Nick Verber is a research registrar working for his PhD at the Sheffield Institute for Translational Neuroscience Institute (SITraN), University of Sheffield. He gave an excellent talk, very successfully overcoming the temptation of many medics to litter their lectures with clinical jargon. It was clearly delivered and easily followed by a large Zoom gathering of 44 Probus members.
Although there is a long way to go before there is a cure for motor neuron disease (MND), the Institute here in Sheffield, led by Dame Prof Pamela Shaw, is a world leader in clinical and scientific research into this and other challenging and distressing conditions.
Nick began with a typical case history which illustrated the progressive nature of MND over a two year period, although there is a great deal of variation in the rate of progression from patient to patient. MND is cruel to patients, relatives and their friends. It affects all voluntary muscles throughout the body and the case history illustrated how it progressed from minor weakness of the limbs to slurred speech, difficulty in swallowing which can result in saliva, food and drink going down into the lungs, and breathing problems.
Cause of MND
This is complicated and not fully understood. The vast number of nerves controlling voluntary muscles become damaged and cease to function properly (in contrast to sensory nerves bringing signals to the brain about touch, smell, sight, pain etc. and to autonomic nerves which control the gut, bowels, waterworks and sexual function, all of which remain unaffected in MND).
Dr Weaver’s amazing dissection – for details see last paragraph
These motor nerves carry signals from the brain to muscles involved with movement, posture, speech, swallowing, laughing, and coordination of eye movements. Eye and facial movements are affected much later. Poor strength in the head and neck leads to deformed posture, as seen in the familiar wheelchair posture of Stephen Hawking.
Stephen Hawking. Note the effect of wasting of head and neck muscles and failure to support the head
As muscles progressively weaken, mental faculties usually remain uncompromised, causing immense distress and frustration. But patients are often pragmatic and positive, and are keen to participate in, and raise funds for, research.
Prevalence
MND is relatively rare, with 5000 people having the condition in the UK. It has the same lifetime risk as the more common multiple sclerosis (MS), but there are substantially fewer people with MND due to the poor life expectancy.
Treatment
Successful treatment is individualised and patient focussed, led by a team of specialists, nurses, physiotherapists, dieticians etc. who make the diagnosis by clinical examination and investigation with blood tests, brain MRI, lumbar puncture. Treatment centres around individualised multidisciplinary care with provision of social, psychological and dietary support.
Medication has limited usefulness but Riluzole may slow nerve deterioration. Other interventions include dietary supplements, homogenised food, gastrostomy (feeding tube inserted through the abdominal wall into the stomach), physiotherapy, splints, highly sophisticated wheelchairs, assisted ventilation, occupational therapy, mobility and cutlery aids.
Mobility and Cutlery aids
Speech and language therapy is important, and voice banking is available. The inability to swallow saliva (normally 500ml per day) and drooling is distressing and helped by simple medication. Approximation of voice with regional accents has recently become possible, overcoming to some extent the impersonal Dalek sound of the computer. Communication problems as speech and motor function decline can be addressed by eye signals facilitating computer typing.
The main aim of treatment and long-term monitoring is to allow the patient to retain independence and quality of life.
Research
Nick touched on how MND research is conducted, using biomarkers
Biomarker research
to assess change in patient condition, with the aim of providing evidence to guide appropriate treatment. Blood tests, nerve conduction studies, MRI and constant monitoring of disease are all part of this process, and are particularly important for assessing progress during clinical trials
Research is expensive. Identifying a useful biomarker is crucial for attracting research funding. Charitable funding is helped by high profile patients such as Doddy Weir and Rob Burrows who make a positive contribution towards disease treatment through research.
MND comprises subgroups of patients with similar but distinct disease profiles. One research aim in Sheffield is to improve definition of these subgroups in order to improve their treatment and avoid any intervention found not to work. Some biomarkers differ between MND patients, or between patients and healthy volunteers.
Skin biopsies are simple, quick, painless (following local anaesthetic administration) and readily accessible (with patient consent). Fibroblasts are present within them. These are immature cells with maturation potential to develop new skin or scar tissue (in the case of trauma). Another research strategy in Sheffield is to give genetic information to these fibroblasts to convert them to nerve tissue in a laboratory setting. This overcomes a major problem in neurological research of being unable to access live brain or nerve tissue for experimentation.
Nick concluded by giving his gratitude to the patients and volunteers that have donated their time and samples to his research.
If anyone has any interest in volunteering for research, then please get in touch via his email address at the bottom.
Figures
Couldn’t resist this one! Dr Weaver’s amazing dissection of Harriet Cole’s nervous system (its huge complexity is illustrated by the fact it took from 1888 to 1893 to complete the dissection, which can still be seen in Philadelphia) (Barton M. The Nervous System of Harriet Cole. Past Medical History. Aug 18, 2018)
Correspondence address:
Those of you who were impressed by the work that Nick and his colleagues are researching can make a difference by donating by copying and paste this into your search engine.
http://sitran.org/support-us/