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01-10-2006 | Case Report

MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical pathology

Authors: Kazunori Hirose, Yasushi Iwasaki, Masayuki Izumi, Mari Yoshida, Yoshio Hashizume, Tetsuyuki Kitamoto, Ko Sahashi

Published in: Acta Neuropathologica | Issue 4/2006

Abstract

We report an autopsy case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) with widespread cerebral neocortical pathology. Initial symptoms were progressive insomnia and mental disturbance. Magnetic resonance imaging revealed no high-signal intensity lesions on diffusion-weighted images and later showed gradually progressive cerebral atrophy. Periodic synchronous discharges and myoclonus were not observed. Upon neuropathologic examination, widespread cerebral neocortical involvement with fine vacuole-type spongiform change was observed. Severe degeneration with almost complete neuronal loss, tissue rarefaction, numerous fat-laden macrophages and hypertrophic astrocytosis of the medial thalamic nucleus was evident. The inferior olivary nucleus showed severe involvement with neuronal loss and hypertrophic astrocytosis. In the cerebellar cortex, moderate depletion of Purkinje neurons was evident, with no spongiform change in the molecular layer and no neuronal loss in the granule cell layer. Immunohistochemistry for prion protein (PrP) revealed widespread synaptic-type deposits with some primitive plaque-type deposits in the cerebral neocortex, basal ganglia and cerebellar cortex. PrP deposition was also observed in the brainstem, particularly the tegmentum, substantia nigra and pontine nucleus, and spinal cord, particularly the posterior horn. In the medial thalamus and inferior olivary nucleus, PrP deposition was sparse. Analysis of the PrP gene showed no mutation but did show methionine homozygosity at polymorphic codon 129. Western blot analysis of protease-resistant PrP indicated the presence of type 2 PrP. We believe that this patient suffered from MM2-thalamic-type sCJD (sporadic fatal insomnia) with widespread cerebral neocortical pathology due to prolonged disease duration. The present case showed different patterns of spongiform degeneration and PrP deposition in the cerebral neocortex than those in previously reported MM2-thalamic-type sCJD cases.

DeArmond SJ, Kretzschmar HA, Prusiner SB (2002) Prion diseases. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology, vol 2, 7th edn. Hodder Arnold, London, pp 273–323

Gambetti P, Kong Q, Zou W, Parchi P, Chen SG (2003) Sporadic and familial CJD: classification and characterization. Br Med Bull 66:213–239PubMedCrossRef

Hamaguchi T, Kitamoto T, Sato T, Mizusawa H, Nakamura Y, Noguchi M, Furukawa Y, Ishida C, Kuji I, Mitani K, Murayama S, Kohriyama T, Katayama S, Yamashita M, Yamamoto T, Udaka F, Kawakami A, Ihara Y, Nishinaka T, Kuroda S, Suzuki N, Shiga Y, Arai H, Maruyama M, Yamada M (2005) Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease. Neurology 64:643–648PubMed

Hirano Y, Katayama S, Yokoyama S, Honma K, Nakajima S (1984) An autopsy case of thalamic degeneration and a review of the literature (in Japanese). Rinsho Shinkeigaku 24:1039–1049PubMed

Hori A, Ikeda K, Kosaka K, Shinohara S, Iizuka R (1981) System degeneration of the thalamus. A clinico-neuropathological study. Arch Psychiatr Nervenkr 231:71–80PubMedCrossRef

Iwasaki Y, Hashizume Y, Yoshida M, Kitamoto T, Sobue G (2005) Neuropathologic characteristics of brainstem lesions in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 109:557–566CrossRef

Iwasaki Y, Yoshida M, Hashizume Y, Kitamoto T, Sobue G (2005) Neuropathologic characteristics of spinal cord lesions in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 110:490–500CrossRef

Kawasaki K, Wakabayashi K, Kawakami A, Higuchi M, Kitamoto T, Tsuji S, Takahashi H (1997) Thalamic form of Creutzfeldt-Jakob disease or fatal insomnia? Report of a sporadic case with normal prion protein genotype. Acta Neuropathol (Berl) 93:317–322CrossRef

Kitamoto T, Shin RW, Doh-ura K, Tomokane N, Miyazono M, Muramoto T, Tateishi J (1992) Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease. Am J Pathol 140:1285–1294PubMed

10.

Kornfeld M, Seelinger DF (1994) Pure thalamic dementia with a single focus of spongiform change in cerebral cortex. Clin Neuropathol 13:77–81PubMed

11.

Kretzschmar HA, Ironside JW, DeArmond SJ, Tateishi J (1996) Diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Arch Neurol 53:913–920PubMed

12.

Manetto V, Medori R, Cortelli P, Montagna P, Tinuper P, Baruzzi A, Rancurel G, Hauw JJ, Vanderhaeghen JJ, Mailleux P, Bugiani O, Tagliavini F, Bouras C, Rizzuto N, Lugaresi E, Gambetti P (1992) Fatal familial insomnia: clinical and pathologic study of five new cases. Neurology 42:312–319PubMed

13.

Mastrianni JA, Nixon R, Layzer R, Telling GC, Han D, DeArmond SJ, Prusiner SB (1999) Prion protein conformation in a patient with sporadic fatal insomnia. N Engl J Med 340:1630–1638PubMedCrossRef

14.

Mizusawa H, Ohkoshi N, Sasaki H, Kanazawa I, Nakanishi T (1988) Degeneration of the thalamus and inferior olives associated with spongiform encephalopathy of the cerebral cortex. Clin Neuropathol 7:81–86PubMed

15.

Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 58:192–197PubMed

16.

Parchi P, Castellani R, Cortelli P, Montagna P, Chen SG, Petersen RB, Manetto V, Vnencak-Jones CL, McLean MJ, Sheller JR, Lugaresi E, Autilio-Gambetti L, Gambetti P (1995) Regional distribution of protease-resistant prion protein in fatal familial insomnia. Ann Neurol 38:21–29PubMedCrossRef

17.

Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AA, Trojanowski JQ, Petersen RB, Gambetti P (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39:767–778PubMedCrossRef

18.

Parchi P, Petersen RB, Chen SG, Autilio-Gambetti L, Capellari S, Monari L, Cortelli P, Montagna P, Lugaresi E, Gambetti P (1998) Molecular pathology of fatal familial insomnia. Brain Pathol 8:539–548PubMedCrossRef

19.

Parchi P, Capellari S, Chin S, Schwarz HB, Schecter NP, Butts JD, Hudkins P, Burns DK, Powers JM, Gambetti P (1999) A subtype of sporadic prion disease mimicking fatal familial insomnia. Neurology 52:1757–1763PubMed

20.

Parchi P, Giese A, Capellari S, Brown P, Schulz-Shaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233PubMedCrossRef

21.

Parchi P, Capellari S, Gambetti P (2000) Intracerebral distribution of the abnormal isoform of the prion protein in sporadic Creutzfeldt-Jakob disease and fatal insomnia. Microsc Res Tech 50:16–25PubMedCrossRef

22.

Piao YS, Kakita A, Watanabe H, Kitamoto T, Takahashi H (2005) Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrP^Sc deposits in the brain. Neuropathology 25:144–149PubMedCrossRef

23.

Puoti G, Giaccone G, Rossi G, Canciani B, Bugiani O, Tagliavini F (1999) Sporadic Creutzfeldt-Jakob disease: co-occurrence of different types of PrP(Sc) in the same brain. Neurology 53:2173–2176PubMed

24.

Scaravilli F, Cordery RJ, Kretzschmar H, Gambetti P, Brink B, Fritz V, Temlett J, Kaplan C, Fish D, An SF, Schulz-Snschaeffer WJ, Rossor MN (2000) Sporadic fatal insomnia: a case study. Ann Neurol 48:665–668PubMedCrossRef

25.

Siska E, Gereby G, Tariska S (1985) Thalamic dementia (in German). Fortschr Neurol Psychiatr 53:302–311PubMedCrossRef

26.

Stern K (1939) Severe dementia associated with bilateral symmetrical degeneration of the thalamus. Brain 62:157–171

27.

Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925PubMedCrossRef

28.

Will RG, Zeidler M, Stewart GE, Macleod MA, Ironside JW, Cousens SN, Mackenzie J, Estibeiro K, Green AJ, Knight RS (2000) Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol 47:575–582PubMedCrossRef

29.

Yagishita T, Kojima S, Arai K, Hirayama K, Akai J, Takemura K (1987) Dementia and disturbance of consciousness in thalamic degeneration (in Japanese). No To Shinkei 39:79–85PubMed

30.

Yamashita M, Yamamoto T, Nishinaka K, Udaka F, Kameyama M, Kitamoto T (2001) Severe brain atrophy in a case of thalamic variant of sporadic CJD with plaque-like PrP deposition. Neuropathology 21:138–143PubMedCrossRef

31.

Zerr I, Schulz-Schaeffer WJ, Giese A, Bodemer M, Schroter A, Henkel K, Tschampa HJ, Windl O, Pfahlberg A, Steinhoff BJ, Gefeller O, Kretzschmar HA, Poser S (2000) Current clinical diagnosis in Creutzfeldt-Jakob disease: identification of uncommon variants. Ann Neurol 48:323–329PubMedCrossRef

Title: MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical pathology
Authors: Kazunori Hirose
Yasushi Iwasaki
Masayuki Izumi
Mari Yoshida
Yoshio Hashizume
Tetsuyuki Kitamoto
Ko Sahashi
Publication date: 01-10-2006
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-006-0131-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical pathology

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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