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A pandemic of what came to be known as encephalitis lethargica spread starting in the winter of 1916-1917 and continued into the 1930s. Neurological after-effects, namely permanent parkinsonian syndromes and various abnormal movements, permanently disabled the survivors of the one or two million victims, often children or young adults. Among them, a small proportion developed a symptom that was little known up to that point and that is currently exceptional: oculogyric crises; that is, a lateralised, dystonic upward movement of the eyes known as a tonic eye fit. This paper proposes a history of the recognition of this symptom, its inclusion in the neurological nosography, and the pathophysiological hypotheses postulated a century ago.

Pandemics in the early 20th century (and now with SARS-CoV-2) have been dominated by respiratory viruses damaging the lungs. Less is known about abnormal respiratory patterns from brain inflammation. One of the first descriptions of respiratory rhythm abnormalities was seen with an acute attack of epidemic encephalitis (encephalitis lethargica), and reports appeared soon after the original description in 1921. We reviewed these ill-remembered disorders of respiration rate, respiratory patterns, and respiratory tics. Most commonly, dysregulations occurred during the phase when ocular signs appeared. The early symptoms were an unrelenting tachypnea (panting) without air hunger and an inspiratory hold (fixés en inspiration forcée). Initially regarded as hysterical in nature, the later bizarre disorders of respiration were considered equally serious with attacks of gasping, panting, puffing, inspiratory breath holding, coughs, giggles, sighing, grunting, and moaning. These respiratory disorders were seen exclusively as part of a parkinsonian syndrome. Most remarkably, these attacks could be provoked by oxygen administration. These respiratory abnormalities with encephalitis lethargica are not well remembered. One purpose of recalling these episodes is to call attention to central causes of respiratory illness even in pandemics with respiratory viruses.

René Cruchet (1875-1959) was a pediatrician from Bordeaux known for his seminal description of encephalitis lethargica during World War I, at the same time as Constantin von Economo (1876-1931) in Vienna published his own description, which, unlike Cruchet's description, provided precious anatomopathological data in addition to the clinical data. Cruchet was interested in tics and dystonia and called for treatment using behavioral psychotherapy that was, above all, repressive. Cruchet was also a physiologist and an innovator in aeronautic medicine-notably, he helped pioneer the study of "aviator's disease" during World War I. Moreover, he possessed an encyclopedic knowledge, while publishing in all medical fields, writing philosophical texts as well as travel logs.

The "second" seminal monograph by Constantin von Economo on encephalitis lethargica appeared in print in German in 1929, following his initial report of the disease (eponymously associated with his name) before the Viennese Society of Psychiatry and Neurology and the publication of his "first" monograph on the subject in 1917. The 1929 book was translated into English and Spanish and published by Humphrey Milford in Oxford and Espasa-Calpe in Madrid in 1931 and 1932, respectively. The present article gives some details of those translations and the neuropsychiatrists who produced them. Moreover, four previously unpublished letters by von Economo are presented, relating to the English edition of Die Encephalitis lethargica. These letters are of historical interest, as they provide insights into von Economo's personality and view of the translation.

Arnold Netter (1855-1936) was a paediatrician who clinically applied the progress that his Pasteurian contemporaries had made possible through their bacteriological discoveries. From a neurological point of view, he brought looking for Kernig's sign into mainstream use to confirm the clinical diagnosis of meningitis and made diagnostic lumbar puncture systematic. He was one of the first to cure meningococcal and pneumococcal meningitis, long before the era of antibiotics, using subtractive lumbar puncture and intraspinal serotherapy. Netter's attentive vigilance enabled him to recognise, from its onset, the first poliomyelitis epidemic of the 20th century which took place in the summer of 1909. He described the clinical and epidemiological characteristics, identifying the viral rather than microbial origin. Netter detected the first cases of encephalitis lethargica in Paris in 1918. The disease had been described by Constantin von Economo (1876-1931) in Vienna the previous year. Netter spent fifteen years studying this new disease, which caused a pandemic a century ago. He filled in the clinical picture and used his understanding of cerebrospinal fluid and pathological anatomy to enhance knowledge and improve treatment of this neurological pathology.

“A Kind of Alaska” is a one-act play by the British playwright and Nobel Prize winner Harold Pinter (1930–2008), based on the book Awakenings by the neurologist Oliver Sacks (1933–2015). This play, first performed in 1982, is centered around the character of Deborah, a middle-aged woman, struck by encephalitis lethargica (“sleeping sickness”) at the age of 16, who wakes up after 29 years of apparent sleep following the injection of an unnamed drug. This article analyzes how Pinter’s drama investigated the mysterious and fascinating relationship between time, memory, and consciousness. The term “awakenings,” chosen by Sacks himself, clearly refers to the restoration of voluntary motor function in patients with postencephalitic parkinsonism who responded to levodopa. However, it also suggests that these patients had an impairment of awareness. Actually, beyond the acute phase, subjects with postencephalitic parkinsonism were not sleeping but severely akinetic and therefore probably aware of the passage of time. Oliver Sacks probably did not entirely recognize the intrinsic contradiction between prolonged sleep (with consequent impairment of awareness and subjective “time gap”) of the acute lethargic phase and the severe akinesia with preserved awareness of the time-passing characteristic of postencephalitic parkinsonism. This confusion was further compounded by Harold Pinter in his play.

Encephalitis lethargica first appeared during World War 1, but reported cases gradually faded over the 1920s, and in the years following, cases were only sporadically reported. The clinical presentation was heterogeneous and typically included both acute and chronic phases. The acute phase was characterized by excessive sleepiness, disorders of ocular motility, fever, and movement disorders. On the other hand, the chronic phase was characterized by Parkinsonism, oculomotor abnormalities, involuntary movements, speech and respiratory abnormalities, and psychiatric manifestations. In Peru, Espejo-Tamayo reported 47 cases of the disease between 1919 and 1924, with an average mortality of 13%. He described three waves of the epidemic in Peru: that of 1919, with a predominance of the lethargic-paralytic syndrome; that of 1920-1921, characterized by the algic-myoclonic syndrome; and the wave that began in 1922, when the disease acquired purely striatum syndromes, as well as those associated with the lethargic-paralytic and myoclonic syndromes and mental manifestations. We summarize six cases of encephalitis lethargica reported in Peru from 1920 through 1940.

Finding a link between COVID-19 and subsequent psychiatric symptoms has resulted in renewed interest in the psychiatric sequelae of pandemics. The first such instance was apparently the encephalitis lethargica pandemic which arose around the time of the First World War, moving in the shadow of a repiratory virus pandemic. The epidemic of encephalitis lethargica (EL), or Von Economo's Disease, in the years 1917-27 was the first pandemic involving the central nervous system. It moved in some places in parallel with the Great Flu Pandemic but does not seem to have been caused by it. Unlike the coronavirus, pandemic EL affected children heavily, leading often to bizarre changes in character and personality. It often left sequelae lasting for decades in the form of postencephalitic Parkinsonism (PEP). Unlike the coronavirus, it had a high mortality of around 20 percent. Although encephalitis lethargica involved a number of systems, psychiatric morbidity was most prominent and entailed severe depression, mania, catatonia and psychosis. It ended without therapeutic or public-health measures; today, sporadic cases of EL continue to be reported. The hypothesis is that we can derive from the EL psychiatric pandemic certain lessons that might be useful in studying tardive COVID symptoms today.

Disease and medicine are found throughout Gabriel García Márquez’s work. This article examines the insomnia plague described in the novel One Hundred Years of Solitude and performs a differential diagnosis exercise with conditions that affect both sleep and memory. The main finding is that the insomnia plague narrated by García Márquez, with its clinical manifestations, the sequence of symptoms, and its resolution, cannot be associated with any specific diagnosis. However, similarities to and differences from several clinical conditions are discussed, as well as the relation between the neurophysiologic phenomena of sleep and memory.

One hundred years ago, neurologists were faced with a surge of cases of uncertain cause manifesting a protean array of symptoms. Through careful semiological description, pattern recognition and histopathological analysis, von Economo and others unified these seemingly disparate cases, defining the epidemic of encephalitis lethargica. Several landmark papers in the Journal of Neurology and Psychopathology (now JNNP) helped to illuminate clinical and pathological aspects of this new disease. In the subsequent hundred years, there have been other infectious epidemics affecting the nervous system, with causative agents including flaviviruses, influenza, enteroviruses (eg, poliomyelitis) and coronaviruses (CoV). Neurologists seeing patients in the age of COVID-19 have much to gain from the historical lessons of the epidemics of the last 100 years in responding to these new challenges. A case of encephalitis lethargica involving chiefly the cerebral cortex Authors : Watson GA Year Published : 1920 Epidemic encephalitis: Clinical papers by various authors Authors : Horder T Year Published : 1920 The first systematic descriptions of encephalitis lethargica were those of von Economo in 1916–1917, who coined the term (figure 1),1 which is also known as ‘von Economo’s disease’.2 However, there were probable cases in 1915 predating the ‘influenza epidemic’, and von Economo and others suggested that earlier epidemics throughout modern history may also have been related.3 Figure 1 Constantin Freiherr Economo von San Serff (von Economo (1876–1931)) Austrian neurologist, psychiatrist, pilot and originator of the diagnosis encephalitis lethargica (https://commons.wikimedia.org/wiki/Category:Constantin\_von\_Economo). Encephalitis lethargica appears to have spread from Eastern Europe to Germany, France and Britain between 1916 and 1918 and and then to have affected much of the rest of the world in the following few years.1 4 It probably affected more than a million people during the first half of the twentieth century, before apparently disappearing, although some clinicians …

Around 100 years ago, the outbreak of peculiar encephalitis promoted knowledge advancement regarding sleep and psychomotricity control. This epidemic is believed to have disappeared ten years after it started, and it remained from 1916 to 1927. Since then, only a few sporadic cases have been reported, but previously, they happened in occasional and epidemics forms. Two pioneers in describing the cases were Jean-Rene Cruchet and his collaborators, and Constantin Von Economo. The firsts described diffuse symptomatology, “sub-acute encephalomyelitis.” However, the reports by the Austrian aristocrat had a localized aspect which was admitted by him as a new disease, “Encephalitis lethargica” (EL). In his suppositions, based on clinical and anatomopathological material analysis, von Economo found distinct centers for sleep, in the rostral hypothalamus, and wakefulness, posterior hypothalamus. He plays an essential role in new achievements about EL and sleep neurobiology comprehension. These basic structural sleep-arousal regulatory neural systems had a lasting impact on contemporary sleep research, unfolded initially mainly by Frederic Bremer, Giuseppe Moruzzi, and Horace Winchell Magoun, based on a passive theory of sleep induction. The lasts arrived at the conception of “diffuse” and “unspecific” ascending reticular activating system (ARAS) of the brain stem. This notion was unfolding until the idea of various interconnected “waking centers” and “sleep centers” levels, and also, active sleep induction.

ObjectiveTo report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) who acutely developed a hypokinetic-rigid syndrome.MethodsPatient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum.ResultsWe report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS–CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment.ConclusionThis case study provides clinical and functional neuroimaging evidence to support that SARS–CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

We commemorate the centenary of Constantin von Economo's description of encephalitis lethargica, a mysterious disease that had a significant effect on 20th-century neuroscience. In the acute phase, encephalitis lethargica was marked by intractable somnolence, which von Economo attributed to lesions in the diencephalon, thereby paving the way for future efforts to localize the regulation of sleep in the subcortical brain. At the same time, neuropathologic findings in postencephalitic parkinsonism affirmed the role of the substantia nigra in the pathophysiology of parkinsonism. The occurrence of psychiatric symptoms in patients with encephalitis lethargica—such as mood disorders, obsessive-compulsive behavior, and bradyphrenia—drew attention to the organic basis of mental illness.

In 1934, Gabrielle Lévy died at the age of 48. She became well known for an article she published on a hereditary polyneuropathy in cooperation with Gustav Roussy, resulting in the eponym Roussy-Lévy syndrome. Not much is known about this extraordinary neurologist/neuropathologist. Her family declared that she died from the disease she was studying. She was a pupil of Pierre Marie, with whom she worked at the Salpêtrière in Paris and wrote on war neurology. In cooperation with Marie, she published a number of articles on postencephalitic syndromes, which also became the subject of her 1922 thesis. Three years later, she became associate physician at the Paul-Brousse Hospital in Paris, where the study of brain tumors became one of the subjects of her scientific work. Remarkably, Lévy was first author in a few of her many articles, although Roussy confirmed that she often initiated the study and even wrote the main part. In this article her career is considered in the context of the struggle of women physicians to improve their position during the early-twentieth century. She probably died from a brain tumor or a postencephalitic syndrome.

In his These de Paris (1919) Konstantin Tretiakoff (1892-1956) described the two main morphological lesions in Parkinson's disease: the loss of pigmented nerve cells in the Substantia nigra and the intracellular inclusion bodies in idiopathic paralysis agitans, calling them "Corps de Lewy," which already had been described by F. H. Lewy in 1912. Tretiakoff's findings on idiopathic Parkinson's disease were confirmed years later by Rolf Hassler in his dissertation on anatomy and pathology of Substantia nigra in Berlin (1938, 1939). German authors in the 1920s underestimated the significance of both findings (Bielschowsky, 1922; Lewy 1923/1924; Spatz 1927), especially Lewy himself. Lewy (1923) and other German neurologists and neuropathologists like Felix Stern (1922, 1928), Goldstein (1922), and Spatz (1927; Luksch & Spatz, 1923) acknowledged the typical Nigra-lesions only for postencephalitic Parkinsonism. It is argued that Tretiakoff's selective attention for the Substantia nigra was guided by the frequency of epidemic encephalitis lethargica and its preponderance of nigral pathology. This impression can be derived from Tretiakoff's early paper on that disease (Marie & Tretiakoff, 1918) and from Paul Foley's opus magnum (2018). Two outstanding neurologists dedicated to this issue are called into memory: Gabrielle Levy, the successor of Tretiakoff in the Salpetriere laboratory, and Felix Stern, who died in 1942 as a victim of Nazi terror. The eponym Lewy-bodies went back to Lafora and Tretiakoff ("Corps de Lewy"). Newly expressed doubts about Lewy's primacy or Lafora's credit for the eponym (Lafora-bodies since 1911) can be refuted with the studies of Greenfield and Bosanquet (1953) and Greenfield (1963) by illustrating their different staining properties.

Lethargic encephalitis is a neurological illness that shows a wide range of symptoms and signs, including neurological and psychiatric spectrum. It presented in an epidemic way, following influaenza relapses. The last relapse started at the beginning of 20th century and it was deeply described by Constantin von Economo. The illness described first in Europe and North America, was described in many others countries including Chile. There were beautiful descriptions by Chilean physicians like Lea-Plaza, Tello, Iturra and Cienfuegos. Their works showed the complexity of the illness like European physicians did too. The etiology is still unknown; however growing evidence about autoinmune aetiology is gaining force with the use of actual medical technology. In this work, we show encephalitis lethargica, focusing in clinical picture, the beauty of medical descriptions that physicians did at this date.Encefalitis letargica. La epidemia en los albores de la neurologia.La encefalitis letargica es un cuadro neurologico con una variada gama de manifestaciones clinicas en el ambito neurologico y tambien en el psiquiatrico. El cuadro se ha presentado de manera epidemica en brotes que han seguido a los de la gripe. El ultimo brote acaecido a comienzos del siglo XX lo describio en profundidad Constantin von Economo. La epidemia notificada inicialmente en Europa y luego en Norteamerica se presento tambien en otras latitudes, incluyendo Chile. Asi, las descripciones de Lea-Plaza, Tello, Iturra, Cienfuegos y otros medicos chilenos dieron cuenta del cuadro en Chile con toda la complejidad que tambien tuvo en Europa. El origen sigue siendo un misterio, aunque la evidencia creciente de que fuera autoinmune gana fuerza con los hallazgos de la tecnologia medica actual. En este trabajo presentamos el cuadro, privilegiando la riqueza clinica y la belleza de las descripciones realizada por los medicos de la epoca en que esta enfermedad se presento.

Viruses have long been implicated in the pathogenesis of classical encephalitis lethargica, which was first described by Constantin von Economo in 1917. In this article, I propose the hypothesis that an airborne virus travels along the olfactory conduit to infect the olfactory bulb; this local infection or induced neuroinflammation, in turn, retrogradely targets certain neuronal populations with sleep–wake regulatory functions in the hypothalamus and midbrain, leading to the development of wakeful inactivity, a hallmark clinical feature of the disease. Furthermore, the olfactory vector hypothesis may also explain the pathomechanism of the debilitating complication of the disease, i.e., postencephalitic parkinsonism, in terms of a recently discovered nigro-olfactory projection.

Von Economo’s encephalitis is a neuropsychiatric disorder of possible autoimmune origin, which affects basal ganglia. This reaction may occur secondary to infection by different viral or bacterial agents. Given that it appears after the acute episode has disappeared, molecular mimetism has been proposed to explain the autoimmune lesion. Several cases have been reported through time, but it was with the 1918 flu pandemic, known as the Spanish flu, that lethargic encephalitis reached epidemic levels with cases reported until 1923 in various countries. The Spanish flu pandemic appeared in Colombia at the end of 1918 in several cities but it affected especially Bogotá where the highest number of patients and deaths was reported. Our purpose with the present work was to commemorate the arrival of the Spanish flu to our country after one hundred years, as well as to reflect on its main complications, which included some lethargic encepahilitis cases.La encefalitis letárgica de von Economo es un trastorno neuropsiquiátrico de posible origen autoinmunitario, en el cual se afectan los ganglios basales. Esta reacción puede ocurrir luego de una infección aguda por diversos agentes virales o bacterianos. Dado que aparece cuando ya se ha resuelto el cuadro agudo, se ha propuesto el mecanismo del mimetismo molecular para explicar la lesión autoinmunitaria. Se han reportado diversos casos a lo largo del tiempo, pero fue con la pandemia de influenza de 1918, conocida como la gripe española, que la encefalitis letárgica alcanzó niveles de epidemia, con casos reportados hasta 1923 en diversos países. La pandemia de la gripe española se extendió a Colombia durante los últimos meses de 1918 y afectó varias ciudades, principalmente Bogotá, donde se reportó el mayor número de enfermos y muertos. Con este trabajo se busca rememorar, cien años después, el ingreso de la gripe española a nuestro país y sus principales complicaciones, entre las que se describieron algunos casos de encefalitis letárgica.

Parkinson disease with and without dementia (PDD and PD, respectively), dementia with Lewy bodies (DLB), and Alzheimer dementia (AD) traditionally have been viewed as distinct clinical and pathologic entities. However, intriguing overlaps in biochemical, clinical, and imaging findings question the concept of distinct entities and suggest a continuous spectrum in which individual patients express PD-typical patterns and AD-typical patterns to a variable degree.Following this concept, we built a topological map based on regional patterns of the cerebral metabolic rate of glucose as measured with (18)F-FDG PET to rank and localize single subjects' disease status according to PD-typical (PD vs. controls) and AD-typical (AD vs. controls) pattern expression in patients clinically characterized as PD, PDD, DLB, amnestic mild cognitive impairment, and AD.The topology generally confirmed an indivisible spectrum of disease manifestation according to 2 separable expression patterns. The expression values derived from the first pattern were highly correlated with individual cognitive, but not motor, disability. The opposite was found for the corresponding expression values of the second pattern.The metabolic imaging analysis supports the notion that there is a continuous spectrum of neurodegeneration between AD and PD. Furthermore, PDD and DLB may in fact represent 1 overlapping disease entity, characterized by the presence of mixed neuropathology and only different by the time course.

Background Incidence of dengue fever as well as dengue hemorrhagic fever is increasing in Sri Lanka especially among elderly population. As the number of cases is rising, rare complications of dengue illness also can be seen in clinical practice when compared to the past few years. Prompt identification and treatment of such complications is challenging due to lack of awareness and unavailability of standard treatment. Case presentation 69 years old man presented with acute onset fever and was diagnosed as having dengue illness. On the 4th day of illness, the disease was progressed into dengue haemorrhagic fever and recovered uneventfully. Although he recovered from primary illness, his general condition continued to deteriorate due to new onset of features of parkinsonism. Cerebrospinal fluid analysis and electro encephalogram showed evidence of encephalitis. Cerebrospinal fluid analysis also revealed positive IgM antibodies against dengue virus. Then the diagnosis of post encephalitic parkinsonism following dengue viral infection was made and started on. He was started on SINEMET (carbidopa 10 mg and levodopa 100 mg) half tablet 6 hourly started. After 1 week of treatment he showed marked improvement and then patient was discharged with further follow up plan. Conclusion Although the management of dengue illness and dengue haemorrhagic fever is straightforward, recognition and treatment of rare complications like post encephalitic parkinsonism following dengue viral infection is difficult without great clinical suspicion.

Summary In 1916, von Economo first described encephalitis lethargica (EL), a CNS disorder presenting with pharyngitis followed by sleep disorder, basal ganglia signs (particularly parkinsonism) and neuropsychiatric sequelae. Since the 1916‐1927 epidemic, only sporadic cases have been described. Pathological studies revealed an encephalitis of the midbrain and basal ganglia, with lymphocyte (predominantly plasma cell) infiltration. The EL epidemic occurred during the same time period as the 1918 influenza pandemic, and the two outbreaks have been linked in the medical literature. However, von Economo and other contemporary scientists thought that the 1918 influenza virus was not the cause of EL. Recent examination of archived EL brain material has failed to demonstrate influenza RNA, adding to the evidence that EL was not an invasive influenza encephalitis. By contrast, the findings of intrathecal oligoclonal bands (OCB) and beneficial effects of steroid treatments have provoked the hypothesis that EL may be immune-mediated. We have recently seen 20 patients with a similar EL phenotype, 55% of whom had a preceding pharyngitis. The patients had remarkable similarity to the historical descriptions of EL: sleep disorder (somnolence, sleep inversion or insomnia), lethargy, parkinsonism, dyskinesias and neuropsychiatric symptoms. CSF examination commonly showed elevated protein and OCB (75 and 69% respectively). Investigation found no evidence of viral encephalitis or other recognized causes of rapid-onset parkinsonism. MRI of the brain was normal in 60% but showed inflammatory changes localized to the deep grey matter in 40% of patients. We investigated the possibility that this phenotype could be a postinfectious autoimmune CNS disorder, and therefore similar to Sydenham’s chorea. Anti-streptolysin-O titres were elevated in 65% of patients. Furthermore, western immunoblotting showed that 95% of EL patients had autoantibodies reactive against human basal ganglia antigens. These antibodies were also present in the CSF in four patients tested. By contrast, antibodies reactive against the basal ganglia were found in only 2‐4% of child and adult controls (n = 173, P < 0.0001). Rather than showing polyspecific binding, these antibodies bound to common neural autoantigens of molecular weight 40, 45, 60 and 98 kDa. Regional tissue comparisons showed that the majority of these autoantigens were specific to or enriched in CNS tissue. Immunohistochemistry with secondary staining localized antibody binding to neurons rather than glial populations. Further investigation is required to determine whether these antibodies affect neuronal function (i.e. whether they are pathogenic anti-neuronal antibodies). Histopathology in one case demonstrated striatal encephalitis with perivenous Band T-lymphocytic infiltration. We believe an EL-like syndrome is still prevalent, and propose that this syndrome may be secondary to autoimmunity against deep grey matter neurons.

Born in Romania of Greek parents and raised in Trieste, Constantin von Economo was educated and influenced by Vienna's medical and scientific tradition. Better known for his description of encephalitis lethargica, a disease bearing his name, he made several contributions to as varied themes as the cytoarchitecture of the cerebral cortex, sleep regulation, evolutionary brain development and, outside medicine, in aviation. While still a student he showed an aptitude for meticulous accuracy and a skill in combining animal experiments with microanatomical techniques. Nurtured in the formidable environment of Viennese histology he produced a monumental account of the cytoarchitecture of the human cerebral cortex. This, in an attempt to correlate structure and function, was unique in its quality of accuracy and paved the way for subsequent achievements two decades later. Despite an untimely death at 55 years, he remains one of the most talented pioneers of modern neuroscience.

2011 marks the 80th anniversary of the death of Constantin Alexander von Economo who conducted advanced research on the cytoarchitectonics of the brain. This Austrian neurologist and the pioneer of aviation described encephalitis lethargica, discovered the spindle neurons, and postulated the existence of the sleep and wakefulness centre in the brain. What is more he realized two of the biggest dreams of humankind: conquering space and getting to know the secrets of the human brain.

The objective of the study is to ascertain the rationale for the diagnosis of postencephalitic parkinsonism (PEP) at Boston City Hospital's Neurological Unit (1930-1981). 5,270 discharge summaries were evaluated for the diagnoses of PEP. Sixteen cases of PEP were identified; the diagnosis of PEP was justified in approximately half of these cases based on the published criteria for distinguishing PEP from Parkinson's disease (PD). In conclusions, the absence of a clear justification for the diagnosis of PEP in many of the 16 cases suggests that the accepted relationship between encephalitis lethargica and PEP may be less definitive than currently believed.

Postencephalitic parkinsonism has been considered unique among disorders with parkinsonian features because it is believed to have a unitary etiology associated with the virus that presumably caused encephalitis lethargica. Careful analysis of the historical record, however, suggests that this relationship is more complex than commonly perceived. In most cases, the diagnosis of acute encephalitis lethargica was made post hoc, and virtually any catarrh-like illness was considered to have represented encephalitis lethargica, often after an oral history-taking that was undoubtedly subject to patient recall and physician bias. Also, postencephalitic parkinsonism and oculogyric crises were not recognized as sequelae to encephalitis lethargica until well after other sequelae such as movement disorders and mental disturbances had been identified (see previous paper). We suggest here that the relationship between encephalitis lethargica and postencephalitic parkinsonism is not simplistic, i.e., encephalitis lethargica was not solely responsible for the etiology of postencephalitic parkinsonism, thus aligning the latter with most other parkinsonian disorders that are now believed to have multiple causes.

A 56-year-old woman, suffering from postencephalitic parkinsonism for 15 years, developed a respiratory disturbance in connection with L-dopa therapy. About 2 hours after the medication she often had attacks of irregular breathing, lasting for 2–4 hours. During the attacks apnoeic periods of 2–30 sec appeared, interspersed in a uniform series of vigorous breaths. Arterial oxygen saturation was never below 90%. The intestinal absorption and the elimination from the blood of L-dopa did not differ from that observed in other patients with parkinsonian symptoms. A single-blind study confirmed the impression from history and clinical observation that the disturbance is caused by L-dopa.

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL.Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and (18)F-FDG PET imaging was performed. Selected cases were videotaped.Our patients (M/F: 5/3) ranged from 2-28 years (mean 9.3 +/- 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. (18)F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series.There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL.

The activity of acetylcholinesterase was studied in various autopsy brain samples of nine parkinsonian patients and eight control subjects without extrapyramidal disorders. Putamen and caudate nucleus showed the highest activities of acetylcholinesterase when different brain areas were compared. Acetylcholinesterase values expressed per wet weight or protein were somewhat lower in the extrapyramidal brain regions of parkinsonian patients than in those of controls. When values were calculated per desoxyribonucleic acid (DNA) it was found that extrapyramidal brain regions, especially substantia nigra, showed higher activities in parkinsonian material than in controls. This difference is due to the decrease of DNA which in the substantia nigra mainly reflects the loss of dopaminergic substantia nigra neurons. Furthermore, analyses of dopamine from the same tissue samples showed many times increased acetylcholinesterase-dopamine ratio in parkinsonian brain than in controls. Levodopa alone or combined with a decarboxylase inhibitor did not have any significant effect on the activity of acetylcholinesterase. It is concluded that the cholinergic mechanisms in the extrapyramidal system of parkinsonian brain are not so severely affected as the dopaminergic ones leading to relative and functional cholinergic dominance.

When opened as a post-graduate teaching and research hospital in 1923, the Maudsley made virtually no provision for the treatment of children. Yet its children's department saw sustained growth during the interwar period. This expansion is explored in relation to novel behaviourist hypotheses and the forging of formal links with local government and charitable bodies. The recruitment of psychologists, educators and specialist social workers fostered a multidisciplinary approach through case conferences. This development would structure the theoretical origins of child psychiatry, in particular influencing the role and interpretation of psychoanalytic theory within it. William Moodie and Rosalie Lucas identified learned behaviour tied to social and familial circumstances as the crucial factor for both diagnosis and therapy. The theoretical orientation of child psychiatry and the practical treatment of children represented an area of dynamic change and innovation at a time when adult psychiatry struggled to discover effective treatments or achieve breakthroughs in causal understanding.

Summary Context Influenza is a viral pathogen that imposes an under-recognized burden of central nervous system (CNS) disease. Objective To describe the epidemiology, clinical features and etiology of the CNS disease entities associated with influenza. Data sources English-language publications from MEDLINE. Data extraction Articles were identified using “influenza, human”[Mesh] AND “nervous system diseases”[Mesh] and screened for inclusion based on relevance and scientific rigor. Results Febrile seizure is the most frequently encountered influenza-associated CNS complication, with one in five children hospitalized with influenza experiencing one or more events. In most instances, symptoms resolve without neurological sequelae, although the risk for subsequent afebrile seizure may be increased. Influenza-associated encephalitis/encephalopathy is a less common but potentially more serious complication that is widely reported in Japanese populations, although cases from other East Asian countries, North America, and Europe have been described. Clinical manifestations are diverse, and typically involve febrile seizures and abnormal behaviors in mild cases, with rapid evolution through decreased consciousness to coma in severe forms. In cases of serious disease, the prognosis is often poor, with outcomes including death or severe neurological sequelae. Influenza is also a known trigger for a number of rarely encountered, yet often serious, CNS diseases, including the encephalopathic condition of Reye's syndrome, the peripheral neuropathy known as Guillain–Barre syndrome, and the lesser known complaints of Kleine–Levin syndrome and post-encephalitic Parkinson's disease. Conclusions Influenza imposes a sizeable burden of CNS disease. Increased awareness and monitoring of CNS function is indicated, especially in infants and young children.

We report a 47-year-old man who is considered to have sporadic encephalitis lethargica (EL). He presented with hyperpyrexia, lethargy, akinetic mutism, and posture of decorticate rigidity following coma and respiratory failure. Intravenous methylprednisolone pulse therapy improved his condition rapidly and remarkably. Electroencephalography (EEG) showed severe diffuse slow waves of bilateral frontal dominancy, and paralleled the clinical course. Our patient fulfilled the diagnostic criteria for malignant catatonia, so we diagnosed secondary malignant catatonia due to EL syndrome. The effect of corticosteroid treatment remains controversial in encephalitis; however, some EL syndrome patients exhibit an excellent response to corticosteroid treatment. Therefore, EL syndrome may be secondary to autoimmunity against deep grey matter. It is important to distinguish secondary catatonia due to general medical conditions from psychiatric catatonia and to choose a treatment suitable for the medical condition.