Michael Samuel

Depression and anxiety related subtypes in Parkinson's disease

Background Depression and anxiety are common in Parkinsons disease (PD) and although clinically important remain poorly understood and managed. To date, research has tended to treat depression and anxiety as distinct phenomena. There is growing evidence for heterogeneity in PD in the motor and cognitive domains, with implications for pathophysiology and outcome. Similar heterogeneity may exist in the domain of depression and anxiety. Objective To identify the main anxiety and depression related subtype(s) in PD and their associated demographic and clinical features. Methods A sample of 513 patients with PD received a detailed assessment of depression and anxiety related symptomatology. Latent Class Analysis (LCA) was used to identify putative depression and anxiety related subtypes. Results LCA identified four classes, two interpretable as ‘anxiety related’: one anxiety alone (22.0%) and the other anxiety coexisting with prominent depressive symptoms (8.6%). A third subtype (9%) showed a prominent depressive profile only without significant anxiety. The final class (60.4%) showed a low probability of prominent affective symptoms. The validity of the four classes was supported by distinct patterns of association with important demographic and clinical variables. Conclusion Depression in PD may manifest in two clinical phenotypes, one ‘anxious–depressed’ and the other ‘depressed’. However, a further large proportion of patients can have relatively isolated anxiety. Further study of these putative phenotypes may identify important differences in pathophysiology and other aetiologically important factors and focus research on developing more targeted and effective treatment.

Parkinson's disease motor subtypes and mood

Parkinsons disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinsons disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious‐depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age‐of‐onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age‐of‐onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinsons disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non‐anxious depression in Parkinsons disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals.

A randomized controlled trial of quetiapine for psychosis in Parkinson's disease.

Introduction: Psychosis (delusions and/or hallucinations) is a well-recognized complication of treatment of Parkinson’s disease (PD). Quetiapine is a currently favored treatment, but data on its efficacy are equivocal. This trial aimed to provide further evidence on the efficacy of quetiapine in PD psychosis. Methods: We conducted a 12 week double blind randomized placebo-controlled trial. Time to dropout due to lack of improvement of psychosis was the primary outcome measure. Other important secondary outcomes were evaluated using standard rating scales for PD and psychiatric symptoms. Results: Twenty-four eligible subjects gave consent. The primary outcome, time to dropout, was examined using survival analysis. It was shown that patients in the quetiapine group dropped out earlier than those in the placebo group, but this difference was not significant (p = 0.68). No significant changes were found for any of the secondary outcome measures in either group. Conclusions: In this study, quetiapine at doses of up to 150 mg/day failed to significantly improve psychosis compared to placebo, however the small sample size does not allow any conclusive interpretation of the results. Quetiapine did not appear to worsen PD motor functioning, but its use was limited by a faster drop out compared with placebo. Significant impediments were difficulty with recruitment and natural fluctuation in symptoms during the trial.

Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Nonmotor versus motor symptoms: How much do they matter to health status in Parkinson's disease?

Evidence suggests that both motor and nonmotor symptoms contribute to health status in Parkinsons disease. Less clear is how much change in health status can be expected if these clinical variables change. In addition, anxiety, separate from depression, has rarely been examined as a predictor of health status. We used hierarchical multiple regression analysis and standardized beta coefficients in a prevalent cohort of 462 patients with Parkinsons disease to explore the relative impact on health status (measured using the Parkinsons Disease Questionnaire) of 5 well‐recognized symptom domains in Parkinsons disease: motor signs, depression, anxiety, cognition, and other nonmotor symptoms. In the health status scores, 19.6% of variance was explained by age, number of comorbidities, disease duration, and levodopa equivalent dose. Younger age predicted worse health status. A full regression model containing baseline variables and all 5 symptom domains explained 56% of the variance in health status. The standardized beta coefficient for depression was 2.1, 1.6, and 1.3 times that of motor signs, anxiety, and other nonmotor symptoms, respectively. Our findings provide a ranking order of clinical variables for their relative impact on health status in Parkinsons disease and show that depression has more than twice the impact of motor signs on health status. Anxiety and other nonmotor symptoms are also important separate determinants of poor health status in Parkinsons disease. Our results will help to guide the development of individual care and service planning for patients with Parkinsons disease.

Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers

Objective: To test the effects of a novel cognitive-behavioral therapy (CBT)–based intervention delivered by a nurse therapist to patients with Parkinson disease (PD) with clinically significant impulse control behaviors (ICB). Methods: This was a randomized controlled trial comparing up to 12 sessions of a CBT-based intervention compared to a waiting list control condition with standard medical care (SMC). A total of 27 patients were randomized to the intervention and 17 to the waiting list. Patients with a Mini-Mental State Examination score of <24 were excluded. The coprimary outcomes were overall symptom severity and neuropsychiatric disturbances in the patients and carer burden and distress after 6 months. Secondary outcome measures included depression and anxiety, marital satisfaction, and work and social adjustment in patients plus general psychiatric morbidity and marital satisfaction in carers. Results: There was a significant improvement in global symptom severity in the CBT intervention group vs controls, from a mean score consistent with moderate to one of mild illness-related symptoms (χ2 = 16.46, p < 0.001). Neuropsychiatric disturbances also improved significantly (p = 0.03), as did levels of anxiety and depression and adjustment. Measures of carer burden and distress showed changes in the desired direction in the intervention group but did not change significantly. General psychiatric morbidity did improve significantly in the carers of patients given CBT. Conclusions: This CBT-based intervention is the first to show efficacy in ICB related to PD in terms of patient outcomes. The hoped-for alleviation of carer burden was not observed. The study demonstrates the feasibility and potential benefit of a psychosocial treatment approach for these disturbances at least in the short term, and encourages further larger-scale clinical trials. Classification of evidence: The study provides Class IV evidence that CBT plus SMC is more effective than SMC alone in reducing the severity of ICB in PD, based upon Clinical Global Impression assessment (χ2 = 16.46, p < 0.001): baseline to 6-month follow-up, reduction in symptom severity CBT group, 4.0–2.5; SMC alone group, 3.7–3.5.

CT/MR Image Fusion in the Postoperative Assessment of Electrodes Implanted for Deep Brain Stimulation

Background/Aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.

Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus

ObjectiveReliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting.MethodsMR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2* mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed.ResultsSWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN.ConclusionSWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting.

Frequency, prevalence, incidence and risk factors associated with visual hallucinations in a sample of patients with Parkinson's disease: a longitudinal 4-year study.

To examine the prevalence, incidence and risk factors associated with visual hallucinations (VHs) amongst people suffering from Parkinsons disease (PD).

Management of impulse control disorders in Parkinson's disease: Controversies and future approaches

Impulse control disorders in Parkinsons disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti‐parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies.