Postencephalitic Parkinsonism (PEP)
by Kurt Jellinger
PEP is a progressive neuro-degenerative disease with clinical features referable mainly to the extrapyramidal and oculomotor systems and cognitive deterioration. It represents a chronic complication of encephalitis lethargica (EL) or Economo’s encephalitis or sleep sickness that emerged during and after World War I.
Symptoms and course
Bradykinesia, rigidity, hypomimia, postural instability, gait disorders with falls and sialorrhea. Ophthalmoplegia and oculogyric crises. Elderly patients suffer from continuous deterioration of motor function with dysphagia, incontinence, Levo-Dopa induced psychoses, dystonia, and cognitive impairment.
Neuropathology: multisystem neuronal degeneration and cell loss, with gliosisin many brainstem nuclei, in particular substantia nigra, locus ceruleus, and others with globous neurofibrillary tangles in residual neurons in many subcortical nuclei. Cortical pathology is common with frequent NFTs in hippocampus, entorhinal, frontal and insular cortices, differing in distribution from those in AD.
Immunohistochemical studies showed deposits of pathologic tau protein in sucortical fibrillary tangesand astroglia, indicating relationship to tauopathies. Ultrastructure and biochemistry of neuronal and glial deposits are similar to those in Alzheimer diseaase: Ultrastructurally NFTs are composed of 22 nm paired helical filaments and rare 15 nm straiht tubules, Biochemistry of tau protein in PEP shows tau triplet wit h 3 prominent bands at 60, 64, and 68 kDa, differing from tau in PSP, CBD, Pick’s disease, and argyrophilic grain disease.
Similar to those in Parkinson’s disease and its late complications.
Causes and risk factors
The causes and risk factors are unknown. Recent microbiological methods were unable to demonstrate any virus, in particular, wild-type influenza virus, that caused influenza pandemic in 1918-21, simultaneously to LE, could not be detected in brain material of PEP patients. Relationship between EL/PEP and influenzy remains enigmatic.
Frequency currently extremely rare; since 1970 only single cases reportedMain occurrence of EL between 1918 and 1924. Between 1925-38, PEP reporesented almost 50% of all cases of parkinsonism diagnosed at that time. Later on, incidence of PEP ranged from 4 - 30% (mean of 13%) of all cases of parkinsonism. In recent years, incidence of PEP in austopsy series dropped from 6% (1957-70) to almost zero in last decade.
Similar to Parkinson disease (PD), but history of EL necessary. No diagnostic test available.Diff. diagnosis: mainly against PD, but significant differences: 1. onset of symptoms in younger age, including children and adults aged 25-40 yrs; 2. rare occurence of rest tremor; 3. progression of disease in discontinous spurts; 44. prior history of acute EL.
Care and treatment
Similar to PD. Patients may variably respond to L-dopa therapy. Late complications to be treated like those in PD.
Ongoing research/Clinical trials
Trials to identify causing viral agent using modern molecular biologic and genetic methods. Due to almost total extinction of PEP, repository archival material represents the only source for modern investigations, that up to the present, failed to identify a causaive or transmissible agent.
The European Parkinson’s Disease Association (EPDA) Lizzie Graham EPDA Liaison/Project Manager 4 Golding Road Sevenoaks Kent TN13 3NJ United Kingdom Tel/Fax: + 44 (0)1732 457683 firstname.lastname@example.org www.epda.eu.com
- J.M.Henry & K.A.Jellinger. Postencephalitic parkinsonism In: Neurodegeneration. The molecular pathology of dementia and movement disorders.
- D.W.Dickson et al., eds. ISN Press, Los Angeles, 2003 (in press).
- Litvan I. et al.; Eur J Neurol 5:451-57 (1998)
- Reid AH et al. J Neuropathol Exp Neurol 60:563-70(2001).
Last Updated: vendredi 09 octobre 2009