Encephalitis lethargica: a dying fall (un-refereed manuscript)

This is the author’s original un-refereed manuscript as submitted for review 20th May 2019. The revised manuscript was published in Brain 29 July 2019 as the original place of publication:

Encephalitis lethargica: a dying fall. Michael S Zandi, PhD FRCP. Brain, awz228, https://doi.org/10.1093/brain/awz228 Published: 29 July 2019 Section: Dorsal Column https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awz228/5540302

Perceptible flames of movement ignite on her left-hand side, in the middle of the densest thickets of akinesia, a paralysis not only of the muscles… but of the will itself – abulia? then flare up one arm, across the shoulders, before exploding into ticcy sparks and so dying away…’ – Will Self. Umbrella. (Bloomsbury Press 2012).

In 1918 the Romanian neurologist and neuropathologist Gheorghe Marinescu (1863–1938) travelled to London to examine the brains of two patients with an ‘obscure disease’. He had been invited by the London Local Government Board, and the brains were held at the Pathological Laboratory of the Maudsley Neurological Clearing Hospital. Marinescu was a pupil of Charcot, and a pioneer from 1898 of the use of cinematography in medicine. He had worked with chronophotographer Étienne-Jules Marey in Paris. His paper with Paul Blocq on symptomatic parkinsonism (due to a destructive tuberculoma) made him an ideal choice for the London Board. Marinescu’s findings were in agreement with those of Constantin Alexander Freiherr von Economo von San Serff (1876–1931). It is von Economo whose name has stuck in association with the heterogeneous and curious syndrome of encephalitis lethargica. Von Economo coined the term encephalitis lethargica in his 10 May 1917 article of the same name published in Wiener klinische Wochenschrift. Working as assistant physician, he had recognised cases among a torrential pouring of injured soldiers with head injuries. He studied medicine against his family’s wishes, trained in Paris, Nancy, Munich and Berlin, and focussed on the midbrain with Karplus. A keen pilot, he volunteered for military service in 1914 but returned to medicine in Vienna after his younger brother was killed. Foley writes that von Economo’s knowledge of and facility with the midbrain, allowed a ‘divine spark of intuition’ that allowed him to pick out seven patients he saw early 1917. Von Economo had thought the drowsiness and sleepiness was reminiscent of the nona associated with the 1889/90 influenza, and the ophthalmoplegia and hyperkinetic forms of encephalitis lethargica helped this new entity take shape.

Why another book on encephalitis lethargica? The history of encephalitis lethargica is the history of early 20th Century neurology, and one shaped by the Great War. Paul Foley attempts, successfully, in this book to bring a new detailed and historical account of the primary literature on encephalitis lethargica. At 1083 pages and in its heavy hardback-form the book is a colossal monument to encephalitis lethargica. Foley’s historical training and emphasis makes this a rich book to dip into to. Foley’s Doctoral dissertation; Beans, roots and leaves: A History of the Chemical Therapy of Parkinsonism (Marburg: Tectum 2003) demonstrates his systematic method. In his doctoral thesis, Foley tackles in turn parkinsonism before Parkinson’s 1817 pamphlet; early therapies including cabbage, beaver testes, sage; and then turns most of his attention to alkaloid therapies and the L-DOPA story. But the most readable and lasting sections of Foley’s 2018 book on encephalitis lethargica are the brief fragments of lives of the individuals affected and those trying to solve the problem, and the opening up of the world of neurology, psychiatry, scientific advances and social care in that dramatic upheaval across Europe. There are timeless lessons here for us all. Foley says that he wrote this book as encephalitis lethargica had ‘been neglected in terms of methodical medico-historical investigations’.

Foley takes us through the 1915 origins and emerging 1919 epidemic (and the later spike in the UK in 1924), the nature of acute and chronic forms, psychiatric manifestations, neuropathology, speculations on causation. Foley tackles the issue of who described encephalitis lethargica first, with jostling between Jean-René Cruchet (1875–1959), von Economo, Henning, Obregia, Urechia and others. Cruchet had described cases of epidemic subacute encephalomyelitis from Commercy, Verdun and a majority from Bar-le-Duc from at least 1915, and Foley interprets Cruchet’s hasty removal to war in 1917 and the resulting abridged reports of these cases to lead to the prominence of von Economo’s paper. Cruchet’s cases were more heterogenous than the Vienna cases. Von Economo’s pathologist colleague Richard Wiesner provided support for encephalitis lethargica being a polioencephalitis with reddish-gray discolouration and inflammation of the brainstem grey matter. As expected given Foley’s background, the descriptions of post encephalitic parkinsonism are treated well. Sicard and Paraf for the first time described, at the Société de Neurologie in Paris in May 1920, cases of parkinsonism in individuals who had recovered from encephalits lethargica. The contributions of Strümpell (‘amyostatic symptom complex), Bostroem (volition and a syndromic approach versus that of disease), and Kudelski (hyperkinetic forms) are each considered in their historical context, and the reader is left feeling the inventiveness and the ideas form as if there at the time.

As for the neuropsychiatry of encephalitis lethargica, the prevalence of psychosis is low, and the symptoms of encephalitis lethargica considered alike to delerium tremens, and often resolved within a few months of the illness course. Pfaundler (1872-1947) from Munich described 21 children with profound sleep reversal or loss (‘agrypnia’) and Folley showcases a catalogue of behavioural disorders seen in adults and children. The use of leucotomy and lobotomy was supported leaving ‘immature but socially acceptible personalities’ until the 1950s. The psychiatric sequelae of chronic encephalitis lethargica are discussed, with emphasis on apathy, compulsive and obsessive symptoms, with contemporaneous descriptions of attempts to explain, often in comparison to schizophrenia and other psychiatric diseases (e.g. Bostroem vs Bonhoeffer (loss of affectivity) vs Staehelin (brainstem disease alone sufficient). Examples from the primary literature are collated and pertinent cases presented to back up the points made. For a discussion on obsessive symptoms in encephalitis lethargica a case is given described by Macdonald Critchley (1900-1997) of a 27 year old man who had ‘developed mild post encephalitic parkinsonism from 1934, having suffered encephalitis lethargica in the great outbreak of 1924’. Critchley presented the case at the Royal Society of Medicine in 1947:

He would be compelled to repeat to himself a number of rhymes or verses of poetry. He was also apt to identify himself in the cinema with the characters on the screen and this feeling would persist for a while even after leaving the theatre. A third feature of his case, which is now a thing of the past, was the occurrence of bouts of rapid noisy breathing. The outstanding characteristic at present is his palilalia whereby he repeats the last few words of a sentence over and over again, perhaps as many as 15 times. But if requested to narrate a preformed speech pattern (days of week, &c.) or to recite something he knew by heart, no palilalia would occur… A final interesting feature is his tendency to continue unduly any repetitive act, such as hammering a nail, combing his hair, or brushing his teeth. Whether this motor perseveration represents a real palipraxia, or whether his involuntary tremor in such circumstances takes control of his volitional movement, is uncertain.

Foley’s book complements the shorter book edited by Joel Vilensky (Oxford, 2011), which stands in the new light cast from Foley’s 2018 book as a lighter companion or introduction. The Vilensky collection included contributors Sid Gilman, Roger Duvoisin, Lindsay Anderson, Judith Cameron, Jennifer Cook, Sherman McCall, Dana Marlowe, Ravil Mukhamedzyanov, Keith Josephs, Hope Owens, Richard Steele, The Sophie Cameron Trust and Paul Foley. Vilensky’s 2011 book brought to life personal accounts of the ‘sleepy sickness’, including the account of ‘X’, a medical practitioner of 49, with a febrile illness followed by ‘curious delusions concerning his anatomical configuration… that he possessed more than one entrance to the pharynx… He associated his legs with those of a grand piano’. X returned to work as a general practitioner the following year, though with persistent diplopia and dysphagia. The Vilensky monograph described in detail the original seven cases of von Economo’s report, twenty eight forms of encephalitis lethargica from the epidemic period including juvenile pseudopsychopathia, the contributions of Dr Josephine Bicknell Neal (Matheson commission; figure 3.), with contribution to the Matheson Commission survey report in 1929, and her 1942 publication “encephalitis: a clinical study”. Matheson a wealthy individual who contracted EL and commissioned the report. There is mention of Kenneth Kroker’s 2004 theory that EL was overdiagnosed by New York neurologists in an attempt to help neurology survive as a speciality. Foley contributed to Vilensky’s book with a survey of pre-1917 sleep-related disorders thought to resemble EL, including mal de mazucho (Pereira 1558), cataphora (Boissier de Sauvages 1763), periodic remittent nervous fever (Frank 1844), and the Turin epidemic of febbri perniciose encefaliche (Bellingeri 1825), followed by reporting of heterogenous cases, some with a likely functional basis (e.g. Chomel’s 1856 descriptions in Paris, subsequent cases in Paris of ‘hysterical sleep’ (Löwenfeld 1889) and a curious prevalence of taphephobia (the fear of being buried alive). An evaluation of Uhthoff’s 1890 influenza related ptosis and accomodation paralysis in the absence of sleepiness leads Foley to conclude that these cases were not EL. In 2011 there is speculation on aetiology and a thorough review of neuropathology including contibutions from Buzzard and Greenfield (1920), Alexander (1921), Bassoe and Hasssin (1919), Hall (1924), Wilson (1940) and Stevenson (1942). The phenomena of oculogyric crises and post-encephalitic parkinsonism, theories of transmissibility, and Oleh Hornykiewicz 1960 article on dopamine depletion in caudate and putamen in Parkinson’s Disease and post-encephalitic parkinsonism are discussed with detailed presentations of the subjects in Oliver Sacks’ book Awakenings (1973).

What evidence has emerged since Vilenksy’s book? First of all, the stories started in Vilensky’s book are expanded on and deepened. In Foley’s book there is welcome though brief discussion of encephalitis outside Europe or America, with possible cases of encephalitis lethargica in Yunnan-fu (now Kunming, central Southern China) in 1915, and Australian ‘X disease’ discussed. There is a sense of further lost stories from around the globe that are not represented in this book. Beyond detailed historical review, Foley offers an analysis of theories of what caused encephalitis lethargica from toxins, to host susceptibility, Wiesner’s diplostreptococcus, Rosenow’s streptococcus, herpes, and of the development of lab and passive-transfer animal experimentation, analysis of new outbreaks and ‘novel diseases’ like the N-methyl D-aspartate receptor antibody encephalitis syndrome. Foley concludes that ‘There have been no reported cases that can be confidently ascertained as genuine EL since the 1970s’. Whether samples of encephalitis lethargica brains will emerge and be sequenced to allow us to identify the causes remains a possible hope. The descriptions of the social problem of encephalitis lethargica particularly for children is a strength of this book. Prejudice and pessism at an institutional level in social care were significant hurdles, as encephalitis lethargica was considered a disease which could cause ‘moral insanity’ and ‘make criminals’. Mis-labelling of symptoms during the war, and the difficulties of attribution and the ‘legal ramifications of the interval’ between a diagnosis of encephalitis lethargica and subsequent post encephalitic parkinsonism led families to fight for war pensions and in one case a pension was granted seventeen years after the presumed acute encephalitis and six years after death. The Northern Hospital (Highlands, Winchmore Hill) Post-Encephalitis Unit opened the 13th November 1925, with Samuel Alexander Kinnier Wilson (1878-1937) the consulting neurologist. Oliver Sacks highlighted the benefits of intensive therapy, attention and holistic rehabilitation seen at the Highlands Hospital (succeeding Winchmore Hill), in comparison with the Beth Abraham in the Bronx at that time. Reform through legal challenges was taken up by Ammon and others and the stories here are instructive.

Chilling fragments of personal stories last in the memory. Encephalitis lethargica sufferer, Alois Schuchardt (1910–1941) was sent to the carbon dioxide gas chamber at Hadamar. Martin Bader (1901–1940), whose story survives from his father’s accounts, murdered at Schloss Grafeneck (among ten thousand that year – and of at least fifty five individuals transferred from the Schussenried sanatorium), his ‘encephalitis epidemia [sic]’ marked out for special attention as his salient feature, and he was deemed by consequence ‘incapable of work’. Bodo S. from Berlin, nick-named ‘Zeitlupe’ (slow-motion) had a documented biography with onset of encephalitis lethargica aged 12. With a course of marked physical decline and parkinsonism he had retained cognition enough to be a reliable witness in the trial of staff at the Waldhof children’s home. His account survives in detail including the proposition of sterilisation, and subsequent decline despite high dose atropine therapy. Later he was killed at Brandenburg on the Havel. Operation Brandt (1943–1945) was the euthanasia of individuals in which some with encephalitis lethargica numbered in an attempt to ‘free beds in sanatoria’. Foley’s account brings to life some of the lost researchers of encephalitis lethargica, including Felix Stern (1884–1941; figure 1). Stern was born in Groß-Glogau (Głogów) and practiced neurology in Göttingen, self-funded. Stern had a meticulous approach and is the subject of a promised biography by Foley. He ‘had examined more than 200 cases of war service pension applications involving alleged encephalitis lethargica’. ‘Among the first professors to be “cleansed” from Göttingen University’, by accounts Stern took his own life in 1941 before ‘scheduled transportation’.

The section on films, books and monographs on encephalitis lethargica is a useful comprehensive resource. Neurological films from Kleist, Herz, Putnam, and Stern among others initially presented aspects of the clinical signs and characteristic movements of encephalitis lethargica to the world, but the films also served as a means to analyse movement (Westphal). Newspapers reported and sensationalised the dramatic aspects of the disease, for example, in the Times (1921) a report of suicide after forty eight hours of hiccups, recruitment of a violinist to wake a 29 year old woman with encephalitis in New York. Foley wonders if encephalitis lethargica took the imagination because of a contemporaneous preoccupation with sleep (commonplace fairground attractions based on Dornröschen ‘the Sleeping Beauty’ by the brothers Grimm, Freud’s Interpretation of Dreams”). In the 1982 Peter Hall production of A Kind of Alaska, at the Cottesloe theatre (now Dorfman Theatre at the National Theatre), Judi Dench played the role of Deborah, awakened from encephalitis lethargica. Written by Harold Pinter, the play was based on the illness of actor Muriel “Kit” Hewitt (1907-1942) who, famous for her portrayal of Ophelia, had contracted encephalitis lethargica in 1927. Other literary accounts dissected and analysed by Foley include Agatha Christie’s 1930 The murder at the vicarage, Ivan Korvatskii’s 1927 short story “Letargiia”, Oliver Sacks’s “Awakings” and Will Self’s 2012 Umbrella.

Oliver Sacks recounted in 1983 his struggle to publish in learned medical journals his 1969 accounts of using levodopa in post encephalitic parkinsonism, and how he forged his approach in describing phenomena and the stories of individuals. It is Oliver Sacks who provides a forward to Vilenksy’s book, and concludes in 2011 with the position that we must still take in 2019: that ‘the essential mystery of encephalitis lethargica remains unsolved’. There are no revelations or scientific advances that make Paul Foley’s 2018 book a necessary addition to the number of monographs on encephalitis lethargica. What makes this book necessary is the richness of detail in the accounts of the abbreviated lives of the sufferers of encephalitis lethargica and of the researchers and doctors like Felix Stern.

Michael S Zandi PhD FRCP Encephalitis and neuroimmunology service

National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG

Michael Zandi is supported by the UCLH/UCL NIHR Biomedical Research Centre and the Medical Research Council.

 

Figures:

Figure 1. Encephalitis Lethargica. The mind and brain virus by Paul Bernard Foley. Springer, 1083 pp, £180, 2018, ISBN 978-1-4939-0383-2

References: Foley PB (2003) Beans, roots and leaves. A history of the chemical therapy of parkinsonism. Marburg: Tectum Verlag.

Sacks O. The origin of “Awakenings”. Br Med J (Clin Res Ed) 1983;287:1968

Vilensky JA (edited). Encephalitis lethargica: during and after the epidemic. Oxford University Press 2011.

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  1. https://www.barbican.org.uk/whats-on/2018/event/yto-barrada-agadir

 

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