title: Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms.
abstract: Long-term results show that benefits from chronic deep brain stimulation in dystonia are maintained for many years. Despite this, the neurophysiological long-term consequences of treatment and their relationship to clinical effects are not well understood. Previous studies have shown that transcranial magnetic stimulation measures of abnormal long-term potentiation-like plasticity (paired associative stimulation) and GABAa-ergic inhibition (short-interval intracortical inhibition), which are seen in dystonia, normalize after several months of deep brain stimulation. In the present study, we examine the same measures in a homogenous group of 10 DYT1 gene-positive patients after long-term deep brain stimulation treatment for at least 4.5 years. Recordings were made 'on' deep brain stimulation and after stopping deep brain stimulation for 2 days. The results show that: (i) on average, prior to discontinuing deep brain stimulation, the paired associative stimulation response was almost absent and short-interval intracortical inhibition was reduced compared with normal. This pattern differs from that in both healthy volunteers and from the typical pattern of enhanced plasticity and reduced inhibition seen in deep brain stimulation-naïve dystonia. It is similar to that seen in untreated Parkinson's disease and may relate to thus far unexplained clinical phenomena like parkinsonian symptoms that have sometimes been observed in patients treated with deep brain stimulation. (ii) Overall, there was no change in average physiological or clinical status when deep brain stimulation was turned off for 2 days, suggesting that deep brain stimulation had produced long-term neural reorganization in the motor system. (iii) However, there was considerable variation between patients. Those who had higher levels of plasticity when deep brain stimulation was 'on', had the best retention of clinical benefit when deep brain stimulation was stopped and vice versa. This may indicate that better plasticity is required for longer term retention of normal movement when deep brain stimulation is off. (iv) Patients with the highest plasticity 'on' deep brain stimulation were those who had been receiving stimulation with the least current drain. This suggests that it might be possible to 'shape' deep brain stimulation of an individual patient to maximize beneficial neurophysiological patterns that have an impact on clinical status. The results are relevant for understanding long-term consequences and management of deep brain stimulation in dystonia.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, 33 Queen Square, London WC1N3BG, UK. d.ruge@ion.ucl.ac.uk
authors.forename: Diane
authors.initials: D
authors.lastname: Ruge
authors.forename: Laura
authors.initials: L
authors.lastname: Cif
authors.forename: Patricia
authors.initials: P
authors.lastname: Limousin
authors.forename: Victoria
authors.initials: V
authors.lastname: Gonzalez
authors.forename: Xavier
authors.initials: X
authors.lastname: Vasques
authors.forename: Marwan I
authors.initials: MI
authors.lastname: Hariz
authors.forename: Philippe
authors.initials: P
authors.lastname: Coubes
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D046690:Deep Brain Stimulation / Q000379:methods*; D004056:Differential Threshold; D004421:Dystonia / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D004576:Electromyography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D018709:Statistics, Nonparametric; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D055815:Young Adult
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human