Parkinson Disease: Kirsch-Darrow L

Sudhyadhom A, Bova FJ, Foote KD, Rosado CA, Kirsch-Darrow L, Okun MS. · Department of Neurology, McKnight Brain Institute, 100 South Newell Drive, Gainesville, FL 32610, USA. · Curr Neurol Neurosci Rep. · Pubmed #17618533 No free full text.

Abstract: The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. · Movement Disorders Center, University of Florida, McKnight Brain Institute, College of Medicine, Department of Neurology, Gainesville, FL 32611, USA. · Ann Neurol. · Pubmed #19288469 No free full text.

Abstract: OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Zahodne LB, Young S, Kirsch-Darrow L, Nisenzon A, Fernandez HH, Okun MS, Bowers D. · Department of Clinical & Health Psychology, University of Florida, Gainesville, Florida 32610-0165, USA. · Mov Disord. · Pubmed #19133658 No free full text.

Abstract: Apathy is a unique, multidimensional syndrome commonly encountered in patients with Parkinson disease (PD). Recently, the Lille Apathy Rating Scale (LARS), a semistructured interview yielding a global score, and composite subscores for different domains of apathy (i.e., cognitive, behavioral, affective, self awareness), was developed and given to a sample of patients with PD in France. This study is the first outside of its original developers to examine the English language version of the LARS in PD. We found the LARS to be a coherent instrument demonstrating both convergent and divergent validity, as compared to the Apathy Scale (AS) and Beck Depression Inventory (BDI-II). Using a receiver operating characteristic (ROC) analysis comparing the LARS to the AS, a validated and widely-used measure, we identified a cut-off score (sensitivity = 64%, specificity = 92%, PPV = 88%, NPV = 75%) that was higher than that proposed by the original authors, who derived their cut-off by comparing LARS global scores to clinical judgments of apathy. Although the present study does not compare the LARS to a diagnostic gold standard or promote its utility for diagnosing apathy, it provides further support for the LARS as a promising instrument to examine apathy in PD.

Zahodne LB, Okun MS, Foote KD, Fernandez HH, Rodriguez RL, Kirsch-Darrow L, Bowers D. · Clinical and Health Psychology, University of Florida, Gainesville, FL 32610-0165, USA. · Clin Neuropsychol. · Pubmed #18821180 No free full text.

Abstract: Conflicting research suggests that deep brain stimulation surgery, an effective treatment for medication-refractory Parkinson's disease (PD), may lead to selective cognitive declines. We compared cognitive performance of 22 PD patients who underwent unilateral DBS to the GPi or STN to that of 19 PD controls at baseline and 12 months. We hypothesized that compared to PD controls, DBS patients would decline on tasks involving dorsolateral prefrontal cortex circuitry (letter fluency, semantic fluency, and Digit Span Backward) but not on other tasks (Vocabulary, Boston Naming Test), and that a greater proportion of DBS patients would fall below Reliable Change Indexes (RCIs). Compared to controls, DBS patients declined only on the fluency tasks. Analyses classified 50% of DBS patients as decliners, compared to 11% of controls. Decliners experienced less motor improvement than non-decliners. The present study adds to the literature through its hypothesis-driven method of task selection, inclusion of a disease control group, longer-term follow-up and use of Reliable Change. Our findings provide evidence that unilateral DBS surgery is associated with verbal fluency declines and indicate that while these changes may not be systematically related to age, cognitive or depression status at baseline, semantic fluency declines may be more common after left-sided surgery. Finally, use of Reliable Change highlights the impact of individual variability and indicates that fluency declines likely reflect significant changes in a subset of patients who demonstrate a poorer surgical outcome overall.

Cooper CA, Mikos AE, Wood MF, Kirsch-Darrow L, Jacobson CE, Okun MS, Rodriguez RL, Bowers D, Fernandez HH. · Department of Neurology, University of Florida, PO Box 100236, Gainesville, FL 32610, USA. · Parkinsonism Relat Disord. · Pubmed #18793864 No free full text.

Abstract: This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.

Kirsch-Darrow L, Mikos A, Bowers D. · University of Florida Department of Clinical and Health Psychology, P.O. Box 100165, Gainesville, FL 32610, USA. · Front Biosci. · Pubmed #18508589 No free full text.

Abstract: Chronic deep brain stimulation (DBS) is an important therapeutic advancement for the treatment of motor symptoms in Parkinson's disease (PD). However, its effects on non-motor symptoms are not well understood. Several studies have reported motivational disturbances and apathy after DBS surgery. Recent studies are beginning to more carefully examine the relationship between DBS and apathy. This review summarizes and evaluates the current state of the literature on apathy after DBS surgery, discusses methodological limitations in the literature, and makes suggestions for future research.

Okun MS, Rodriguez RL, Mikos A, Miller K, Kellison I, Kirsch-Darrow L, Wint DP, Springer U, Fernandez HH, Foote KD, Crucian G, Bowers D. · Department of Neurology, Movement Disorders Center, University of Florida, Gainesville, FL 32610, USA. · Clin Neuropsychol. · Pubmed #17366283 No free full text.

Abstract: Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinson's disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourette's syndrome, and depression. The neuropsychologist plays a crucial role in patient selection, follow-up, and management of intra-operative and post-operative effects (Pillon, 2002; Saint-Cyr & Trepanier, 2000). There is now emerging evidence that DBS can induce mood, cognitive, and behavioral changes. These changes can have dramatic effects on patient outcome. There have been methodological problems with many of the studies of DBS on mood, cognition, and behavior. The neuropsychologist needs to be aware of these issues when following up patients, and constructing future studies. Additionally, this article will review all aspects of the DBS procedure that can result in mood, cognitive, and behavioral effects and what role(s) the neuropsychologist should play in screening and follow-up.

Bowers D, Miller K, Mikos A, Kirsch-Darrow L, Springer U, Fernandez H, Foote K, Okun M. · Department of Clinical and Health Psychology , McKnight Brain Institute, University of Florida, Gainesville, FL, USA. · Brain. · Pubmed #17095520 links to  free full text

Abstract: The amygdala is closely linked to basal ganglia circuitry and plays a key role in danger detection and fear-potentiated startle. Based on recent findings of amygdalar abnormalities in Parkinson's disease, we hypothesized that non-demented patients with this illness would show blunted reactivity during aversive/unpleasant events, as indexed by diminished emotional modulation of the startle eyeblink response. To test this hypothesis, 23 idiopathic patients with Parkinson's disease and 17 controls viewed standardized sets of aversive, pleasant and neutral pictures for 6 s each. During this time, white noise bursts (50 ms, 95 db) were binaurally presented to elicit startle eyeblink responses, measured from electrodes over the orbicularis oculi. After viewing each picture, subjects provided ratings of valence and arousal. The Parkinson's disease patients were in the early to middle stages of their disease, not demented or depressed, and were tested 'on' dopaminergic medication. The two groups were similar in age, education, gender and cognitive screening status. The control group had larger startle responses when viewing negative, aversive pictures than neutral or pleasant pictures. As predicted, startle enhancement during aversive pictures was significantly muted in the Parkinson's disease patients. This blunting was not due to abnormalities in the mechanics of the startle eyeblink per se. Nor was it related to depression symptoms, medications (psychotropics), or failure to perceive/appreciate the negative meaning of aversive pictures (i.e. normal valence ratings). Reduced startle reactivity in the disease group was related to disease severity (Hoehn-Yahr) and occurred in the context of reduced arousal ratings of aversive pictures. These findings of blunted startle reactivity add to the literature on emotional changes associated with Parkinson's disease. The basis for this muted reactivity is unknown but may involve an amygdala-based translational defect whereby the results of cognitive appraisal are not appropriately transcoded into somato-motor-arousal responses normally associated with an aversive motivational state. This may arise from faulty dopaminergic gating of the amygdala, resulting in 'inhibition' of the amygdala in the manner described by Marowsky et al. (Marowsky A, Yanagawa Y, Obata K, Vogt E. Neuron 2005; 48: 1025-37). More broadly, the findings of muted reactivity to aversive stimuli may reflect a 'bradylimbic' affective disturbance in patients with Parkinson's disease. Future studies are needed to address whether the physiologic blunting observed here might be a useful correlate of apathy.

Kirsch-Darrow L, Fernandez HH, Fernandez HF, Marsiske M, Okun MS, Bowers D. · Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville 32608, USA. · Neurology. · Pubmed #16832074 No free full text.

Abstract: OBJECTIVE: To examine the hypothesis that apathy is a core feature of Parkinson disease (PD) and that apathy can be dissociated from depression. METHODS: Eighty patients with PD and 20 patients with dystonia completed depression and apathy measures including the Marin Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), and Centers for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, 41/80) than in dystonia (frequency = 20%, 4/20). Apathy in the absence of depression was frequent in PD and did not occur in dystonia (PD = 28.8%, dystonia = 0%). CONCLUSIONS: Patients with Parkinson disease (PD) experienced significantly higher frequency and severity of apathy when compared with patients with dystonia. Apathy may be a "core" feature of PD and occurs in the absence of depression.