I (John Shields ) have spent the major part of my working life involved in research and development of instrumentation used for the infrared analysis of organic compounds.

From 1977 until my forced retirement through ill health in 1988,I together with a team of engineers and scientists built a very successful international organisation for design manufacturing and sales into the world market (see my CV). In 1983 we received the Queen’s Award for Export Achievement. More recently I have made several very significant advances in the design of computerised optical instrumentation for the accurate analysis of protein compounds.

I appeared to contract a very debilitating illness apparently based on progressively worsening migraine attacks accompanied by aura and facial and left finger numbness . Within the last few years these attacks developed into minor strokes and since I was unable to obtain medical assistance following frequent visits to various paid consultants in UK., France and Canada was determined to search computer web literature for clues to the cause of the illness. For a period of about a year I strongly suspected that I had contracted an inherited disease called CADASIL. As a student of family history it quickly became evident that I had inherited a mutated gene from the maternal side of my family (see copy of my family tree.) After suffering a further more serious stroke like event I concluded that there must be now sufficient brain damage to show on an MRI scan. I managed to arrange a test privately through a paid consultant Neurologist at the Newcastle Royal Victoria Infirmary.

There was damage illustrated by the scan to cause me to press for diagnostic blood tests. Unfortunately it is clear that through utter carelessness on the part of someone within the hospital department the samples that were taken never did arrive in the intended possession of Prof Raj Kalaria who could have diagnosed the mutation within weeks. Several months then elapsed without reason given for the delay, but after long negotiation with the Southern General Hospital Glasgow I managed to arranged for a diagnostic blood test to be carried out in their neurological department. Further delays in this procedure caused me to approach Prof Hugh Marcus and his assistant of St Georges Healthcare in South London who I learned was currently testing for CADASIL mutations.
Eventually, my diagnosis was confirmed as CADASIL, and the mutation described as a C499 mutation (R141C) in exon 4 of the notch 3 gene. This test was eventually carried out in Glasgow and, later verified in London.

A fortunate feature of this genetic condition is that once a parent is known and the mutation identified, any offspring not identifiable with a simple swab test for the same DNA will not carry the disease to further generations. I thus, was relieved to find that my son did not carry the mutation (my son David has two children ).

Unlike David, Alison my daughter displays all identical symptoms of the disease to mine. She has however, declined to be tested which is of course her prerogative. She has four children, any one of which has a 50% chance of contracting this disease if she is subsequently proven to be a carrier. At the present there is very little known about the mutation by the medical profession. But, CADASIL is now recognised to be common worldwide and in the UK there are more than 100 families. This statistic suggests CADASIL, often under and misdiagnosed, is certainly more common than familial Alzheimer’s disease. Until the condition is generally better known by the medical profession the much needed aspect of genetic counselling is sorely missed it would certainly assist in correct decision making in such circumstances.

Complex migraine is a common feature of the disease but for some, as yet, unknown reason this does not occur in every case. For example, although his mother is now known to have died at an early age of CADASIL, we cannot recall her having migraine, but she did suffer frequent headaches. A ‘complex’ migraine of the type my daughter have suffer from, from puberty are such that in addition to sick headaches there are often short term neurological symptoms, most commonly, disturbances of vision, numbness in parts of the face and one side of the body often accompanied by speech disturbance.

CADASIL is commonly characterised by recurrent strokes, most frequently first occurring in the 30 to 50 age group although this has been known to vary in some individuals. It is thought that the most persistent disability through arm and leg weakness, slurring of speech and severe nerve pain.

Researchers have now generally recognised that CADASIL results from a mutation in a very small part of the notch 3 gene. Thus normal protein reactions do not take place and the resultant abnormalities cause the dreadful features from which patients suffer. Very little is known about the disease mechanism but all patients suffer from progressive damage to the vascular system which causes reduced blood flow and an inability of the blood vessels to regulate blood flow. The abnormalities in micro-vessels supplying various centres of the brain with oxygen feature largely in the multiple small strokes experienced by CADASIL patients.

There are indeed many problems involved in suspected sufferers obtaining satisfactory diagnosis of the disease, the principle one being the lack in awareness in the medical profession of the very existence of the mutation in the first place. As a consequence in recent months many patients with similar symptoms, thought to be MS sufferers have later been diagnosed as actually having CADASIL. At the present time it is highly unlikely that a confirmatory test for CADASIL such as skin biopsy or a DNA test would be carried out before an MRI brain scan was performed to search for characteristic brain damage. Those lucky enough to be offered a diagnosis often decline because they cannot contemplate the finality of knowing that they have got the disease. My sister is one such person and whilst I believes she has not got CADASIL my daughter shows all the main features of the Illness but also declines to take a DNA test even though I can now arrange for this to be carried out by Professor R J Kalaria, one of the very few experts in the UK able to do this effectively. In the case of near relatives they would simply require a swab test to see if they possesses this Notch 3 mutation. My daughter has four children, any one has a 50% possibility of inheriting the illness if Alison shows positive. I do not object to her not having the test ,of course it must be her own decision but it is a worry. The legal aspects involved in learning that one has inherited a fatal disease when trying to provide insurance cover are easily understood, this is of course another draw back.

By conducting a search on the world wide web I have found many references to papers in the literature on research that is currently being carried out on CADASIL but unfortunately much of it is repetitious and most of very little direct value to the sufferer. As an example it is an established fact that after as long as three years of knowledge of the existence of the disease, medical progress is such that the only recognised prescribed medication is 75mg of aspirin administered daily

I am not a trained medical practitioner but I can claim that over the same period of time, by personal knowledge of my ailment and by the application of pure common sense I believe I have found a natural amino-acid (protein) treatment for migraine-with-aura that has worked successfully now for a period of eighteen months.
I confidently believe that migraine and stroke run concurrently which is evidenced by the fact that I have not experienced any strokes during the same interval. Professor Kalaria has witnessed my findings and is now engrossed in evaluating my treatment using sixteen known CADASIL sufferers and standard statistically recognised methods approved by the Medical Council.

My research and personal experience has shown that, amongst the medical profession and the public at large, little is known about the disease. It has been established however that a large pool of individuals display the classic symptoms and were there to be a greater awareness many more would come to light. Many of those now found to be CADASIL sufferers have been given inappropriate treatment for years because of previous misdiagnosis. As I mentioned earlier I know personally of several such people.

Many more meetings of the type organised between ourselves, known authorities on the disease, patients such as myself and specific area medical staff will require to be organised to lecture on the subject such as the type Prof. Kalaria and I presented at Northgate and Prudhoe Regional Health Centre. Despite the small beginning it has been regarded by many as an important start to the principle of taking expert knowledge to where it is most urgently needed.