SCORacle Newsletter - April 2024 Edition
As with most neurological disorders, making an accurate diagnosis of Parkinson’s disease (PD) is often complicated. The standard diagnosis of PD is clinical, meaning there’s no test, such as a blood test, that can give a conclusive result. Instead, certain physical symptoms need to be present to qualify a diagnosis of PD.
Because there is no conclusive screening or test, those affected with very early PD may not meet the clinical diagnosis criteria. This lack of specificity means that a diagnosis of PD can be made which over time is changed to another condition that mimics PD and studies suggest that misdiagnosis of PD occurs in 1 in 4 cases. Therefore, from an underwriting and claims assessor’s perspective, PD can be particularly challenging. There are, however, some fascinating developments that in the next few years could potentially have enormous impact in diagnosing PD earlier and more accurately, including the use of “Intelligent Medical Devices” (IMDs) and also a simple chemical swab. These exciting developments and their relevance are discussed in this article in more detail.
Parkinsonian disorders
James Parkinson was a London based physician who in 1817 published a paper “The Shaking Palsy” that first described the symptoms in PD. However, similar symptoms are also found in other conditions that includes slowness of movement, stiffness and tremor that give rise to the term “Parkinsonism”.
Most people with a form of Parkinsonism have “idiopathic” PD when there is no identifiable condition responsible for causing symptoms. Other less common forms of Parkinsonism include multiple system atrophy (MSA), progressive supranuclear palsy (PSP), drug-induced parkinsonism and vascular Parkinson’s, which is caused by damage to the brain due to small strokes.
PD usually presents with the typical motor symptoms of tremor and slowness of movement. However it is likely that the underlying disease process starts many years before these symptoms develop. Research demonstrates that by the first time of presentation, 70% of the dopaminergic nigrostriatal neurons in the brain cells are lost, that is directly related to the symptoms of PD.
Early signs of PD – “Prodromal” pre-motor symptoms
Prior to the development of typical motor symptoms such as tremor and slowness of movement, a variety of “prodromal” non-specific symptoms may occur for approximately 7 years or even longer, before a formal diagnosis can be given. These prodromal symptoms may include the loss of sense of smell (90%), depression/anxiety (50%), sleep disturbance, Rapid Eye Movement (REM) behaviour disorder, constipation, restless leg syndrome and autonomic features such as urinary urgency and hypotension.
Motor symptoms with PD
The main motor features associated with PD develop slowly and insidiously and are often attributed to ageing.
These include:
- Shaking or tremor
- Akinesia/Bradykinesia: Slowness of movement of the limbs, face, walking;. including rising from a chair or getting into or out of bed
- Rigidity: Stiffness in the arms or legs
- Postural instability: Problems with balance
Investigations for Parkinsonism
Magnetic Resonance Imaging (MRI) or computerised tomography (CT) scans are usually normal and may be used to confirm or exclude pathologies such as vascular or metabolic causes of symptoms.
Dopamine Transporter (DAT) imaging using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) scan enables the examination of the brain’s dopamine system. This involves the injection of a small amount of a radioactive drug that binds itself to the dopamine transmitters showing where in the brain the dopaminergic neurons are and can be valuable to show the extent of any destruction.
With advancing technology, doctors may soon have more tools in their arsenal to have more comfort in diagnosing PD, whilst excluding other possible diagnoses. Intelligent medical devices (IMDs), as described below, is one such example.
IMDs – revolutionising healthcare in neurodegenerative disease
In August 2022, it was reported that the National Institute for Health and Care Excellence (NICE) was evaluating a number of monitoring systems for people with PD created by several high-tech medical device companies. This has the potential to benefit 150,000 people with the illness in the UK, with plans to achieve clinical validation of the devices in early 2023.
The results from one of the monitors has published feedback from PD sufferers who have monitored their symptoms for up to two years showing that many of them feel their condition stabilised (43%) or improved (35%) after starting to use the technology. Clinical trials in Germany, Italy and Greece have already recorded high reliability and specificity levels, and symptom detection accuracy of up to 93%.
Research into neurodegenerative conditions such as Alzheimer’s disease and PD through interpretable «white- box» machine learning may in time show how patient data can be used to arrive at a diagnosis and manage their condition.
Challenges in Parkinson’s disease management
As has been already mentioned, the main challenges in PD relate to the difficulties in diagnosing the condition that often results in misdiagnosis and also the problems encountered with the management of medication.
Misdiagnosis of PD
It is widely accepted that 1 in 4 people who have been told they have PD do not have the condition, but have instead a related neurodegenerative condition. Some sources suggest this rate may be much higher. Research by Thomas G. Veach MD, Ph.D. and Charles H. Adler, MD. Ph.D. in 2018 suggests a much higher misdiagnosis rate of 40%1. A diagnosis is important to ensure the correct treatment, as the treatment for PD can be very different from the treatment for conditions like progressive supranuclear palsy or multiple system atrophy. This misdiagnosis can be resolved by medical professionals after 12-18 months, but much can be done to secure a diagnosis much earlier through objective assessment of patients.
Management of medication
For people with PD, medications can help for many years. However, as the condition progresses it can become very difficult to get the right combination of drugs to help individuals achieve the best quality of life. Therefore, it is important to monitor for side-effects of medication and to adjust the treatments accordingly.
Medical tech companies are tackling these challenges by leading the way in research into neurodegenerative disease and potentially could have a significant impact in enabling earlier diagnosis and improved care for people with neurological diseases including PD.
An example of a medical tech organisation that is developing monitors is “ClearSky Medical Diagnostics.” They are a spin-out company from the University of York’s School of Physics, Engineering and Technology, specialising in medical devices for the diagnosis and monitoring of PD, Alzheimer’s disease and a range of other neurodegenerative conditions.
The core technology behind their devices is based on unique biologically-inspired computer algorithms developed at the university in close collaboration with leading medical centres worldwide. Research has been carried out with medical specialists from Leeds Teaching Hospitals NHS Trust, including Leeds General Infirmary, to ensure that the work is clinically-led. The result is a portfolio of non-invasive devices that provide a safe, quick and objective assessment of symptoms.
PD-Monitor to assist in the diagnosis and monitoring of people with Parkinson’s disease
Picture below shows ClearSky’s device that is used to diagnose and monitor people with PD. Small, non-invasive sensors positioned on the finger and thumb measure ‘ movements in response to the finger-tapping test, in which the examinee repeatedly taps the forefinger and thumb of each hand for a period of 10-30 seconds. Readings from the sensors are transmitted to a tablet computer and then analysed by specialist software employing biologically inspired algorithms. These algorithms have been trained to recognise patient movements characteristic of tremor and bradykinesia.
LID-Monitor to monitor side-effects and adjust medication
Levodopa-induced dyskinesia (LID) is a consequence of long-term treatment for PD, which is often characterised by symptoms of slow movement and rigidity. It is claimed the LID monitor reduces the risk from LID by adjusting medication dosage to find a tolerable balance between the benefits and side effects.
LID-Monitor as shown in Picture 2 enables a safe, simple, and unobtrusive way of monitoring dyskinesia in a person’s home that allows specialists to measure the effectiveness of the treatment. This involves attaching 6 small sensors for over periods of up to 24 hours. Movements associated with dyskinesia and the symptoms of PD are recognised by the system and transmitted electronically to specialists in a graphical format.
These medical-grade wearable devices offer continuous monitoring and may herald a new frontier in the management of people with Parkinson’s, with the potential to transform patient care away from a face-to-face environment and easing the burden on front-line services.
A new test being developed – thanks to a woman that can smell PD
In 2015, it was discovered that a Scottish lady named Joy Milne could “smell” people afflicted with PD. Whilst Mrs. Milne’s ability to smell PD seems unbelievable, it is possible due to a hereditary condition called hyperosmia. This is a condition that gives people a hypersensitivity to smell.
Since then, Mrs. Milne has been working with a group of scientists to pinpoint the molecules that give PD its distinct odour. As a result of the research, the team has been able to identify a set of molecules specific to the disease, which has enabled them to create a simple skin-swab-based test to detect them.
Mrs. Milne discovered that she could sense PD by smell after noticing her now late husband, Les, was emitting a musky odour that she had not detected in him before. Initially chastising him for not washing properly, she eventually linked this change in scent to PD when he was diagnosed with the disease many years later.
Following his diagnosis, Mr. and Mrs. Milne attended a support group for people diagnosed with PD. Upon entering the room full of PD patients, Mrs Milne immediately recognised the same smell emitting from her husband.
As Mrs. Milne theorised she could smell PD, she approached Tilo Kunath, a neuroscientist at the University of Edinburgh, at an event organised by the research and support charity Parkinson’s UK. Although sceptical at first, Kunath and his colleagues decided to put Mrs. Milne’s claims to the test. They gave her 12 T-shirts, six from people with PD and six from healthy individuals. She correctly identified the disease in all six cases—and the one T-shirt from a healthy person she categorised as having PD belonged to someone who went on to be diagnosed with the disease less than a year later.
The experiment further supported that Mrs. Milne could not only smell PD but could smell it even in the absence of its typical medical presentation, further supporting the view that the disease is present significantly before its clinical manifestation.
Researchers hoped the finding could lead to a test being developed to detect Parkinson’s, working under the assumption that if they were able to identify a unique chemical signature in the skin linked to Parkinson’s, they may eventually be able to diagnose the condition from simple skin swabs.
A new diagnostic tool?
In 2019, researchers at the University of Manchester, announced that they had identified molecules linked to the disease found in skin swabs. The scientists believed that the scent may be caused by a chemical change in skin oil, known as sebum, that is triggered by the PD.
The findings, which have been published in the Journal of the American Chemical Society, detail how sebum can be analysed with mass spectrometry – a method which weighs molecules – to identify the disease.
And now the scientists have developed a test using this information. The tests have been successfully conducted in research labs and now scientists are assessing whether they can be used in hospital settings that potentially could be used in the NHS including GP practices.
The long-term aim is to develop a tool that can accurately detect PD in the early stages of the disease before it starts to cause clinical symptoms. This could then allow potential therapies to prevent or mitigate PD.
With Mrs. Milne’s identified hyperosmia, researchers all over the world have started working with her and have discovered that she can potentially identify several kinds of illnesses, such as tuberculosis, Alzheimer’s disease, cancer and diabetes. Research is in the very early phase, but the potential benefits are very exciting!
What does this mean for insurance?
Insurers in the UK and Ireland cover PD within their Critical Illness products. The typical definition of the disease is as follows:
| Parkinson’s disease – resulting in permanent symptoms |
|---|
A definite diagnosis of Parkinson’s disease by a Consultant Neurologist or Consultant Geriatrician.
|
As described in this article, it is highly likely that PD will be diagnosed much earlier in the course of the disease, and possibly before the onset of symptoms. Therefore, for future- proofing purposes it is essential that the need for permanent symptoms remains a requirement in policy definitions. Once these improved diagnostic tools have been further developed, there may also be some scope to introduce severity-based payments with scaled benefits.
PD is the fastest-growing neurological condition in the world, and currently there is no cure. With population growth and ageing, the number of people diagnosed is expected to increase by around a fifth to around 172,000 people in the UK, by 2030.
With the developments described, the average age of diagnosis could be much younger than it is currently which is likely to have a significant impact on claims experience.
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