Brain Injury & Repair - Recent Highlights

Head Injury

In head injury, we have documented fMRI connectivity in brain regions based on motor and cognitive tasks, providing endpoints that can be used as biomarkers of plasticity in interventional studies.

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In head injury, we have documented fMRI connectivity in brain regions based on motor and cognitive tasks, providing endpoints that can be used as biomarkers of plasticity in interventional studies.  Rigorous evaluation of 1H MRS and diffusion tensor MRI, including test-retest reliability has been used both in healthy volunteers and TBI, with estimation of sample size in experimental medicine and Phase IIa studies. Applying monitoring of brain chemistry, oxygenation and intracranial pressure as part of standard care of patients with acute brain injury in neuro-critical care has shown relationships between monitored parameters and clinical outcome. This work continues to define the impact of specific therapy on cerebral chemistry. We have completed the NIHR-HTA funded RAIN study – a prospective validation of risk prediction models for adult patients with head injury - and applied this to evaluate the optimum location and comparative costs of neurocritical care. Data from the Trauma and Audit Research Network for 2013 show Cambridge achieving excellent performance of adjusted outcome measures. In multiple sclerosis, we have replicated our finding that serum IL-21 is a reliable biomarker for autoimmunity after alemtuzumab although not detectable using all commercially-available assays.

March 2014


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Licensing of Alemtuzumab

Alemtuzumab reduces disease activity in previously untreated patients with ...

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Alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment. Our work has led to the licensing of Alemtuzumab in the European Union and Mexico as a first line treatment for active relapsing- remitting multiple sclerosis, with second line licences in Canada and Australia. In work not supported by commercial funding we have shown that the principal adverse effect of alemtazumab, secondary autoimmunity, occurs when the immune system reconstitute by homeostatic proliferation of residual lymphocytes.


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Scientists awarded funding to create an iPad app to monitor brain function

Scientists have been awarded £800,000 to develop a bedside machine which would give hospital doctors images of their patients' brains. The money will be spent on technology for brain injury patients.

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The National Institute of Health Research funding has been given to a team from Addenbrooke's Hospital and the University of Cambridge. Scientists have been awarded £800,000 to develop a bedside machine which would give hospital doctors images of their patients' brains. The money will be spent on technology for brain injury patients. As well as creating a bedside brain imaging device, the team wants to make an iPad app to detect memory problems. The university-hospital partnership is called the Cambridge Brain Injury Healthcare Technology Cooperative (HTC).

The cooperative hopes the bedside machine will give doctors high quality images of their patients' brains. Such images are currently only available at a handful of centres in the world. Professor John Pickard, director of the Cambridge Brain Injury HTC, said the partnership would be working with patients and carers as well as some of the technology sector businesses based in and around Cambridge. Other projects planned during the next two years includes developing a machine which reliably detects seizures and a system for better tracking of brain injury patients when they leave hospital.

December 2012


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Brain injury and neurocritical care

(1) Locating the Wolfson Brain Imaging Centre (providing functional MR, spectroscopy and PET imaging) adjacent to the Neurosciences Critical Care Unit supports many different studies of acute brain injury including randomised control trials. The radiopharmaceuticals laboratory is accredited with...

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(1) Locating the Wolfson Brain Imaging Centre (providing functional MR, spectroscopy and PET imaging) adjacent to the Neurosciences Critical Care Unit supports many different studies of acute brain injury including randomised control trials. The radiopharmaceuticals laboratory is accredited with MHRA-GMP licences and generates the widest range of PET radiotracers available in the UK. Software developed for physiological brain monitoring is used by around 40 centres worldwide.

  • Brain_imaging_centre

A novel approach has been introduced based on transcranial Doppler interrogation of compartmental compliances within the brain for non-invasive prediction of intracranial hypertension, cerebral vasospasm and carotid artery stenosis. Near Infrared Spectroscopy has been introduced for the continuous monitoring of cerebral autoregulation and hence individual optimisation of arterial blood pressure and brain protection during cardiopulmonary bypass and in pediatric neuro-intensive care. Novel studies of drug penetration, 13C labelled investigations of glucose, lactate and pyruvate utilisation and cytokines following brain injury have been carried out in association with PET and MR spectroscopy. These technologies show that multimodal, computer-supported, brain monitoring in acute brain injury can be used to optimize cerebral perfusion pressure for the individual patient, a concept which has already been taken up in the International Guidelines for the management of severe traumatic brain injury.

(2) The assessment of cerebrospinal fluid dynamics in patients suffering from hydrocephalus and idiopathic intracranial hypertension has improved the management of complex disorders. The 3-D topography of changes in white matter around the ventricles before and after shunting is being explored using diffusion-weighted MR techniques and correlated with cognitive function.

(3) Collaboration with the MRC Cognition and Brain Sciences Unit pioneered the study of awareness in coma using functional MR; to date, 5 of 54 patients have demonstrated responses that could not be detected on clinical assessment. This work has led to the refinement of Management Guidelines; and brain computer interfaces are being developed.

(4) Several phase III trials are in progress: chronic subdural haematoma randomised study of drains versus no drain; RESCUEicp decompressive craniectomy trial (www.RESCUEicp.com) involving 267 patients from 43 centres in 17 countries, the largest surgical trial for the management of head injury to date; STASH ' a multicentre placebo controlled trial of acute statin therapy following aneurysmal subarachnoid haemorrhage based on extensive phase I/II studies (midway through recruitment); and the SILVER trial of uncoated versus silver coated external ventricular drains in the prevention of infection has been completed and shows a significant benefit.


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Multiple sclerosis

Genome wide association studies, performed as co-founders of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium, have identified 23 susceptibility alleles, and a further 72 strongly associated single nucleotide polymorphisms. Most have an...

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Genome wide association studies, performed as co-founders of the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Wellcome Trust Case Control Consortium, have identified 23 susceptibility alleles, and a further 72 strongly associated single nucleotide polymorphisms. Most have an immunological 'flavour'.

Since 2012, we have recruited 268 patients locally into the Cambridge BioResource, and 4583 nationally, into our ‘Genetic Analysis of Multiple Sclerosis’ study. The most recent work of the IMSGC involved typing 45885 individuals with Immunochip increasing the list of non-MHC variants associated with multiple sclerosis to 110. Future work will focus on functional studies and the genetics of disease course and progression. Following the appointment in 2013 of a Professor in Stroke Medicine we will extend genetic studies of complex traits to stroke and small vessel disease.

March 2014

 


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