It was my first encounter with a real patient, which explains why it had such an indelible impact. The patient was a lady in her mid-40s. I entered her room apprehensively. I introduced myself and asked her if she minded being examined so that I could present her on a teaching round. Despite being exhausted, she was accommodating and agreed to help. Her main complaints were unsteadiness when walking and double vision on looking to the right.
She had MS and had been admitted with a relapse. She had a long story to tell and had numerous symptoms that included bladder problems, constipation, depression, anxiety, fatigue, back pain and restless legs that kept her awake at night. She had a musty odour of urine about her. She was incontinent; she couldn’t get to the toilet quickly enough to empty her bladder. Her bed clothes were damp and her hospital sheet had the tell-tale signs of the problem, but she was too tired to be embarrassed.
I examined her and to this day I remember just how excited I was to elicit so many clinical signs. As a medical student hungry for knowledge and experience, my notes were a catalogue of a failing nervous system – a clinical treasure trove.
When I reflect on this experience, I realise now how brash and unsympathetic I must have seemed. My attention was focused only on her medical problems. I had yet to learn the skill of how to be empathetic at the bedside. I had yet to become a doctor. After I had finished taking notes, she threw me a curve ball. She asked me if I knew her son. It turns out he was in my medical school class.
Embarrassingly I did not know him well, but this short exchange of personal details changed the mood. She broke down in tears and confided in me that she was not coping – the majority of people with MS don’t cope. One of her biggest fears was that she would be unable to attend her son’s graduation. What suddenly struck me was just how debilitating and stressful, the uncertainty of living with MS is.
I met her again 18 months later; I had decided by then to become a neurologist. She was now using a crutch indoors and a wheelchair outdoors. She had fallen and had broken her wrist. In less than two years she had gone from being mobile to needing a wheelchair. At my graduation I made a point of looking out for her; I never saw her, nor did I see a wheelchair.
Some of us have shifted our sights from simply reducing damage to preventing damage, with the hope of protecting the brain so that people with MS can age normally
In 1985, when I first met this lady, there were no treatments for MS. This changed in 1993 when the first trial of interferon-beta showed that by injecting it under your skin every other day you reduced the MS attack rate by a third and reduced the number of MS lesions that come and go on MRI scans by more than 70 per cent.
Although only moderately effective, the arrival of the beta interferons showed the world that MS could be treated and established MS as a new and very lucrative blockbuster drug market. Interferon-beta opened the flood gates and, over the next 20 years, a whole raft of new drugs has been licensed to treat MS.
In addition to new drugs, our understanding and aims of treatment have shifted during this time. Some of us have shifted our sights from simply reducing damage to preventing damage, with the hope of protecting the brain so that people with MS can age normally.
Most disease activity in MS occurs below the surface of the water, hence the iceberg analogy. For every clinical attack there are ten or more lesions that can be seen to come and go on MRI. People with MS often don’t report symptoms compatible with a relapse; these undocumented relapses can be costly for the individual. The absolute number of relapses is important when deciding whether or not a person is eligible for a treatment under the NHS and if you are on a treatment it may indicate you are not responding.
Similarly, subclinical attacks, which occur when new lesions are seen on MRI, but are not associated with physical symptoms, also indicate the person is not responding to treatment.
Current MRI imaging only detects large lesions and we now know from studying the brain after death that more than half of the disease activity is occurring in areas of the brain that can’t be seen with the MRI scans we use in day-to-day practice. A large number of MRI-invisible lesions are found in the gray matter on the surface of the brain or cerebral cortex; these lesions are associated with cognitive deficits, depression, anxiety and fatigue. These symptoms are often referred to as hidden symptoms; they lie under the surface of the water.
With new imaging techniques we can now see that the brains of people with MS are shrinking at two to three times the rate of normal brains. The good news is that a handful of highly effective MS treatments are showing promise and are able to slow this brain shrinkage.
We are also seeing the clinical impact of these more effective treatments; people with MS going on to these treatments are coming back with improvements in their disabilities. Severe relapses are almost a thing of the past and the future is looking much rosier. We are beginning to ask the question, “What does an MS cure look like?” and “How do we define an MS cure so that we can look for it?” We are moving away from simply targeting inflammation and are trying to reduce end-organ damage; the pathology at the bottom of the MS iceberg.
If the woman with MS, who influenced my early career so much, came into my consulting room today, the story I would tell her would be a very different one – an inspiring story of innovation and hope. I predict a future in which people with MS live healthy lives into old age free of disability and the worry that is such an integral part of living with MS.