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Variably protease-sensitive prionopathy mimicking frontotemporal dementia

Variably protease-sensitive prionopathy mimicking frontotemporal dementia
Variably protease-sensitive prionopathy mimicking frontotemporal dementia

Sporadic prion diseases are fatal neurodegenerative disorders characterized clinically by rapidly progressive dementia and myoclonus. Variably protease-sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder that may present with a lengthy atypical clinical history. Here, we describe a case of VPSPr in a patient with a long history of suspected frontotemporal dementia (FTD). A 61-year-old man presented with speech difficulties, including naming objects and constructing multipart sentences, while there was no difficulty in comprehension. Movement abnormalities included slightly jerky pursuit, minor dysmetria of saccades and brisk reflexes. There was no family history of dementia. Later he developed swallowing difficulties and the possibility of FTD with motor neuron disease was suspected. He died at the age of 71 and his brain was donated to the London Neurodegenerative Diseases Brain Bank. The brain (1004 g) showed mild to moderate atrophy, predominantly in the frontal lobe. Histology revealed moderate spongiform microvacuolation mostly affecting the frontal and parietal cortices, but also present focally in the basal ganglia and the cerebellum. Only mild Alzheimer pathology was found by extensive immunohistochemistry, in keeping with BrainNet Europe stage II. Trans-activation response DNA-binding protein 43 kDa and α-synuclein immunostains were negative. Immunostaining for prion protein (PrP) showed granular/synaptic positivity in a patchy distribution, mainly within the deeper cortex, and also revealed microplaques in the cerebellum and basal ganglia. Western blotting confirmed a low molecular weight protease-resistant PrP band with a faint ladder-like pattern in the absence of types 1 and 2 isoforms. These features are diagnostic of VPSPr. VPSPr can mimic various neurodegenerative conditions; diagnosis requires both PrP immunohistochemistry and Western blotting. The presence of patchy spongiform change in the absence of other neurodegenerative pathology should raise suspicion of VPSPr, even in elderly patients with a lengthy clinical history.

Creutzfeldt–Jakob disease, prion diseases, prion protein, prions, variably protease-sensitive prionopathy
0919-6544
1-6
Aizpurua, Miren
5b44a8c6-5576-4ecc-853b-c9cc339cf555
Selvackadunco, Sashika
26e1eee2-86bb-4b43-b585-af488eeda96c
Yull, Helen
26d65d08-591e-464a-9ff8-ce24405af469
Kipps, Christopher M.
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
Ironside, James W.
4e5c33fb-efca-46b6-8efe-b7ef642b00a5
Bodi, Istvan
d205dd11-e1f6-483c-a477-2ad274edb8f7
Aizpurua, Miren
5b44a8c6-5576-4ecc-853b-c9cc339cf555
Selvackadunco, Sashika
26e1eee2-86bb-4b43-b585-af488eeda96c
Yull, Helen
26d65d08-591e-464a-9ff8-ce24405af469
Kipps, Christopher M.
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
Ironside, James W.
4e5c33fb-efca-46b6-8efe-b7ef642b00a5
Bodi, Istvan
d205dd11-e1f6-483c-a477-2ad274edb8f7

Aizpurua, Miren, Selvackadunco, Sashika, Yull, Helen, Kipps, Christopher M., Ironside, James W. and Bodi, Istvan (2019) Variably protease-sensitive prionopathy mimicking frontotemporal dementia. Neuropathology, 1-6. (doi:10.1111/neup.12538).

Record type: Article

Abstract

Sporadic prion diseases are fatal neurodegenerative disorders characterized clinically by rapidly progressive dementia and myoclonus. Variably protease-sensitive prionopathy (VPSPr) is a recently identified sporadic human prion disorder that may present with a lengthy atypical clinical history. Here, we describe a case of VPSPr in a patient with a long history of suspected frontotemporal dementia (FTD). A 61-year-old man presented with speech difficulties, including naming objects and constructing multipart sentences, while there was no difficulty in comprehension. Movement abnormalities included slightly jerky pursuit, minor dysmetria of saccades and brisk reflexes. There was no family history of dementia. Later he developed swallowing difficulties and the possibility of FTD with motor neuron disease was suspected. He died at the age of 71 and his brain was donated to the London Neurodegenerative Diseases Brain Bank. The brain (1004 g) showed mild to moderate atrophy, predominantly in the frontal lobe. Histology revealed moderate spongiform microvacuolation mostly affecting the frontal and parietal cortices, but also present focally in the basal ganglia and the cerebellum. Only mild Alzheimer pathology was found by extensive immunohistochemistry, in keeping with BrainNet Europe stage II. Trans-activation response DNA-binding protein 43 kDa and α-synuclein immunostains were negative. Immunostaining for prion protein (PrP) showed granular/synaptic positivity in a patchy distribution, mainly within the deeper cortex, and also revealed microplaques in the cerebellum and basal ganglia. Western blotting confirmed a low molecular weight protease-resistant PrP band with a faint ladder-like pattern in the absence of types 1 and 2 isoforms. These features are diagnostic of VPSPr. VPSPr can mimic various neurodegenerative conditions; diagnosis requires both PrP immunohistochemistry and Western blotting. The presence of patchy spongiform change in the absence of other neurodegenerative pathology should raise suspicion of VPSPr, even in elderly patients with a lengthy clinical history.

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Accepted/In Press date: 21 January 2019
e-pub ahead of print date: 7 March 2019
Keywords: Creutzfeldt–Jakob disease, prion diseases, prion protein, prions, variably protease-sensitive prionopathy

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Local EPrints ID: 429040
URI: https://eprints.soton.ac.uk/id/eprint/429040
ISSN: 0919-6544
PURE UUID: da00dde0-3328-44e0-89c1-668019e37e59

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Date deposited: 20 Mar 2019 17:30
Last modified: 19 Jul 2019 16:38

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Contributors

Author: Miren Aizpurua
Author: Sashika Selvackadunco
Author: Helen Yull
Author: Christopher M. Kipps
Author: James W. Ironside
Author: Istvan Bodi

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