A subtype of sporadic prion disease mimicking fatal familial insomnia

Parchi, Piero; Capellari, Sabina; Chin, Steven S.; Schwarz, Heidi B.; Schecter, Nathan; Butts, John D.; Hudkins, P.; Burns, Dennis K.; Powers, James M.

doi:10.1212/wnl.52.9.1757

Cited by 160 publications

(124 citation statements)

References 11 publications

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“…8 The analyses showed: (1) methionine homozygosity at codon 129 and lack of mutation in the prion protein gene; (2) severe neuronal loss and astrogliosis in the thalamic nuclei; (3) the presence of PK-resistant PrP Sc type 2; (4) glycoform ratios different from those of fatal familial insomnia and consistent with those associated with sFI 8,15 ; and (5) lower amounts of PKresistant PrP Sc in subcortical regions than the cerebral cortex. 16 No evaluation of insomnia or dysautonomia was performed, and their presence or absence is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Densitometric analyses on PK-resistant PrP Sc in the cerebral cortex revealed a glycoform ratio similar to other sFI cases (Fig 3). 8 Methionine homozygosity at codon 129 with no mutations was established with prion protein gene analysis, performed as described previously. 14 …”

Section: Diagnostic Studiesmentioning

confidence: 99%

“…6 Patients with sFI share phenotypic similarities with patients who have the genetic prion disease fatal familial insomnia 7 but lack a mutation at codon 178 of the prion protein gene. 8 Fatal insomnia patients usually suffer from insomnia, motor abnormalities, and altered autonomic functions. 7,8 Polysomnography typically shows reduction of sleep-related EEG activities, such as K-complexes and spindles, 9 and positron emission tomography scans may show focal thalamic hypometabolism.…”

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confidence: 99%

“…8 Fatal insomnia patients usually suffer from insomnia, motor abnormalities, and altered autonomic functions. 7,8 Polysomnography typically shows reduction of sleep-related EEG activities, such as K-complexes and spindles, 9 and positron emission tomography scans may show focal thalamic hypometabolism. 10 Neuropathologic studies demonstrate prominent lesions in the thalamus relative to other brain regions.…”

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confidence: 99%

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Sporadic Fatal Insomnia in an Adolescent

et al. 2014

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The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient’s autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation.

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Section: Discussionmentioning

confidence: 99%

Section: Diagnostic Studiesmentioning

confidence: 99%

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confidence: 99%

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Sporadic Fatal Insomnia in an Adolescent

et al. 2014

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“…sCJD subtypes were classified according to Parchi et al 28 They included 10 MM1, 5 MV1, 3 VV1, 9 MV2 with kuru plaques, 15 VV2, 3 MM2-cortical, 5 MM2-thalamic, a disease subtype also known as sporadic fatal insomnia, 36 and 3 MM sCJD cases in which standard PrP Sc typing demonstrated the co-occurrence of types 1 and 2, as described by Parchi et al 29 Brain tissues were obtained at autopsy and were kept frozen at À801C until use. One sample from the frontal cerebral cortex (FC), usually the middle frontal gyrus (MFG), was available in all cases.…”

Section: Materials and Methods Patients And Tissuesmentioning

confidence: 99%

A refined method for molecular typing reveals that co-occurrence of PrPSc types in Creutzfeldt–Jakob disease is not the rule

Notari

Capellari

Langeveld

et al. 2007

Laboratory Investigation

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Molecular typing in Creutzfeldt-Jakob disease (CJD) relies on the detection of distinct protease-resistant prion protein (PrP Sc ) core fragments, which differ in molecular mass or glycoform ratio. However, the definition and correct identification of CJD cases with a co-occurrence of PrP Sc types remains a challenge. With antibodies recognizing a linear epitope in the octapeptide repeat PrP region, supposed to distinguish between the two major PrP Sc isoforms (ie, types 1 and 2), it was recently shown that all type 2 cases display an associated band with a type 1 migration pattern, which led to the conclusion that multiple PrP Sc types regularly coexist in CJD. We studied brain samples from 53 sporadic CJD and 4 variant CJD subjects using a high-resolution electrophoresis, a wide range of proteinase K (PK) activities, the 'type 1-selective' antibody 12B2, and several unselective antibodies. We found that the type 1-like band detected by 12B2 in all CJD subtypes associated with PrP Sc type 2 is not a PK-resistant PrP Sc core but rather matches the physicochemical properties of partially cleaved fragments, which result from the several PK cleavage sites included in the N-terminal portion of PrP Sc . Furthermore, using gels with high resolution and a relatively high PK activity, we were able to increase the detection sensitivity of either type 1 or 2, when coexisting, to amount corresponding to 3-5% of the total PrP Sc signal (ie, weak band of one type/total PrP Sc ). Our results show that there are many pitfalls associated with the use of 'type 1 selective' antibodies for CJD typing studies and that co-occurrence of PrP Sc types in CJD is not the rule. The present results further validate the rationale basis of current CJD classification and the qualitative nature of molecular typing in CJD.

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