Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution.

OBJECTIVE: To describe the clinical features of Creutzfeldt-Jakob disease with a substitution of arginine for methionine (M232R substitution) at codon 232 (CJD232) of the prion protein gene (PRNP). PATIENTS AND METHODS: We evaluated the clinical and laboratory features of 20 CJD232 patients: age of onset, initial symptoms, duration until becoming akinetic and mute, duration until occurrence of periodic sharp and wave complexes on EEG (PSWC), MRI findings, and the presence of CSF 14-3-3 protein. Immunohistochemically, prion protein (PrP) deposition was studied. RESULTS: None of the patients had a family history of CJD. We recognized two clinical phenotypes: a rapidly progressive type (rapidtype) and a slowly progressive type (slow-type). Out of 20 patients, 15 became akinetic and mute, demonstrated myoclonus, and showed PSWC within a mean duration of 3.1, 2.4, and 2.8 months, respectively (rapid-type). Five showed slowly progressive clinical courses (slow-type). Five became akinetic and mute and four demonstrated myoclonus within a mean duration of 20.6 and 15.3 months, respectively, which were significantly longer than those in the rapid-type. Only one demonstrated PSWC 13 months after the onset. Diffuse synaptic-type deposition was demonstrated in four rapidtype patients, and perivacuolar and diffuse synaptic-type deposition in two, and diffuse synaptic-type deposition in one slow-type patient. Three of 50 suspected but non-CJD patients had the M232R substitution. CONCLUSIONS: Patients with CJD232 had no family history like patients with sCJD, and showed two different clinical phenotypes in spite of having the same PRNP genotype. More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression.

"Hydrocephalus-parkinsonism complex": progressive hydrocephalus as a factor affecting extrapyramidal tract disorder-an experimental study.

OBJECTIVE: To experimentally clarify the symptomatological and pathophysiological aspects of a newly proposed clinical entity, we produced an experimental rat "hydrocephalus-parkinsonism complex" model. METHODS: A total of 60 male Sprague-Dawley rats were used. Twenty rats were treated with only kaolin as controls. Hemiparkinsonism was induced in the other 40 rats by stereotactic injection of 6-hydroxydopamine (6-OHDA) directly into the right substantia nigra. Twenty of these 40 rats were then treated with an injection of kaolin into the cisterna magna 3 days after the induction of parkinsonism. Neurological features were assessed weekly for 1 to 6 weeks after 6-OHDA injection by an apomorphine-induced turning test. RESULTS: The mortality rate was 25% in the rats injected with kaolin and 10% in those with the 6-OHDA injection. The frequency of the induction of parkinsonism-like signs was minimal in the first 2 weeks and reached a maximum point 4 weeks after the 6-OHDA injection. In contrast, the rats injected with both 6-OHDA and kaolin developed hemiparkinsonism-like signs in the early stage of the progression of hydrocephalus, and the peak incidence was reached in the 2nd week after induction ( p<0.05 compared with the 6-OHDA group). The severity of the neurological disturbance was also significantly more prominent in the latter group. CONCLUSION: These results suggest that the hydrodynamic effect in the early period of ventriculomegaly is the mechanism for signs of parkinsonism in 6-OHDA-treated rats. It could be concluded that the hydrocephalic state aggravates parkinsonism, if any as the associated condition, and it may be a new clinical entity of hydrocephalus symptomatology with a specific pathophysiology.