MULTIPLE SCLEROSIS - A TIMELINE from earliest recorded beginnings to the latest developments in research ......

1200-1400 - Two cases leading to the proposal of a 'Viking gene' hypothesis.

1200 - A young woman called Halldora, who lived in Iceland, suddenly lost her vision and mobility, but after praying to the saints, recovered them seven days after.

1400 - Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of 16 until her death at 53, she suffered intermittent pain, weakness of the legs, and vision loss — symptoms typical of MS. Historical texts reveal that she was afflicted with a debilitating disease, sharing many characteristics with multiple sclerosis; age of onset, duration and course of disease. St Lidwina’s illness began soon after her fall developing walking difficulties, headaches and violent pains in her teeth. By the age of 19, both her legs were paralysed and her vision was disturbed. Over the next 34 years, Lidwina's condition slowly deteriorated, although with apparent periods of remission, until her death aged 53.

1820s-40s - Sir Augustus Frederic D'Este KCH - (b.1794, d.1848) Son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and illegitimate grandson of King George III of Great Britain. Earliest posthumus diagnosis of MS from his diaries.

D'Este left a detailed diary describing his 22 years living with the disease. His diary begins in 1822 and ends in 1846 four years before he died, although it remained undiscovered until 1948. His symptoms began suddenly at age 28 with a transient visual loss after the funeral of a friend. During the course of his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began using a wheelchair.

The History of Multiple Sclerosis

c1840 - Jean Cruveilhier (1791–1873), French professor of pathologic anatomy, describes and illustrates many of the clinical details of MS.
1868 - Jean-Martin Charcot, professor of neurology at the University of Paris, writes the first complete description of MS and the changes in the brain accompanying it. He discovered the characteristic scars or "plaques" and named the condition "Sclérose en plaques" after the Greek 'sklerosis', from skleroun ‘harden’.
c1870 - Dr. Sigmund Freud's first patient was his former Nanny, who had Multiple Sclerosis. "Creeping paralysis" as it was called in those days, was considered it to be a mental condition caused by "female hysteria". (Freud was a student of Charcot.)
1873 - MS recognized by Dr. Moxon in England.
1878 - Myelin was discovered by Dr. Ranvier. MS recognized in the United States by Dr. Edward Seguin.
c1880 - Georg Eduard von Rindfleisch (1836-1908) German pathologist attained the chair of pathology at the University of Würzburg. Famous for his work in the field of histology writing an influential work on pathological histology which was later translated into English. Writing on MS he noted: "If one looks carefully at freshly altered parts of the white matter ... one perceives already with the naked eye a red point or line in the middle of each individual focus, ... the lumen of a small vessel engorged with blood ... All this leads us to search for the primary cause of the disease (MS) in an alteration of individual vessels and their ramifications; all vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation."
1890's - caused by the supression of sweat; treated with herbs & bedrest; life expectancy after diagnosis, 5 years.
1890's - Uhthoff's symptom first described by Wilhelm Uhthoff, a renowned clinical neuro-ophthalmologist, as a temporary worsening or loss of vision in patients with optic neuritis. Later work revealed the link between exercise and increased heat-production causlng a reversible conduction block in demyelinated optic nerves. The phenomenon can occur with any neurologic deficit caused by demyelination and is possibly due to the effect of increased temperature on nerve conduction.
1906 - Nobel Prize for medicine awarded to Drs. Camillo Golgi and Santiago Ramony Cajal for perfecting chemicals to enhance the visibility of nerve cells under the microscope.
1910's - Possible cause? Unknown blood toxin; treated with purgatives and stimulants. Life expectancy after diagnosis, 10 years.
1916 - James Dawson reveals the basic damage done in MS by detailed microscopic study.
1919 - Abnormalities in the spinal fluid were discovered in MS, but signifigance remained a puzzle for decades.
1920 - Men were thought to be more susceptible to MS than women. Why? Because women were often mistakenly diagnosed with "hysteria" and MS symptoms tend to flair each month.
1925 - Lord Edgar Douglas Adrian recorded the first electrical nerve transmissions, which helped prove demyelinated nerve cannot sustain electrical impulses.
1928 - Discovery of oligodendrocyte - the cells which produce myelin.
1935 Dr. Tracy J. Putnam MD, Boston, USA, experimenting with dogs notice "venular obstruction is the essential immediate antecedent to the formation of typical sclerotic plaques".
1935 - Dr. Thomas Rivers demonstrated that nerve tissue, not viruses, produced a MS-like illness. This animal form of MS, experimental allergic encephalomyelitis (EAE), paved the way to present-day theories of auto-immunity, for it demonstrated the body can generate an immunologic attack against itself.
1938 - Dr. V.B. Dolgopol described a case of optic neuritis, caused by severe demyelination and attributed it to Devic's Syndrome. At this time, it was considered to be a subclass of Multiple Sclerosis.
1940's - Possible cause? blood clots and poor circulation; treated with drugs that improve circulation; life expectancy after diagnosis, 18 years.
1948 - Elvin Kabat and others discover oligoclonal bands in the spinal fluid providing a diagnostic test.
1960's - Possible cause? allergic reaction; treated with vitamins and antihistimines; life expectancy after diagnosis, 25 years.
1965 - White blood cells that react against a protein in nerve insulating myelin discovered in MS. Definite criteria for MS diagnosis developed by NMSS expert committee.
1969 - Using newly standardized diagnostic criteria, ACTH used to treat MS exacerbations.
c1980 - Dr. Franz Schelling, Austrian family doctor trained in radiology and neurology, theorizes that poor blood-flow from their brains of patients might contribute to MS. Schelling's requests for more study rejected by MS specialists.
1981 - MRI first used to examine a person with MS. MRI revolutionized diagnosis and provided evidence that MS is a constantly active disease even when symptoms abate.
1993 - Beta-interferon 1b (Betaseron) approved as the first drug to alter the course of MS.
1996 - Possible cause? Autoimmune reaction possibly linked to virus; treatment: steriods and immune-system regulating drugs; life expectancy after diagnosis, essentially normal.
2009 - Dr Hugh Brady, Department of Life Sciences at Imperial College London, and the Medical Research Council succeed in 'knocking out' a gene, E4bp4, in a mouse model, creating the world's first animal model entirely lacking disease-fighting 'Natural Killer' (NK) immune cells cells, leaving all other blood cells and immune cells intact. This breakthrough should help solve the mystery of the rôle that NK cells play in autoimmune diseases, such as MS.
2009 - Dr. Paolo Zamboni, vascular surgeon and professor at the University of Ferrara, Italy, investigating his wife, Elena, after she was diagnosed with MS using an MRI scanner noticed "chronic cerebro-spinal venous insufficiency" (CCSVI). Dr. Zamboni's team of scientists believe that veins in the neck and upper chest to twist, narrow or become blocked; in some cases, these veins never form at all. The result is poor blood drainage from the brain. Scientists found that more than 90% of patients with MS have these malformed veins, and improper blood flow from the brain.
2009 Team led by Dr Hugh Brady from the Department of Life Sciences at Imperial College London, identified a master gene E4bp4 which causes blood stem-cells to turn into disease-fighting 'Natural Killer' autoimmune cells. Using a mouse model scientists successfully 'knocked out' the gene known as E4bp4, creating the world's first animal model entirely lacking 'Natural Killer' cells, leaving all other blood cells and immune cells intact. This breakthrough model should help solve the mystery of the role that Natural Killer cells play in autoimmune diseases, such as diabetes and multiple sclerosis. This could now lead to new ways of treating these conditions with a drugs which will react with the protein expressed by their E4bp4 gene.
2011 UK and Canadian scientists, comparing DNA changes found against existing databases, identified the mutated gene, CYP27B1, in 35 parents of children with MS and, in every case, the child inherited this gene. Researchers say this adds weight to suggestions of a link between vitamin D deficiency and MS. When people inherit two copies of this gene they develop a genetic form of rickets - a disease caused by vitamin D deficiency which is the major cause of infantile rickets. Just one copy of the mutated CYP27B1 gene affects a key enzyme which leads people with this gene to have lower levels of vitamin D.There are high levels of both vitamin D deficiency and MS among Scotland's 10,500 MS sufferers, the highest incidence of MS anywhere in the world.