3.5 YEAR COURSE FOR PATHOLOGY-PROVEN SPORADIC JAKOB-CREUTZFELDT DISEASE or sCJD
ONLINE FIRST
Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive
Aphasia
David Y. Johnson, MD; Diana L. Dunkelberger, MA; Maya Henry, PhD; Aissatou
Haman, MD; Michael D. Greicius, MD, PhD; Katherine Wong, BA; Stephen J.
DeArmond, MD, PhD; Bruce L. Miller, MD; Maria Luisa Gorno-Tempini, MD, PhD;
Michael D. Geschwind, MD, PhD Arch Neurol. 2012;():1-4.
doi:10.1001/jamaneurol.2013.139.
Published online November 5, 2012
ABSTRACT
ABSTRACT | REPORT OF A CASE | COMMENT | AUTHOR INFORMATION |
REFERENCES
Objective To report the clinical, neuropsychological, linguistic, imaging,
and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt
disease in which the patient presented with a logopenic variant of primary
progressive aphasia.
Design Case report.
Setting Large referral center for atypical memory and aging disorders,
particularly Jakob-Creutzfeldt disease.
Patient Patient presenting with logopenic variant primary progressive
aphasia initially thought to be due to Alzheimer disease.
Results Despite the long, slow 3.5-year course, the patient was shown to
have pathology-proven sporadic Jakob-Creutzfeldt disease.
Conclusions These findings expand the differential of primary progrssive
aphasia to include prion disease.
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in
BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
AS OF AUGUST 2012 ;
CJD UPDATE USA
1 Listed based on the year of death or, if not available, on year of
referral; 2 Cases with suspected prion disease for which brain tissue and/or
blood (in familial cases) were submitted; 3 Disease acquired in the United
Kingdom; 4 Disease was acquired in the United Kingdom in one case and in Saudi
Arabia in the other case; *** 5 Includes 8 cases in which the diagnosis is
pending, and 18 inconclusive cases; *** 6 Includes 10 (9 from 2012) cases with
type determination pending in which the diagnosis of vCJD has been excluded. ***
The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42
cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2224 cases of
sporadic Creutzfeldt-Jakob disease (sCJD).
SEE FULL TEXT ;
Tuesday, November 6, 2012
Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and
Sporadic CJD, November-December 2012 update
Wednesday, August 01, 2012
Behavioural and Psychiatric Features of the Human Prion Diseases:
Experience in 368 Prospectively Studied Patients
Monday, August 06, 2012
Atypical neuropathological sCJD-MM phenotype with abundant white matter
Kuru-type plaques sparing the cerebellar cortex
Saturday, October 13, 2012
On the issue of transmissibility of Alzheimer disease: A critical review
TSS
posted by Terry S. Singeltary Sr. at
3:10 PM
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