Catharine J. Lewis

Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern

Objective To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course. Methods We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [123I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up. Results There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments. Conclusions This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.

Patients’ expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson's disease: a mixed-method approach

Objective To study patients’ expectations of subthalamic deep brain stimulation (STN-DBS) and their subjective perceived outcome, by using qualitative and quantitative methods in Parkinsons disease (PD). Methods PD patients were prospectively examined before and 3 months after surgery. Semistructured interviews regarding preoperative expectations and postsurgical subjective perceived outcome were conducted. These were analysed using content analysis. For statistical analyses, patients were classified according to their subjective perceived outcome, resulting in three different subjective outcome groups (negative, mixed, positive outcome). The groups were used for multiple comparisons between and within each group regarding motor impairment, quality of life (QoL), neuropsychiatric status and cognitive functioning, using standard instruments. A logistic regression analysis was conducted to find predictors of subjective negative outcome. Receiver operating characteristic curves were used to analyse cut-off scores for predictive tests. Results Of the 30 PD patients participating, 8 had a subjective negative outcome, 8 a mixed and 14 a positive outcome. All groups significantly improved in motor functioning. Patients with subjective negative outcome were characterised by preoperative unrealistic expectations, no postsurgical improvement in QoL, and significantly higher presurgical and postsurgical apathy and depression scores. Higher preoperative apathy and depression scores were significant predictors of negative subjective outcome. Cut-off scores for apathy and depression were identified. Conclusions The mixed-method approach proved useful in examining a patients subjective perception of STN-DBS outcome. Our results show that significant motor improvement does not necessarily lead to a positive subjective outcome. Moreover, PD patients should be screened carefully before surgery regarding apathy and depression. (DRKS-ID: DRKS00003221).

Impaired self-awareness of motor deficits in Parkinson's disease: association with motor asymmetry and motor phenotypes.

This study investigated impaired self‐awareness of motor deficits in nondemented, nondepressed Parkinsons disease (PD) patients during a defined clinical on state.

Hypomania and mania related to dopamine replacement therapy in Parkinson's disease.

OBJECTIVES To investigate hypomania and mania related to dopamine replacement therapy (DRT) in Parkinsons disease (PD). METHODS We recruited 108 non-demented PD patients without deep brain stimulation from a movement disorders in and outpatient clinic. Forty-five age- and gender-matched controls were also included. Disease characteristics, cognitive functioning, comorbid psychiatric diseases, dopaminergic and psychiatric medication were evaluated. Diagnosis of DRT-related hypomania and mania was based on DSM-IV-TR criteria with supplementary assessment of two mania self-rating scales. First, patients and controls were compared. Patients with DRT-related hypomania or mania were then compared to the remaining patients. A binary logistic regression analysis was performed to identify correlates of DRT-related hypomania. RESULTS Patients scored significantly higher on mania self-rating scales than controls. Twelve patients (11.1%) had DRT-related hypomania and six patients (5.6%) had DRT-related mania. Both groups had significantly higher self-rating mania-scores than patients without these mood states. DRT-related hypomania was significantly related to younger age, younger age at PD onset, dyskinesias, higher levodopa equivalent daily dose, dopamine dysregulation, and amantadine treatment. In contrast, DRT-related mania was significantly associated with hallucinations and delusions, history of levodopa-induced psychosis, quetiapine treatment, higher depression and daily levodopa dose, and cognitive deficits. Regression analysis revealed dopamine dysregulation, dyskinesias, amantadine treatment, and younger age at PD onset as significant correlates of DRT-related hypomania. CONCLUSION DRT-related hypomania and mania are relevant comorbidities in PD. DRT-related hypomania may exist as a distinct psychiatric symptom complex in young patients with early disease onset. Different patient profiles likely underlie DRT-related hypomania and mania.

Subjective perceived outcome of subthalamic deep brain stimulation in Parkinson's disease one year after surgery

OBJECTIVES Dissatisfaction with subthalamic deep brain stimulation (STN-DBS) despite motor improvements has been observed in Parkinsons disease (PD). Hence, we compared patients subjective perceived outcome 12 months after surgery (12mFU) with clinical measures to identify risk factors of dissatisfaction. METHODS Patients were examined at baseline and 12mFU. Quality of life (QoL), neuropsychiatric, cognitive and neurological functioning was measured. Patients were classified concerning their subjective outcome (negative = dissatisfaction; mixed; positive = satisfaction) at 12mFU using semi-structured interviews. First, the three groups were compared concerning interview statements. Second, repeated measures ANOVAs with group as between-subjects factor were applied to find significant effects of time, group, or interaction. Third, binary logistic regression determined predictors of dissatisfaction. RESULTS Of the 28 enrolled patients, 25% perceived their outcome as negative, 32.1% as mixed, and 42.9% as positive. Concerning interview statements, dissatisfied patients mentioned significantly less often improved QoL and reduced medication, and reported worsening of mental state, and social interaction. For the whole sample, significant improvement over time was found for motor functioning, daily dopamine dosages, and QoL. Apathy significantly worsened over time, but dissatisfied patients were overall more apathetic and depressed than the other groups. Significant interaction of group and time was identified for QoL, which only improved in the mixed and satisfied group. Finally, preoperative apathy and axial symptoms predicted dissatisfaction with STN-DBS. CONCLUSIONS Although motor symptoms and QoL improved in the whole sample, 25% of patients showed disappointment with STN-DBS. Especially apathy predicts dissatisfaction and should be considered preoperatively.

Development and psychometric evaluation of a scale to measure impaired self-awareness of hyper- and hypokinetic movements in Parkinson’s disease

OBJECTIVE Patients with Parkinsons disease (PD) can show impaired self-awareness of motor deficits (ISAm). We developed a new scale that measures ISAm severity of hyper- and hypokinetic movements in PD during medication on state and defined its psychometric criteria. METHOD Included were 104 right-handed, non-depressed, non-demented patients. Concerning ISAm, 38 motor symptoms were assessed using seven tasks, which were performed and self-rated concerning presence of deficit (yes/no) by all patients. The whole procedure was videotaped. Motor symptoms were then evaluated by two independent experts, blinded for patients ratings, concerning presence, awareness of deficit, and severity. Exploratory principal component analysis (promax rotation) was applied to reduce items. Principal axis factoring was conducted to extract factors. Reliability was examined regarding internal consistency, split-half reliability, and interrater reliability. Validity was verified by applying two additional measures of ISAm. RESULTS Of the initial 38 symptoms, 15 remained, assessed in five motor tasks and merged to a total severity score. Factor analysis resulted in a four factor solution (dyskinesia, resting tremor right hand, resting tremor left hand, bradykinesia). For all subscales and the total score, measures of reliability (values 0.64-0.89) and validity (effect sizes>0.3) were satisfactory. Descriptive results showed that 66% of patients had signs of ISAm (median 2, range 0-15), with ISAm being most distinct for dyskinesia. CONCLUSIONS We provide the first validation of a test for ISAm in PD. Using this instrument, future studies can further analyze the pathophysiology of ISAm, the psychosocial sequelae, therapeutic strategies and compliance with therapy.

The deep brain stimulation impairment scale (DBS-IS) - response to Jahanshahi

Reply to the letter by Prof. Jahanshahi We thank Prof. Jahanshahi for the valuable comment on our paper “Development and validation of the deep brain stimulation impairment scale (DBS-IS)” [1]. As she stated the newly developed questionnaire “DBS-IS” consists of 6 subscales which are “postural instability and gait difficulties”, “cognitive impairment”, “speaking problems”, “apathy”, “impulsivity” and “difficulties related to the DBS device”. Prof. Jahanshahi remarks that all but one subscale (“difficulties related to the DBS device”) relate to symptoms that may either be caused by the ongoing progression of Parkinsons disease (PD) or that can be a result of the surgery. Hence, the DBS-IS will not be able to discriminate between these opportunities. We agree in this point because the scale was not created to distinguish between these options. Instead, it was designed to measure impairments that were specifically reported by DBS patients who were stimulated in the nucleus subthalamicus (STN) and their relatives. Equally to other questionnaires such as the Parkinsons Disease questionnaire-39 (PDQ-39, [2,3]), the DBS-IS was developed on the basis of subjective patient and caregiver opinions. PD patients and their caregivers of course do not have the expertise or the methodological knowledge to differentiate between symptoms that are a consequence of disease progression or of the STN-DBS itself. It was our intention to capture this subjective opinion since in our view, next to standard measures of motor impairments, the subjective benefit from STN-DBS determines the usefulness of the procedure. Therefore, the methodological procedure of the study was data driven and all DBS-IS subscales relate to relevant impairments which were reported by our patients with STN-DBS and their caregivers. As we have outlined in our paper in detail, all subscales are of significant importance for our STN-DBS patients such as “apathy” or “speaking problems” and are often reported as more impaired in PD patients with STN-DBS compared to those without [4,5]. Whether these arise from the stimulation itself or e.g. from a