Andrew Evans

Tremor of the upper limbs is a disabling symptom that is present during several neurological disorders and is currently without treatment. Functional MRI (fMRI) is an essential tool to investigate the pathophysiology of tremor and aid the development of treatment options. However, no adequately or standardized protocols for fMRI exists at present. Here we present a novel, online available fMRI task that could be used to assess the pathology of tremor. This study aims to validate the tremor-evoking potential of the fMRI task in a small group of tremor patients outside the scanner and assess the reproducibility of the fMRI task related activation in healthy controls. Twelve HCs were scanned at two time points (baseline and after 6-weeks). There were two runs of multi-band fMRI and the tasks included a "brick-breaker" joystick game. The game consisted of three conditions designed to control for most of the activation related to performing the task by contrasting the condition...

Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical asse...

Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PD) to HC off medications (HC) were pooled for meta-analysis by pain modality. Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings....

In Australia 1% of individuals aged over 50 years have Parkinson's disease (PD). Guidance for commencing device-assisted therapies (DATs) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important ...

Parkinson's disease (PD) is a complex motor and non-motor disorder and management is often challenging. In this review, we explore emerging approaches to improve the care of patients, drawing from the literature regarding patient-centred care, patient and caregiver perspectives and priorities, gaps in knowledge among patients and caregivers and the need for accurate information, individual variability in disease manifestations, prognostication of disease course, new developments in health technologies and personalized medicine, specialty care, pharmacological and non-pharmacological management, financial burden, lifestyle and work-related issues, support groups and palliative care.

This clinical update review focuses on the classification and description of common neuropsychiatric manifestations in Parkinson's disease (PD). We conducted a systematic search of the literature using Pubmed and selected the most recent and relevant papers for this review. Neuropsychiatric manifestations in PD are are very frequent and may arise from an abnormal psychopathological response to the disease, neurobiological changes related to the disease itself, complications of treatments or a combination of all of these. Neuropsychiatric symptoms may precede the motor clinical presentation of PD. Early recognition is essential.

... Parkinson's Disease: Non-Motor and Non-Dopaminergic Features, First Edition. Edited by C. Warren Olanow, Fabrizio Stocchi, and Anthony E. Lang. c 2011 Blackwell Publishing Ltd. Published 2011 by Blackwell Publishing Ltd. 315 Page 2. 316 Chapter 29 ...

In spite of the recognized physical and psychosocial effects of caring for patients with Parkinson's disease (PD), caregiver burden (CB) in this setting is poorly understood. The objective of this research was to identify factors that were associated with CB in an Australian population of PD caregivers using a novel instrument - the Parkinson's Disease Caregiver Burden (PDCB) questionnaire. Fifty patient-caregiver couples were recruited from three movement disorders clinics in Melbourne, Australia. Burden on caregivers was rated using the PDCB questionnaire. Burden scores were correlated with patient factors, including motor symptom severity (Unified Parkinson's Disease Ratings Scale and Hoehn & Yahr (H&Y) scale), patient cognition (Neuropsychiatry Unit Cognitive Assessment Tool; NUCOG), presence of impulsive and compulsive behaviors (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease), and patient olfaction. Caregiver and patient demographics, a...

Drug induced dyskinesias remain a challenging problem in the long term management of Parkinson's disease (PD). We have assessed the effect of quetiapine on dyskinesias in a double blind placebo controlled cross over study. Nine patients with PD were enrolled and received 25 mg of quetiapine or placebo at night for two weeks in prerandomised order, with one week of wash out between treatment periods. Assessments were made using on-off diaries, self assessment of dyskinesias, and L-dopa challenges at baseline and after each treatment period. Videotapes were rated blindly by two raters using modified Abnormal Involuntary Movement Scale and Goetz scores. Patients subsequently went on open label quetiapine at 50 mg/day, for a mean duration of 30 days, and completed the same self assessment forms. During the double blind phase, no significant change in dyskinesias was found on either 25 mg of quetiapine or placebo. Duration of off states and Unified PD Rating Scale motor scores also r...

There is a need for objective measures of dyskinesia and bradykinesia of Parkinson's disease (PD) that are continuous throughout the day and related to levodopa dosing. The output of an algorithm that calculates dyskinesia and bradykinesia scores every two minutes over 10 days (PKG: Global Kinetics Corporation) was compared with conventional rating scales for PD in PD subjects. The algorithm recognises bradykinesia as movements made with lower acceleration and amplitude and with longer intervals between movement. Similarly the algorithm recognises dyskinesia as having movements of normal amplitude and acceleration but with shorter periods without movement. The distribution of the bradykinesia and dyskinesia scores from PD subjects differed from that of normal subjects. The algorithm predicted the clinical dyskinesia rating scale AIMS with a 95% margin of error of 3.2 units compared with the inter-rater 95% limits of agreement from 3 neurologists of -3.4 to +4.3 units. Similarly ...

ABSTRACT Dopaminergic medications used to treat Parkinson’s disease (PD) improve symptoms, reduce motor handicap and may prolong survival [1]. However, in some individuals, they may induce a range of disabling symptoms beyond those attributable to the disease process. These include a variety of compulsive and addictive behaviours. The term ‘dopamine dysregulation syndrome’ (DDS) is used to refer to the compulsive use of dopaminergic medications well beyond the dose needed to optimally control motor disability and in the face of a mounting number of harmful physical, psychiatric and social sequelae. Impulse control disorders (ICDs) are defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others [2]. These may be induced by dopaminergic therapy, particularly dopamine agonists. Moreover, ICDs are seen frequently in patients with DDS, indicating a global sensitizing effect of dopaminergic drugs on motivational systems. Some PD patients display repetitive and mindless behaviours that tend to reflect pre-morbid interests and may be socially disabling. These behaviours, called punding, may be part of dopaminergic dysregulation but may occur without a tendency to increase doses. Punding was initially observed in psychostimulant users and is thought to be analogous to motor stereotypies seen in rodents under chronic psychostimulant regimes. Punding is currently not well described by any DSM-IV criteria. It is important to note that, while many patients with DDS also have ICDs as part of the clinical syndrome and many ICD patients overuse medication, these behavioural disorders may occur in isolation. Similarly, punding may be associated with DDS, ICDs or both, but may also occur without associated other disorders Table (28.1). Dopamine has a central role in modulating movement as well as behavioural processes underlying motivation. Drug-induced neuroadaptations within the dopaminergic accumbens-related circuitry are central to many models of addiction. In PD, regular dopaminergic therapy may induce sensitization to natural as well as drug rewards. Nearly all patients with PD receive dopaminergic medications for the management of motor symptoms but only a small percentage develop medication-related compulsive behaviours. Therefore, individual vulnerability factors are critical in the expression of these disorders and put some persons at greater risk than others. Important clinical risk factors are summarized in Table 28.2. Their identification may help the clinician in prevention or early identification of these disorders.

Impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized psychiatric complication in Parkinson's disease (PD). Other impulsive-compulsive behaviors (ICBs) have been described in PD, including punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Possible risk factors for ICDs include male sex, younger age and younger age at PD onset, a pre-PD history of ICDs, and a personal or family history of substance abuse, bipolar disorder, or gambling problems. Given the paucity of treatment options and potentially serious consequences, it is critical for PD patients to be monitored cl...

The prevalence of pathological gambling is 3.4% to 6% in treated Parkinson's disease, which is higher than the background population rate. In this review we discuss current evidence to indicate that dopamine agonists are much more likely to trigger this behavior than either L-dopa or selective monoamine oxidase B inhibitor monotherapy. New insights from recent behavioral and functional imaging studies and possible treatment approaches are also covered. A PubMed literature search using the terms "gambling" and "Parkinson's disease," "impulse control disorder," "impulsive compulsive behaviour," "dopamine agonist," of individual dopamine agonists, and of ongoing drug trials, using http://www.clinicaltrials.gov, was carried out for the period up to January 2011.

The neuroacanthocytoses are a group of disorders characterised by peripheral blood acanthocytes, central nervous system as well as neuromuscular symptoms. These disorders uniformly result in pathology in the basal ganglia, which account for the characteristic motor symptoms such as chorea or dystonia, but may also account for the apparent elevated rates of major mental disorders in these syndromes. Elevated rates of dysexecutive syndromes, obsessive-compulsive disorder, depression and schizophrenia-like psychosis appear to occur in chorea-acanthocytosis, McLeod's syndrome, pantothenate kinase-associated neurodegeneration, and Huntington's disease-like 2. Disruptions to key frontostriatal loops secondary to pathology in the striatum and pallidum appear to predispose individuals to major neuropsychiatric syndromes; however, treatment can be instituted for a number of these manifestations, which lessens the overall burden of disease in neuroacanthocytosis patients and their families.

To determine whether onset seizures after subarachnoid hemorrhage (SAH) carry independent prognostic information and to investigate the risk factors for late seizures after SAH. Modern management of SAH, including early operation, has substantially reduced mortality. No study has adequately assessed the importance of onset seizures in a contemporary SAH cohort. The authors analyzed the records and initial CT scans of 412 consecutive patients with aneurysmal or nonaneurysmal SAH admitted to the Royal Melbourne Hospital from 1990 to 1996. Each patient with an onset seizure (n = 32, 7.8% of cohort) was age and sex matched to two nonseizure patients of the same cohort. Each patient with a late seizure (n = 17, 5.1% of cohort) was matched to five control subjects of the same cohort. With use of logistic regression analysis, onset seizures correlated with the sum score of blood on initial CT scan (OR = 1.1, p = 0.05), but there was no significant correlation with duration of loss of consciousness at onset, Glasgow Coma Score (GCS), presence of aneurysm, or past history of hypertension or epilepsy. Disability 6 weeks after SAH according to the Glasgow Outcome Scale was independently predicted by initial GCS of <6 (OR = 13.7, p < 0.01) and onset seizure (OR = 7.8, p = 0.04). Late seizures within the first 6 weeks were independently related to rebleeding (OR = 94, p < 0.01) and onset seizures (OR = 27, p < 0.01) but not to other onset variables, development of hydrocephalus, or vasospasm. In this single-institution cohort of patients with SAH, onset seizures were an independent risk factor for late seizures and a predictor of poor outcome.

To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD). We studied 16 patients with advanced PD with [(11)C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET. All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release. In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms.

In the course of treatment, a small group of patients with Parkinson disease (PD) develop a harmful pattern of compulsive dopaminergic drug use, called the dopamine dysregulation syndrome (DDS). Individual factors may influence susceptibility. To identify predisposing factors to DDS in a population of outpatients with PD. The authors compared clinical features, impulsive sensation seeking (ISS) personality traits, past experimental drug use, alcohol consumption, smoking behaviors, and depressive symptoms in 25 patients with DDS to an outpatient sample of 100 patients with PD who were not compulsively overusing dopaminergic medication. Patients with DDS had a significantly younger age at disease onset, higher dopaminergic drug intake, greater past experimental drug use, more depressive symptoms, scored higher on ISS ratings, and tended to have higher alcohol intake. Using logistic regression analysis, we found that novelty seeking personality traits, depressive symptoms, alcohol intake, and age at PD onset were significant predictors of DDS. These factors may help to identify early patients who are more vulnerable to developing a pattern of compulsive dopaminergic drug use and help minimize its consequences.