The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis

BACKGROUND: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. OBJECTIVE: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. METHODS: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. RESULTS: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. CONCLUSIONS: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs

Wilson's disease: update on pathogenesis, biomarkers and treatments

Wilson’s disease is an autosomal–recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson’s disease from the neurological perspective, with a focus on recent advances. The genetic and molecular mechanisms associated with ATP7B dysfunction have been well characterised, but despite extensive efforts to identify genotype–phenotype correlations, the reason why only some patients develop neurological or psychiatric features remains unclear. We discuss pathological processes through which copper accumulation leads to neurodegeneration, such as mitochondrial dysfunction, the role of brain iron metabolism and the broader concept of selective neuronal vulnerability in Wilson’s disease. Delayed diagnoses continue to be a major problem for patients with neurological presentations. We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson’s disease, before discussing future directions for translational research

Neuropsychiatric Features of Punding and Hobbyism in Parkinson's Disease

BACKGROUND: Little is known about the cognitive and neuropsychiatric profile associated with punding and hobbyism in Parkinson's disease (PD). OBJECTIVE: To compare the clinical and neuropsychological features of PD patients with punding and hobbyism to PD controls. METHODS: The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was used as a screening tool, and a structured interview was used to diagnose punding/hobbyism. Clinical and neuropsychological assessment was conducted with validated questionnaires/scales. RESULTS: Twenty-one patients with PD and punding (PD + pu) were compared to 26 with hobbyism (PD + h) and 25 PD controls. PD + pu patients showed higher levels of anxiety, non-motor symptoms and motor symptoms, and lower Frontal Assessment Battery scores. The PD + h group exhibited similar levels of anxiety and motor fluctuations to the PD + pu group. CONCLUSION: PD + pu showed increased anxiety and frontal lobe dysfunction, similar to PD + h. Hobbyism could be a prodromal phase with increased risk of leading to punding

Dystonia

INTRODUCTION: Dystonia is a clinically heterogeneous group of hyperkinetic movement disorders. Recent advances have provided a better understanding of these conditions with significant clinical impact. SOURCES OF DATA: Peer reviewed journals and reviews. PubMed.gov. AREAS OF AGREEMENT: A recent consensus classification, including the assessment of phenomenology and identification of the dystonia syndromes, has provided a helpful tool for the clinical assessment. New forms of monogenic dystonia have been recently identified. AREAS OF CONTROVERSY: Despite recent advances in the understanding of dystonia, treatment remains symptomatic in most patients. GROWING POINTS: Recent advances in genetics have provided a better understanding of the potential pathogenic mechanisms involved in dystonia. Deep brain stimulation has shown to improve focal and combined forms of dystonia and its indications are constantly expanding. AREAS TIMELY FOR DEVELOPING RESEARCH: Growing understanding of the disease mechanisms involved will allow the development of targeted and disease-modifying therapies in the future

Neuroendocrine abnormalities in Parkinson's disease

Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research

Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology

AIMS: Growing evidence suggests a shared pathogenesis between Parkinson's disease and diabetes although the underlying mechanisms remain unknown. The aim of this study is to evaluate the effect of type 2 diabetes on Parkinson's disease progression and to correlate neuropathological findings to elucidate pathogenic mechanisms. METHODS: In this cohort study, medical records were retrospectively reviewed of cases with pathologically-confirmed Parkinson's disease with and without pre-existing type 2 diabetes. Time to disability milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and survival were compared to assess disease progression and their risk estimated using Cox hazard regression models. Correlation with pathological data was performed, including quantification of α-synuclein in key brain regions and staging of vascular, Lewy and Alzheimer's pathologies. RESULTS: Patients with PD and diabetes (male 76%; age at death 78.6 ± 6.2 years) developed earlier falls (P < 0.001), wheelchair dependence (P = 0.004), dementia (P < 0.001), care home admission (P < 0.001) and had reduced survival (P < 0.001). Predating diabetes was independently associated with a two to three-fold increase in the risk of disability and death. Neuropathological assessment did not show any differences in global or regional vascular pathology, α-synuclein load in key brain areas, staging of Lewy pathology or Alzheimer's disease pathology. CONCLUSIONS: Pre-existing type 2 diabetes contributes to faster disease progression and reduced survival in Parkinson's disease which is not driven by increased vascular, Lewy or Alzheimer's pathologies. Additional non-specific neurodegeneration related to chronic brain insulin resistance may be involved

Liver transplantation for late-onset acute liver failure in Wilson’s disease: the UK experience over two decades

BACKGROUNDS AND AIMS: Acute liver failure as the initial presentation of Wilson’s disease is usually associated with onset in childhood, adolescence or early adulthood. Outcomes after transplantation for late-onset presentations, at or after 40 years, are seldom reported in the literature METHODS: We report a case, review the literature and provide unpublished data from the UK Transplant Registry on late-onset acute liver failure in Wilson’s disease. RESULTS: We describe a 62-year-old man presenting with acute liver failure who was successfully treated with urgent liver transplantation. We identified seven cases presenting at age 40 years or over in the literature where individual outcomes were reported; three were treated with transplantation and two survived. We identified a further eight cases listed for transplantation in the UK between 1995 and 2014; seven were treated with transplantation and six survived. One patient was de-listed for unknown reasons. CONCLUSIONS: We discuss the need to consider Wilson’s disease in older adults presenting with acute liver failure and importance of making the diagnosis prior to transplantation. We suggest that urgent liver transplantation has good outcomes for late-onset presentations and recommend that urgent transplantation should always be considered in Wilson’s disease presenting with acute liver failure