Lancet. 1998 Oct 3;352(9134):1116-7.
Research letters Volume 352, Number 9134, 3 October 1998
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio
Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited,
acquired, and sporadic mammalian neurological disorders, and are
characterised by the conversion of the cellular prion protein (PrP) in an
insoluble and protease-resistant isoform (PrPres). In human TSE, four types
of PrPres have been identified according to size and glycoform ratios, which
may represent different prion strains. Type-1 and type-2 PrPres are
associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with
iatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence that
variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion
strain.2-4 The BSE strain has been identified in three cats with feline
spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in
the UK.5 We report the simultaneous occurrence of sporadic CJD in a man and
a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November,
1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and
myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta
activity. A brain magnetic resonance imaging scan was unremarkable. 10 days
later, he was speechless and able to follow only simple commands. Repeat
EEGs showed periodic triphasic complexes. 2 weeks after admission, he was
mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November,
1993, with episodes of frenzy, twitching of its body, and hyperaesthesia.
The cat was usually fed on canned food and slept on its owner's bed. No
bites from the cat were recalled. In the next few days, the cat became
ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and
there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient
and the cat were methionine homozygous at codon 129. Histology of the
patient's brain showed neocortical and cerebellar neuronal loss,
astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed a
punctate pattern and paralleled spongiform changes (figure B). The cat's
brain showed mild and focal spongiosis in deeper cortical layers of all four
lobes (figure C), vacuolated cortical neurons (figure D), and mild
astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed.
Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and
caudate nucleus (figure E). Western blot analysis of control and affected
human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After
digestion with proteinase K and deglycosylation, only samples from the
affected patient and cat showed type-1 PrPres, with PrP glycoform ratios
comparable to those observed in sporadic CJD1 (details available from
author).
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform
degeneration and neuronal loss (haematoxylin and eosin) and B: punctate
perineuronal pattern of PrP immunoreactivity; peroxidase
immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex
showing mild spongiform degeneration (haematoxylin and eosin).D:
vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase
immunohistochemistry with antibody 3F4 shows punctate perineuronal
deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline
prion diseases. The clinical features of the cat were different from
previously reported cases of FSE which were characterised by gradual onset
of behavioural changes preceding locomotor dysfunction and ataxia.5
Neuropathological changes were also at variance with the diffuse spongiosis
and vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern of
PrP deposition, similar in the cat and in the patient, was atypical for a
BSE-related condition. Evidence of a new type of FSE was further provided by
the detection of a type-1 PrPres, other than the BSE-associated type 4.2
Taken together, our data suggest that the same agent strain of sporadic CJD
was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal
transmission in either direction, infection from an unknown common source,
or the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic
variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39:
767-78 [PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of
prion strain variation and the aetiology of 'new variant' CJD. Nature 1996;
383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that
'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501
[PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD
and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform
encephalopathy: a review. Vet Annual 1993; 33: 1-10.
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Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della
Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy
(S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico
Sperimentale della Lombardia e dell' Emilia, Brescia
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9798590&dopt=Abstract