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Innovative machine-learning approach for future diagnostic advances in Parkinson’s disease

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Parkinson’s disease (PD) is the second most common neurodegenerative disease, with patient numbers being expected to double worldwide in the next 20 years. The detailed molecular and cellular mechanisms underlying its pathogenesis remains unclear, although recent evidence has pointed towards the role of mitochondrial dysfunction in the onset of the disease.

Mitochondria — small cellular ‘subunits’ involved in cell metabolism and energy generation — constantly and dynamically interact with each other, forming perpetually changing networks known as mitochondria interaction networks (MINs).

The researchers therefore sought to understand the correlation between the mitochondrial impairments observed in PD and any specific network topological changes in MINs, with the aim of advancing the early diagnosis and classification of PD patients.

“Since conventional analysis focusing on individual mitochondria has not provided satisfying insights into PD pathogenesis, our pioneering work has gone a step forward by investigating the interaction networks between these organelles”, explains Dr Feng He, Group Leader of the Immune Systems Biology Group of the LIH Department of Infection and Immunity and corresponding author of the publication.

Leveraging their strong expertise in network analysis and machine learning, the scientists analysed a large 700 Gigabyte dataset of three-dimensional mitochondrial images of colonic neurons, collected from PD patients and healthy controls, and dopaminergic neurons, derived from stem cells.

They found that particular network structure features within MINs were altered in PD patients compared to controls. For instance, in PD patients, mitochondria formed connected subnetworks that were generally larger than in healthy individuals.

In line with this result, the efficiency of the energy and information transmission and distribution among the different mitochondria in PD patient MINs was significantly lower than in controls, suggesting that the longer ‘transmission delays’ were associated with the larger diameter of the components of the MINs observed in PD subjects.

“These different topological patterns in MINs may mean that energy and information are possibly produced, shared and distributed less competently in the neuronal mitochondria of PD patients relative to healthy controls, suggesting their connection to mitochondrial damage, deficiencies and fragmentation typical of neurodegenerative disorders”, adds Dr He.

Moreover, the research team found these different MIN patterns to be highly correlated with the commonly-used PD clinical scores of individual patients, i.e. the Unified Parkinson’s Disease Rating Scale (UPDRS).

Indeed, when applying a machine learning approach to analyse these MIN characteristics, the researchers observed that the use of a combination of those network features alone allowed them to accurately distinguish between PD patients and healthy controls.

“Our findings bring forward the potential of using particular mitochondrial network features as novel biomarkers for the early diagnosis and classification of PD patients, which might help develop a new health index. As a next step, we will explore how our results may offer new perspectives for the understanding of various other neurodegenerative diseases characterised by mitochondrial dysregulation, such as Huntington disease and Alzheimer’s, making our work a true instance of translational and transversal research”, states Prof Rejko Krüger, Director of Transversal Translational Medicine at LIH and contributing author of the study.

“This publication also constitutes a major step forward in the application of advanced machine-learning techniques to unravel the complex network interactions of cellular organelles for disease stratification. Indeed, data analytics and innovative digital technologies are a core priority area for our department and for LIH as a whole”, concludes Prof Markus Ollert, Director of the Department of Infection and Immunity and contributing author of the paper.

The inter-disciplinary study relied on the close cooperation between clinicians, neuroscientists, network biologists, big data and machine learning experts from the Luxembourg Institute of Health (LIH), the Luxembourg Centre for Systems Biology (LCSB) and the Central Hospital of Luxembourg (CHL), particularly via clinical neurologist Dr Nico Diederich, as well as on the collaboration with other international partners such as the Instituto de Física Interdisciplinar y Sistemas Complejos IFISC (Spain).

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Two major neuro events postponed due to COVID-19

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The Neuro Convention and The National Paediatric Brain Injury Conference have both been postponed

Two significant events in neuro practitioners’ calendars have been delayed until later in the year, as the effects of the COVID-19 pandemic continue to be felt.

The National Paediatric Brain Injury Conference, which was already revised from an in-person to online event, will now not go ahead as planned in February due to the continuing demands on frontline healthcare professionals as COVID-19 cases continue to rise and the country is plunged back into lockdown.

The event, organised by The Children’s Trust, is now earmarked for May 13, although that is subject to further developments in the pandemic.

The ‘Connections and Collaborations’ conference is set to attract an international audience and will hear from an array of speakers from around the world, many of whom are global leaders in the field of paediatric neuro care.

Explaining the postponement, Dalton Leong, chief executive of The Children’s Trust, says: “Over the years, a high number of attendees are from the NHS, including consultants, doctors, surgeons, nurses, and therapists.

“We know that many of these staff are being redeployed to support the Covid pandemic.

“To run a conference at this time, taking them away from delivering vital frontline services, does not seem a sensible option. We look forward to holding the conference later in the year when, hopefully, these pressures have reduced.”

As well as the conference, the Neuro Convention too has been postponed, moving from March until September to enable delegates to attend in person.

The event, held at the Birmingham NEC, typically attracts around 3,000 people from across the country, and organisers hope that by delaying the date, it will give the best chance of lockdown and social distancing measures being lifted to allow them to go ahead.

In addition to the event planned for September 15 and 16 – although that too may be subject to change – an additional digital version of Neuro Convention is set to go ahead in March, enabling neuro professionals to still receive the insight and analysis planned for the NEC event in an online format.

Neuro Convention is hailed as being Europe’s only specialist trade event for brain and spine experts, and boasts an array of internationally-respected speakers and leaders in their field.

“We have been in consultation with various Government departments and whilst the rollout of the vaccine has given the country much needed optimism, we have been advised that we will be unable to host the Neuro Convention event in the spring,” say event organisers Roar B2B.

“The safety of our visitors, customers, partners and staff is paramount. We are confident that moving the event to September will enable us to run the safe, successful event the industry demands.

“To support our exhibitors, partners and the wider industry we are delighted to announce an additional digital version of Neuro Convention. This will provide a digital meeting place, world-class speaking sessions and access to the latest products and services.”

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Arm and hand function could be regained following spinal cord injury through new pioneering research

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Treatment could be developed for arm and hand dysfunction in people living with spinal cord injury through a pioneering new research project.

A pilot study of new therapy for improving upper extremity function is now underway, following funding from BrainQ Technologies – an Israel-based startup which is working widely in precision medicine to reduce disability following neurodisorders – to the Kessler Foundation.

The study is titled ‘The safety and effectiveness of the use of a brain-computer interface-based electromagnetic field treatment in the management of patients with chronic spinal cord injury: A pilot study’ and is seen as a potentially significant breakthrough in researching possible treatment.

It will be led by Dr Ghaith Androwis, a research scientist in the Centre for Mobility and Rehabilitation Engineering Research at Kessler Foundation, and Dr Steven Kirshblum, senior medical officer and director of the Spinal Cord Injury Program for Kessler Institute for Rehabilitation, who received the grant to further their work in the field.

Thousands of new traumatic spinal cord injuries occur each year, with statistics showing around 17,500 of those are from the United States alone, and more than half of those people experience loss of motor function of the upper extremities which limits their independence and adversely affects their quality of life.

“To achieve the best outcomes after spinal cord injury, restoring arm and hand function must be a priority in rehabilitative care,” says Dr Kirshblum.

“This study is an important first step towards increasing the ability of individuals to function more independently at home, in their communities, and the workplace.”

During the study – which will be conducted in the US and Israel – researchers will test the safety and efficacy of noninvasive low frequency electromagnetic field stimulation delivered via the BQ System.

Individuals with spinal cord injury (duration 18-30 months) will participate in the 34-week study. Functional status will be measured at baseline and compared with status following the experimental treatment.

By quantifying gains in motor function, motor control and activities of daily living, this pilot study will provide preliminary information on the potential application of BrainQ’s therapy in rehabilitation programs for individuals with disability.

“We are very interested in testing the effectiveness of this novel and non-invasive approach in persons with spinal cord injury,” adds Dr. Androwis.

“Such interventions may improve participants’ performance of activities of daily living leading to gains in their overall quality of life. This particularly is important when an intervention can be provided simultaneously with conventional therapy.”

This multi-site study is being conducted at Kessler Foundation, The Miami Project to Cure Paralysis, Miami, and Sheba Medical Center, Israel.

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‘My brain is slipping into my spine’

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Karl Johnston suffers from a rare condition called Chiari Malformation Type 1

After years spent in pain and struggling for a diagnosis, Karl Johnston felt relief when he was confirmed as having a little-known condition where the brain effectively slips into the spine. Here, he shares his story.

“Some dads get to put their children on their shoulders, but I’ve never got to do that.”

That is just one of the day-to-day realities facing Karl Johnston, whose condition, Chiari Malformation Type 1, means his brain is effectively slipping into his spine.

For eight years, Karl had experienced a catalogue of symptoms, including intense and debilitating neck pain, light-headedness, fatigue and numbness in his arms, but without securing a diagnosis of his condition.

But now, the 35-year-old admits he feels some relief at the knowledge he has Chiari Malformation Type 1, as devastating as the diagnosis was to receive.

“A lot of people felt sorry for me when I finally got a diagnosis, but it was a relief because I’d been telling people that I was suffering for years and they hadn’t believed me,” says Karl, from Wallasey, on Merseyside.

“You start to question yourself about things. Just knowing takes a lot of the weight off you.

“Some days the pain is so much that it’s difficult to move around and all I want to do is lie down.”

The biggest difficulty emotionally, says Karl, is the impact it has on his ability to play with his daughter Seren.

“It’s devastating when she wants to play and I’m not up to it,” he says.

“Some dads get to put their children on their shoulders, but I’ve never got to do that.”

While Chiari Malformation Type 1 is most commonly diagnosed in adults, it is believed to often be present from birth.

Many people with the condition are asymptomatic, meaning it is only found if they have an MRI scan.

Karl had symptoms from when he was a teenager, but getting a diagnosis was difficult due to the lack of awareness around the condition.

He is now determined to help raise awareness of Chiari Malformation Type 1, in the hope that others may be able to secure a diagnosis quicker than his.

“There needs to be a way to make doctors and people in general more aware of these rarer conditions because otherwise people just fall through the cracks,” says Karl.

The dad-of-one has been supported by The Brain Charity, a national charity based in Liverpool that supports people with all forms of neurological conditions. Statistics show that 1 in 6 people in the UK is currently living with such a condition.

The charity recently told NR Times that demand for its services had soared by over 70 per cent since the start of lockdown in March, with predictions that the numbers of people needing support with issues including mental health, Long Covid and employment rights would grow further still.

Having turned to the charity last year, Karl is now getting the practical and emotional support he needs to get on with his life.

“The Brain Charity helped me get a better understanding of what was going on with my condition,” he says.

“It has felt like so many people haven’t taken me seriously but The Brain Charity has.

“They didn’t pity me but tried to understand what I was going through.”

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