The history of neuromyelitis optica. Part 2: 'Spinal amaurosis', or how it all began.

Neuromyelitis optica (NMO) was long considered a clinical variant of multiple sclerosis (MS). However, the discovery of a novel and pathogenic anti-astrocytic serum autoantibody targeting aquaporin-4 (termed NMO-IgG or AQP4-Ab), the most abundant water channel protein in the central nervous system, led to the recognition of NMO as a distinct disease entity in its own right and generated strong and persisting interest in the condition. NMO is now studied as a prototypic autoimmune disorder, which differs from MS in terms of immunopathogenesis, clinicoradiological presentation, optimum treatment, and prognosis. While the history of classic MS has been extensively studied, relatively little is known about the history of NMO. In Part 1 of this series we focused on the late 19th century, when the term 'neuromyelitis optica' was first coined, traced the term's origins and followed its meandering evolution throughout the 20th and into the 21st century. Here, in Part 2, we demonstrate that the peculiar concurrence of acute optic nerve and spinal cord affliction characteristic for NMO caught the attention of physicians much earlier than previously thought by re-presenting a number of very early cases of possible NMO that date back to the late 18th and early 19th century. In addition, we comprehensively discuss the pioneering concept of 'spinal amaurosis', which was introduced into the medical literature by ophthalmologists in the first half of the 19th century.

Area postrema syndrome: A short history of a pearl in demyelinating diseases.

In this topical review, we discuss the history of the area postrema syndrome, with special attention given to early studies aimed at identifying the area postrema and its function, possible early cases of the syndrome and its current relevance in neuroimmunology and demyelinating diseases. In 1896, Retzius named a structure in the posterior medulla oblongata as the area postrema. The work of Borison in the middle of the 20th century led to the elucidation of its function as a "vomiting center." The historical medical literature is filled with excellent examples that could be described as "area postrema syndrome." While severe and bilateral optic neuritis and transverse myelitis still constitute the classic components of neuromyelitis optica spectrum disorder (NMOSD), intractable vomiting and hiccups due to area postrema involvement is now recognized as essentially pathognomonic, indeed a shiny pearl in neuroimmunology and demyelinating diseases.

The first Japanese report on neuromyelitis optica rediscovered: acute bilateral blindness, tetraparesis and respiratory insufficiency in a 35-year-old man (1891).

The term 'neuromyelitis optica' (NMO, Devic syndrome) is used to refer to a syndrome characterized by optic neuritis and myelitis. For many decades NMO was classified as a clinical variant of multiple sclerosis (MS). Recent research has shown, however, that NMO differs from MS in terms of immunopathogenesis, clinical presentation, and optimum treatment. In most cases, NMO is caused by autoantibodies to aquaporin-4 or myelin oligodendrocyte glycoprotein. While the history of classic MS has been studied extensively, only relatively little is known about the early history of NMO. Although NMO is considered to be much more prevalent among Asian than among European patients with CNS demyelination, all early reports of NMO reviewed by Eugène Devic and Fernand Gault in their seminal 1894 review and all other reports from the 19th century re-discovered by us over the past years related cases of NMO in patients of European descent. Here, we would like to draw the attention to an early report on NMO in a Japanese patient, published by Tanemichi Aoyama (1859-1917), one of the most eminent physicians of the Meiji period, an era characterized by a Western-style revolution in Japanese medicine. The report was published in 1891, i.e. 3 years before Devic and Gault's disease defining study on NMO. To the best of our knowledge, this is the earliest report on an Asian patient with NMO. We give an English translation of the original Japanese report written in bungo (pre-modern Japanese) and discuss the case both in the light of current knowledge on NMO and from a historical perspective.

Devic's disease before Devic: On the contribution of Friedrich Albin Schanz (1863-1923).

Neuromyelitis optica (NMO, Devic's disease) is an autoimmune disorder of the CNS that mainly affects the optic nerves and spinal cord and, if not treated, can leave patients blind and wheelchair-bound. NMO was long considered a clinical variant of multiple sclerosis (MS). While the history of MS has been studied extensively, relatively little is known about the early history of NMO. A dissertation written by Fernand Gault (1873-1936), a doctoral student to Eugène Devic (1858-1930), a Lyon-based neurologist after whom the disease would later be named, is considered by many the first review of NMO. We would like to draw attention to a forgotten earlier review by the German oculist Friedrich Albin Schanz (1863-1923)-still known to ophthalmologists as one of the inventors of the corneal microscope ("slit lamp")-on which Devic and Gault's work was based and which points to most of the clinical and pathological features nowadays considered characteristic for NMO. The discovery of aquaporin-4 antibodies (NMO-IgG) has revived the interest in NMO, which is now extensively studied as a prototypic autoimmune condition. We believe it is now time to do justice to those who were seminal in describing this rare yet intriguing disease.

Neuromyelitis optica: Application of computer diagnostics to historical case reports.

The retrospective diagnosis of illnesses by medical historians can often be difficult and prone to bias, although knowledge of the medical disorders of historical figures is key to the understanding of their behavior and reactions. The recent application of computer diagnostics to historical figures allows an objective differential diagnosis to be accomplished. Taking an example from clinical neurology, we analyzed the earliest reported cases of Devic's disease (neuromyelitis optica) that commonly affects the optic nerve and spinal cord and was previously often confused with multiple sclerosis. We conclude that in most identified cases the software concurred with the contemporary physicians' interpretation, but some claimed cases either had insufficient data to provide a diagnosis or other possible diagnoses were suggested that had not been considered. Computational methods may, therefore, help historians to diagnose the ailments of historical figures with greater objectivity.

Devic's disease before Devic: Bilateral optic neuritis and simultaneous myelitis in a young woman (1874).

Neuromyelitis optica (NMO, Devic's disease) is an often severely disabling disorder of the central nervous system (CNS) which mainly affects the optic nerves and spinal cord. NMO was long considered a clinical subform of multiple sclerosis (MS). In 2004, however, Lennon and colleagues described a novel autoantibody in NMO which targets aquaporin-4, the most abundant water channel in the CNS, and which was later shown to be directly pathogenic. This has led to the recognition of NMO as a distinct disease entity in its own right. While the history of 'classical' MS has been extensively studied, only little is known about the early history of NMO. The term neuromyelitis optica was coined in 1894 by Eugène Devic (1858-1930) and Fernand Gault (1873-1936), who were the first to provide a systematic description of that disorder. Here we re-present a very early description of a case of NMO by a Polish physician, Adolf Wurst, which appeared in 1876 in Przeglad Lekarski, one of the oldest Polish medical journals. This report predates Devic and Gault's seminal work on NMO by more than two decades. The patient, a 30-year-old woman, subacutely developed simultaneous bilateral optic neuritis with papilloedema and bilateral blindness and transverse myelitis with severe paraparesis, anaesthesia, and bladder and bowel dysfunction. At last follow-up, one year after onset, she had recovered except for a residual spastic gait and some visual deficit on the right side. Of note, this is the first known case of NMO in a Caucasian patient ever reported outside Western Europe.

'Spinal amaurosis' (1841). On the early contribution of Edward Hocken to the concept of neuromyelitis optica.

While the history of classical multiple sclerosis has been extensively studied, only little is known about the early history of neuromyelitis optica (Devic's syndrome). Here we discuss a forgotten report by Edward Octavius Hocken (1820-1845) published in The Lancet in 1841. Hocken's report is important from a historic point of view for two reasons. Firstly, apart from a French language report by Antoine Portal, no earlier case of spinal cord inflammation and amaurosis is known. Secondly and much more importantly, Hocken, who upon his untimely death at the age of just 25 years was honoured by his contemporaries as a "precocious talent" of "very early reputation", in that article propagated the novel concept of 'spinal amaurosis', i.e. the concept of acute amaurosis and spinal cord disease being pathogenetically connected. Hocken's ideas predate Devic and Gault's seminal works on 'neuromyelitis optica' by more than 50 years.

Computer-based diagnosis of illness in historical persons.

Retrospective diagnosis of illness in historical figures is a popular but somewhat unreliable pastime due to the lack of detailed information and reliable reports about clinical features and disease progression. Modern computer-based diagnostic programmes have been used to supplement historical documents and accounts, offering new and more objective approaches to the retrospective investigations of the medical conditions of historical persons. In the case of King George III, modern technology has been used to strengthen the findings of previous reports rejecting the popular diagnosis of variegate porphyria in the King, his grandson Augustus d'Esté and his antecedent King James VI and I. Alternative diagnoses based on these programmes are indicated. The Operational Criteria in Studies of Psychotic Illness (OPCRIT) programme and the Young mania scale have been applied to the features described for George III and suggest a diagnosis of bipolar disorder. The neuro-diagnostic programme SimulConsult was applied to Augustus d'Esté and suggests a diagnosis of neuromyelitis optica rather than acute porphyria with secondarily multiple sclerosis, as proposed by others. James VI and I's complex medical history and the clinical features of his behavioural traits were also subjected to SimulConsult analysis; acute porphyria was rejected and the unexpected diagnosis of attenuated (mild) Lesch-Nyhan disease offered. A brief review of these approaches along with full reference listings to the methodology including validation are provided. Textual analysis of the written and verbal outputs of historical figures indicate possible future developments in the diagnosis of medical disorders in historical figures.

The history of neuromyelitis optica.

The discovery of a novel serum autoantibody (termed NMO-IgG or AQP4-Ab) in a subset of patients in 2004 has revived interest in neuromyelitis optica (NMO). While the history of classical multiple sclerosis has been extensively studied, only little is known about the history of NMO. In the present article, we provide a comprehensive review of the early history of this rare but intriguing syndrome. We trace the origins of the concept of NMO in the 19th century medical literature and follow its evolution throughout the 20th and into the 21st century. Finally, we discuss recent proposals to revise the concept of NMO and explain why there is indeed a need for a more systematic and descriptive nomenclature.

On the contribution of Thomas Clifford Allbutt, F.R.S., to the early history of neuromyelitis optica.

The term neuromyelitis optica was coined by Eugène Devic and Fernand Gault in 1894 and refers to the co-occurrence of optic neuritis and myelitis. Neuromyelitis optica (NMO), regarded for many decades as a clinical variant of multiple sclerosis (MS), has only very recently been recognized as a disorder in its own right with distinct pathogenesis, prognosis, and treatment. While the history of classical MS has been extensively studied, only very little is known about the early history of NMO. Here we re-present three forgotten early reports on patients with possible NMO by the later Cambridge Regius Professor of Physic Thomas Clifford Allbutt (1836-1925). To the best of our knowledge, these reports have never been cited before and were also overlooked by Devic and Gault in their seminal review of NMO. One of these reports is likely to correspond to the case briefly mentioned in Allbutt's lecture "On the Ophthalmoscopic Signs of Spinal Disease", published in The Lancet in 1870, which was until very recently considered the first account of NMO in the Western literature. In addition, we discuss the question of Allbutt's primacy in the description of NMO as a syndrome, Allbutt's ideas on the pathogenetic relationship of spinal cord and optic nerve damage, and the reception of those ideas in the medical literature of the nineteenth century.

The case of the Marquis de Causan (1804): an early account of visual loss associated with spinal cord inflammation.

The recent discovery of disease specific and pathogenic autoantibodies in neuromyelitis optica (NMO, Devic's disease) has revived the interest in this intriguing yet often devastating condition. While the history of classic multiple sclerosis has been studied extensively, only very little is known so far about the early history of NMO. Here we discuss a now forgotten report by the famous French anatomist and pathologist Antoine Portal (1742-1832), first physician to Louis XVIII and founding and lifelong president of the Académie Nationale de Médecine. Portal's report, which fascinated some of the most renowned 19th century pioneers in the field of neurology but fell into oblivion later, represents the first account of visual loss in a patient with spinal cord inflammation but no brain pathology in the Western literature known so far--published more than 60 years prior to Thomas Clifford Allbutt's much cited note on a patient with myelitis and a "sympathetic eye disorder".

'Noteomielite' accompanied by acute amaurosis (1844). An early case of neuromyelitis optica.

So far, only very little is known about the early history of neuromyelitis optica (Devic's syndrome). Here, we discuss a then widely recognized but now forgotten 1844 report by the Genoese physician Giovanni Battista Pescetto (1806-1884) on a 42-year-old man, who simultaneously developed acute amaurosis and cervical myelitis. Pescetto's report represents the earliest account of a case of neuromyelitis optica in the Western literature known so far.

An early case of neuromyelitis optica: on a forgotten report by Jacob Lockhart Clarke, FRS.

We discuss a forgotten report by the famous British neuroanatomist, neuropathologist and neurologist Jacob Augustus Lockhart Clarke (1817-1880) about a 17-year-old girl with bilateral optic neuritis and longitudinally extensive transverse myelitis. This report, which appeared in 1865, i.e. 15 years prior to Wilhelm Erb's much-cited paper on the coincidence of optic neuritis and acute myelitis, represents the first known account of a case of Devic's syndrome or neuromyelitis optica in the English-language medical literature.

The borderland of neuromyelitis optica.

Neuromyelitis optica (NMO), also known as Devic's disease, is an emerging clinical and pathological entity originally thought to be a variant of multiple sclerosis. Characterised by episodes of demyelination confined to the optic nerve and spinal cord, the discovery in such patients of antibodies to the aquaporin-4 channel has been largely responsible for defining the phenotype to date. Recently it has become clear that there is a borderland where there are patients with optic neuritis-only and myelitis-only forms of the disease, and these may be seronegative in the early phase. We describe two cases of optic neuritis-only NMO, and explore the current understanding of the diagnosis and spectrum of NMO disorders.

Wilhelm Uhthoff: a phenomenon 1853 to 1927.

The name of Wilhelm Uhthoff is associated with several aspects of progress in neurology in the 19th and 20th Century but is best known for his contribution to the pathophysiology of transient visual disturbance. Uhthoff was born on 31 July 1853 in Klein Warin, Germany and died on 21 March 1927 in Breslau, Germany. This ophthalmologist described for the first time that increased body temperature from physical exertion may lead to transient impairment of vision in patients with multiple sclerosis.