

“…Consequently, decreased neuronal activity in the GPi results in increased thalamic and cortical activity and emergence of chorea (Albin et al 1989). These case studies reported improvement of chorea (Fasano et al 2008;Fawcett et al 2005;Hebb et al 2006;Huys et al 2013;Kang et al 2001;Moro et al 2004;Velez-Lago et al 2013) however in some instances the worsening of bradykinesia was reported (Huys et al 2013). The frequencies used for brain stimulation were between 40 and 180 Hz, with the best results obtained with 130 Hz.…”

“…Based on the success of the deep brain stimulation (DBS) in the treatment of movement disorders like Parkinson's disease (Deuschl et al 2006), experimental DBS was applied to attenuate hyperkinetic motor symptoms in HD patients (Fawcett et al 2005;Fasano et al 2008;Hebb et al 2006;Huys et al 2013;Kang et al 2011;Moro et al 2004;Tang et al 2005;Temel et al 2006;Velez-Lago et al 2013). In HD there is an apparent early loss of striatopallidal D2-positive MSNs in the striatum that leads to the attenuation of striatal inhibitory activity in the external segment of the globus pallidus (GPe), increased GPe firing and reduced activity in the subthalamic nucleus (STN) resulting in decreased firing of neurons in the internal segment of the globus pallidus (GPi).…”

“…The frequencies used for brain stimulation were between 40 and 180 Hz, with the best results obtained with 130 Hz. The majority of DBS case reports in HD, although limited to a small number of individual cases, suggest that it may be a treatment choice for drug-resistant chorea in HD (Huys et al 2013). One case study found significant improvement of reflective and voluntary saccades, which are known to be impaired in HD patients (Fawcett et al 2005).…”

Deep Brain Stimulation in Huntington’s Disease—Preliminary Evidence on Pathophysiology, Efficacy and Safety

“…On the other hand, DBS stimulation of the GPi led to far more inconsistent effects, up to now. The effects of GPi-DBS on patients cognition range from a progressive decline similar to non-stimulated HD patients [ 58 , 61 , 67 ] to stable cognitive functions for at least 4 years [ 59 ] and even to alleviation in distinct cognitive abilities [ 68 , 62 ]. Various causes have been discussed for the numerous observed effects of GPi-DBS.…”

Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans

“…In particular, DBS has been applied in the treatment of Parkinson's disease 3,4,5 , essential tremor 6 , primary/generalized segmental dystonia 7,8,9 , Huntington's disease 10,11 , treatment-resistant-depression 12,13 , nicotine and alcohol addiction 14 , Alzheimer's disease 15,16 , Tourette's syndrome 17 and chronic disorder of consciousness (DOC) 18,19,20 .…”