Fatal familial insomnia: Clinical and pathologic study of five new cases

V. Manetto, R. Medori, P. Cortelli, P. Montagna, P. Tinuper, A. Baruzzi, G. Rancurel, J. J. Hauw, J. J. Vanderhaeghen, P. Mailleux, O. Bugiani, F. Tagliavini, C. Bouras, N. Rizzuto, E. Lugaresi, P. Gambetti

Research output: Contribution to journalArticle

Abstract

In 1986, we reported two anatomoclinical observations of a familial condition that we called “fatal familial insomnia” (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with “torpedoes,” and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalNeurology
Volume42
Issue number2
Publication statusPublished - 1992

Fingerprint

Fatal Familial Insomnia
Atrophy
Sleep Initiation and Maintenance Disorders
Pedigree
Cerebral Cortex
Olivary Nucleus
Anterior Thalamic Nuclei
Ventral Thalamic Nuclei
Mediodorsal Thalamic Nucleus
Hyperhidrosis
Thalamic Nuclei
Prion Diseases
Gliosis
Age of Onset
Tachycardia
Fever
Pathology
Hypertension
Clinical Studies
Familial

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Manetto, V., Medori, R., Cortelli, P., Montagna, P., Tinuper, P., Baruzzi, A., ... Gambetti, P. (1992). Fatal familial insomnia: Clinical and pathologic study of five new cases. Neurology, 42(2), 312-319.

Fatal familial insomnia : Clinical and pathologic study of five new cases. / Manetto, V.; Medori, R.; Cortelli, P.; Montagna, P.; Tinuper, P.; Baruzzi, A.; Rancurel, G.; Hauw, J. J.; Vanderhaeghen, J. J.; Mailleux, P.; Bugiani, O.; Tagliavini, F.; Bouras, C.; Rizzuto, N.; Lugaresi, E.; Gambetti, P.

In: Neurology, Vol. 42, No. 2, 1992, p. 312-319.

Research output: Contribution to journalArticle

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, vol. 42, no. 2, pp. 312-319.
Manetto V, Medori R, Cortelli P, Montagna P, Tinuper P, Baruzzi A et al. Fatal familial insomnia: Clinical and pathologic study of five new cases. Neurology. 1992;42(2):312-319.
Manetto, V. ; Medori, R. ; Cortelli, P. ; Montagna, P. ; Tinuper, P. ; Baruzzi, A. ; Rancurel, G. ; Hauw, J. J. ; Vanderhaeghen, J. J. ; Mailleux, P. ; Bugiani, O. ; Tagliavini, F. ; Bouras, C. ; Rizzuto, N. ; Lugaresi, E. ; Gambetti, P. / Fatal familial insomnia : Clinical and pathologic study of five new cases. In: Neurology. 1992 ; Vol. 42, No. 2. pp. 312-319.
@article{3967eb7a4bc440d899d8b7eb4b18c7d2,
title = "Fatal familial insomnia: Clinical and pathologic study of five new cases",
abstract = "In 1986, we reported two anatomoclinical observations of a familial condition that we called “fatal familial insomnia” (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with “torpedoes,” and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.",
author = "V. Manetto and R. Medori and P. Cortelli and P. Montagna and P. Tinuper and A. Baruzzi and G. Rancurel and Hauw, {J. J.} and Vanderhaeghen, {J. J.} and P. Mailleux and O. Bugiani and F. Tagliavini and C. Bouras and N. Rizzuto and E. Lugaresi and P. Gambetti",
year = "1992",
language = "English",
volume = "42",
pages = "312--319",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Fatal familial insomnia

T2 - Clinical and pathologic study of five new cases

AU - Manetto, V.

AU - Medori, R.

AU - Cortelli, P.

AU - Montagna, P.

AU - Tinuper, P.

AU - Baruzzi, A.

AU - Rancurel, G.

AU - Hauw, J. J.

AU - Vanderhaeghen, J. J.

AU - Mailleux, P.

AU - Bugiani, O.

AU - Tagliavini, F.

AU - Bouras, C.

AU - Rizzuto, N.

AU - Lugaresi, E.

AU - Gambetti, P.

PY - 1992

Y1 - 1992

N2 - In 1986, we reported two anatomoclinical observations of a familial condition that we called “fatal familial insomnia” (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with “torpedoes,” and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

AB - In 1986, we reported two anatomoclinical observations of a familial condition that we called “fatal familial insomnia” (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with “torpedoes,” and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

UR - http://www.scopus.com/inward/record.url?scp=0026563279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026563279&partnerID=8YFLogxK

M3 - Article

C2 - 1736158

AN - SCOPUS:0026563279

VL - 42

SP - 312

EP - 319

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 2

ER -