Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease.

Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.

Seven years of cranioplasty in a regional neurosurgical centre.

INTRODUCTION: In recent years craniectomy has been widely used in the management of traumatic brain injury and ischaemic stroke. The objective of this study was to evaluate the indications, techniques and outcomes for patients undergoing cranioplasty over a recent 7-year period in a geographically distinct population. MATERIALS AND METHODS: An observational study was performed retrospectively, with review of case records from 2004 to 2011. Demographic, clinical and outcome data were collected, and complications were classified as major and minor. A multi-variant analysis was performed to identify patient and management factors that influenced outcome. RESULTS: Data were collected on a total of 87 cranioplasty patients with a median age of 42 and a mean follow-up time of 3 years and 10 months. The main indications for craniectomy were trauma (46%), infection (19%) intracranial haemorrhage (15%), tumour (13%) and ischaemic stroke (6%). Eight percent of patients had a synchronous craniectomy and cranioplasty, 14% had cranioplasty within 3 months of craniectomy, 21% within 3-6 months, 35% within 6-12 months, 14% over 1 year and 8% over 2 years later. The most frequently implanted cranioplasty material was titanium (53%), followed by autologous bone (26%) and acrylic (15%). Administration of prophylactic antibiotics was recorded in 97% of cases. Major complications occurred in 20% of patients, including 2 deaths (2%), 5 extradural haemorrhages (6%) and 9 infections (10%). A further 10% of cases experienced minor or cosmetic complications. CONCLUSIONS: Cranioplasty is often considered as a low-risk procedure following craniectomy. In our cohort, a 20% risk of major complications, including death, was identified. These findings contribute to the literature, emphasising that cranioplasty is a high-risk procedure. Whilst compelling reasons may guide the undertaking of craniectomy, it is essential that consideration is given to the significant subsequent risks of cranioplasty.

Proposal for establishment of the UK Cranial Reconstruction Registry (UKCRR).

BACKGROUND: The increasing utilisation of decompressive craniectomy for traumatic brain injury and stroke has led to an increase in the number of cranioplasties undertaken. Cranioplasty is also undertaken following excision of tumours originating from or invading the skull vault, removal of bone flaps due to post-operative infection, and decompressive craniectomy for the management of rarer causes of brain oedema and/or refractory intracranial hypertension. The existing literature which mainly consists of single-centre, retrospective studies, shows a significant variation in practice patterns and a wide range of morbidity. There also exists a need to measure the outcome as perceived by the patients themselves with patient reported outcome measures (PROMs; functional outcome, quality of life, satisfaction with cosmesis). In the UK, the concept of long-term surveillance of neurosurgical implants is well established with the UK shunt registry. Based on this background, we propose to establish the UK Cranial Reconstruction Registry (UKCRR). AIM: The overarching aim of the UKCRR is to collect high-quality data about cranioplasties undertaken across the UK and Ireland in order to improve outcomes for patients. METHODS: Any patient undergoing reconstruction of the skull vault with autologous bone, titanium, or synthetic material in participating units will be eligible for inclusion. Data will be submitted directly by participating units to the Outcome Registry Intervention and Operation Network secure platform. A Steering Committee will be responsible for overseeing the strategic direction and running of the UKCRR. OUTCOME MEASURES: These will include re-operation due to a cranioplasty-related issue, surgical site infection, re-admission due to a cranioplasty-related issue, unplanned post-operative escalation of care, adverse events, length of stay in admitting unit, destination at discharge from admitting unit, mortality at discharge from admitting unit, neurological status and PROMs during routine follow-up. CONCLUSION: The UKCRR will be an important pillar in the ongoing efforts to optimise the outcomes of patients undergoing cranioplasty.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Reported Outcomes.

The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in the development of an evidence-based treatment strategy, largely due to heterogeneous outcome measures that preclude cross-study comparisons and guideline development. This study aimed to identify and quantify the heterogeneity of outcome measures reported in the CSDH literature and to build a case for the development of a consensus-based core outcome set. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO international prospective register of systematic reviews (CRD42014007266). All full-text English language studies with >10 patients (prospective) or >100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. There were 14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%) cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort studies. Outcome domains reported by the studies included mortality (63.8% of included studies), recurrence (94.1%), complications (48.0%), functional outcomes (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity in the definitions of the outcome measures, as evidenced by the seven different definitions of the term "recurrence," with no definition given in 19 studies. The time-points of assessment for all the outcome domains varied greatly from inpatient/hospital discharge to 18 months. This study establishes and quantifies the heterogeneity of outcome measure reporting in CSDH and builds the case for the development of a robust consensus-based core outcome set for future studies to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project.