1/22. Dopaminergic therapy in acute encephalitis lethargica. We describe a patient with an acute illness, with clinical features characteristic of encephalitis lethargica, who responded repeatedly to trials of an apomorphine infusion and subsequently to oral levodopa therapy. This observation implies a direct acute neurotropic effect of the encephalitis on nigral dopaminergic cells. Dopaminergic medication may therefore be helpful in the acute stage of encephalitis lethargica as well as in the delayed post-encephalitic parkinsonian phase of the syndrome. ( info) |
2/22. The coincidence of schizophrenia and Parkinsonism: some neurochemical implications. The hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the patholophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-straital sites. ( info) |
3/22. An autopsy case of postencephalitic parkinsonism of von Economo type: some new observations concerning neurofibrillary tangles and astrocytic tangles. An autopsied case of postencephalitic parkinsonism of von Economo type with a 71-year duration is reported. Several cases of postencephalitic parkinsonism of von Economo type have been reported in japan but this is the first reported case from western japan. The patient was a Japanese man who was 74 years of age at the time of death. He developed encephalitis of unknown etiology at the age of 3 years. The first symptom was antisocial behavior, which developed at 30 years of age. At the age of 40 years, the patient showed progressive parkinsonism. Neuropathological findings disclosed marked neuronal loss with gliosis in the substantia nigra, locus ceruleus, and raphe nuclei, as well as the appearance of neurofibrillary tangles in the aforementioned areas. There were also widespread tuft-shaped astrocytes (Tu-SA) in the central nervous system, including the thalamus. Tuft-shaped astrocytes are considered to represent non-reactive astrocytes because the distributions of neurofibrillary tangles (NFT) and Tu-SA are clearly different. Therefore, the primary astrocytic lesions in postencephalitic parkinsonism of von Economo type may be more widespread. Ultrastructurally, the Tu-SA consisted of straight filaments, 15 nm in width, which formed tight bundles. Ultrastructurally, NFF in this case revealed paired helical filaments but straight filaments, 15 nm in width, which were also found in the neurons of the substantia nigra. ( info) |
4/22. FDG- and Dopa-PET in postencephalitic parkinsonism. We report a case of a 74-year old woman who following an acute virus encephalitis developed an akinetic-rigid Parkinson syndrome with tremor, hypokinesia, hypomimia, rigidity and cogwheel phenomenon in all four extremities, brady-dysdiadochokinesia as well as myoclonic jerks of the arms. Many of the clinical features of this postencephalitic parkinsonism (PEP) suggested the diagnosis of sporadic encephalitis lethargica, first described by von Economo 1917. Cerebral spinal fluid showed signs of a viral encephalitis, and a positive influenza A IgA-antibody titer (1:>160) in the viral serologic screen was found. Positron emission tomography (PET) showed an altered pattern of glucose- and dopa-metabolism clearly different from findings in idiopathic Parkinson syndrome (IPS). The acute lack of inhibitory input from the substantia nigra pars compacta to the striatum could explain the different metabolic patterns in our case in comparison to IPS patients. Our findings indicate that PEP may also be caused by influenza A and furthermore that PET clearly distinguishes PEP from IPS. ( info) |
5/22. A contemporary case of encephalitis lethargica. We present a clinicopathological report of a recent fatal case of a 27-year-old woman whom we consider to have had encephalitis lethargica. Clinical features of note were a presentation with vertigo, persistent vomiting and sleep disturbance including marked daytime somnolence and vivid nightmares. On examination, she had impaired slow pursuit vertical eye movements, dysarthria, an expressionless face and slow tongue movements. She went on to develop gross supranuclear gaze palsy, neck rigidity, bradykinesia, blepharospasm, profound somnolence and anarthria but no tremor, weakness or impairment of cognition. She died after an illness lasting 12 months. On investigation, the cerebrospinal fluid was found to contain a very high level of IgG with oligoclonal bands but no cells. Post-mortem examination revealed an active encephalitis, mainly centered on the upper brainstem and diencephalon with extensive Purkinje cell loss and marked plasma cell infiltrates and morula cells. No virus was recovered. ( info) |
6/22. Influenza rna not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases. 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. ( info) |
7/22. Postvaccinal parkinsonism. A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear-cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features. ( info) |
| 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. ( info) |
9/22. Progressive supranuclear palsy: new disease or variant of postencephalitic parkinsonism? We review the etiological importance of the epidemic encephalitis for progressive supranuclear palsy (PSP) and addresses the question of whether the explosion of PSP literature in the mid-20th century reflects the appearance of a new disease. We examined 2,000 studies on Parkinson's disease from 1861 to 1963 and found PSP-like cases in the past, before the epidemic encephalitis era. It can be assumed that PSP is neither a new disease nor a variant of postencephalitic parkinsonism. ( info) |
10/22. encephalitis lethargica-like illness in a five-year-old. A five-year-old boy presented with an encephalitis lethargica-like illness, characterised by somnolence, mutism and Parkinsonian rigidity two weeks after an acute exanthem. Investigation revealed increased serum measles antibody titre. He made a complete recovery. encephalitis lethargica associated with Parkinsonism in childhood is rare and usually carries a poor prognosis. ( info) |