The neuropathologic diagnostic criteria of frontal lobe dementia revisited. A study of ten consecutive cases

  • J. J. Hauw
  • C. Duyckaerts
  • D. Seilhean
  • S. Camilleri
  • V. Sazdovitch
  • G. Rancurel
Part of the Journal of Neural Transmission Supplement book series (NEURAL SUPPL, volume 47)


Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of:
  • dementia and prominent symptoms and signs of the frontal type;

  • a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions.

We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type:
  1. 1.

    If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease.

  2. 2.

    If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II–III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers.

  3. 3.

    When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.



Amyotrophic Lateral Sclerosis Motor Neuron Disease Progressive Supranuclear Palsy Motor Neuron Disease Primary Progressive Aphasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baldwin B, Förstl H (1993) “Pick’s disease”-101 years on. Still here, but in need of reform. Br J Psychiatry 163: 100–104PubMedCrossRefGoogle Scholar
  2. Brion S, Plas J, Jeanneau A (1991) Maladie de Pick. Point de vue anatomo-clinique. Rev Neurol (Paris) 147: 693–704Google Scholar
  3. Brun A (1987) Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch Gerontol Geriatr 6: 193–208PubMedCrossRefGoogle Scholar
  4. Brun A (1993) Frotal lobe degeneration of non-Alzheimer type revisited. Dementia 4: 126–131PubMedGoogle Scholar
  5. Budka H, Aguzzi A, Brown P, Brucher M, Bugiani O, Collinge J, Diringer H, Gullota F, Haltia M, Hauw JJ, Ironside JW, Kretzschmar HA, Lantos P, Masullo C, Pocchiari M, Schlote W, Tateichi J, Will RG (1995) Tissue handling in suspected CreutzfeldtJakob disease (CJD) and other human spongiform encephalopathies (Prion Diseases). Brain Pathol 5: 319–322PubMedCrossRefGoogle Scholar
  6. Constantinidis J, Richard J, Tissot R (1974) Pick’s disease. Histological and clinical correlation. Eur Neurol 11: 208–217Google Scholar
  7. Daniel SE, Geddes F, Revesz T (1994) Clinicopathological overlap between cases of Pick’s disease and corticobasal degeneration (Abstract). Brain Pathol 4: 516Google Scholar
  8. Delay J, Brion S (1962) Les démences tardives. Masson, ParisGoogle Scholar
  9. Delay J, Brion S, Sadoun R (1954) Lésions anatomiques de la maladie de Pick à la phase préatrophique. Rev Neurol (Paris) 91: 81–91Google Scholar
  10. Dickson DW, Yen SH, Suzuki KH, Davies P, Garcia JH, Hirano A (1986) Ballooned neurons in selected neurodegenerative diseases contain phosphorylated neuro-filament epitopes. Acta Neuropathol 71: 216–223PubMedCrossRefGoogle Scholar
  11. Escourolle R (1958) La maladie de Pick. Etude critique d’ensemble et synthèse anatomoclinique. R Foulon, ParisGoogle Scholar
  12. Giaccone G, Tagliavini F, Street JS, Ghetti B, Bugiani O (1988) Progressive supranuclear palsy with hypertrophy of the olives: an immunohistochemical study of argyrophilic neurons. Acta Neuropathol 77: 14–20PubMedCrossRefGoogle Scholar
  13. Hauw J-J, Daniel SE, Dickson D, Horoupian D, Jellinger K, Lantos P, McKee A, Tabaton M, Litvan I (1994) Preliminary NINDS neuropathologic criteria for SteeleRichardson-Olszewski syndrome (Progressive supranuclear palsy). Neurology 44: 2015–2019PubMedGoogle Scholar
  14. Higuchi Y, Iwaki T, Tateishi J (1995) Neurodegeneration in the limbic and paralimbic system in progressive supranuclear palsy. Neuropathol Appl Neurobiol 21: 246–254PubMedCrossRefGoogle Scholar
  15. Hof PR, Bouras C, Perl DP, Morrison JH (1994) Quantitative neuropathologic analysis of Pick’s disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer’s disease. Acta Neuropathol 87: 115–124PubMedCrossRefGoogle Scholar
  16. Hulette CM, Crain BJ (1992) Lobar atrophy without Pick bodies. Clin Neuropathol 11: 151–156PubMedGoogle Scholar
  17. Jackson M, Lennox G, Ward L, Lowe J (1995) Frontal lobe dementia with MND inclusions without clinical ALS: report of eleven cases. Neuropathol Appl Neurobiol 21: 148–149CrossRefGoogle Scholar
  18. Jellinger KA (1994) Rare neurodegenerative disorders. In: Caine DB (ed) Neuro-degenerative diseases. Saunders, Philadelphia, pp 909–931Google Scholar
  19. Jellinger KA, Bancher C (1994) Classification of dementias based on functional morphology. In: Jellinger KA, Ladurner G, Windisch M (eds) New trends in the diagnosis and therapy of Alzheimer’s disease. Springer, Wien New York, pp 9–39Google Scholar
  20. Kertesz A, Hudson L, Mackenzie IRA, Munoz DG (1994) The pathology and nosology of primary progressive aphasia. Neurology 44: 2065–2075PubMedGoogle Scholar
  21. Kirshner HS, Tanridag O, Thurman L, Whetsell WO (1987) Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 22: 527–532PubMedCrossRefGoogle Scholar
  22. Knopman DS (1993) Overview of dementia lacking distinctive histology: pathological designation of a progressive dementia. Dementia 4: 132–136PubMedGoogle Scholar
  23. Knopman DS, Mastri AR, Frey WHea (1990) Dementia lacking distinctive histological features: a common non-Alzheimer degenerative dementia. Neurology 40: 251–256PubMedGoogle Scholar
  24. Lantos PL (1992) Neuropathology of unusual dementias: an overview. Unusual dementias. Baillière Tindall, London, pp 485–516Google Scholar
  25. Lippa CF, Cohen R, Smith TW, Drachman DA (1991) Primary progressive aphasia with focal neuronal achromasia. Neurology 41: 882–886PubMedGoogle Scholar
  26. Love S, Saitoh T, Quijada S, Cole GM, Terry RD (1989) Alz-50, ubiquitin and Tau immunoreactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. J Neuropathol Exp Neurol 47: 393–405CrossRefGoogle Scholar
  27. Mann DMA, South PW, Snowden JS, Neary D (1993) Dementia of frontal lobe type-neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry 56: 605–614PubMedCrossRefGoogle Scholar
  28. Martin JJ (1975) Thalamic degenerations. In: Vinken PJ, Bruyn GW (eds) System disorders and atrophies. Handbook of clinical neurology, vol 21. North Holland, Amsterdam Oxford, pp 587–604Google Scholar
  29. Masters CL, Richardson EP (1978) Subacute spongiform encephalopathy (CreutzfeldtJakob disease). The nature and progression of spongiform changes. Brain 101: 333–344PubMedCrossRefGoogle Scholar
  30. McKee AC, Cole DG, Lee JM, Kowall NW, Growdon JH (1993) Distinctive cortical neuronal degeneration in progressive supranuclear palsy. J Neuropathol Exp Neurol 52: 292CrossRefGoogle Scholar
  31. Minagawa M, Nagazato T (1973) A special form of presenile dementia. A case of progressive subcortical gliosis (Neumann). Psychiat Neurol Jpn 75: 36–38Google Scholar
  32. Mizutani T, Kakimi S, Yamaguchi H, Takasu T (1994) Ubiquitin-positive filamentous inclusions in amyotrophic lateral sclerosis (ALS) and other neurological diseases (Abstract). Brain Pathol 4: 528Google Scholar
  33. Munoz-Garcia D, Ludwin SK (1984) Classic and generalized variants of Pick’s disease: a clinicopathological, ultrastructural, and immunocytochemical comparative study. Ann Neurol 16: 467–480PubMedCrossRefGoogle Scholar
  34. Neary D, Snowden JS, Mann DMA (1993) The clinical pathological correlates of lobar atrophy. Dementia 4: 154–159PubMedGoogle Scholar
  35. Okamoto K, Hirai S, Yamazaki Y, Sun X, Nakazato Y (1991) New ubiquitin-positive intraneuronal inclusions in the extra-motor cortices in patients with amyotrophic lateral sclerosis. Neurosci Lett 129: 233–236PubMedCrossRefGoogle Scholar
  36. Pasquier F, Lebert F (1995) Les démences fronto-temporales. Masson, ParisGoogle Scholar
  37. Petersen RB, Tabaton M, Chen SG, Monari L, Richardson SL, Lynches T, Manetto V, Lanska DJ, Markesbery WR, Currier RD, Autilio-Gambetti L, Wilhelmsen KC, Gambetti P (1995) Familial progressive subcortical gliosis: presence of prions and linkage to chromosome 17. Neurology 45: 1062–1067PubMedGoogle Scholar
  38. Seilhean D, Duyckaerts C, Vazeux RM, Bolgert F, Brunet P, Katlama C, Gentilini M, Hauw J-J (1993) HIV-1 associated cognitive/motor complex: absence of neuronal loss in the cerebral cortex. Neurology 43: 1492–1499PubMedGoogle Scholar
  39. Sima AAF, D’Amato C, Defendini RF, Jones MZ, Foster NL, Lynch T, Wilhelmsen KC (1994) Primary limbic lobe gliosis. Familial and sporadic cases. Brain Pathol 4: 538Google Scholar
  40. Snowden JS, Neary D, Mann DMA, Goulding PJ, Testa HJ (1992) Progressive language disorder due to lobar atrophy. Ann Neurol 31: 174–183PubMedCrossRefGoogle Scholar
  41. Suenaga T, Matsushima H, Nakamura S, Akiguchi I, Kimura J (1993) Ubiquitin immunoreactive inclusions in anterior horn cells and hypoglossal neurons in a case with Joseph’s disease. Acta Neuropathol (Berlin) 85: 341–344Google Scholar
  42. The Lund and Manchester groups (1994) Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57: 416–418CrossRefGoogle Scholar
  43. Tissot R, Constantinidis J, Richard J (1975) La maladie de Pick. Masson, ParisGoogle Scholar
  44. Torack RM, Morris JC (1988) The association of ventral tegmental area histopathology with adult dementia. Arch Neurol 45: 497–501PubMedCrossRefGoogle Scholar
  45. Vermersch P, Bordet R, Ledoze Fea (1995) Mise en èvidence d’un profil particulier de protèines tau pathologiques dans des cas de dèmence fronto-temporale. C R Acad Sci (Paris) 318: 439–445Google Scholar
  46. Wightman J, Anderson VER, Martin J, Swash M, Anderton BH, Neary D, Mann D, Luthert P, Leigh PN (1992) Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia. Neurosci Lett 139: 269–274PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • J. J. Hauw
    • 1
    • 3
  • C. Duyckaerts
    • 1
  • D. Seilhean
    • 1
  • S. Camilleri
    • 1
  • V. Sazdovitch
    • 1
  • G. Rancurel
    • 2
  1. 1.Laboratoire de Neuropathologie R Escourolle, La Salpêtrière HospitalParis VI University and INSERM U 360, Association Claude BernardParisFrance
  2. 2.Service de Neurologie, La Salpêtrière HospitalParis VI UniversityFrance
  3. 3.Laboratoire de Neuropathologie R EscourolleHôpital de la SalpêtrièreParis Cedex 13France

Personalised recommendations