Classification of advanced stages of Parkinson's disease: translation into stratified treatments.

Advanced stages of Parkinson's disease (advPD) still impose a challenge in terms of classification and related stage-adapted treatment recommendations. Previous concepts that define advPD by certain milestones of motor disability apparently fall short in addressing the increasingly recognized complexity of motor and non-motor symptoms and do not allow to account for the clinical heterogeneity that require more personalized approaches. Therefore, deep phenotyping approaches are required to characterize the broad-scaled, continuous and multidimensional spectrum of disease-related motor and non-motor symptoms and their progression under real-life conditions. This will also facilitate the reasoning for clinical care and therapeutic decisions, as neurologists currently have to refer to clinical trials that provide guidance on a group level; however, this does not always account for the individual needs of patients. Here, we provide an overview on different classifications for advPD that translate into critical phenotypic patterns requiring the differential therapeutic adjustments. New concepts refer to precision medicine approaches also in PD and first studies on genetic stratification for therapeutic outcomes provide a potential for more objective treatment recommendations. We define novel treatment targets that align with this concept and make use of emerging device-based assessments of real-life information on PD symptoms. As these approaches require empowerment of patients and integration into treatment decisions, we present communication strategies and decision support based on new technologies to adjust treatment of advPD according to patient demands and safety.

Laboratory assessments in the course of Parkinson's disease: a clinician's perspective.

Physicians, caregivers and patients themselves must be alert to the onset of and changes in motor and non-motor features during the course of Parkinson's disease (PD). Parallel laboratory routine assessments are necessary because of the evolving impairment of the general health status of the individual. A number of potential biomarkers for the diagnosis of PD are currently under investigation, with diagnosis early in the disease course a particular goal, even before the onset of motor symptoms. The aim of this guideline article is to provide user-friendly, clinical evidence-based recommendations for using laboratory pathological testing for the diagnosis and differential diagnosis of PD, for assessing its time course, and managing complications of long-term dopaminergic therapy and the disabling motor features that develop in the later stages of the disease.

Diurnal variation of hypothalamic function and chronic subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinson's disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients. METHODS: Basal hormone levels of the HP-adrenal (HPA), HP-gonadal and HP-somatotropic axis were determined before surgery as well as 3 and 6 months after electrode implantation. In addition, 24-hour cortisol profiles and dexamethasone suppression tests were obtained. Postoperative hormone changes were correlated with individual neuropsychological test performance, psychiatric status and anthropometric measures. RESULTS: While PD patients experienced weight gain (p = 0.025) at follow-up, most neuropsychological data and basal HP hormone levels did not change over time. HPA regulation and diurnal rhythmicity of cortisol remained intact in all patients. The 24-hour mean cortisol levels decreased 6 months after surgery (p = 0.002) correlating with improved postoperative depression (p = 0.02). CONCLUSIONS: Chronic application of high-frequency electrical stimuli in the STN was not associated with HP dysfunction in patients with advanced PD. The diurnal variability of peripheral cortisol secretion as one important element of the endogenous biological clock remained intact. Evening cortisol levels decreased after surgery reflecting a favorable regulation of the cortisol setpoint. STN-DBS can be considered safe from a neuroendocrine perspective, but the origin of unwanted side effects warrants further elucidation.

Scales in Parkinson's disease.

The search for valid instruments to measure different domains of health disturbances becomes increasingly important for the assessment of Parkinson's disease. The most widely used tool is the Unified Parkinson's Disease Rating Scale (UPDRS) which was introduced in 1987 and is currently awaiting revision. In addition, a variety of instruments have been used to capture non-motor aspects of Parkinson's disease but only a minority of these instruments has been validated for this particular disease condition. Measurements of quality of life are being incorporated into an increasing number of studies in order to reflect a more integral view of health and have contributed to a better understanding of the impact of disease and interventions. The International Classification of Functioning, Disability and Health introduced by the WHO in 2001 offers a multidimensional approach to human functioning and participation that can also be applied to the assessment of health status in PD. This workshop report will focus on the present state of clinimetry in PD and discuss future perspectives.

Thrombolysis in a stroke patient on dabigatran anticoagulation: case report and synopsis of published cases.

We present the case of an aphasic 77-year-old stroke patient with left distal M1 occlusion who received rt-PA for thrombolysis while on oral anticoagulant treatment with dabigatran (150 mg b.i.d.). Coagulation parameters were normal (thrombin time 20 s, aPTT 20 s, INR 1.08) and the patient improved from an NIHSS of 15 to 5 within 24 h with sonographic evidence of M1 recanalization. She did not develop intracranial bleeding complications but showed unusually large diffuse skin ecchymoses. In our report, we give an overview of all reported cases of thrombolysis under dabigatran anticoagulation and discuss the questions of medication adherence under novel oral anticoagulants (NOA) and the safety of NOA in terms of secondary intracerebral hemorrhage after stroke.

Structure and markers of appropriateness, quality and performance of drug treatment over a 1-year period after hospital discharge in a cohort of elderly patients with cardiovascular diseases from Germany.

In a group of elderly patients over 65 years of age with at least two cardiovascular diagnoses requiring chronic medication (n=424), drug therapy at hospital discharge and at home thereafter was followed for a 1-year period. Two home visits took place at 3 months and 12 months after initial discharge. A median of six prescriptions had already been given at the time of discharge; this number increased slightly during ambulatory follow-up. After 1 year, about 30% of the patients had to take more than ten dosing units per day. After discharge, about 50% of all prescriptions were subject to changes in the choice of the preparation (brand-generic) or the agent used [within a class of similar agents, e.g. angiotensin converting enzyme inhibitors (ACIs)]. The prescription of some problematic agents (benzodiazepines, non-steroidal anti-inflammatory agents) increased during the ambulatory follow-up, but pivotal medications for cardiovascular indications (e.g., ACI) given at discharge were maintained. Over-the-counter (OTC) drugs-which were not part of the discharge medication-contributed to 12% of all drugs taken at V4. The majority of the prescriptions (95% of about 2,000 prescriptions surveyed at each visit) was in agreement with the drug's approval status and was appropriate in terms of absence of contraindications. At home visits, therapy with ACI or beta-blocking agents was in agreement with clinical guidelines, although under-dosing was obvious. Blood pressure control (<140/90 mmHg) was achieved in 61% of the patients at discharge and deteriorated to 45% after 1 year; international normalized ratio control in patients with oral anticoagulation also declined (control rate 57% at discharge, 46% after 1 year). Statins as secondary prevention were given at discharge in only 60% of suitable patients, declining to about 50% in ambulatory visits. Diabetic control was not present in 35% of the patients at discharge or at home. Properties of or reason for their medication could be given for the majority (70-80%) of the prescriptions; these quotations were, however, cursory and almost nothing was known about medication risks. At home visits, non-compliance was admitted for approximately 8% of the prescriptions. In conclusion, for pivotal indications, family doctors widely followed the discharge recommendations, but deficits in ambulatory prescriptions and poor performance of the medication were in part already employed at the time of discharge from the hospital. The lack of a patient's knowledge about their own medication is precarious.