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Stroke

Genetic clues found in ‘silent’ strokes

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New genetic clues have been found in people who have had ‘silent’ strokes, in a breakthrough which could lead to the discovery of much-needed new treatments. 

Researchers discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke – a type of stroke caused by weakening of the small blood vessels deep within the brain. 

Over time, damage to the blood vessels and subsequent interruption to blood flow can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia.

To date, only one genetic fault has been associated with lacunar strokes, which affect around 35,000 people in the UK each year. 

However, after over a decade of research, Professor Hugh Markus and a at the University of Cambridge, working with researchers from around the world, now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.

“These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to,” says neurologist Professor Markus. 

“Although small, their consequences for patients can be enormous. 

“They cause a quarter of all strokes, and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

In research funded by the British Heart Foundation, the team scanned and compared the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not. Participants were recruited from across Europe, the United States, South America and Australia after they attended hospital and had an MRI or CT brain scan.

They discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit. 

These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain, and meaning that messages travelling around the brain slow down or don’t arrive at all.

The team now plan to test whether new treatments can correct these abnormalities on brain cells in the lab. They hope to begin human clinical trials in the next ten years.

The study also highlighted that high blood pressure, type 2 diabetes and a history of smoking are causally associated with an increased risk of lacunar stroke, identifying things that we can immediately tackle.

Professor Sir Nilesh Samani, medical director at the British Heart Foundation, adds: “This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes.

“These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.”

Stroke

Stroke risk after TBI ‘can last five years’

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The risk of stroke for patients with TBI is at its highest in the first four months after injury and remains significant for up to five years, new research has revealed. 

TBI patients have an 86 per cent increased risk of stroke, when compared to patients who have not experienced a TBI. 

Stroke risk may be at its highest in the initial four months post-injury, but remains a potential risk for the following five years, the University of Birmingham-led research finds. 

Significantly, the findings suggest that TBI is a risk factor for stroke regardless of the severity or subtype of the injury – statistics show that up to 90 per cent of TBIs are mild, which researchers highlight as showing the stroke risk applies to even those who had few symptoms and are fully recovered.   

Traumatic brain injury affects over 60 million people a year globally and studies have revealed the long-term risk of neurological diseases including dementia, Parkinson’s and epilepsy. The topic has come under renewed scrutiny through the recent investigations into links between concussion in sport and lasting neurological consequences.

The new research brings together 18 studies from four countries and is the first of its kind to investigate post-injury stroke risk.

“Stroke is the second leading cause of death and third leading cause of disability worldwide, however, urgent treatment can prevent stroke related death and long-term disability,” says Dr Grace Turner, lead author of the study from the University of Birmingham’s Institute of Applied Health Research. 

“As our review has shown, TBI patients should be informed of the potential for increased stroke risk and with the risk of stroke at its highest in the first four months post-injury, this is a critical time period to educate patients and their care givers on stroke risk and symptoms,” says Dr Turner. 

“This initial four-month period should also be used by clinicians to administer stroke prevention medication and lifestyle advice to mitigate the excess risk of stroke associated with TBI.”

Researchers also found that the use of anti-coagulants, such as VKAs and statins, could help to reduce stroke risk post-TBI, while the use of some classes of anti-depressants are associated with increased stroke risk post-TBI.

However, more research is required to investigate the effectiveness of stroke prevention drugs post-TBI to help inform clinicians’ prescribing and facilitate shared decision making, adds Dr Turner.

“Our review found some evidence to suggest an association between reduced stroke risk post-TBI and the stroke prevention drugs VKAs and statins but, as previous studies have found, stroke prevention drugs are often stopped when an individual experiences a TBI,” she says. 

The review, published in the International Journal of Stroke, was funded by the National Institute for Health Research’s Surgical Reconstruction and Microbiology Research Centre based at University Hospitals Birmingham NHS Foundation Trust. 

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Patient story

‘I didn’t know this could happen to a child’

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When Lily had a stroke aged only eight, such a diagnosis never crossed her family’s minds. Here, her mum Natalie shares their story of rebuilding their lives and why they are committed to raising awareness of childhood stroke

 

Almost a year ago, in April last year, eight-year-old Lily was rushed to Queens Hospital in Romford after collapsing at home. 

“It was a Monday afternoon during the first national lockdown, and we were preparing to do some schoolwork,” recalls her mum, Natalie. 

“Lily had been playing with her older brother all morning, laughing, and having fun. 

“We could never have imagined what was about to happen. There were no warning signs.

“She came to me and said her hand felt weird. I told her it was probably pins and needles and if she just wiggled her fingers around it would go away. 

“Lily was sure it wasn’t pins and needles and kept saying she ‘felt weird and didn’t like it’. I laid her down in my bed to see if that would help her feel any better.

“We laid for a couple of minutes before Lily said she needed the toilet. As she went to get up, she collapsed down the right side of her body. 

“I had no idea what was happening. I picked her up and sat her on the toilet, and she couldn’t even hold herself up.”

Natalie immediately called 999 and was advised that an ambulance was 40 minutes away. After just five minutes, Lily appeared very confused and could no longer talk.

“I called 999 again and told them we couldn’t wait, we needed them to come quickly,” she says. 

“This had all happened within half an hour. Lily had gone from giggling with her brother to being completely paralysed down the right side of her body. 

“When she arrived at the hospital, Lily had lots of different tests and scans.

“We were then blue lighted to Great Ormond Street Hospital (GOSH) in London. There they confirmed that Lily had suffered a stroke. 

“All the typical stroke symptoms that they tell you to look out for had happened to Lily – Face, Arm, Speech – but it just never occurred to me that this could happen to a child. 

“I had always assumed that it just happened to older people. I was wrong.”

Lily spent four weeks at GOSH and the hugely difficult time for the family was made worse by the COVID-19 lockdown rules in place at the time. 

The restrictions meant that only one parent was able to be with Lily in hospital, and they couldn’t switch.

“As Bill, Lily’s dad, had gone in the ambulance with her, he was the only parent allowed to stay,” says Natalie. 

“I couldn’t see her at all. We are a very close family, and this meant we were totally split. Even on Lily’s birthday. 

“The nurses made it as special as they could for her, but I just desperately wanted to be there. It was the toughest time of our lives.”

At the end of May, Lily moved from GOSH to The Children’s Trust in Tadworth, Surrey. 

“I think we were all excited. When her team at the hospital first mentioned it, it sounded amazing, exactly what Lily needed. It also meant that as soon as she got there, I would be allowed to see her as two parents could visit on site,” continues Natalie.

“I was so thankful to be a part of her rehabilitation. Bill had been amazing, but I wanted my turn, and he needed a break – although he wouldn’t admit it. 

“He hadn’t been home for a month, seen our son Alfie, or even sat on a sofa. All the things you normally take for granted.

“Unfortunately, due to ongoing COVID-19 restrictions, Alfie wasn’t able to visit, so it was still really challenging for us and the family still felt somewhat separated. 

“I think Lily felt a bit apprehensive about it all. Meeting lots of new people, including a new rehabilitation team, and moving into a new room was all a bit scary for her. But all the staff were amazing, and they really helped settle Lily and make her feel welcome.”

Lily’s busy rehabilitation schedule meant she had sessions from 9.30am until 4pm every day. These included occupational therapy, physiotherapy, speech and language therapy, school lessons and play therapy.

“Lily was an absolute delight to work with,” says Mairi, specialist occupational therapist at The Children’s Trust.

“One of her goals was to improve the strength in her right arm for activities such as dressing herself and being able to do arts and crafts. 

“It was a joy to work towards this with Lily as she always encouraged us to find lots of ways to make therapy more fun. 

“This included learning lots of TikTok dances that included the use of Lily’s right arm, making bracelets and making slime whilst using both hands. 

“By the end of her placement Lily’s right arm was much stronger and we could barely keep up with her in her TikTok dances!”

On July 2, Lily was able to ring the ‘going home bell’ to celebrate all that she had achieved during her time at The Children’s Trust. 

“It was such a special day for us, and we are so proud of her,” remembers Natalie. 

“Since being home, Lily still has to attend appointments at GOSH, to have further scans and angiograms, and these sometimes involve overnight stays, but she is doing so well. She’s also continuing the TikTok dances, she just loves it!

“Family life is starting to feel normal again. In September 2020, Lily went back to school, doing just two hours a day.

“Just before Christmas, she had progressed to staying until 12.30pm every day and was managing this really well.

“I still feel anxious about everything that has happened and I think it will take time for us as a family to fully ‘recover’ from what happened to Lily. 

“Going forward I would like to help raise awareness of childhood strokes, as it’s something I had not heard of, and bring families together who had been through similar experiences.”

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News

GripAble secures funding for further expansion

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A startup business which is digitalising upper limb rehabilitation from hospital to home has secured £1.6million in funding to develop its work internationally.

GripAble will use its initial funding round to further scale its assessment and training platform throughout the UK and Europe, preparing for its upcoming US market launch.

It will also support the delivery of its digitally-led remote patient engagement platform, which collects empirical data on adherence and persistence, as well as objective data on rehabilitation outcomes to support therapists and users.

Through its digital platform, including bespoke hand-held sensors, software and data services, GripAble is allowing more patients to access gold standard care from professional therapists for longer periods, driving improved outcomes while decreasing the burden on healthcare systems.

With close to 1,000 GripAble units deployed over the last six months, GripAble has established itself as the leading technology in the upper limb remote-rehab space in the UK.

In excess of 35,000 activity sessions have been completed on the platform, registering over 7.5million movement repetitions and counting, highlighting a richness of data through which GripAble can provide insight into patient engagement with therapy programmes and increased adherence to prescribed care.

The funding round was led by the Triple Point Venture Fund, with additional funding from the Oxford Technology Fund and Imperial College Innovation Fund, and brings the company’s total funding to date to nearly £4million.

“At GripAble, we know this market better than anyone and understand that any solution must be therapist driven and must allow them to engage and empower their patients to self-manage beyond standard therapy hours,” says Dr Paul Rinne, CEO and co-founder of GripAble.

“We have already achieved considerable provider adoption across both NHS and private healthcare, with neurological, musculoskeletal and paediatric care providers showing they are truly ready to adopt our digital solution.

“Our goal is to build on these foundations, creating an end-to-end technology-led platform to enable every therapist to deliver further gold standard, evidence based, care remotely, and for us to then drive and support patient self-management.

“GripAble’s 24-hour delivery, rapid set-up and ongoing virtual support are also key drivers for adoption.”

The rapid provider adoption and data driven approach of GripAble in the UK has attracted partnership discussions with big pharma companies and international distributors, as well as health insurance firms seeking to improve outcomes at a more cost-effective rate.

The company has also partnered with a number of organisations including the Association of Chartered Physiotherapists in Neurology UK (ACPIN), which is the first tech partnership of its kind for ACPIN.

Upcoming Series A funding in late summer will help GripAble to become the gold standard upper limb technology provider in the UK and Europe, and to establish a significant foothold in the US, where GripAble is already deployed across several pilot sites.

The GripAble platform provides the opportunity for further home-based technological advances with current development work seeking to tackle finger dexterity through to elbow and whole arm training, with the aim of looking beyond the horizons of upper limb therapy in the future.

Dr Rinne adds: “It is a challenging task to build a product for both neurological and musculoskeletal disorders, for individuals of all ages and with all ranges of cognitive abilities, but we have succeeded in delivering to market a product with incredibly broad applicability by putting the users – therapists and patients – front and centre of everything we do.”

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