Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease

Ana Lia Taratuto, P. Piccardo, E. G. Reich, S. G. Chen, G. Sevlever, M. Schultz, A. A. Luzzi, M. Rugiero, G. Abecasis, M. Endelman, A. M. Garcia, S. Capellari, Z. Xie, E. Lugaresi, P. Gambetti, Stephen Dlouhy, Bernardino Ghetti

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Abstract

Background: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. Objective: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. Methods: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. Results: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrPsc) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrPsc. N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. Conclusions: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

Original languageEnglish
Pages (from-to)362-367
Number of pages6
JournalNeurology
Volume58
Issue number3
StatePublished - Feb 12 2002
Externally publishedYes

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Creutzfeldt-Jakob Syndrome
Sleep Initiation and Maintenance Disorders
Haplotypes
Endopeptidase K
Gliosis
Protein Sequence Analysis
Thalamus
Fatal Familial Insomnia
Western Blotting
Agraphia
Olivary Nucleus
Dysarthria
Bulimia
Myoclonus
Polysomnography
Hallucinations
Neocortex
Memory Disorders
Glycine
Cerebellum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Taratuto, A. L., Piccardo, P., Reich, E. G., Chen, S. G., Sevlever, G., Schultz, M., ... Ghetti, B. (2002). Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease. Neurology, 58(3), 362-367.

Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease. / Taratuto, Ana Lia; Piccardo, P.; Reich, E. G.; Chen, S. G.; Sevlever, G.; Schultz, M.; Luzzi, A. A.; Rugiero, M.; Abecasis, G.; Endelman, M.; Garcia, A. M.; Capellari, S.; Xie, Z.; Lugaresi, E.; Gambetti, P.; Dlouhy, Stephen; Ghetti, Bernardino.

In: Neurology, Vol. 58, No. 3, 12.02.2002, p. 362-367.

Research output: Contribution to journalArticle

Taratuto, AL, Piccardo, P, Reich, EG, Chen, SG, Sevlever, G, Schultz, M, Luzzi, AA, Rugiero, M, Abecasis, G, Endelman, M, Garcia, AM, Capellari, S, Xie, Z, Lugaresi, E, Gambetti, P, Dlouhy, S & Ghetti, B 2002, 'Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease', Neurology, vol. 58, no. 3, pp. 362-367.
Taratuto AL, Piccardo P, Reich EG, Chen SG, Sevlever G, Schultz M et al. Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease. Neurology. 2002 Feb 12;58(3):362-367.
Taratuto, Ana Lia ; Piccardo, P. ; Reich, E. G. ; Chen, S. G. ; Sevlever, G. ; Schultz, M. ; Luzzi, A. A. ; Rugiero, M. ; Abecasis, G. ; Endelman, M. ; Garcia, A. M. ; Capellari, S. ; Xie, Z. ; Lugaresi, E. ; Gambetti, P. ; Dlouhy, Stephen ; Ghetti, Bernardino. / Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease. In: Neurology. 2002 ; Vol. 58, No. 3. pp. 362-367.
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abstract = "Background: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. Objective: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. Methods: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. Results: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrPsc) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrPsc. N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. Conclusions: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.",
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T1 - Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease

AU - Taratuto, Ana Lia

AU - Piccardo, P.

AU - Reich, E. G.

AU - Chen, S. G.

AU - Sevlever, G.

AU - Schultz, M.

AU - Luzzi, A. A.

AU - Rugiero, M.

AU - Abecasis, G.

AU - Endelman, M.

AU - Garcia, A. M.

AU - Capellari, S.

AU - Xie, Z.

AU - Lugaresi, E.

AU - Gambetti, P.

AU - Dlouhy, Stephen

AU - Ghetti, Bernardino

PY - 2002/2/12

Y1 - 2002/2/12

N2 - Background: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. Objective: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. Methods: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. Results: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrPsc) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrPsc. N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. Conclusions: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

AB - Background: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. Objective: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. Methods: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. Results: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrPsc) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrPsc. N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. Conclusions: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

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