René Cruchet (1875-1959), beyond encephalitis lethargica.

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.

Post-Encephalitic Parkinsonism and Sleep Disorder Responsive to Immunological Treatment: A Case Report.

We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control.

Contemporary Encephalitis Lethargica: phenotype, laboratory findings and treatment outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Contemporary encephalitis lethargica presenting with agitated catatonia, stereotypy, and dystonia-parkinsonism.

Encephalitis lethargica (EL) syndrome was classically described by Von Economo and has somnolent-ophthalmoplegic, hyperkinetic, and amyostatic-akinetic forms. We describe 2 recent cases of EL characterized by an acute encephalitis with mixed movement disorders (dystonia-Parkinsonism plus stereotypy) and psychiatric disorders (agitated catatonia, coprolalia, and echo phenomena). Both patients suffered concurrent hyperkinetic and Parkinsonian features resulting in therapeutic challenges. Bradykinetic features responded to dopamine replacement therapy and both patients also had adverse affects to dopamine antagonists (oculogyric crises plus neuroleptic malignant syndrome). Investigation was unremarkable other than the presence of CSF lymphocytosis and oligoclonal bands. Despite prolonged in-patient stays and intensive care management, both patients have made complete recoveries. We believe these cases support the hypothesis that this syndrome is an inflammatory encephalitis that specifically effects dopamine neurotransmission.

[Post-encephalitic syndromes in the Spanish medical literature]. / Síndromes postencefalíticos en la literatura médica española.

AIM: A large number of patients with encephalitis lethargica developed different post-encephalitic syndromes (PES), which have an important medical and social impact. We studied the clinical and historical aspects of PES in Spain by reviewing the medical literature published in this country between 1918 and 1936. DEVELOPMENT: There are no statistical data concerning PES in Spain, although Spanish physicians drew attention to their high rate of prevalence and their repercussions on community health. Most of the 140 patients that were reviewed (74%) presented predominant Parkinsonism, but some features of Parkinsonism were observed in nearly all cases. Other movement disorders (focal dystonias, chorea, myoclonus, oculogyric crises, abnormalities affecting breathing rate) were described, as well as sleep, endocrine and vegetative disorders. Psychiatric disorders were often reported, the most frequent being bradyphrenia associated to Parkinsonism, but a hypomanic picture with impulsive behaviour was very characteristic among young people. PES was diagnosed on average two years after the episode of acute encephalitis lethargica, although it often appeared immediately afterwards. Many studies discuss the contribution made by PES to further our knowledge of the pathophysiology of extrapyramidal diseases and about the involvement of the basal ganglia in psychiatric and behavioural disorders. CONCLUSIONS: Despite the absence of statistical data, Spanish authors highlighted the important repercussions the PES had on community health, as well as the role they played in extending our knowledge of the pathophysiology of the basal ganglia. Cases of Parkinsonism were predominant, although all kinds of post-encephalitic manifestations were reported.

Neuropsychiatric interpretations of postencephalitic movement disorders.

This study reviews the impact of encephalitis lethargica (EL) on concepts of behaviour and movement during the 1920s and 1930s. Clinicopathological correlations were imprecise but supported the role of subcortical structures in complex patterns of motor behaviour. This possibility challenged the widely assumed hegemony of the cerebral cortex. There was a perceived link between involuntary movements and reduced impulse control and also between parkinsonism and a defect in volition. Contemporary observers interpreted postencephalitic phenomena such as oculogyria in psychodynamic as well as in neurophysiological terms. EL also gave some support to the idea that neuroses such as obsessional neurosis and hysteria might have an organic basis. These speculations recently have acquired more credibility. The large amount of literature on EL and its sequelae could perhaps make further contributions to understanding the pathology of voluntary movement and action.

An akinetic-rigid syndrome, depression, and stereotypies in a young man.

A young man is presented who developed an akinetic-rigid syndrome shortly after a minor illness. Rituals and stereoptypies were prominent. At its most severe he was unable to feed himself. There was no response to L-dopa/cardopa treatment. A course of ECT was followed by a marked improvement in his condition. Attempts to stop ECT for more than a week have led to recurrence of his bradykinesia.

Stereotactic limbic leucotomy--a follow-up at 16 months.

Sixty-six patients were assessed clinically, psychologically and physiologically before operation, at six weeks and at a mean of 16 months following stereotactic limbic leucotomy. Seventy-three per cent were clinically improved at six weeks and 76 per cent at 16 months. In obsessional neurosis, 89 per cent of patients showed definite clinical improvement at 16 months; in chronic anxiety, 66 per cent were improved; in depression, 78 per cent; and in the small number of schizophrenics treated the improvement rate was over 80 per cent. Self-assessment and observer-assessment questionaires and scales measuring Depression, Anxiety, Neuroticism, Hysterical symptoms and Obsessional symptoms and traits all showed highly significant reductions of mean scores at 16 months. There was no fall-off in intelligence, and adverse effects were minimal. Limbic leucotomy, with its enhanced accuracy and safety, compares very favourably with similarly assessed, more extensive 'free-hand' procedures, and in obsessional neurosis and chronic anxiety the results are superior.