Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study.
BACKGROUND
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment.


METHODS
156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911.


RESULTS
60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohen's d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events.


CONCLUSIONS
DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period.


BACKGROUND
German Federal Ministry of Education and Research (01GI0201).
Christian-Albrechts-University, Kiel, Germany.
Karsten
K
Witt
Christine
C
Daniels
Julia
J
Reiff
Paul
P
Krack
Jens
J
Volkmann
Markus O
MO
Pinsker
Martin
M
Krause
Volker
V
Tronnier
Manja
M
Kloss
Alfons
A
Schnitzler
Lars
L
Wojtecki
Kai
K
Bötzel
Adrian
A
Danek
Rüdiger
R
Hilker
Volker
V
Sturm
Andreas
A
Kupsch
Elfriede
E
Karner
Günther
G
Deuschl
D000368:Aged; D001007:Anxiety / Q000209:etiology / Q000628:therapy; D001526:Behavioral Symptoms / Q000209:etiology / Q000628:therapy*; D003071:Cognition / Q000502:physiology / Q000528:radiation effects*; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D011340:Problem Solving / Q000502:physiology; D011788:Quality of Life; D020531:Subthalamic Nucleus / Q000502:physiology* / Q000528:radiation effects