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Ptosis was a typical sign. The disease then began appearing in increasing frequency throughout the world, with official figures showing peaks of about 10, cases in and Neal , with a possible total mortality of , cases Ravenholt and Foege during the entire epidemic period, which lasted until about Sporadic reports of encephalitis lethargica cases have continued to appear since then.


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Kroker convincingly argued that curing encephalitis lethargica became the foremost aim of American neurology especially New York City neurologists during this period, and that the secondary goal of this effort was to increase significantly the prominence and potential of American neurology Kroker Thus, there may have been some political aspects to the large number of encephalitis lethargica diagnoses. This possible overdiagnosis was also noted during the epidemic period Ford Even after years, many issues related to encephalitis lethargica remain elusive.

Authors are still struggling to answer the questions—what causes it? How is this disease transmitted? Could an epidemic of encephalitis lethargica happen again? Because there was no pathognomonic sign or symptom, or diagnostic test, encephalitis lethargica was diagnosed based on the exclusion of other conditions.

It seems reasonable that encephalitis lethargica was a heterogeneous group of conditions, rather than a unitary entity, that presented with unexplained neurological symptoms. Post-mortem examinations of alleged encephalitis lethargica cases during the epidemic period sometimes revealed an alternate diagnosis such as tubercular meningitis, cerebral tumours, meningismus, or other neurological pathology.

However, due to the variability in neuropathology, even a post-mortem diagnosis of encephalitis lethargica could not be verified. There was no overall sex predilection, although specific outbreaks had higher incidences in one sex or the other. There were higher incidences of encephalitis lethargica in large cities and industrial centres than in rural areas; however, this may have been due to these areas having larger populations and better diagnostic facilities than the rural areas.

After years of research, the aetiology of encephalitis lethargica is still unknown. Although a number of theories have been proposed, there are two main categories of plausible aetiologies: More recently, however, there is evidence to support a third theory: It is also possible that encephalitis lethargica has multiple causes, which could explain the wide array of aetiological hypotheses that have been advanced over the years. When confronted with his first cases of encephalitis lethargica in , von Economo speculated on the cause of the disease.

He ruled out any toxic process such as food poisoning because patients exhibited no gastrointestinal disturbances. Furthermore, there was often only a single case within a household, and some victims were exclusively breast-fed infants. He also ruled out poison gas, typhoid, polio, and syphilis as causes of the disease.

Noting that all of the patients had presented with an influenza-like prodrome, and considering the contemporaneous Spanish influenza epidemic, von Economo considered the possibility that encephalitis lethargica was an influenza encephalitis. Indeed, there have been prior accounts of sleeping sickness or encephalitis associated with influenza epidemics. Although there were neuropathological differences in the brains of patients who died of encephalitis lethargica compared with those who died of influenza encephalitis, von Economo could not deny that there seemed to be an epidemiological connection between influenza and encephalitis lethargica.

Based on experimental studies using brain tissue from deceased patients, von Economo concluded that encephalitis lethargica was caused by an infectious virus. He, and other clinicians at the time, proposed that influenza might predispose a person to infection with encephalitis lethargica, possibly by increasing the permeability of the nasal mucous membranes allowing the encephalitic virus to enter more easily. In the years since the epidemic, studies have both supported and refuted the influenza aetiology.

Modern experimental studies have examined the association between influenza and encephalitis lethargica using serology, which examine antibodies against influenza present in the serum of postencephalitic patients; reverse transcriptase polymerase chain reaction RT-PCR , which tests for influenza viral RNA in brain tissue samples, and immunohistochemistry, which uses anti-influenza antibodies to search for influenza proteins in brain tissue samples.

Although the findings in the majority of studies refute the influenza hypothesis, this aetiology would provide a convenient explanation for the disappearance of encephalitis lethargica because the influenza strains that caused the influenza epidemic ceased human circulation sometime before During the epidemic period, a massive search was undertaken to identify the causative agent of encephalitis lethargica. Brain tissue, CSF, blood, and nasopharyngeal fluids from encephalitis lethargica victims were injected into various animal species in attempts to develop an animal model of the disease.

Most experiments were largely inconclusive and no recognized strain of virus could be identified. Writing in , Josephine B. Neal, a neurologist with expertise in bacteriology, dismissed much of the experimental work that had been conducted, proposing instead that encephalitis lethargica was most likely caused by an unidentified virus. Neal had been appointed by the Matheson Commission to direct clinical trials on encephalitis lethargica.


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  • An early 21st century hypothesis proposed by Dale et al. The authors suggested that encephalitis lethargica may be secondary to autoimmunity against basal ganglia and may be a paediatric autoimmune neuropsychiatric disorder associated with streptococcal infection PANDAS disease.

    Dale and colleagues, in a later paper Dale et al.


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    • Anti-NMDA receptor encephalitis is an autoimmune encephalitis that is commonly associated with ovarian teratomas in young females. It has a striking resemblance to encephalitis lethargica in its symptomatology and often begins with an influenza-like prodrome. Similarly, narcolepsy has been found to result from antibodies against aquaporin-4 in hypothalamic neurons. Furthermore, several European countries reported an increase in cases of narcolepsy following influenza vaccination or infection with influenza during the H1N1 influenza pandemic, which could explain the apparent connection between Spanish influenza and encephalitis lethargica following World War I.

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      All of these observations point to an auto-immunological trigger as a potential cause of CNS disorders, and lend additional credibility to the autoimmune hypothesis. In the most recent study on the aetiology of encephalitis lethargica, Dourmashkin et al. This was a carefully conducted study but, unfortunately, has not been replicated, presumably because of the severe limitations on encephalitis lethargica material.

      Current research on the aetiology of encephalitis lethargica is limited by the scarcity and poor quality of existing specimens from the epidemic period and the rarity of new cases. Without another encephalitis lethargica epidemic, we, unfortunately, may never learn the cause of this disease. However, current research on similar CNS disorders such as narcolepsy and anti-NMDA receptor encephalitis could help to shed additional light on this mystery. Without a true understanding of what causes encephalitis lethargica, it is also difficult to determine how it is transmitted.

      There are numerous, often conflicting, theories regarding how the disease was spread. Some documented cases from the epidemic period provide substantial evidence that encephalitis lethargica was contagious, but these cases seem to be the exception rather than the rule. One of the most convincing examples was the outbreak of encephalitis lethargica at the Derby and Derbyshire Rescue and Training Home for girls in August Within a period of 2 weeks, 12 of 21 girls and women in the house were affected and six died within 10 days of onset.

      A thorough investigation of the outbreak was conducted by Dr A. Salusbury MacNalty, a specialist in epidemiology, who concluded that the disease had been transmitted from person to person. While the cases at the Derby school and many others suggest that encephalitis lethargica is contagious, there are just as many anecdotal reports to refute such a claim, as in the case of a family with five children living in a small apartment.

      One child was sick with encephalitis lethargica for weeks while the remainder of the family remained unaffected. Further, among cases in Vienna, cases in Germany, and cases in France, there was little to no evidence of direct transmission of encephalitis lethargica from person to person. Possibly, there may have been multiple strains of encephalitis lethargica, with some strains being highly contagious, and others not.

      It is also possible that encephalitis lethargica was spread by healthy carriers who had some type of innate immunity that others lacked. The Matheson Report lists about 80 treatments for encephalitis lethargica that were used during the epidemic period; however, none of these treatments were particularly effective for treating acute encephalitis lethargica. Approximately one-third of patients died during the acute phase of the illness, one-third survived without sequelae, and one-third showed neurological sequelae.

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      Likewise, there were few treatments for parkinsonism during the epidemic period or in the decades following. Prior to the introduction of l -DOPA in the s, the most effective treatments for parkinsonism were anticholinergic agents. Subsequent to publication of this compendium, an enterovirus was discovered in EL cases from the epidemic. Diplococcus has been implicated as a cause of EL.

      Encephalitis lethargica

      There have been several proposed diagnostic criteria for Encephalitis Lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Modern treatment approaches to encephalitis lethargica include immunomodulating therapies, and treatments to remediate specific symptoms.

      Treatment for encephalitis lethargica in the early stages is patient stabilization, which may be very difficult. Treatment is then symptomatic. Hawes, the curate in Agatha Christie 's book The Murder at the Vicarage , was described as suffering from this syndrome.

      Meshuggah - Lethargica (instrumental cover)

      The disease plays a prominent role in the first issue of Neil Gaiman 's comic book Sandman ; [29] the disease, usually referred to by its nickname "sleepy sickness" and only once by its medical name, is attributed to the imprisonment of the sleep-master Dream in by an occultist. The disease is described in moderate detail in Peter Cummings' novel The Neuropathology of Zombies , in which a proposed mutated form of the disease is considered as the possible cause of a 'zombie' outbreak. Encephalitis lethargica inspired the disease at the heart of Forrest Carr's post-apocalyptic sci-fi novel A Journal of the Crazy Year , and is investigated in the plot as a potential cause of the world-ending outbreak.

      Mentioned as potential disease vector in Darci Stone's award-winning short story Mara's Shadow. Encephalitis lethargica is researched and mentioned in the Canadian television show ReGenesis , in the last few episodes of the second series The disease is involved in one of the episodes in the American science fiction television show Alphas , called a "A Short Time in Paradise" , in which the antagonist causes encephalitis lethargica to afflict his victims.

      Encephalitis lethargica

      Awakenings is a film starring Robin Williams and Robert De Niro which is the dramatization of real-life neurologist Oliver Sacks ' work with encephalitis lethargica patients. The plot of Cemetery of Splendour , a film by Apichatpong Weerasethakul , revolves around soldiers stricken with an epidemic of sleeping sickness. From Wikipedia, the free encyclopedia. This article has multiple issues.

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