ENCEFALITE LETARGICA PDF

The role of influenza in the etiology of EL was vigorously debated until It is notable, however, that the unitarian camp were largely reactive in their argumentation; while the influenza skeptics provided detail descriptions of EL and the features they argued to be unique or at least unusual, influenza supporters focused on sequentially refuting the evidence of their opponents. The impression which emerges from this debate is that the individual features identified by the skeptics were not absolutely pathognomic for EL, but, on the other hand, their combination in one disorder had not previously been described for any other disease. The adage that the pathologist has the final word regarding diagnosis is particularly pertinent when considering neurological disease.

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The role of influenza in the etiology of EL was vigorously debated until It is notable, however, that the unitarian camp were largely reactive in their argumentation; while the influenza skeptics provided detail descriptions of EL and the features they argued to be unique or at least unusual, influenza supporters focused on sequentially refuting the evidence of their opponents.

The impression which emerges from this debate is that the individual features identified by the skeptics were not absolutely pathognomic for EL, but, on the other hand, their combination in one disorder had not previously been described for any other disease. Encephalitis lethargica EL L is a neuropsychiatric disorder which in recent times has occurred only once in epidemic form: Between and it was reported from around the world, but was most prominent in Europe, North America and the Soviet Union.

Despite intensive investigations throughout the s, the etiology of the disorder was never conclusively determined. Even in its time, EL was remarkable in this obdurate refusal to divulge its origins.

By the s, the influenza virus had been discovered and was being investigated, as were the arthropod-borne viruses arboviruses responsible for other encephalitides first described in the wake of the EL epidemic.

EL, however, defied elucidation. By the time EL began to fade from public consciousness, two major etiological theories had established themselves, without either being able to claim victory in what was at times as much a nationalistic as a scientific controversy: those who regarded the herpes virus as the major pathogen of EL, and those who assigned this role to streptococcal infection.

Two distinct but related questions are being addressed in these papers:. From the outset, the relationship between EL and pandemic influenza had been subject to lively discussion. Constantin von Economo — , author of the first paper on EL, was convinced that EL was a disorder sui generis , a distinct condition and not simply a neurological response to influenza Economo a ; ; a , pp — Some who shared his view nevertheless suspected that EL and influenza might be somehow related, just as measles and whooping cough were then regarded as allied disorders as they often occurred together in a population.

But as fresh EL cases continued to be diagnosed despite the passing of the influenza pandemic, the unitarian position lost ground, and was revived only after EL itself appeared to have vanished. In Reimert T. Ravenholt and William H. In the first, the distributions of influenza-pneumonia deaths by month of death and of EL deaths by month of illness onset in Seattle-King County northwest USA between and were compared. The Ravenholt-Foege data are cogent, but not compelling.

Given the difficulties associated with establishing what constituted authentic EL in Western countries, it would be speculative to interpret all fa-aniniva as genuine EL, particularly in the absence of neuropathological data.

The data for Seattle are stronger in this respect, but are nevertheless subject to a problem recognized by the authors: the data include only a subset of all EL cases, those with a fatal outcome. The correlation established by these authors would be more convincing had the number of cases of each disease, rather than deaths , been analyzed. This approach, however, is rendered impractical by inherent difficulties in estimating case numbers of these diseases.

EL might be reported early in its course by an informed physician, but more frequently following the later presentation of post-encephalitic sequelae, or even post mortem on the basis of neuropathology.

In Australia, for example, the reported EL deaths for a given period often exceeded the number of reported cases Foley, unpublished data. It was also generally recognized that a proportion — perhaps the majority — of EL infections were undiagnosed or unreported see, for example, Neel ; Amsel The Ravenholt-Foege data are thus interesting, but not conclusive.

This is especially the case as the literature of the s is replete with reports in which a discernible link between EL and influenza had been explicitly excluded. There is, however, even stronger evidence for an etiological distinction: the long-term dissonance between the rhythms of EL and influenza epidemiology. Particularly significant is that EL cases were reported in numbers before pandemic influenza cast its shade over Europe.

Further cases from —17 had been unrecognized and were only diagnosed retrospectively for example: Hall , p 7. Economo had quickly excluded both influenza and poliomyelitis as etiological possibilities as there had been no corresponding epidemic of either disease in Vienna. These early EL reports all pre-date the arrival in Europe of the first wave of pandemic influenza in May , and occurred long before the deadly second wave of August-November The third and final wave of the influenza pandemic receded from Europe in early , before EL had achieved its peak in most countries.

This disjuncture is difficult to reconcile with EL and pandemic influenza sharing a common etiology. Even should one accept his argument, some alignment between the rise and fall of influenza and EL would be expected; it was the lack of such a correlation between EL and poliomyelitis data that an etiologic link between these two considerably more similar disorders had been rejected. The peak year for EL differed from place to place. Influenza throughout the period in question, however, was more consistent in its ebb and flow across Europe, with the consequence that no correlation between occurrences of the two disorders is evident.

These epidemiological discrepancies cannot be ascribed to an interval between infection with influenza and the development of EL. There was typically a symptom-free interval between the acute and chronic stages of EL, but proposing that a similar interval existed between influenza infection and symptomatic EL is purely speculative.

This is particularly true in light of the common finding that post-influenzal nervous symptoms manifested themselves within a few weeks of the onset of influenza for example, Marcus Finally, while recidivism was a noted feature of influenza, relapses generally involved the return of catarrhal symptoms and prostration, not the evolution of a completely new clinical picture Jordan c , pp f; Thomson et al , pp — Evidence for the independence of EL from influenza outbreaks increased through the s.

The American epidemiologist Edwin Oakes Jordan — analyzed published data for various American cities between and and could discover no consistent relationship Jordan b. Similarly, the course of the major British epidemic of , the greatest single outbreak in the history of EL, was not paralleled by changes in influenza statistics:.

In some places the peak of influenza measured by reported mortality anticipates that of encephalitis reported cases by many weeks, as in London, while in others, as in Manchester, encephalitis begins to wane before influenza reaches its highest point. There were also areas where the rise and fall of EL and influenza were inversely related, and the case of Portugal where EL preceded influenza Jorge In the United States the influenza pandemic moved with incredible speed from east to west, whereas EL required almost a year to cover the same distance.

The epidemiological situation was nicely encapsulated by David and Robert Thomson Pickett-Thomson Research Laboratory, London , who concluded their discussion of EL in an encyclopedic review of influenza thus:. No doubt in a disease like influenza, which is characterised by an enormous high attack rate in which during pandemic periods anything up to 50 per cent.

In this respect it has often been observed that the first symptoms of general paralysis of the insane appeared to follow an attack of influenza.

In summary: the temporal overlap between pandemic influenza and EL was limited to the height of the influenza pandemic; EL was extant in parts of Europe both before and long after this window. Further, there is no evidence to suggest that EL occurred in North America before it appeared in Europe, but this may well have been the case for influenza Barry ; but see Oxford et al Further, there was no recognizable correlation between the relative impacts of EL and influenza in particular countries or regions.

This cannot be attributed to poor record-keeping, as investigators diligently sought cases in non-Western countries in the hope that they might illuminate the EL problem. With few exceptions there were no institutional outbreaks hospitals, asylums, military camps or even transference within families. The Prague pathologist Franz Lucksch — reported that was no evidence in Germany for even a single person-to-person transmission of EL Lucksch Silent carriers may have played a role in its dissemination, as in poliomyelitis, but would still not entirely overcome the epidemiological difficulties which encumbered the unitarian position see, for example, Levaditi ; Stiefler , pp — Even transplacental transmission was more the exception than the rule, and the few cases reported impressed some observers as evidence for the specificity of the EL virus Jorge Influenza was a very public invader, while EL was much stealthier; those who contracted influenza generally returned to full health within months, whereas survival of the acute phase of EL was often the segue to life-long debility.

The preferred age of onset by EL did not vary significantly throughout the s, with those aged 12 to 35 years most at risk. EL generally spared infants to a greater extent than did influenza Almasio, Finally, influenza played no favorites with respect to gender , but it was widely reported that there were up to twice as many male as female EL cases, although the prognosis in the latter tended to be worse Stern The second major argument for the unitarian hypothesis is that EL-like disorders had been reported during previous influenza epidemics.

Medical journals of the late 19th century teemed with cases of influenza sufferers reportedly crippled physically or psychiatrically by the disorder. It might therefore seem reasonable to suppose that EL was simply chronic influenza in yet another nervous guise. He described three major forms of influenza — nervous, gastro-intestinal and catarrhal, according to their most prominent features — and noted that, in any particular epidemic year, one of these forms tended to dominanate to the relative exclusion of the others Althaus Nervous symptoms linked to influenza ranged from headache, muscular pain and weariness to paralyses of varying degree, as well as conditions resembling fully elaborated psychoses.

Post-influenzal encephalitis was described in detail at this time by the respected German clinician Otto Leichtenstern — in his monograph on the pandemic Leichtenstern characterized this encephalitis as:.

The clinical picture is often so similar to apoplexy caused by brain hemorrhage or embolism with obligate hemiplegia that it is only the usually young age of the patient, the acute onset with chills, the concomitant high fever and the occurrence of such cases during an influenza epidemic which permits distinction from a normal case of apoplexy Leichtenstern , p He specifically noted that encephalitis grippalis often attacked the cerebral motor zone, and that there had been no confirmed cases in which:.

All reported cases of nuclear oculomotor paralysis had developed after the influenza had run its course, usually a considerable period afterwards, without fever or notable cerebral symptoms, and thus along the lines of a degenerative neuritis or neuronucleitis Leichtenstern , p f. The onset of EL, in contrast, was usually less tempestuous, and EL rarely developed during a well-defined bout of influenza or pneumonia.

The German neurologist and leading EL expert Felix Stern — addressed this difference in , attaching a brief discussion of influenza encephalitis as an appendix to his comprehensive depiction of EL:. Influenza or epidemic encephalitis? The difficulty is relative small if massive encephalitic symptoms are presented in the course of influenza or of an influenza-like disease.

Influenza encephalitis is, in any case, now quite rare; otherwise one can orient oneself diagnostically according to the two poles: Either frequently apoplectic symptoms erupt suddenly at the height of severe catarrhal influenza, Jacksonian fits and gross focal losses, such as hemiplegia, aphasia and even hemi-cerebellar disturbances develop, the cerebrospinal fluid is sometimes clear, or containing blood; then one thinks of focal influenza encephalitis.

When the ailment commences with what is usually milder influenza or only after an influenza-like complaint, less abruptly and primarily in the form of brainstem symptoms, then one should suspect epidemic encephalitis Stern , p The somnolence persisted for a period of hours to weeks, and could be associated with cataleptic or catatonic symptoms. Nevertheless, it was often invoked by later proponents of the unitarian position, who, however, often confused this form with the more common influenza encephalitis.

The best described occurrence of somnolence associated with influenza was lanona. Whatever the truth, the disease caused anxious excitement in affected areas and in the popular press, where it was described as an extreme somnolence which often terminated in death review: Longuet Official investigations by the Italian and Austrian governments concluded that nona was simply a form of meningo-encephalitis associated with the then prevalent influenza.

After the disorder was gradually forgotten by the medical community, but it survived in the memories of those who had experienced it; Economo, for example, was reminded by his initial EL cases of tales of the nona related by his grandmother. Too little was known about the nona to validly infer its identity with EL. The published medical literature was limited to a few cases; official circles dismissed it entirely. The only specific link between this curiosity and EL was the deep somnolence which drew puzzled attention, and even this similarity was more misleading than enlightening: it was very difficult to rouse a nona patient from sleep, whereas this was remarkably easy in EL.

None of the other features associated with acute EL, most notably the ocular symptoms, were described in the scant literature devoted to the nona. The ascertainable situation regarding EL-like disorders during the s influenza pandemic was later summarized by Edwin Jordan:. In point of fact, no unusual prevalence of encephalitis appears to have been noted in the United States or in Northern Europe during the influenza pandemic of —, and the form of encephalitis that was occasionally observed seems to have been different clinically and anatomically from the present epidemic disease Jordan b.

This event was much cited by many during the EL period, but few appear to have noticed that Economo had been quick to correct his own early reference to this event. He admitted that his source had misconstrued the Latin original, in which the author noted that he himself had not seen evidence of the somnolence apparently reported elsewhere cf. Economo a , p 13 and Camerarius Although isolated cases of parkinsonism attributed to influenza have been described since the s pandemic, and despite the fact that the influenza A virus exhibits a certain tropism for the substantia nigra in laboratory animals Mattock et al ; Takahashi et al ; Yamada et al ; Casals et al ; Mihara et al ; Takahashi and Yamada , EL-like symptoms have not been associated to any degree with influenza.

A causal association between the two disorders must therefore contingently imply that influenza between the World Wars was uniquely capable of eliciting EL in humans. Attempts to find evidence in EL brains of infection with the influenza virus such as the presence of specific nucleic acid have generally met with negative results review: McCall et al Even today, influenza virus and genetic material can only rarely be isolated from cerebrospinal fluid CSF or autopsied brain material incases of presumed influenza CNS infection Johnson , pp f.

An Austrian study of influenza encephalopathy found that even highly sensitive PCR techniques could ascertain its presence in CSF in only 1 of 18 cases Steininger et al Others isolated a variety of cocci, but could not be certain that their presence was not the result of secondary infection Ribbert ; Parsons

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Encephalitis lethargica

Encephalitis lethargica is an atypical form of encephalitis. The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless. Nearly five million people were affected, a third of whom died in the acute stages. Many of those who survived never returned to their pre-existing "aliveness". They would be conscious and aware — yet not fully awake; they would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect or desire; they registered what went on about them without active attention, and with profound indifference. They neither conveyed nor felt the feeling of life; they were as insubstantial as ghosts, and as passive as zombies.

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