Assessment of spontaneous cardiovascular oscillations in Parkinson's disease

Parkinson's disease (PD) has been reported to involve postganglionic sympathetic failure and a wide spectrum of autonomic dysfunctions including cardiovascular, sexual, bladder, gastrointestinal and sudo-motor abnormalities. While these symptoms may have a significant impact on daily activities, as well as quality of life, the evaluation of autonomic nervous system (ANS) dysfunctions relies on a large and expensive battery of autonomic tests only accessible in highly specialized laboratories. In this paper we aim to devise a comprehensive computational assessment of disease-related heartbeat dynamics based on instantaneous, time-varying estimates of spontaneous (resting state) cardiovascular oscillations in PD. To this end, we combine standard ANS-related heart rate variability (HRV) metrics with measures of instantaneous complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra). Such measures are computed over 600-s recordings acquired at rest in 29 healthy subjects and 30 PD patients. The only significant group-wise differences were found in the variability of the dominant Lyapunov exponent. Also, the best PD vs. healthy controls classification performance (balanced accuracy: 73.47%) was achieved only when retaining the time-varying, non-stationary structure of the dynamical features, whereas classification performance dropped significantly (balanced accuracy: 61.91%) when excluding variability-related features. Additionally, both linear and nonlinear model features correlated with both clinical and neuropsychological assessments of the considered patient population. Our results demonstrate the added value and potential of instantaneous measures of heartbeat dynamics and its variability in characterizing PD-related disabilities in motor and cognitive domains

A stochastic delay differential model of cerebral autoregulation

Mathematical models of the cardiovascular system and of cerebral autoregulation (CAR) have been employed for several years in order to describe the time course of pressures and flows changes subsequent to postural changes. The assessment of the degree of efficiency of cerebral auto regulation has indeed importance in the prognosis of such conditions as cerebro-vascular accidents or Alzheimer. In the quest for a simple but realistic mathematical description of cardiovascular control, which may be fitted onto non-invasive experimental observations after postural changes, the present work proposes a first version of an empirical Stochastic Delay Differential Equations (SDDEs) model. The model consists of a total of four SDDEs and two ancillary algebraic equations, incorporates four distinct delayed controls from the brain onto different components of the circulation, and is able to accurately capture the time course of mean arterial pressure and cerebral blood flow velocity signals, reproducing observed auto-correlated error around the expected drift

Autonomic Nervous System and Rem Behavior Sleep Disorder: a new tool to identify Idiopathic or Parkinsonians patients through Heart Rate Variability Polysomnography Analysis

Objective: RBD is a sleep disorder known to be associated in a very high percentage of cases with alfa-synucleopathies. During rapid eye movement (REM) sleep, the cardiovascular system is unstable and greatly influenced by sympathetic activity. Heart Rate Variability (HRV) indirectly tests functions and activities of the ANS during sleep. We evaluate whether HRV and Hypnogram Indices are polysomnographic valid biomarkers to distinguish subjects with idiopathic RBD from those with Parkinson's Disease. METHODS: Our study examines HRV linear and non-linear indices of 37 patients aged 53 years and older (median 72.7; mean 72.3 ± 7.4; range 53-84), 7 women (18.9%) and 30 men (81.1%). 22 pts were idiopathic REM sleep behavior disorder (59.5%; age: median 72.5; mean 74.5 ± 5.2; range 68 83), of which 3 women (13.6%) and 19 men (86.4%); 15 pts had REM Sleep Behavior Disorder secondary to Parkinson's disease (40.5%; a ge: median 73; mean 69.5 ± 9 ; range 53 84), including 4 women (26.7%) and 11 men (73.3%). A parallel Analysis was made on Hypnogram Parameters. RESULTS: The REM sleep phase allowed to record the greatest number of significant differences in HRV Index between the two groups of patients. Among the Frequency HRV Linear Indices, VLF signal band recorded the highest number of significant results suggesting that the sympathetic component may be the one most compromised in the autonomic neurodegeneration process of RBD. HRV Complexity Non-Linear Indices (LZC and KC) have the highest number of statistically significant results so that could be the right parameter to use to distinguish our two RBD populations. Hypnogram Indices Analysis showed no significant value for not even a parameter. CONCLUSIONS: HRV can be a valid biomarker to distinguish the two populations of patients affected by RBD, both idiopathic and affected by Parkinson's disease. It could represent a new and easy tool to identify, among the REM Behavior Sleep Disorder, patients affected or not by Parkinson’s desease or could be even useful when an early diagnosis is needed or it is necessary monitoring a probable conversion from idiopathic form to PD or evaluate the effectiveness of RBD therapies

Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as ‘critically important;’ these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome ‘off’ periods (>1–2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS

VIBRATION TRAINING IN REHABILITATION

Voluntary muscular activation is disturbed in both neurological disorders and orthopaedic injuries. Methods that enable bypassing this activation circle are of fundamental importance in order to set functional training stimuli. Besides electrical stimulation and robot supported gait the app'lication of vibration has become an alternative and complemental treatment method in rehabilitation. The most findings of physiological and motor control, effects of vibratory stimuli result from studies in sport science and basic neurophysiological research. Transferring the effects found in healthy subjects to the different areas of application in rehabilitation seems not possible in a linear way. This paper summarizes the different findings and discusses transfer possibilities and problems

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Studying Glutamatergic Gliotransmission as a Functional Model to Assess Physio-Pathological Conditions and Receptor Cross-Talk

SUMMARY This thesis is divided into two parts; in the first part, we characterized the effect of acute stress on the astrocytic glutamate release in the prefrontal cortex of rat brain. In the second part, we evaluate the interaction of the Oxytocin receptor (OXTR) with both Adenosine receptor A2A and Dopamine D2 receptors in the brain striatum of male rats. First Part: Stress is known to disturb the physiological homeostasis of the body (McEwen et al., 2000). The number of studies demonstrated that stress leads to damage the prefrontal cortex the brain and results in the modulation in the secretion of various neurotransmitters (Karats Oreos and McEwen, 2011, Sousa and Almeida, 2012). Stress was recognized as a predominant risk factor for many diseases, together with cardiovascular, metabolic, and neuropsychiatric diseases. Among the latter, stress interacts with the variable genetic background of vulnerability in the pathogenesis of mood anxiety disorder (Laura et al., 2010). It may be acute or chronic, can involve neuropsychiatric components such as stress, depression, mood, and anxiety (Laura et al., 207) and produces many behavioral and neurochemical changes, as determined in human (De Kloet et al., 2005, Kim & Diamond 2002). Studies in the literature truly indicated that acute stress have an effect on glutamatergic neurotransmission in the prefrontal cortex, inducing changes in glutamate release, receptor and glutamate clearance and metabolism (Popoli et al., 2012: Licznerski and Duman 3013). The effects of acute footshock stress on glutamate release and transmission were still unknown. In this study, we investigated the release of glutamate from astrocytes. The analyses have been performed in the prefrontal cortex (PFC) at different time intervals straight away after 40 min of stress and 6 and 24 hours after stress start, to monitor the early and delayed effects of acute stress on glutamate release. After the acute stress, animals were subjected to sucrose test to distinguish vulnerable and resilient rats. Second Part: There has been a growing interest in the investigation of the role of astrocytes in neurodegenerative and neuropsychiatric diseases and their complex neuron-astrocytes network function. The receptor\u2013receptor interactions (RRI) can have an important function in the signalling transduction pathways. A previous well established study evaluate the interactions between the G-protein coupled receptors of adenosine A2A receptors (A2A) and dopamine D2 receptors (D2) in several experimental models (Ferr\ue9 et al., 2008), while it\u2019s barely investigated in astrocytes. Growing evidence shows that adult striatal astrocytes largely express both D2 and A2A receptors (Cervetto et at., 2017). Moreover, the presence of A2A-D2 heteroreceptor complexes has led to a new perspective of molecular mechanisms involved in Parkinson\u2019s disease (PD), providing novel drug targets. Therefore in the present study, we investigate the physical and functional interactions of A2A and D2 with another G protein-coupled receptors i.e. OXTR in astrocytes processes from adult rat striatum. We also evaluate the effect of this interaction on the astrocytic glutamate release in rat striatum