Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient, a clinical case of parkinsonism, was a 32-year-old man, born in 1942, long after the prevalence of von Economo's lethargic encephalitis in Japan. Anatomically, the neurons in the substantia nigra of the mid-brain were extensively degenerated, and presented Alzheimer's neurofibrillary tangles. At the same time, melanin pigment was scattered in the tissue and was phagocytized by glia cells. Perivascular cuffing was observed in the frontal lobe, parietal lobe, temporal lobe, hippocampus, and thalamus as well as in the substantia nigra. Neuronophagia was noted in the thalamic nuclei. The present case was believed to have parkinsonism not clinically or pathologically related to von Economo's encephalitis or to Japanese encephalitis, but following a mild encephalitis of unknown etiology.
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PMID:Parkinsonism following encephalitis of unknown etiology. 83 14

In 1954, when he was five years old, a patient suffered from encephalitis with a prolonged lethargic state. Following this episode, he presented a severe parkinsonian syndrome which was associated, after a few years, with an axial dystonia and stereotyped involuntary movements of the upper limbs. These abnormal movements were particular by their coordinated appearance, their rhythmicity and their relative slowness. Treatment with L-dopa suppressed all akinetic, dystonic and dyskinetic symptoms. At age of 40 years, all the akinetic, dystonic and dyskinetic symptoms reappeared after drug withdrawal. Cerebral computed tomography, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were normal. Fluorodopa positron emission tomography revealed a significant bilateral reduction of tracer accumulation in the posterior part of both putamen, similar to that observed in patients with idiopathic Parkinson's disease. In this patient, pharmacological tests revealed that effectiveness of L-dopa was abolished by administration of a D2 antagonist, and was fully reproduced by a D2 agonist. Clinical signs, pharmacological data and past-medical history strongly suggested a limited lesion of the zona compacta of substantia nigra induced by viral agression. This complex and progressive extrapyramidal syndrome had strong similarities with the lethargic encephalitis of Von Economo and its late symptoms. Other diseases associating akinesia and dyskinesia or dystonic phenomena, like dopa-sensitive dystonia and juvenile Parkinson's disease, are very unlikely. Thus, the persistance of sporadic forms of Von Economo's encephalitis could be discussed.
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PMID:[Parkinsonian syndrome and post-encephalitic stereotyped involuntary movements responsive to L-dopa]. 876 55

In 1954, at the age of 5 years, our patient had an encephalitic syndrome associated with a prolonged lethargic state. After this episode, he developed a severe parkinsonian syndrome that, after a few years, was associated with axial dystonia and stereotyped abnormal movements of the upper limbs. This complex and progressive extrapyramidal syndrome had many similarities to the encephalitis lethargica as described by von Economo. Results of cerebral computed tomography and magnetic resonance imaging were normal. Fluorodopa positron emission tomography showed a significant bilateral reduction of tracer accumulation in both putamen, similar to that observed in patients with idiopathic Parkinson's disease. However, in this patient, treatment with L-Dopa suppressed all akinetic, dystonic and dyskinetic symptoms. The effectiveness of L-Dopa was abolished by administration of a D2 antagonist and was fully reproduced by a D2 agonist. In conclusion, this patient presented a complex postencephalitic, extrapyramidal syndrome, with akinetic symptoms and involuntary movements. These symptoms appeared to be related to a limited lesion of the dopaminergic neurons of the zona compacta of the substantia nigra.
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PMID:Postencephalitic stereotyped involuntary movements responsive to L-Dopa. 886 99

Influenza viruses rarely cause acute encephalopathy. Post-influenzal encephalitis, which occurs a few weeks after recovery from influenza is thought to be an autoimmune process associated with demyelination and vasculopathy. It has been suggested that Economo lethargic encephalitis followed by postencephalitic Parkinsonism was associated with the influenza A epidemic of 1918 (Spanish flu). The incidence of Reye's syndrome has markedly decreased due to the avoidance of salicylates in the treatment of influenza or varicella. One inactivated flu vaccine is thought to have caused Guillain Barre syndrome due to molecular mimicry between viral protein and myelin, which triggered autoimmune responses. The persistence of influenza virus genes in neural cells as one of the causes of chronic degenerative diseases of the central nervous system by inducing apoptosis of the host cells is yet to be proven.
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PMID:Influenza virus and neurological diseases. 931 61

Encephalitis lethargica (EL) was a mysterious epidemic. temporally associated with the 1918 Spanish influenza pandemic. Numerous symptoms characterized this disease, including headache, diplopia, fever, fatal coma, delirium, oculogyric crisis, lethargy, catatonia, and psychiatric symptoms. Many patients who initially recovered subsequently developed profound, chronic parkinsonism. The etiologic association of influenza with EL is controversial. Five acute EL autopsies and more than 70 postencephalitic parkinsonian autopsies were available in the Armed Forces Institute of Pathology (AFIP) tissue repository. Two of these 5 acute EL cases had histopathologic changes consistent with that diagnosis. The remaining 3 cases were classified as possible acute EL cases as the autopsy material was insufficient for detailed histopathologic examination. RNA lysates were prepared from 29 CNS autopsy tissue blocks from the 5 acute cases and 9 lysates from blocks containing substantia nigra from 2 postencephalitic cases. RNA recovery was assessed by amplification of beta-2-microglobulin mRNA and 65% of the tissue blocks contained amplifiable RNA. Reverse transcription-polymerase chain reaction (RT-PCR) for influenza matrix and nucleoprotein genes was negative in all cases. Thus, it is unlikely that the 1918 influenza virus was neurotropic and directly responsible for the outbreak of EL.
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PMID:Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases. 1170 41

Starting from the Constantin Von Economo's description of a "new" disease, the lethargic encephalitis, the author delineates the history of an infectious sleeping sickness that caused epidemics in Europe from 1917 to 1928 and led to create, in Italy, the "Institutes for Encephalitis".
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PMID:[The Costantin Von Economo's lethargic encefalitis] 1276 90

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 B- and 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.
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PMID:Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. 1467 31