There are two types of Parkinson’s disease, and each may require different treatment, a leading Parkinson’s researcher has found.
It’s long been understood that the disease could start in the nervous system of the gut and spread to the brain via the vagus nerve.
But Per Borghammer, professor and consultant of nuclear medicine at Aarhus University Hospital in Denmark, says there is another way Parkinson’s starts.
Over the last six years, Borghammer has explored this theory.
“Our previous studies support that this gut-start idea could be right. In short, that Parkinson’s starts in the gut and spreads through the brain via the vagus nerve,” he says.
In one Danish study, and a similar Swedish study that later reproduced their results, Borghammer found out that patients who had their vagus nerve cut showed a 50 per cent reduced risk of developing Parkinson’s.
“This finding makes sense, since patients with a surgically severed vagus nerve should be protected against Parkinson’s because the main gut-to-brain spreading highway is no longer there,” he says.
However, the risk reduction was only 50 per cent. This This led him to wonder – what about the other 50 per cent?
Borghammer knew that all Parkinson’s cases probably didn’t start in the gut, because scans show that, in some early-stage Parkinson patients, their nerves to the heart and gut are damaged, but in others they’re not.
“I wanted to design a study that showed that the right way to think about Parkinson’s is that it can start in the gut and move to the brain, but it can also start in the brain and move down through the brain stem into the peripheral nervous system.”
This would mean that, in both group of people, the disease eventually looks the same – but in the early stages it looks completely different.
The motor symptoms of Parkinson’s disease only become apparent when the dopamine system is damaged – which would probably occur much earlier if the disease starts in the brain, not the gut. “The body-first disease seems to be the worst one,” Borghammer says.
“It has the poorest prognosis and these patients have a larger symptom burden than those where it starts in the brain. In body-first patients, you see a lot of early symptoms from the damaged peripheral nervous system.”
Such patients will experience symptoms including constipation, sexual dysfunction and orthostatic hypertension.
And when the disease has advanced far enough it will reach the middle of the brain stem, giving rise to REM sleep behaviour disorder.
“This particular sleep disorder often have a detrimental effect on patients’ quality of life,” Borghammer says.
Normally, when we enter REM sleep, which is when we dream, the body is paralysed. But in the fraction of Parkinson’s patients who develop the sleep disorder, Borghammer says, this paralysis stops working and the person will thrash around in the night.
“We know that patients who get the sleep disorder early will progress through cognitive decline and dementia faster than other patients. We don’t know exactly why, but statistically, that’s a fact.”
In Borghammer’s latest study, he set out to see if there were two types of the disease – a brain-first and body-first.
The first starts in the brain and spreads to the peripheral autonomic nervous system, and the second starts in the peripheral autonomic nervous system and spreads to the brain via the vagus nerve.
In the body-first type of Parkinson’s, he says, the disease damages the heart and gut early, then spreads to the brain stem, where at which time the patient will get the Parkinson’s diagnosis.
“In the brain first subtype, the pathology starts inside the brain, probably most often in the amygdala, where it’s clinically silent and the person doesn’t know there’s anything wrong.
“From there, it spreads in all directions, into the dopamine system, down through the brainstem and eventually into the peripheral nerves, which likely takes five to 10 years.”
It’s too early to know the implications of this, he says, but it’s likely the type types of Parkinson’s should be treated differently.
He urges researchers looking into Parkinson’s to consider these findings.
“If we want to cure the disease, and eventually prevent it, we likely need two different strategies,” he says.
“One tailored to the body-first and one for the brain-first types.”
In recent years there has been a huge increase in studies looking at the gut microbiome.
It’s likely that, if the gut can give someone Parkinson’s, this will result in the body-first type, Borghammer says.
For example, there are several studies currently looking at faecal transplants, which Borghammer guesses will help more in body-first patients of Parkinson’s.
“This is important knowledge, because studies might benefit from including only body-first patients, but that’s not what’s being done. All Parkinson’s patients are put into one big pot.”
But, he says, there needs to be focus on both types of the disease.
If it turns out that certain bacteria in the gut put people at a higher risk of developing Parkinson’s, for example, Borghammer says in an ideal world there would be efforts to ensure people don’t have these bacteria.
But this might only prevent body-first Parkinson’s. Borghammer plans to double the number of patients and repeat the study again on a larger scale, and hopes other researchers will replicate his research in other countries.
“Hopefully the entire field will realise there are these two different types of patients. We’ve shown how they can be identified. If we’re lucky, maybe we can discover the genetic risk factor that predisposes people to the gut-first or brain-first Parkinson’s.”
Lastly, Borghammer clarifies that not all Parkinson’s patients will necessarily fall into one of the two groups, and there could be rare cases that fall outside of these two main categories.
£1m dedicated to MND research through 7 in 7 Challenge
A £1million fund has been created to lead new research into potential treatments for Motor Neurone Disease (MND) through the efforts of an iconic challenge by Kevin Sinfeld.
Kevin, director of rugby at Leeds Rhinos, raised over £2million through his 7 in 7 Challenge, inspired by his former team-mate and close friend Rob Burrow.
Rhinos legend Rob was diagnosed with MND in December 2019, and Kevin completed seven marathons in as many days to help boost badly-needed research into the condition.
Now, with £500,000 of the money raised through the 7 in 7 Challenge ring fenced for research, that sum has been matched by medical research charity LifeArc.
The move has created a £1million joint fund established by the MND Association and LifeArc, which will support research projects focused on developing new therapies or repurposing drugs already approved for use for other conditions.
“This is fantastic news and an amazing contribution from LifeArc,” says Kevin.
“When we set out to complete the 7 in 7 Challenge we hoped to raise awareness and funds to support the MND community but it is so wonderful to see the inspiration it has given people and organisations, like LifeArc, so they too can support the need for more research.
“Our hope, like that of everyone affected by this brutal disease including Rob, is that this money will make a real difference and help find the breakthrough we all desperately want.”
Researchers are now able to apply for a share of the funding, with the criteria that they will be expected to conclude their project within three years and be target driving with set milestones and a credible delivery plan – including a clear route to reach MND patients.
Dr Brian Dickie, director of research development at the MND Association says: “We are so grateful to LifeArc for this generous contribution and are looking forward to working with them to identify projects which have a real chance of making a difference to our community in the coming years.”
Melanie Lee, LifeArc’s chief executive, emphasised that the focus of the new funding is on boosting research around potential treatment options based on the latest understanding of the disease.
“The ambition around stimulating the search for new treatments fits with LifeArc’s approach over the last 25 years to translate early science into health care treatments or diagnostics that can transform patients’ lives,” she says.
“Our partnership with the MND Association is the latest in a series of strategic partnerships that maximise LifeArc’s expertise in translating strong discoveries from the lab into benefitting patients with conditions with few or no effective treatment options.”
What causes a stroke?
Over 100,000 people in the UK suffer a stroke each year, with there currently being around 1.2 million survivors living in the country.
Many people note that despite how common strokes are they remain unaware of what the actual causes of a stroke are.
Depending on which of the two types develops, causes and outcomes can differ.
What both have in common is they restrict blood flow to the brain. This leads to a reduction in the brain’s oxygen levels, which can cause tissue damage.
Here, NR Times breaks down why a stroke may occur and what risk factors there are behind each different type.
What are the different types of stroke?
There are two main types of strokes: ischaemic and hemorrhagic.
Ischemic strokes make up nearly 90 percent of all cases and they materialise when an artery which provides blood and oxygen to the brain becomes blocked.
A hemorrhagic stroke is much less common, but happens when an artery leading to the brain bursts and starts to leak blood around or in the brain.
Causes of an ischaemic stroke
The brain is only able to function properly when its arteries supply it with oxygen-rich blood, meaning any blockages can cause lasting damage.
With a lack of blood flow, the brain is unable to make enough energy to work. If this consists for more than a few minutes, brain cells will begin to die.
This is exactly what happens in an ischaemic stroke, but there are a range of reasons as to why these blockages develop.
One of the main causes is when the arteries around the head narrow, which makes it harder for the blood to pass through.
This can also lead to something called atherosclerosis, which is where substances in the blood (such as fat or cholesterol) stick to the sides of the arteries.
Blood can build up on these deposits, causing a further increase in pressure and a reduction to the brain’s oxygen supply.
There are a number of reasons for these blockages, with the most common ones being around a person’s lifestyle.
For example, smoking can increase the risk of a stroke by up to 50 percent.
This is because nicotine not only narrows the arteries, but it also makes the heart beat faster, causing an increase in blood pressure.
Excessive alcohol intake, obesity and high cholesterol levels are also all listed as major risk factors when it comes to ischaemic strokes.
Problems with the arteries around the heart can also lead to an ischaemic stroke.
Irregular heartbeats, heart attacks and other irregularities around this area can again limit the blood’s oxygen levels.
Causes of a hemorrhagic stroke
Hemorrhagic strokes are most common in people ages 45 to 70, but they affect a lot more younger people than an ischaemic stroke.
These are caused after the arteries around the brain burst and cause bleeding.
Depending on where the artery is can affect the outcome of the hemorrhagic stroke.
If the bleeding occurs within the brain, blood shooting out at high pressure can kill some cells.
Bleeding on the surface increases the pressure in the protective layer between the brain and the skull, potentially causing more cell loss.
This bleeding is normally caused by chronically high blood pressure. In many cases, the increased pressure can cause the arteries to expand and weaken, meaning a split in them is more likely to take place.
A rarer cause of hemorrhagic stroke is where the blood vessels around the brain are connected abnormally, causing further stress on the brain. These are congenital (present at birth) but the reason for their occurrence is currently unknown.
Again, the best way to reduce the risk of an hemorrhagic stroke is to make healthy lifestyle choices.
NHS pilots video service for epilepsy diagnoses
A new clinical video service which supports epilepsy diagnoses and management in the era of coronavirus and beyond has been launched in the UK.
vCreate Neuro allows registered patients and carers to share smartphone-recorded videos of potential seizures or unknown movements with their clinical team via a secure, NHS-trusted system.
The data and footage act as a visual aid to assist clinical teams with rapid precision diagnostics, creating a digitised clinical pathway that minimises the need for face-to-face clinic appointments and invasive tests.
The system is currently being piloted across Scotland and, following its initial success, across England including Great Ormond Street Hospital, Evelina London and Sheffield Children’s Hospital.
The system is available to families who are concerned that they, their child or loved one may be experiencing seizures or unexplained episodes including epilepsy.
Since May 2020, more than 2,000 families have shared over 5,000 videos with their clinical teams across the platform.
Dean MacLeod was referred to the service when her seven-year-old daughter, Olivia, began having unknown movements in May 2020.
Dean uploaded videos of Olivia during these episodes as Olivia’s seizures grew more frequent.
The videos were reviewed by Paediatric Neurology professionals at the Royal Hospital for Children, Glasgow, and, supported with telephone appointments, Olivia was diagnosed with a form of epilepsy and quickly started on treatment.
Speaking about her experience, Dean said: “I’ve found vCreate to be invaluable in Olivia’s journey since she started having seizures last summer.
“We live in a remote location on the Isle of Lewis, Scotland, and we have a very limited paediatric service on the Island. The service has made it easy to access the specialist clinical knowledge needed by sending recordings of various seizure events to the Paediatric Neurology team at Glasgow.
“Since the diagnosis, I have kept in regular contact with the clinical team through the platform, sending videos and typically receiving advice from a Consultant within 24 hours which is fantastic. Between the vCreate service and telephone discussions, our family have not needed to have face-to-face consultations which has been hugely beneficial during the pandemic.”
Professor. Sameer Zuberi, consultant paediatric neurologist at the Royal Hospital for Children, Glasgow, said: “vCreate Neuro has transformed how we use carer-recorded video in our service. We are diagnosing epilepsy more rapidly, preventing misdiagnosis and saving unnecessary investigations. Families feel in more control and better connected to the service.
During the Covid-19 pandemic, many people experiencing seizures and seizure-like episodes, including children, have been unable to see a clinician.
Create Neuro aims to help by empowering patients to use asynchronous video technology for self-management, reducing the need for physical appointments.
Founder Ben Moore said: “We’re passionate about family-forward care, and worked closely with clinical teams, patients and carers to develop the vCreate Neuro service.
“The system aims to improve patient care, reduce the number of clinic investigations – and resulting costs to the NHS – and digitise the patient pathway. We want families to be in control of their healthcare journey and have a direct link to their clinical team despite the pandemic restrictions.”
The vCreate platform has been independently assessed and approved by Information Governance teams in over 100 UK NHS Trusts.
Within the platform, a clinical database is available as a learning resource for clinicians to study seizure types, events, and other symptoms.
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