Sleep apnea syndrome and subthalamic stimulation in Parkinson's disease.

OBJECTIVES: Τhe association between Parkinson's disease (PD) and sleep apnea syndrome (SAS) is not fully elucidated and very few studies reported on SAS outcome after deep brain stimulation (DBS). Here, we compare the clinical profile of PD patients with and without SAS and assess, for the first time, the value of pre-DBS SAS as predictor of post-DBS outcome in PD. METHODS: Fifty patients were grouped into PD with SAS (PD-SAS+,n = 22) and without (PD-SAS-,n = 28), based on the Apnea-Hypopnea-Index (AHI≥5) in polysomnography. We used novel multivariate statistical models to compare pre-DBS profiles and assess post-DBS motor, non-motor and quality of life (QoL) changes in both groups. RESULTS: In the entire cohort, 44% of patients had at least mild SAS (AHI≥5), while 22% had at least moderate (AHI≥15). Mean AHI was 11/h (NREM-AHI = 10.2/h and REM-AHI = 13.5/h). The two groups had equal demographics and PD characteristics, and did not differ in respect to unified Parkinson's disease rating scale (UPDRS)-IIOFF, Body-Mass-Index, polysomnographic features, RBD, depression, sleepiness and QoL scores. The PD-SAS+ group had significantly higher scores in UPDRS-IIIOFF (41.1 ± 17.7 vs. 30.9 ± 11.7,p < 0.05) compared to PD-SAS- group. The groups did not differ in respect to post-DBS change in UPDRS-II, UPDRS-III, Epworth sleepiness scale, Hamilton depression rating scale and PDQ39 scores. Positive airway pressure therapy had no impact on post-DBS outcome. CONCLUSIONS: In patients with PD and candidates for DBS, the presence of SAS is associated with increased motor signs, but not with a specific non-motor, QoL or sleep-wake profile. The presence of SAS prior to STN-DBS is not associated with worse outcome after surgery.

A case series and systematic review of rapid eye movement sleep behavior disorder outcome after deep brain stimulation in Parkinson's disease.

REM-sleep behavior disorder (RBD) is a parasomnia and a common sleep disorder in Parkinson's disease (PD). While deep brain stimulation (DBS) is an established treatment for advanced PD with beneficial effects on cardinal PD motor symptoms, the data on the impact of DBS on RBD are limited and often controversial. We reviewed published articles that reported on RBD in the context of DBS surgery via systematic PubMed search. We identified 75 studies and included 12 studies, involving a total of 320 subjects, in our review. Results in respect to EMG activity outcome after subthalamic stimulation are inconsistent. We found no study that reported on RBD outcome after pallidal DBS and no DBS study quantified complex behavior during REM sleep. We also added data on RBD outcome after subthalamic (N = 4 patients) or pallidal (N = 3 patients) DBS from patients with PD with RBD, obtained as part of a prospective DBS study in our centre. Our case series showed an increase of complex behavior during REM (CB-REM) after surgery, independent of DBS target. Conversely, we found a trend towards increasing REM sleep without atonia (RSWA) in subthalamic-stimulated patients and a trend towards decreased RSWA in pallidal stimulated patients. We conclude that CB-REM and RSWA might represent two distinct elements in RBD and should be assessed separately, especially in studies that report on RBD outcome after treatment interventions. Further, larger, prospective, controlled studies in different DBS targets, reporting separately on the different RBD modalities, are needed.

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.

Parasomnia overlap disorder, Parkinson's disease and subthalamic deep brain stimulation: three case reports.

BACKGROUND: Parasomnia overlap disorder (POD) is a distinct parasomnia and characterized by concomitant manifestation of rapid-eye-movement (REM)- and non-REM (NREM)-parasomnias. Although not uncommon among patients with Parkinson's disease, POD is often under-investigated. CASE PRESENTATION: This is the first report of patients with PD and features of POD that underwent deep brain stimulation. Our patients exhibited different outcomes of POD features after subthalamic deep brain stimulation. CONCLUSIONS: We expect that the reporting of these first patients will open the discussion about the need for more detailed and broad-spectrum assessments regarding parasomnias in PD patients that undergo deep brain stimulation. The implications of our observations are both clinical and neurobiological.

Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications.

BACKGROUND: Recent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. OBJECTIVES: We assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. METHODS: We applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. RESULTS: In the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. CONCLUSIONS: Our decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. © 2016 International Parkinson and Movement Disorder Society.

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

BACKGROUND: Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. METHODS: We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. RESULTS: Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. CONCLUSION: These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

Cardiogoniometric parameters for detection of coronary artery disease at rest as a function of stenosis localization and distribution.

Cardiogoniometry (CGM), a spatiotemporal electrocardiologic 5-lead method with automated analysis, may be useful in primary healthcare for detecting coronary artery disease (CAD) at rest. Our aim was to systematically develop a stenosis-specific parameter set for global CAD detection. In 793 consecutively admitted patients with presumed non-acute CAD, CGM data were collected prior to elective coronary angiography and analyzed retrospectively. 658 patients fulfilled the inclusion criteria, 405 had CAD verified by coronary angiography; the 253 patients with normal coronary angiograms served as the non-CAD controls. Study patients--matched for age, BMI, and gender--were angiographically assigned to 8 stenosis-specific CAD categories or to the controls. One CGM parameter possessing significance (P < .05) and the best diagnostic accuracy was matched to one CAD category. The area under the ROC curve was .80 (global CAD versus controls). A set containing 8 stenosis-specific CGM parameters described variability of R vectors and R-T angles, spatial position and potential distribution of R/T vectors, and ST/T segment alterations. Our parameter set systematically combines CAD categories into an algorithm that detects CAD globally. Prospective validation in clinical studies is ongoing.

Accuracy of the clinical diagnosis of 'psychogenic disorders' in the presence of physical symptoms suggesting a general medical condition: a 5-year follow-up in 162 patients.

OBJECTIVE: The range of unnoticed physical disorders in patients diagnosed with a psychogenic disorder varies widely. We investigated the accuracy of the clinical diagnosis of 'psychogenic disorder' where physical symptoms suggesting a somatic condition (PDPS) are present. METHOD: All 162 cases of PDPS diagnosed between 01.01.1986 and 31.12.1987 in a medical clinic specializing in psychosomatic medicine were reviewed after 5 years. 148 follow-ups were complete. Initial diagnoses had been established using positive criteria for psychogenic diagnosis in a semistructured interview and a comprehensive clinical workup by trained clinicians. RESULTS: In 2 (1.35%) foreign-language patients of 148 an orthopedic diagnosis had been missed. In 6 patients, the family physician gave formerly known findings a different interpretation. Half of these patients were foreigners; 5 were men; none improved; 5 had back pain. CONCLUSION: A semistructured interview and positive criteria for psychogenic diagnosis permitted high diagnostic accuracy with an error of 1.35% in 148 cases.