Gemma Cummins

Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD).

The immune system is a promising therapeutic target for disease modification in Parkinsons disease (PD), but appropriate immune‐related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD.

Smartphone- and internet-assisted self-management and adherence tools to manage Parkinson’s disease (SMART-PD): study protocol for a randomised controlled trial (v7; 15 August 2014)

BackgroundNonadherence to treatment leads to suboptimal treatment outcomes and enormous costs to the economy. This is especially important in Parkinson’s disease (PD). The progressive nature of the degenerative process, the complex treatment regimens and the high rates of comorbid conditions make treatment adherence in PD a challenge. Clinicians have limited face-to-face consultation time with PD patients, making it difficult to comprehensively address non-adherence. The rapid growth of digital technologies provides an opportunity to improve adherence and the quality of decision-making during consultation. The aim of this randomised controlled trial (RCT) is to evaluate the impact of using a smartphone and web applications to promote patient self-management as a tool to increase treatment adherence and working with the data collected to enhance the quality of clinical consultation.Methods/DesignA 4-month multicentre RCT with 222 patients will be conducted to compare use of a smartphone- and internet-enabled Parkinson’s tracker smartphone app with treatment as usual for patients with PD and/or their carers. The study investigators will compare the two groups immediately after intervention. Seven centres across England (6) and Scotland (1) will be involved. The primary objective of this trial is to assess whether patients with PD who use the app show improved medication adherence compared to those receiving treatment as usual alone. The secondary objectives are to investigate whether patients who receive the app and those who receive treatment as usual differ in terms of quality of life, quality of clinical consultation, overall disease state and activities of daily living. We also aim to investigate the experience of those receiving the intervention by conducting qualitative interviews with a sample of participants and clinicians, which will be administered by independent researchers.Trial registrationISRCTN45824264 (registered 5 November 2013)

The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington’s disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington’s disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington’s disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington’s disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington’s disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington’s disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

Treatment of superficial siderosis with iron chelation therapy.

Superficial siderosis is caused by recurrent haemorrhage in the subarachnoid space leading to haemosiderin deposition. It typically causes the triad of ataxia, deafness and myelopathy. We report a patient who developed superficial siderosis following neurosurgery for syringomyelia and who had an improvement in his hearing and mobility following treatment with a new iron chelation therapy that can penetrate the blood–brain barrier. It provides an intriguing insight into a therapy that could potentially modify the course of this rare neurodegenerative disorder. Further studies are required to assess the clinical efficacy of deferiprone in superficial siderosis.

What is the most promising treatment for Parkinson’s disease: genes, cells, growth factors or none of the above?

Author for correspondence: Cambridge Centre for Brain Repair & the Department of Neurology, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK Tel.: +44 1223 331160 Fax: +44 1223 331174 rab46@cam.ac.uk have received levodopa for more than 5 years, in 80% of patients treated for 10 years, and in nearly all patients with young-onset disease. In a bid to control these motor fluctuations, patients’ therapy may need to be escalated to include more intensive pharmacotherapies such as infusions of subcutaneous apomorphine and jejunal Duodopa infusions. In addition, deep brain stimulation (DBS) surgery, either of the subthalamic nucleus or the globus pallidus pars interna, can be useful for treating PD patients at this stage when the motor fluctuations and dyskinesias cannot be adequately managed with pharmacological manipulation. The 5-year follow-up of patients who have received bilateral stimulation of the subthalamic nucleus in PD clearly shows that their improvement in motor function is sustained over time. However, disability still progresses from year to year, indicating ongoing degeneration in both dopaminergic and nondopaminergic sites. Furthermore, DBS is also associated with significant cognitive and psychiatric side effects, including severe depression, impulsivity and apathy, all of which may help explain the discrepancy between changes in quality-of-life assessment and motor disability in patients having had this therapy [3]. None of the currently available therapies for PD can slow or halt the disease progression. Therefore, there is a clear need for new therapies in PD that not only are capable of providing dopamine replacement more effectively, but also serve to replace or protect the substantia nigra pars compacta dopamine neurons from further degeneration. In a bid to meet this clinical challenge, novel therapeutic approaches have evolved over the last 20 years, which include a variety of gene therapy approaches, neurotrophic factor delivery and cell replacement therapies. Three main strategies under investigation using gene transfer for targeted protein expression include: “...it has to be realized that cell therapies are not a cure for Parkinson’s disease...” What is the most promising treatment for Parkinson’s disease: genes, cells, growth factors or none of the above?

Comparative epidemiology of incident Parkinson's disease in Cambridgeshire, UK

Despite the increasing global importance of Parkinsons disease (PD), its exact incidence in the general population is not known. Comparing published studies, incidence rates from 1.5 to 19/100 000 person-years have been reported but such differences cannot simply be attributed to between-population differences in PD risk as no two studies have used the same case ascertainment strategy.1 We have previously published the results of a community-based study of incident parkinsonism including PD in Cambridgeshire, UK: CamPaIGN (Cambridgeshire Incidence of PD from GP to Neurologist).2 We now report the findings of a novel second incidence study in the same base population, using the same case ascertainment strategy: PICNICS (Parkinsonism: Incidence and Cognitive and Non-motor heterogeneity In CambridgeShire). This unique undertaking enables us to present a comparative analysis of these studies, representing the most complete set of PD incidence data yet reported in a defined population. The PICNICS study recruited newly diagnosed cases of PD and parkinsonism resident in Cambridgeshire between 1 April 2008 and 31 January 2010. Detailed methods including inclusion and exclusion criteria are available from the author. To summarise, case ascertainment was performed using a service-based screen of the normal routes of UK/National Health Service (NHS) healthcare referral. All general practitioners (GPs) and hospital specialists working with suspected/newly diagnosed PD operating in the county were regularly contacted by mail and electronically throughout the study period. They were instructed to refer all consenting cases …

Parkinson's disease: diagnosis and current management

Treatment for Parkinsons should be tailored to the needs of the patient and adjusted regularly to ensure maximum efficacy and tolerability. Our drug review outlines diagnosis, drug options and advanced therapies, and the management of complications, followed by an analysis of the prescription data.

Teaching NeuroImages: Internal carotid artery dissection presenting as Villaret syndrome

A 63-year-old man presented with headache, hoarseness, and dysphagia. He had a left-sided Horner syndrome and wasting of the left sternocleidomastoid muscle. His tongue was deviated to the left on protrusion (figure 1). MRI and CT angiography revealed a distal left internal carotid artery dissection (figure 2).

PO002 Bacterial meningitis with myelopathy and cranial neuropathy

Acute meningococcal meningitis in adults can be complicated by cranial neuropathies and more rarely by myelopathy. A 55-year-old woman presented with acute bacterial meningitis requiring intubation and was treated with intravenous antibiotics and dexamethasone. Cerebrospinal fluid 16S PCR was positive for Neisseria meningitidis and latex agglutination confirmed the W135 serotype. Ten days after presentation she developed mild upper limb and severe lower limb weakness with hyperreflexia, despite resolution of meningism and improvement of inflammatory markers. On the next day she developed complete bilateral hearing loss and bilateral facial palsy. Magnetic resonance imaging with contrast showed bilateral enhancement of VIIth and VIIIth cranial nerves, with focal signal change within the thoracic spinal cord. Audiometry confirmed complete sensorineural deafness. She was treated with five days of intravenous methylprednisolone and continued a further nine days of intravenous antibiotics. Four weeks after onset, she remained completely deaf with mild improvement of limb and facial weakness. We report a case of acute meningococcal meningitis complicated by presumed extensive vasculitis leading to myelopathy and delayed onset of multiple cranial neuropathies. There was an unusual biphasic presentation and the vasculitis was apparently ameliorated by glucocorticoids, suggesting conventional steroid recommendations may occasionally be inadequate.

Hallucinations in Parkinson’s Disease

A 74-year-old male with a 7-year history of idiopathic Parkinson’s disease (PD) presented with visual hallucinations and memory difficulties. One year ago, he started experiencing a “feeling of presence” of someone out of the corner of his eye. This sensation was fleeting and occurred once or twice per week. However, over recent months he was having more well-formed visual hallucinations, occurring on an almost daily basis. His wife had noted a significant deterioration in his memory over the last 2 years, whereby he was forgetting appointments and having difficulty in managing his medications and finances. He was becoming increasingly dependent on his family members for activities of daily living. He had a 10-year history of REM sleep behavior disturbance and tended to be sleepy during the day. His medications included co-benyldopa 25/100 qds, co-benyldopa-controlled release 25/100 OD nocte, and rasagiline 1 mg OD.