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Researchers unlock key prognostic tool for brain injured patients

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In 1974, leading neuroscientist Graham Teasdale co-created the Glasgow Coma Scale (GCS) while at the Institute of Neurological Sciences in Glasgow. This scale has since been used to assess coma and impaired consciousness in patients who have had a brain injury.

The scale is used to describe variations in a patient’s eye, motor, and verbal responses. Each feature is assigned numerical scores depending on the quality of the response, and total scores range from three, which is a deep coma, to 15, which is full consciousness.

The GCS is used in clinics all around the world by physicians, nurses, and emergency medical technicians; and is also applied more widely in other, more complex systems that are used in assessing acute brain damage.

However, all three features of the GCS can’t always be determined in patients. Most commonly, the verbal response can’t be tested, as it’s not possible to determine this response in patients with severe brain injury who are intubated.

When the verbal score cannot be measured, the GCS can still be used in routine assessment and communication about a patient’s condition.

“The GCS should be reported in its component parts, so there is still useful information in the motor and eye components, and the verbal score can simply be reported as not testable,” Paul Brenan, senior clinical lecturer in neurosurgery at the University of Edinburgh says.

“The missing verbal score is problematic, though ,when determining the GCS sum score (eyes + verbal + motor). The sum score is used in clinical prognostic tools, such as the GCS -pupils score, so until now, missing verbal data has prevented clinicians from using these tools.”

But now, Teasdale and Brennan, along with Gordon Murray at the University of Edinburgh, have created a tool to use to assess impaired consciousness when the verbal component of the GCS is missing.

The researchers first examined a database of GCS assessments, and found that the verbal component of GCS was missing in 12,000 patients with traumatic brain injury (TBI), which made up 11 per cent of GCS assessments. These verbal scores were most often missing in patients with low eye and motor scores.

Using GCS data recorded in a database of 54,000 patients, the researchers calculated the distribution of verbal scores for each combination of eye score and motor score. They then combined GCS eye and motor scores into EM scores, and determined the distribution of verbal scores for each EM score. Based on this, they identified a verbal score that clinicians could impute for every EM score.

“Without the verbal component of the GCS, the GCS sum score (eyes + Verbal + motor) cannot be determined, so we developed this imputation tool to enable clinicians to benefit from these prognostic tools for decision making in patients with the most severe brain injuries, where the verbal score is not testable,”  Brennan says.

To test these imputed verbal scores, the researchers substituted imputed verbal scores for actual verbal scores within the framework of prognostic charts, which the authors had previously developed.

These charts take into account the total GCS score, pupil response, age of the patient, and findings of abnormalities. The charts provide predictions about patient outcomes, and are designed to help clinicians make decisions and communicate across teams.

The authors outline in their paper, ‘A practical method for dealing with missing Glasgow Coma Scale verbal component scores,’ published in the Journal of Neurosurgery, that they found that the information gleaned from imputing verbal scores according to each EM score was similar to the variations between precise eye and motor scores, and from full information on verbal, eye, and motor responses.

Imputing verbal scores doesn’t add new information, but allows clinicians to use prediction and prognostic models by filling in verbal data needed for those systems to work.

“We have developed several tools related to the GCS that enhance its ease of use and clinical application, including the GCS Aid, the GCS-pupils score and the GCS pupils Age CT prognostic charts,” Brennan tells NR Times.

“These have been designed to address specific needs. For example, the GCS Aid was developed to support training in assessment of the GCS and to enhance reproducibility of assessment. The GCS pupils score and prognostic charts provide a simple but robust prognostic tool that can be used in the clinic.”

“Prognostic scores are helpful for clinicians to get a reliable prediction of patient outcome, to inform clinical decision-making and to support communication with a patient’s family.

“We know from previous research that clinicians can tend to predict overly pessimistic outcomes for patients, particularly those with severe brain injuries, so these prediction models are designed to prevent that. With our imputation tool, the sum score can be determined and prognostic models used in real-time in the clinic.”

The researchers believe that being able to add verbal scores will help clinicians quickly determine the severity of acute brain injury and estimate patient outcomes.

“We know from the enquires we get and from the number of downloads of materials from our website, that these are very popular and are having a positive impact on clinical care around the world.

“We are confident this missing verbal score imputation tool will be just as positively received,” Brennan says.

 

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Astrocytes identified as master ‘conductors’ of the brain

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In the orchestra of the brain, the firing of each neuron is controlled by two notes – excitatory and inhibitory – that come from two distinct forms of a cellular structure called synapses.

Synapses are essentially the connections between neurons, transmitting information from one cell to the other. The synaptic harmonies come together to create the most exquisite music–at least most of the time.

When the music becomes discordant and a person is diagnosed with a brain disease, scientists typically look to the synapses between neurons to determine what went wrong. But a new study from Duke University neuroscientists suggests that it would be more useful to look at the white-gloved conductor of the orchestra – the astrocyte.

Astrocytes are star-shaped cells that form the glue-like framework of the brain. They are one kind of cell called glia, which is Greek for “glue.” Previously found to be involved in controlling excitatory synapses, a team of Duke scientists also found that astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. The astrocytes reach out thin, fine tentacles to the inhibitory synapse, and when they touch, the adhesion is formed by NrCAM. Their findings were published in Nature on November 11.

“We really discovered that the astrocytes are the conductors that orchestrate the notes that make up the music of the brain,” said Scott Soderling, PhD, chair of the Department of Cell Biology in the School of Medicine and senior author on the paper.

Excitatory synapses — the brain’s accelerator — and inhibitory synapses — the brain’s brakes — were previously thought to be the most important instruments in the brain. Too much excitation can lead to epilepsy, too much inhibition can lead to schizophrenia, and an imbalance either way can lead to autism.

However, this study shows that astrocytes are running the show in overall brain function, and could be important targets for brain therapies, said co-senior author Cagla Eroglu, PhD, associate professor of cell biology and neurobiology in the School of Medicine. Eroglu is a world expert in astrocytes and her lab discovered how astrocytes send their tentacles and connect to synapses in 2017.

“A lot of the time, studies that investigate molecular aspects of brain development and disease study gene function or molecular function in neurons, or they only consider neurons to be the primary cells that are affected,” said Eroglu. “However, here we were able to show that by simply changing the interaction between astrocytes and neurons — specifically by manipulating the astrocytes — we were able to dramatically alter the wiring of the neurons as well.”

Soderling and Eroglu collaborate often scientifically, and they hashed out the plan for the project over coffee and pastries. The plan was to apply a proteomic method developed in Soderling’s lab that was further developed by his postdoctoral associate Tetsuya Takano, who is the paper’s lead author.

Takano designed a new method that allowed scientists to use a virus to insert an enzyme into the brain of a mouse that labeled the proteins connecting astrocytes and neurons. Once tagged with this label, the scientists could pluck the tagged proteins from the brain tissue and use Duke’s mass spectrometry facility to identify the adhesion molecule NrCAM.

Then, Takano teamed up with Katie Baldwin, a postdoctoral associate in Eroglu’s lab, to run assays to determine how the adhesion molecule NrCAM plays a role in the connection between astrocyte and inhibitory synapses. Together the labs discovered NrCAM was a missing link that controlled how astrocytes influence inhibitory synapses, demonstrating they influence all of the ‘notes’ of the brain.

“We were very lucky that we had really cooperative team members,” said Eroglu. “They worked very hard and they were open to crazy ideas. I would call this a crazy idea.”

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Carers at risk of being forgotten

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A study has found that 68% of people believe they should ‘reach out’ to carers more often – with 60% of respondents only asking carers how they are ‘now and again’, ‘rarely’ or ‘almost never’; leaving carers at risk of feeling forgotten.

Furthermore, 72% of respondents worried that carers struggled with ‘loneliness’ thanks to the full-on nature of care leaving them little time for socialising.

Throughout the pandemic, caregivers have been at the forefront of the fight, looking after the most vulnerable in society and putting their own lives on the line to do so. In light of this, a campaign called #ReachOutAndHelpOut has been launched to encourage support for carers as they continue to deliver essential care to those in need – amidst fears that carers’ wellbeing is often overlooked.

Spearheaded by Sentai, a British technology start-up focused on helping the elderly live more independently in their own homes, the campaign looks to highlight the vital role that carers play.

Respondents, mindful of the associated health impact of winter, believe the biggest fears to be faced by carers in coming months is another ‘national lockdown’ (60%), while 53% of respondents saw ‘excessive workload’ as a primary worry. 50% also believed ‘difficulty visiting family and friends due to their care commitments’ was a central concern, while ‘juggling different responsibilities’ was a key issue according to 46%.

Other concerns included ‘lack of time’ (32.9%) and carers ‘feeling they’re not doing enough’ (25%).

Professor Ray Jones, professor of health informatics at Plymouth University and director of eHealth Productivity and Innovation in Cornwall and the Isles of Scilly (EPIC), which focuses on the provision of internet based healthcare services (eHealth) voiced his support for the campaign, highlighting the difficulties carers face.

He said: “The impact of the coronavirus crisis has been profound on almost all aspects of society. For carers though, this impact has been magnified to a far higher degree. The physical and psychological toll of caring during a pandemic is huge. We must be mindful of the burden placed on carers and do what we can to help. The service they provide is essential, and we’re all indebted to their hard work. The very least we can do then is simply ask them how they’re doing and offer whatever assistance we’re able to give.”

These sentiments were echoed by Philip Marshman, founder of Sentai and orchestrator of #ReachOutAndHelpOut, who said: “The role of a carer is often overlooked. It’s all too easy to ask how the recipient of care is without extending that concern beyond to take into account the person looking after them. Carers are people, not robots, and now, more than ever we must do what we can to consider and support their wellbeing and mental health.”

Sentai has launched a Kickstarter campaign to raise funds for the next stage of its smart device development, the success of which will see its pioneering technology brought to mass market – allowing those in need to benefit from its advanced offering.

Philip said: “The experience of looking after my own father led me to create Sentai, and it’s been developed to help both the care recipient and the caregiver. Through revolutionary voice technology it initiates intelligent conversations, helping to alleviate boredom and loneliness, while also providing helpful reminders. It’s safety properties also allow the caregiver to monitor the care recipient remotely and unobtrusively, providing reassurance that the care recipient is OK and acting as normal, thereby helping to ease stress and worry for the caregiver.”

He added: “We have everything in place to deliver a successful solution – we want to get Sentai into people’s homes as quickly as possible – whether that’s someone’s own home, or a care home. Raising funds in this way means we can stay true to our mission which is helping people live more independently, for longer.”

Further details of the Kickstarter campaign can be found via https://www.kickstarter.com/projects/sentai/sentai.

To find out more about the #ReachOutAndHelpOut campaign and the different ways to get involved, including the chance to win a well-deserved break away, please visit sentai.ai/ReachOut.

Others in the care industry who have expressed support for the #ReachOutAndHelpOut campaign, include Dr Stephen Ladyman, founder of Oak Retirement and former Minister of Health responsible for Social Care, and Shaleeza Hasham, founder of the Adopt a Grandparent scheme and head of hospitality at care home and home care provider, CHD Living.

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PhysioFunction setting the trend for telerehab

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Having been an early adopter of telerehab, PhysioFunction was perhaps less daunted than most at the prospect of responding to the COVID-19 lockdown and ensuring their clients’ needs were met.

The specialist neuro physiotherapy practice has, for the past year, used video calls to enable its clients to receive one-to-one sessions in addition to those provided in person, with its staff supporting them to install and use the technology remotely.

It is also an early adopter of the MindMotion GO, a first-of-its-kind mobile neurorehabilitation therapy system which uses gaming to support the recovery of brain injury and neuro patients.

PhysioFunction has reported strong levels of engagement and progress among clients as a result of its telerehab programme, which has increased in its use during the past few months amidst the pandemic.

From its specialist outpatient rehabilitation unit in Northampton, PhysioFunction supports patients from a 100-mile radius, which was a key driver in the adoption of virtual means of delivering therapy.

Claire Everett, clinical operations manager at PhysioFunction and a senior neurological physiotherapist, said: “For some time now, we have tried to embrace the use of online means for therapy, and it has really helped many of our clients. By doing sessions in their own homes, we see them taking ownership of their rehabilitation and it delivers benefits to them in their own settings.

“For example, we might be doing a session by video with a client on how to cope in the kitchen – but because it’s their own kitchen they’re in, that makes it even more relatable.

“It is a very useful way for some clients who perhaps struggle to get to us once a week, but cope much better with two half-hour weekly sessions by telerehab. We do carry out home visits, and will combine the remote sessions with hands-on therapy wherever we can, but some clients live quite a distance away or maybe it isn’t easy for them to get out of the house.

“By holding sessions by video, it doesn’t matter where they live, whether it’s round the corner or two hours away, and we’ve had a great response to our telerehab work. It’s changed our practice in some really positive ways.”

When lockdown came, while for many organisations a swift and seismic move to the adoption of remote communication was needed, PhysioFunction were in the enviable position of being able to build on what they had already created.

“With us already being established with many clients, we didn’t have to start from scratch, and we could look at how to build on what we had already done. By extending our telerehab programme, we could continue to support our clients effectively,” says Claire.

“The team were able to take our classes online from a very early stage, with Taher Dhuliawala and Keiran Cox very much holding the fort during lockdown. The classes followed the same format as in person, with small numbers of participants so we can easily spot if someone needs help, but we were able to increase the frequency of them. Being able to do these kinds of sessions in your own living room was really welcomed.

“With clients who were already able to use video, we also were able to introduce the MindMotion GO, which is fantastic as we can interact with the technology and, for example, increase the intensity as required. But at the start of the pandemic, we still had some clients who didn’t use video, and the fact we have supported them to use it meant they had an extra channel of communication with their family during lockdown, and that was a lovely extra benefit.

“Even aside from COVID, with the flu and winter weather coming, we are expecting further demand for our telerehab sessions. We’re currently running a blended approach of online and in-person sessions, although a few people are still choosing not to come in at all, but they have found our telerehab so effective that they’re still progressing with their therapy.”

While remote working was a ‘needs must’ for many practices during lockdown, and to help mitigate ongoing restrictions, PhysioFunction intend to continue to build telerehab as a core function.

“We are very into innovation and technology here and our team have worked really hard to do what we’ve done, I’m really proud of what we’ve achieved,” adds Claire.

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