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Russell Brain's review of MS.

Introduction

The annals of history are fickle when recognizing contributions. Great discoverers may be applauded when alive, but quickly forgotten once dead. Minor figures may have lasting fame if their name is attached to some sign or syndrome. Those who discover things first may be ignored while we forever remember the one who makes the discovery public. As an example, there are at least thirteen who knew and described multiple sclerosis (MS) prior to Jean-Martin Charcot, with whom the disease has been forever associated. (1)

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We seldom credit an important meeting or a well-written review of MS, even though these can focus understanding and set new directions for treatment and research. Two meetings that were milestones in the growing knowledge of MS were the ARNMD 1921 meeting in New York and the 1982 Grand Island meeting covering the design of clinical trials for MS. (2,3)

Another catalyst for change in thinking can be a well-researched and balanced review, such as that of MS in 1930 by the young neurologist, Russell Brain. (4)

Brain's Early Career

Born in Reading on 23 October 1895, young Russell Brain attended Mill Hill School and then, with a scholarship, New College, Oxford, initially looking towards a career in law. It is noteworthy that he had influential teachers in the sciences such as Julian Huxley and JBS Haldane.

As a young man he became a Quaker and when war broke out in 1914 his pacifist belief directed him to enlist in the Friends' Ambulance Unit where he became Head of the X-ray department in York. There, he met his future wife, who was serving in the Volunteer Aid Detachment (VAD). She encouraged him to consider medicine when the war was over. (5)

He began his medical studies at the London Hospital, planning a career as a psychiatrist, but on the advice and encouragement of neurologist George Riddoch he switched to neurology. (5) Following his training he was appointed to the Maida Vale Hospital for Nervous Diseases (1925) and the London Hospital (1927). Three years after joining the London Hospital he published his lengthy review on MS. Some thought him too young to publish a sweeping review so early in his career, but this was not to be the last time he was the cause for raised eyebrows.

Brain's Critical Review of MS

His landmark review of the current understanding of MS (then called disseminated sclerosis), together with his personal views and conclusions, was published in the Quarterly Review of Medicine in 1930. (4) It covered all aspects of the disease, and was supported by 218 references.

He began with a survey of reports on the prevalence and the geographical distribution of MS, noting that it was more common in Britain than in the USA, where World War I recruitment figures suggested the disease was only one third as common, but with a higher incidence in states bordering on the Great Lakes. MS was common in Europe and there was double the incidence in Switzerland, but less evident in studies from Italy and Romania. It was noted to be uncommon in China, Japan and Chile. The American recruitment figures also showed a higher incidence in those of foreign-born extraction, particularly those of Scandinavian and Finnish extraction. Surprisingly, a review of the reports suggested a greater incidence in males.

He listed the conflicting reports on rural versus city incidence of MS and found little to support a difference. He questioned the way that the evidence was gathered to suggest a higher incidence in woodworkers, ironworkers, workmen, and occupations with heavy exposure to water, and dismissed the idea of an occupational risk.

He accepted that cases can occur in families, but concluded a better explanation could be found in a common environmental exposure, or mutual infection, rather than heredity, a view he would later revise in his textbooks.

Reviewing the many reports on the pathological changes in MS, particularly the detailed cases of Dawson in 1916 and the review by Hassin in 1922, he concluded that the changes were in keeping with an initial infective agent, precipitating an infiltration by lymphocytes and plasma cells, phagocytosis of myelin, fibroglial overgrowth and axonal loss. He noted the changes that we now recognize as the shadow plaques, indicating remyelination. Although he saw other viewpoints on the pathological changes, he returned to his conclusion that an infective process was at the basis of the disease. Considering the opinions on which tissue was primarily affected, he said whatever was the 'noxa' affecting the tissues, the degeneration of the myelin was the most constant finding. As to the route of infection he felt the perivascular demyelination suggested a haematogenous dissemination, although the periventricular location of many lesions also would implicate a cerebrospinal fluid (CSF) route, and it was conceivable that both were involved.

There had been many conflicting reports of transmission of MS by various methods to animals, as first observed by Bullock (formally Gye in earlier publications, as he later took his wife's name), and concluded these experiments were mostly flawed. He was not convinced by any of the reports, but was keeping a watching brief on the work of the prominent consultant Sir James Purves-Stewart and his junior research colleague, Catherine Chauvassut, who had adjoining articles in the Lancet that year, suggesting they not only had a cause, but also a vaccine for MS. They said they had discovered the causative agent, insula spirularis, and had already produced a vaccine and were treating patients with good results. (1)

As to the list of potential precipitating factors for MS, Brain was not convinced by the theory of metallic poisoning suggested by Oppenheim, and felt the evidence for other factors such as trauma, cold, heat and electric shock was scanty at best.

He outlined the types of course, age of onset and clinical symptoms and physical findings in MS. The CSF examination and tests available were mostly adapted from the tests for syphilis, and were useful in confirming the diagnosis in some cases, but he also noted that some had reported exacerbation of symptoms in the weeks after lumbar puncture. He was concerned that some of the observations gleaned from the literature were probably confused by the problem of misdiagnosis.

In his review of available therapies he cautioned that none probably produced a result that wouldn't have happened spontaneously. He recommended a patient should rest and avoid activities that would cause fatigue, but should stay mobile as long as possible. If patients embroider their symptoms they need the encouragement, optimism and understanding of the physician, and he regarded the personality of the medic as more effective than any drugs.

Although he was cynical about most therapies, it is a surprise that he was impressed by the benefits of pyrexial therapy and methods of creating a fever such as inducing malaria and administering typhoid vaccine. Others had tried to cause fever with injections of milk or the inoculation of the spirochete of African relapsing fever, but he was doubtful of the results of these methods. Compounds of arsenic were the most common therapy used for MS in that era, but the results, he felt, were uncertain. Viewing the long list of therapies available for MS he concluded, "The multiplication of remedies is eloquent of their inefficacy".

He then discussed other diseases that might or might not have some relationship to MS such as neuromyelitis optica, ADEM, Schilder's Disease, post-vaccinial and post-infectious encephalitis.

Looking to the future search for the cause of the disease he said that the relapsing-remitting pattern of the disease was likely to provide the clue.

Brain's Later Career

Brain was a prolific author on neurology early in his career. (5) He co-authored with EB Strauss, Recent Advances in Neurology, (6) and soon after wrote Diseases of the Nervous System (1933), (7) which became a classic text for students in its many editions. He was just 38-years-old, when he wrote such a comprehensive book on the field of neurology, which some felt was too young and a task more appropriate for a senior, experienced consultant. Despite this, it became one of the most popular texts on neurology. Compston, who followed Brain's changing views on MS through the many editions of the book, commented, "No work has so dominated the 20th Century and influenced neurologists in the English speaking world as Russell Brain's Diseases of the Nervous system." (8) In subsequent editions he incorporated newer ideas and observations such as the genetic data of Curtius, the 'allergic' nature of the brain changes, the importance of axonal damage, and the use of steroids as therapy. After his death, editions were edited first by Lord Walton and then Michael Donaghy. (12th edition 2009). (9)

He was recognized as a formidable figure in the world of neurology from the beginning and produced papers and books on many clinical and historical subjects, displaying his strong humanistic beliefs, his Quaker principles and his continuing interest in philosophy, psychiatry, religion and education. Because of his wide interests and reading he was as comfortable writing about Samuel Johnson, Charles Dickens, Socrates or the sculpture of Jacob Epstein as on exophthalmic ophthalmoplegia carpal tunnel syndrome, cervical spondylosis, the non-metastatic manifestations of malignancy, speech disorders and mind-body problems, to which he made notable contributions. (5) In his obituary to Lord Brain, RA Henson commented that his continuous flow of papers were noted for their "clarity and verbal felicity". (10)

Although a large and imposing figure, he seemed shy and aloof, and somewhat off-putting due to his frequent long silences, but many noted his courteous and calm nature, his humour and his clarity of thought. (10,11) He was knighted in 1952, made a baronet in 1954 and a baron in 1962. Once a member of the House of Lords, Lord Brain advocated liberal reforms on abortion, homosexuality and birth control. (5)

Lord Brain was equally prominent in the world of medicine, neurology and medical education. He was editor of the journal Brain, President of the Royal College of Physicians, the Association for the Study of Medical Education, the Association of Physicians, the Association of British Neurologists and the International Society of Internal Medicine. He was appointed by the Canadian Government to assess the needs for the medical and hospital services in Newfoundland, which led eventually to the establishment of Memorial Medical School in St John's.

Conclusion

Russell Brain was one of those physicians who had a broad view of life, medicine, philosophy, history, ethics and society, and throughout his life published about many of these areas with great effect. Early in his career, he took a particular interest in the confused and complex field of MS and with one review, accompanied by his personal interpretations, influenced thinking about the disease for decades. He then updated his thinking through his later editions of his textbooks.

Every so often, when so many active researchers and clinicians are working at their part of the puzzle, someone should step back and with vision and balance, provide an overview to encapsulate the current understanding. Then we can move forward.

Conflicts of Interest

No conflicts of interest were declared in relation to this article.

Received: 15 December 2009

Accepted: 17 December 2009

References

(1.) Murray TJ. Multiple Sclerosis: The History of a Disease. New York; Demos 2005.

(2.) Association for Research in Nervous and Mental Disease. Multiple Sclerosis and the Demyelinating Diseases. New York; Paul B. Hoeber, 1922.

(3.) Herndon RM, Murray TJ. Proceeding of the International Conference on therapeutic Trials in Multiple Sclerosis. Arch Neurol 1983; 40:663-710.

(4.) Brain WR. Critical review: disseminated sclerosis. Q J Med 1930; 23:343-391.

(5.) Storey G.O. Walter Russell Brain (1895-1966), Baron Brain of Eynsham, Lord Brain MA, DM, DSc, LLD, DCL, FRCP, FRCS, FRCOG, FRCPEd, FRCP.Glas, FRACP, FACP, FCPSA, FRS. J Med Biog 2009; 17:30-34.

(6.) Brain WR. Strauss EB. Recent Advances in Neurology. London; Churchill, 1929.

(7.) Brain WR. Diseases of the Nervous System. London: Cumberlege, 1933.

(8.) Compston A. Reviewing Multiple Sclerosis. Postgrad Med 1992; 68:507-516.

(9.) Brain's Diseases of the Nervous System, Michael Donaghy, Editor. Oxford; Oxford University Press, 12th Edition, 2009.

(10.) Henson RA. Russell Brain, DM, FRCP, FRS 1895-1966. (obituary) Archives Neurology 1967; 16:559-560.

(11.) Howie J. Sir Walter Russell Brain, FRS, FRS, FRCP (later Lord Brain). Brit Med J1987; 295:108-109.

TJ Murray

Dalhousie University, Halifax, Novia Scotia, Canada

Address for Correspondence

T Jock Murray

Room 2L-A2

2nd Floor Link

Sir Charles Tupper Medical Building

Dalhousie University

Halifax B3H 4H7

Canada

E-mail: jock.murray@dal.ca
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Author:Murray, T.J.
Publication:The International MS Journal
Article Type:Clinical report
Geographic Code:4EUUK
Date:Jul 1, 2010
Words:2089
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