A Prospective Pilot Trial for Pallidal Deep Brain Stimulation in Huntington's Disease.
Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial.



In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability, and quality-of-life.



Intention-to-treat analysis of all patients (n = 3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p = 0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. Eight adverse events and two additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred.



Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington's disease. Their effects on chorea and dystonia and on quality-of-life should be examined in larger controlled trials.
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Lars
L
Wojtecki
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Stefan J
SJ
Groiss
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Stefano
S
Ferrea
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Saskia
S
Elben
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Christian J
CJ
Hartmann
Brain Repair Group, School of Biosciences, Cardiff University , Cardiff , UK.
Stephen B
SB
Dunnett
Brain Repair Group, School of Biosciences, Cardiff University , Cardiff , UK.
Anne
A
Rosser
Department of Neurology, St. Josef-Hospital, Ruhr University , Bochum , Germany.
Carsten
C
Saft
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Martin
M
Südmeyer
Coordinating Centre for Clinical Trials, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany.
Christian
C
Ohmann
Department of Neurology, Centre for Movement Disorders and Neuromodulation, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany ; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich- Heine-University Düsseldorf , Düsseldorf , Germany.
Alfons
A
Schnitzler
Department of Stereotactic and Functional Neurosurgery, Medical Faculty, Heinrich-Heine-University Düsseldorf , Düsseldorf , Germany.
Jan
J
Vesper
chorea; deep brain stimulation; pallidum; Huntington's Disease