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Parkinson’s Disease
dopamine dysregulation syndrome, medication–stimulation interactions, or operative data on at least one standardized neuro-psychological test, and
a phenomenon that is part of hypomania. provided sufficient information to allow calculation of effect sizes, identified 28
studies that met inclusion criteria. These studies yielded a maximum combined
Subthalamic Deep Brain Stimulation sample size of 612 for calculation of the effect size of changes in various
Controversy exists concerning the frequency, nature, and extent of cognitive domains of cognition. Given the large number of techniques used in the
changes after STN DBS and the factors underlying such changes. The reported literature, the tests were assigned to the functional domains they are
frequencies under which neurobehavioral changes occur after STN DBS are commonly accepted to measure (e.g. verbal memory, language, attention).
quite variable. A recent review
26
estimated that cognitive problems Analyses revealed that STN DBS (considered in its entirety as a treatment
(unelaborated upon) are observed in 41% of patients after STN DBS. However, procedure) was associated with moderate declines in verbal fluency and mild
examination of clinical studies suggests that profound changes in cognition are declines in verbal memory and executive function. Mild improvements were
fairly rare. Rodriguez-Oroz and colleagues,
27
who carefully defined severity of observed in psychomotor/information processing speed.
impairment, found that severe impairments (incapacitating ones) occurred in
1–2% of cases. Moderate impairments (requiring treatment or exerting mild Overall, the uncontrolled, controlled, and meta-analytic findings agree that STN
functional impact) and mild deficits (without functional impact) occurred DBS is relatively safe from a cognitive perspective. However, it should be borne
in about 20% of patients. This latter figure is quite similar to that reported in in mind that meta-analysis does not, despite attaching greater weight
another series,
28
but considerably higher than the approximate 4% incidence to studies with larger samples, redress the methodological shortcomings of the
of cognitive impairment observed in a recent controlled multicenter trial studies included in the analyses. In addition, research has been unable to
(although it is not clear how this impairment was defined).
29
Most studies reliably identify factors underlying cognitive declines after STN DBS, but
employing formal neuropsychological evaluations have been uncontrolled and potential factors include advanced patient age, pre-existing cognitive
used fairly small samples, and methodological limitations of these studies have impairment, misplacement of electrodes and/or current spread to limbic and
been reviewed.
30–34
These studies, with few exceptions,
20,35–39
have observed associative territories, stimulation parameters, depression, apathy, and changes
small and circumscribed cognitive changes, most often in verbal fluency (timed in medication after surgery. Mood changes and psychiatric complications after
oral word generation according to different phonemic or semantic STN DBS have received increasing attention. A meta-analysis of 22 studies
constraints).
16,17,37,39–58
Even among studies reporting more widespread cognitive published between 1993 and 2004
60
estimated that about 7% of patients
declines there is disagreement as to the clinical meaningfulness of these develop depression after STN DBS, that hypomania or a manic episode occurs
changes. Alegret and co-workers
35
interpreted the changes not to be of clinical in about 2%, and that other psychiatric disorders such as hypersexuality,
significance, in contrast to Saint-Cyr et al.
38
and Smeding et al.
39
lability, psychosis, and hallucinations occur in 4% of patients. Similar figures
were reported in a review by Temel and colleagues:
26
depression 8%,
As many of the neuropsychological studies of STN DBS have small sample sizes, hypomania or mania 4%, anxiety disorders <2%, and personality changes,
greater weight should be given to the five controlled neuropsychological hypersexuality, apathy, and aggressiveness <0.5%. These figures coincide with
studies (excluding studies limited to language or cognitive screening the overall rate of psychiatric matters requiring treatment (9%) in a controlled
evaluations), even though each has significant methodological and/or study of 99 patients.
39
conceptual limitations. The first controlled neuropsychological study of STN
DBS
45
compared outcomes in eight patients with bilateral STN DBS, eight Despite the similarity of average estimates, the range of the reported rates of
patients undergoing unilateral pallidotomy, and eight unoperated PD patients. behavioral alterations is quite broad:
32
depression 1.5–25%, attempted and
In that study, a selective decline in semantic verbal fluency was observed in the completed suicide 0.5–2.9%, and (hypo)mania 4–15%. One retrospective
STN DBS group. Similar findings were observed in three other controlled analysis reported transient mood disturbance in as many as 64% of patients.
61
studies
48,50,59
and one study was helpful in defining the roles of surgery and Factors possibly related to this variability in outcomes include patient
stimulation in the changes.
50
While the procedure as a whole (surgery selection/exclusion criteria, especially with regard to psychiatric illness,
plus stimulation) was associated with subtle declines in delayed verbal recall ascertainment and definition methods, surgical and post-operative
and language, the effect of stimulation per se (comparing test performance management differences, rigor of study methodology, and surgical experience
with stimulators turned on and off relative to change observed in a control of a center (in that morbidity typically decreases as center experience
group) revealed no significant changes. increases).
62
An informal review of studies raises the hypothesis that earlier
published studies, studies with small samples (both of these factors may be
Another controlled study has found more widespread and serious cognitive associated with the experience of treatment centers), and studies with longer
changes
39
among 99 STN DBS patients evaluated within three months before follow-up are apt to report a higher incidence of post-operative psychiatric
surgery and six months after surgery compared with 36 medically treated PD morbidity. For example, one study of 11 patients over five years reported
patients tested six months apart. The STN DBS group had more marked decline mania/hypersexuality in almost 20% and apathy in almost 10%.
41
Another
in overall level of cognitive function (approaching statistical significance), verbal study of 37 cases collected between 1996 and 1999, using five-year follow-up,
fluency, delayed recall, and visual attention, and showed diminished positive reported attempted suicide or suicide in 13.5%, apathy in 22%, disinhibition
effect and increased emotional lability after surgery. However, as noted by the in 35%, psychosis and/or hallucinations in 27%, aggression in 8%, and
authors of the study, some effects may have been medication-related. For dopamine dysregulation syndrome (levodopa addiction) in 8%. In contrast, a
example, the decline in memory was no longer significant from the change in recent controlled study of 78 patients using a six-month follow-up reported
the control group once anticholinergic medication intake was accounted for. depression in 5%, suicide in 1% and psychosis in 5%.
29
Potential mechanisms
A quantitative meta-analysis
8
of peer-reviewed English-language studies from underlying psychiatric phenomena after DBS include pre-operative
1990 to April 2006 that reported interval or ratio data provided pre- and post- vulnerability,
63
stimulation, effects of surgery, psychosocial stressors, and
70 US NEUROLOGY
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