Clinicopathological Correlates in aPRNPP102L Mutation Carrier with Rapidly Progressing Parkinsonism-dystonia.
Parkinsonism-dystonia is rare in carriers of PRNP P102L mutation. Severity and distribution of prion protein (PrP) deposition may influence the clinical presentation. We present such clinic-pathological correlation in a 56-year-old male with a PRNP P102L mutation associated with a phenotype characterized by rapidly progressing parkinsonism-dystonia. The patient was studied clinically (videotaped exams, brain MRIs); molecular genetically (gene sequence analysis); and neuropathologically (histology, immunohistochemistry) during his 7-month disease course. The patient had parkinsonism, apraxia, aphasia, and dystonia, which progressed rapidly. Molecular genetic analysis revealed PRNP P102L mutation carrier status. Brain MRIs revealed progressive global volume loss and T2/FLAIR hyperintensity in neocortex and basal ganglia. Postmortem examination showed neuronal loss, gliosis, spongiform changes, and PrP deposition in the striatum. PrP immunohistochemistry revealed widespread severe PrP deposition in the thalamus and cerebellar cortex. Based on the neuropathological and molecular-genetic analysis, the rapidly progressing parkinsonism-dystonia correlated with nigrostriatal, thalamic, and cerebellar pathology.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.
Chizoba C
CC
Umeh
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.
Piyush
P
Kalakoti
Charles County Neurology, Waldorf, MD.
Michael K
MK
Greenberg
National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH.
Silvio
S
Notari
National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH.
Yvonne
Y
Cohen
National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH.
Pierluigi
P
Gambetti
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.
Adrian L
AL
Oblak
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.
Bernardino
B
Ghetti
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.
Zoltan
Z
Mari
Gerstmann-Sträussler-Scheinker disease; P102L mutation; dystonia; parkinsonism; prion protein