Parkinson’s Disease

On Wednesday 22nd January, I attended a talk by Samuel Deutsch entitled ‘Predicting Parkinson’s in our Sleep’.

He began by talking generally about the field of neurology – the study and treatment of disorders of the Central and Peripheral Nervous system. It therefore includes a wide range of disorders including psychological, and psychiatric disorders. But it is a complicated field as often the disorders’ causes aren’t clear cut. For example phantom limb syndrome, with 80-100% incidence, has no clear cause. Some people believe that it is due to a cortical re-organisation, while others believe that it is due to nervous pathways being hijacked. Furthermore, neurological diseases rarely have a cure – it is more about management symptoms; there is no ‘one pill treats all approach’. So, in the case of phantom limb syndrome, therapies include mirror therapy, stimulation therapy, and virtual/augmented reality. Furthermore, with our now ageing population, ‘the brain is dying before the body does’, and neurological diseases are therefore on the rise.

Image result for mirror therapy for phantom limb pain"Image result for virtual reality for phantom limb pain"

He then went on to speak about Parkinson’s, a motor-system disorder which includes cognitive, homeostatic and psychological issues. It is usually diagnosed in the 60s, and in 2018, 145 000 people were diagnosed; but this is expected to rise by 20%, by 2025. It is caused by a build up of alpha-synuclein in the synapses, which results in the death of neurones in the basal ganglia of the brain.

Parkinson’s has many symptoms, the main four being a tremor, rigidity (how well limbs move), bradykinesia (global slowness of movement), and postural instability. Alone, any one of these symptoms doesn’t mean Parkinson’s, for example, tremors could just be an essential tremor, which is very common. Other results of this disorder include psychiatric symptoms, dementia, cognitive impairment, and other motor problems. However it is extremely difficult to diagnose as it doesn’t occur the same in everyone; it could be cognitive first and motor later, or vice versa.

The treatments of Parkinson’s are wide-ranging. There are some drugs which can be used, such as: levodopa (produces more dopamine), DA agonists, MAO-B inhibitor and COMT inhibitor. All of these aim to increase the amount of dopamine in the nervous system, and therefore cocaine can have the same effect – however this isn’t recommended. Dopamine disregulation can occur as a side-effect to any of these drugs. This results in an inability to control urges, such as gambling. Therapies can also help, such as exercise, diet, SALT (speech and language therapy) and occupational therapy. We even discussed the possible future of stem cells in the treatment of Parkinson’s, helping to regrow cells in the basal ganglia. Although this wouldn’t cure the disease as the build up of alpha-synuclein in the synapses, would continue to kill cells in the basal ganglia.

He then went on to talk about RBD, which is a REM sleeping disorder when you act out your dreams while you are asleep. Usually you are paralysed during REM sleep, but with this disorder you aren’t. This can be extremely dangerous as, in 2010, an man who lived in Oregan with RBD beat up his wife while he was asleep, but he had no idea what he was doing. He was then sentenced to prison. RBD is usually diagnosed in your 50s.

The link between these two diseases is that on autopsy, 98% of people with RBD had a build up of alpha-synuclein. Furthermore, roughly 50% of patients with RBD have Parkinson’s. So, Mr Deutsch and his team at the John Radcliffe are trying to draw links between the two diseases. Since RBD develops 10 years earlier, they are trying to use this as a predictor of Parkinson’s, as one of the most important parts to treatment of Parkinson’s is catching it early.

Mr Deutsch currently has a cohort of 1 000 patients with Parkinson’s, 300 healthy patients, 150 relatives of people with Parkinson’s, and 300 RBD patients. His work is attempting to find whether there are cognitive phenotypes in prodromal Parkinson’s Disease – this is easy, and cheap to screen. This shows heterozygous profiles, and can be compared to RBD results for the same test.

If a link is found, anti-inflammatory or anti-oxidant promoting diets have been found to reduce microgial activation in rats (whether this is reliable is questionable, as it has only currently been tested on rats). Furthermore, exenatide, a glucagon-like peptide-1 receptor agonist that is used for treatment of diabetes, has been found to slow Parkinson’s Disease.

Another research project that occurred earlier this year (2020) across vast expanses of the population of China has found that the genes: LRRK2, PARKN, SNCA, PARK7, PINK1 and GBA have a link to Parkinson’s. Therefore, you can tell people at birth that they are at risk to developing Parkinson’s, and ensure that they have a good diet, and exercise regime to reduce the chances of getting it in the future. Specific genes being affected also points towards the future of treatments of Parkinson’s, in changing the expression of genes – however this isn’t currently possible.

He concluded by reinstating the fact that there is currently no cure to Parkinson’s, and that his work, and the work of doctor’s generally isn’t always about curing diseases – it is about making lives better by alleviating pain.

 

AlzEye

The instruments that doctors use to monitor health are often expensive, as is the training required to wield them. This means that regular scanning isn’t an option, so doctors work hard to manage symptoms, rather than spotting early signs of an illness before it occurs.

AlzEye is a project run from Moorfields Eye Hospital in London in collaboration with University College London (UCL). It is attempting to use the eye (more specifically the retina) as a way to view signals about health of other organs in an individual’s body. Every patient from 2008 to 2018, over the age of 40 who visited Moorfields (overall 300,000 patients, all of whom’s names and other identifiable information was preserved, using a legal provision called the section 251 assent). The idea is to examine the changes in people’s eyes over that period, and correlate these with the emergence of illnesses in those patients.

Dr Wagner and Dr Keane, the two leading doctors on this project, will begin with a focus on Alzheimer’s disease, and, if successful, they will move to other diseases. They will, with the help of machine learning algorithms developed by DeepMind with whom they have partnered, search for patterns in patients.

It is a very cheap project, the total budget being just £15,000, and the equipment required to perform an eye scan is becoming ubiquitous. There are many  places where eye-scanning is possible such as Specsavers (in half of their 800 stores), Costco (for £24.99), and Notal Vision (developing an eye scanning machine small enough to operate at home), to name a few. The algorithms required for machine learning of an eye-scan are available to anyone, through cloud computing services (e.g. Amazon or Google). Furthermore, it will reduce the time taken for a referral, patient care, and reduce delays.

The impact of Alzheimer’s disease on ocular anatomy was first convincingly demonstrated in 1986 when widespread axonal degeneration was found in the optic nerve of eight recently deceased patients with the disease. Though subsequent work showed some evidence of an association between retinal venous diameter and Alzheimer’s disease, true relationships only began to emerge when cross sectional measurement of the retinal nerve fiber layer became possible. In particular, the introduction of OCT, and the establishment of large prospective cohort studies that incorporate ocular imaging have demonstrated that people with Alzheimer’s show thinning of the retinal nerve fiber (RNFL), and ganglion cell-inner plexiform layers. However, thinning of the inner retina is not just a feature of prevalent Alzheimer’s; rather, it may be predictive of its development. Last September, it was shown that participants with thinner RNFL were significantly more likely to develop cognitive decline and Alzheimer’s.

The Moorfields data set has far more linked cases than any similar project ever attempted, far outweighing one of the biggest medical data collections about individual people, UK Biobank. On the disease that the project will begin its focus on, Alzheimer’s, it has 15,100 cases contrasted with 86 on the only comparable study. The data linkage strategy and information governance measures have been complimented by the UK Research Ethics Committee and NHS Digital with the independent panel, IGARD.

If this were to work, the potential impact would be huge. Estimates suggest that 50 million people were living with Alzheimer’s in 2017. With the progressive ageing of the population, the number is predicted to reach 75 million by 2030. Yet it has been noted that 50-80% of cases remain undiagnosed, even in high income-countries. Part of the issue lies with the logistics of making a diagnosis. Research into newer techniques, such as amyloid positron emission tomography scanning and cerebrospinal fluid analysis, has supported their utility as potential biomarkers; however, these tests are invasive, expensive, and not pragmatic on a large scale.

Furthermore, even if this technique isn’t possible for Alzheimer’s, it may work for a different illness – Dr Wagner and Dr Keane plan to search for patterns, as they already have data linking retinal photographs and OCT scans with NHS Digital Hospital Episode Statistics (HES) data on cardiovascular disease and neurodegenerative disease with additional covariate labels including diabetes, hypertensive diseases, disorders of lipoprotein metabolism and all diseases of pulmonary circulation.

Image result for retinal scan

Medicinal advances 2019

2019 is over! What a fantastic year for medicine, from pictures of a baby’s heart being taken whilst still in the womb, to the ultimate limit of human endurance being found by scientists analysing a 3,000 mile run, the Tour de France, and other elite events, to the a diet for malnourished children on bananas, chickpeas, and peanuts, which can boost gut bacteria helping them to grow, and so much more!

Firstly, 30 year old Thibault, who was an optician before he fell 15m in an incident at a night club four years ago, leaving himself paralysed. In 2017, he began to be involved in a trial by Clinatec and the University of Grenoble, which is a mind-controlled exo-skeleton. This 65kg machine works as Thibault had 2 implants on the surface of his brain, each of which had 64 electrodes which read the brain activity and beam the instructions to a nearby computer which reads the brainwaves and turns them into instructions for controlling the exoskeleton. Thibault still needs to be attached to a ceiling-harness to minimise the risk of him falling over in the exoskeleton, hence, the device is not yet ready to move outside the laboratory. As to its success, when rotating his wrists and moving his arms, it was successful 71% of the time, but overall shows a huge improvement into the treatment of paralysis.

Image result for exoskeleton which helps

Another paralysis project was a trial involving patients with quadriplegia, affecting movement in all their limbs except for some muscles in their upper arms. If you have quadriplegia, your functioning nerves leading from the spinal cord to these muscles were rewired. The nerves were cut and then attached to nerves that control other muscles. For example, nerves that once turned the palm up to face the ceiling could be used to extend all the fingers in the hand. So now when a patient thinks of rotating their hand, their fingers extend. Dr van Zyl said that they were ‘definitely not restoring normal hand function’ by rewiring these nerves. The focus is on two areas – opening and closing the hand and being able to extend the elbow to reach for something. Dr van Zyl added that this would allow ‘your hand open, get it around something and then grasp and pinch’. So, it can make a massive difference to people’s lives.

Another fantastic project was the creation of a unique drug for a girl with batten disease. Mila Makovec, 8, suffered from an incredibly rare disease, and, by the age of six, she was blind, could hardly speak, and had many seizures. It is caused due to the buildup of fatty substances called lipopigments in the body’s tissues. As these substances accumulate, they cause the death of cells called neurons in the brain, retina and central nervous system. Mila’s family set up the ‘Mila’s Miracle Foundation’ resulting in the Boston Children’s hospital creating a drug that corrected the errors in Mila’s DNA, as it is a genetic condition. Although not cured, she is now having fewer seizures.

There are many diseases which result in the loss of ability to speak, such as: motor neurone disease, throat cancer, some strokes, or neurodegenerative diseases (such as Parkinson’s).The University of California have developed a ‘mind-reading’ technology, an electrode is implanted into the brain, which picks up electrical signals that manoeuvre the lips, tongue, voice box, and jaw. Then computing simulates how the movements in the mouth and throat would form different sounds, resulting in synthesised speech coming out of a ‘virtual vocal tract’. Previous attempts have searched for individual words in one’s brain, and then turned this into speech, however these have had limited success. This trial focuses on shaping the mouth, and the sounds that it would produce, and, as Professor Edward Chang (one of the researchers) said, ‘for the first time, this study demonstrates that we can generate entire spoken sentences based on an individual’s brain activity.’ So far it has had fair amounts of success. In trials, people could work out what was said by the synthesised voice 70% of the time, and could therefore make massive improvements in people’s lives.

Finally, in the US, Biogen says it will seek regulatory approval for a groundbreaking drug, called aducanumab, which targets a protein called amyloid that forms abnormal deposits in the brains of people with Alzheimer’s. Several drugs have been designed to target this process, but none has yet succeeded in improving outcomes for people living with Alzheimer’s disease. The findings of their trial indicated that people who received the drug had lower levels of amyloid in the brain on brain scans and a slower decline in memory and thinking skills. Those who received the highest, 10mg/kg dose, showed the strongest signs of a benefit.

Therefore, 2019 has been a fantastic year for medical developments, and I hope that the same is true of 2020, and the following years.

Loneliness

Recently, I read an article in the Royal College of Psychiatrists Insight magazine, which talked about combating loneliness especially among the elderly. This began to get me thinking about the issues surrounding loneliness, a complex and usually unpleasant emotional response to isolation. Loneliness typically includes anxious feelings about a lack of connection or communication with other beings, both in the present and extending into the future.

According to Age UK, half a million older people go at least five to six days a week without speaking to someone, with approximately 1.2 million chronically lonely older people in the UK – this can have very serious health issues. Furthermore, according to projections by Age UK more than two million people of that age will be lonely by 2025-26, a 49% increase on the 1.36m who were socially isolated in 2015-16. It is associated with an increase in mortality on par with smoking, and worse than obesity. It can cause mental distress and also increase the chance of heart disease, dementia, anxiety, depression and suicidality.

A nationwide survey carried out by the University of Manchester, the University of Exeter and Brunel University London which assessed 55,000 people over 16, said that 40% of people aged 16-24 say that they feel lonely very often, contrasted with 29% of 65-74 year olds, and 29% of 75+ people saying that they often feel lonely. I would question the validity of this survey, due to changes in psychology through the ages. Furthermore, the turn towards technology in the youth certainly effects the way that people think, which perhaps hasn’t been felt as much by those over 64, due to a less regular use of technology, as seen in the NCBI ‘Diffusion of Technology’ paper.

However, the elderly seem to be most at risk of loneliness. The English Longditudinal Study of Ageing identified this and the likely causes of this – therefore loneliness effects all age groups. For example, as one might expect, widowers are more than five times as likely to report feeling ‘often lonely’ as peers who are in a relationship. Having someone to open up to about their lives is often a predictor of loneliness. Furthermore, people over 50 who are struggling with financial problems are twice as likely to feel lonely as those who are not. Similarly, those over 50 are four times more likely to feel ‘often lonely’ if they are in poor health compared with those who continue to have good or excellent health.

Lonely older patients are usually regular health service users, but this is rarely picked up by medical professionals, and, in many cases, this loneliness can be the stem of the conditions that they require the health services for. To me this seems crazy, and comes back to what I spoke about in an earlier blog post (‘Medlink 2019’). We need to prevent patients from getting ill by detecting signs of an illness, leading up to their symptoms. By spotting signs of loneliness and doing something about this loneliness, this can be achieved. But how can we prevent loneliness from becoming an issue?

The ways which loneliness can be combated are wide-ranging. One way is talking therapies; although NHS guidance says ‘older people, especially those with depression, are as likely to benefit from talking therapies as everyone else’, fewer than 1 in 5 people over 60 have received counselling following a death. In fact, they can often be more effective for people over 65 according to the NHS.

Another way of combating loneliness is social prescribing, where possible, taking into account a person’s mobility and ability. For example the Downshall intergenerational project in Illford where elderly people visit a primary school to help the children with reading and other activities. Furthermore, the NHS’s plans aim to put 1,000 social prescribing link workers in place by the end of 2020/2021. The issue that lies in this is that often these social prescribing projects are run by small local charities and close after a short amount of time and short-termism isn’t helpful for loneliness.

If social prescribing isn’t possible due to a lack of mobility or ability, the youth could visit the elderly. Projects such as GoodGym has come up with a solution which contributes to an improved quality of life for the elderly, and the youth. Volunteer runners are matched with older people and, at a prearranged time, they run to the elderly people’s house, pay them a social visit, and then run home.

Furthermore, after community connector services have been cut recently, a spokesperson for the Department for Digital, Culture, Media and Sport, which is leading the government’s efforts to tackle loneliness said that they ‘have set up an £11m fund to better connect people across the country and our soon-to-be-launched loneliness strategy.’

On top of it all however, we need to embed the issue of loneliness into everyday healthcare, and indeed everyday life. Everyone should aim to keep up to date with available services, and aim to build relationships with providers in order to contribute to the issue of loneliness. On an individual level, asking questions such as ‘Are you seeing people as much as you like? Do you feel lonely?’ to the potentially lonely in our society is also important.

 

The Young Doctor Programme

On November 11th I went to King’s College London’s Greenwood Theatre to attend InvestIn Education’s Young Doctor Programme. This gave me a great understanding of the fundamental concepts of the medical profession and an insight into the key qualities of a doctor, and how to enhance them. This was given in a live, collaborative, and hands on environment.

It included talks from doctors in a variety of areas and levels in the hospital, from medical students, to consultants. It began with a talk about the world of a doctor and the reality of the profession. It also included talks on medical school interviews and the application process giving detailed step by step advice from choosing the right university to accepting you offer (hopefully).

The interactive parts of the day included an interactive A&E session, where one would put on a VR headset, and treat a variety of patients in whatever way seemed fit. It showed us the direction that medical school teaching was going, towards technology. Because it was designed for medical students, it was found by many, myself included, to be extremely complicated and detailed. We didn’t quite feel prepared for it, but it was a fantastic experience, which really threw us in at the deep end.

The next interactive session was suturing. This gave us a first hand insight into what one has to carry out in the medical profession. Although I wasn’t very good at it on the day, I think that, with some practice, I will get better.

It ended with a panel discussion with ten doctors and medical students. This was accompanied by a website which allowed us to ask questions anonymously, and for them to be answered by professionals at every level.

Although this short description only skims the surface of the sheer amount of knowledge that I gained from the day, I had a fabulous time, and learned a lot. I also left with a detailed information pack talking about CVs, universities, and the life of a doctor, to name but a few things.

Hampshire Medical Fund Medical Careers Seminar

On Tuesday 15th October, I traveled to Basingstoke Hospital to hear doctors at various stages of their career speaking about their career’s. It included talks from GPs, a consultant hepatobiliary and general surgeon, a consultant urological surgeon, an FY1 doctor,  a GP trainee, a pharmacist and a radiographer.

It was therefore extremely varied and, with multiple perspectives on the vocation, I believe that it gave an accurate depiction of what life in medicine is like – a lot of hard work, long hours, late nights, early mornings, some high stress situations, but it comes with a lot of satisfaction; the general view seemed to be that ‘I wouldn’t want to do any other job’.

I also learned about choosing medical schools and perfecting applications, which was an extremely useful thing to do so that I didn’t enter into the task blindly.

At the break, there were stands with a number of other medical professionals. These included some radiographers talking about their careers and showing off some of their technology. There was also a surgeon who showed us some of his fabulous technology as well, as he used them on a steak. This offered a fabulous insight into the work of a surgeon.

Finally I learned about a couple of other potential careers related to medicine. This gave me a really good insight into both, other options for a career, but also gave me a picture of the whole hospital team, and how many people from different parts of a hospital comes together to treat a patient. One of these was a radiographer who talked about the now multi-million pound machines that some hospitals use, and the potential future of the career with yet more advanced machinery.

Therefore, this day spurred me on to pursue a career in medicine.

Medlink 2019

Today, I attended Medlink at Nottingham University to gain a better understanding of life as as a medical professional, the pathway to medicine, and the plethora of universities that are on offer.

Firstly there were various seminars from many different speakers, ranging from an employee at UCAS, to a speech on the future of A.I. – I found this particularly interesting and it gave me a lot to think about. The argument was not that doctors would not be needed if A.I. were to hold a more important role in medicine, but that the role of the doctor would change. No longer would someone see a doctor with symptoms, but they would have been sent in after the contents of their toilet, toothbrush, and many other things had been analysed and predicted an illness. This would perhaps be linked to one localized device such as a watch. This, I think, is a revolutionary way of practicing medicine and is fantastic for us to think about, but, although it may be cheaper in the long run, with many patients no longer feeling the symptoms that they may have otherwise felt, I am unsure where the money to kick start this would come from.

We then had the opportunity to meet students and lecturers from many universities including Nottingham, Sunderland, Newcastle, Bristol, Cardiff, Belfast, Leicester, Hull, and many others, including a couple of overseas European universities. This gave me the fantastic opportunity to begin to think about what I may want in a university, and began even to start thinking about the universities that I felt suited me.

We then received the opportunity to learn about other professions that we may want to consider regarding medicine, such as a prosthetist. Finally we received advice on personal statements, and MMI interviews.

Overall, it was an extremely useful day, as it was very informative. It was also very inspiring and I came away feeling extremely passionate about pursuing a medical career.