Motor symptoms in Parkinson's disease: A unified framework

Parkinson’s disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement

Classification of handwriting kinematics in automated diagnosis and monitoring of Parkinson's disease

Parkinson's disease is one of the most prevalent neurodegenerative conditions. Currently, there is no standard clinical tool available to diagnose PD. One of the research priorities is to come up with biomarkers which will improve the diagnostic process and can be used for the clinical test. At present, the only way to assess this disease is by visually observing the symptoms of the patient which is performed only by expert neurologists. As of now, there is no treatment to prevent the progression of PD. However, there is an elemental drug `Levodopa' (L-dopa) available to control the disease by increasing dopamine cells in the brain. It is important to detect PD and start treatment in the early stages as it helps to control the symptoms and significantly delays the development of motor complications. In this study fine motor symptoms handwriting has been studied. As a first objective I have conducted the experiments on the significant number of patients and age-matched control (112 Participants:56 PD and 56 controls), and thus completed the task of data collection. The system developed extracts the dynamic features of the handwriting/drawing, reports the possible strength of dynamic features providing a basis for automated analysis. The advantage of this approach is that patients are not required to follow complex commands, and the analysis can be fully automized. I anticipate that following appropriate clinical tests already planned, the system will be able to detect early disease symptoms remotely outside hospitals or clinics. It could also be used for self-evaluation by patients with neuromuscular and motor neuron disorders. This device can be used without compromising on the comfort level of Patients who may still prefer writing with an ink pen on plain paper. This study proposes a new feature `Composite Index of Speed and Pen-pressure' (CISP) to distinguish between different stages of Parkinson's disease. The experiment also demonstrated a method which can be used with guided spiral drawing to improve classification results to predict Parkinson's disease. Further, I recommend using a panel of writing tasks which might prove to be an effective biomarker for cell loss in the substantia nigra and the associated dopamine deficiency. Thus, models developed can be used in designing an automated application for predicting and monitoring Parkinson's diseas

Variability of Graphomotor Task Performance in Adults with ADHD: A Kinematic Approach

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention and/or a combination of hyperactivity and impulsivity. Motor problems, including poor graphomotor skills, are frequently found in those with ADHD and have been noted to be undertreated. Variability of performance within several domains has also been indicated as a hallmark of ADHD. The present study sought to 1) determine whether the variability of performance observed in other psychological domains in those diagnosed with ADHD manifests within kinematic variables of graphomotor output and 2) determine whether a novel writing task differentially affects the graphomotor output of adults diagnosed with ADHD versus controls. Findings and implications are discussed

PHARMACOKINETIC AND PHARMCODYNAMIC STUDIES OF APOMORPHINE IN THE TREATMENT OF IDIOPATHIC PARKINSON'S DISEASE

There were two aspects to the study of apomorphine in the treatment of Parkinson' s disease: (i) a clinical pharmacokinetic-pharmacodynamic (PK-PD) study was designed and implemented in response to the challenges of apomorphine dose-titration in Parkinson's disease, and in view of the scarcity of available literature on the PK-PD relationships of apomorphine in Parkinson's disease, (ii) the PK(and tolerability)of apomorphine dosing using novel delivery/formulation combinations were explored in view of the inherent limitations associated with the conventional (ie. subcutaneous) route of administration of apomorphine (e.g. cutaneous nodule formation, needle-phobia). An HPLC assay was developed for the quantification of apomorphine in plasma, and stability issues relating to sample storage and assay were investigated. With regards to the first aspect of the research, simultaneous PK-PD modelling was performed, using an effect compartment model to account for counterclockwise hysteresis in a sub-group of patients. According to the traditional two-stage approach to data analysis, mean (standard deviation) clearance following subcutaneous bolus was 2.2 (0.5) L/kg/h, (apparent) volume of distribution was 1.9 (0.8) L/kg, absorption half-life was 4.1 (2.1) minutes and elimination half-life was 69.5 (21.1)minutes (n=7). Equilibration half-life was estimated for two patients at 8.3 and 16.5 minutes. Focus was given to investigating the relevance of a potential correlation (which had previously been identified using in-house pilot data) between post-distributional apomorphine PK and apomorphine-induced anti-parkinsonian response in patients with Parkinson's disease. It was hypothesised that this particular correlation may be of use in a dose-optimisation scheme. However it was demonstrated that, in the patients studied, the concept could not be applied to apomorphine dose-optimisation. The novel delivery systems under scrutiny were: (i) Britaject® (Britannia Pharmaceuticals Ltd.) apomorphine formulation administered subcutaneously using a needle-free (jet) injector (J-TIP®, National Medical Products Inc.), (ii) an intranasal apomorphine powder formulation delivered using a turbospin insufflator (CDFS), and (iii) an apomorphine hydrogel co-polymer produced as a dosage-form for buccal delivery (Controlled Therapeutics (Scotland) Ltd.). As a result of this work, a rationale for subsequent development of the novel systems was provided. Indeed, the needle-free and buccal systems were, in their existing format, shown not to convey a net advantage over the existing system. However the intranasal formulation, with a mean (standard deviation) relative bioavailability of 41 (18)% (n=16) compared to subcutaneous bolus administration (and with a favourable outcome as regards to tolerability), was considered to be potentially suitable for further development

Computer analysis of handwriting dynamics during dopamimetic tests in Parkinson's disease

Studies of dynamic descriptors characteristic of Parkinsonian handwriting have clearly shown potential in identifying various stages of Parkinsonism. This study compares stroke-level analyses of handwritten samples during apomorphine and levodopa "challenge" tests. Six patients with Parkinsonism, diagnosed with or suspected of having Parkinson's Disease generated ordinary handwriting patterns before medication and once again at peak motor performance, after doses of apomorphine or levodopa had been administered. Results show that movement efficiency parameters in addition to standard dynamic handwriting parameters are indicative of positive responses to dopamimetic drugs. Furthermore, it is observed that parameters dependent on higher processing fend to be unaffected during dopamimetic drug cycles