Neurological Sciences

, Volume 33, Issue 4, pp 905–909 | Cite as

Sporadic diffuse leucoencephalopathy with axonal spheroids: report of a profuse and rapid cortical–spinal degeneration

  • A. Maues De Paula
  • B. Michel
  • D. W. Dickson
  • Z. K. Wszolek
  • J. F. Pellissier
Case Report


Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical–spinal involvement.


Diffuse leucoencephalopathy with spheroids Adult onset leucodystrophy Pigmentary orthochromatic leucodystrophy Adult-onset leucoencephalopathy with pigmented glia and spheroids 



We thank Philippe Morando and Alexander Lock for technical support.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Axelsson R, Roytta M, Sourander P, Akesson HO, Andersen O (1984) Hereditary diffuse leucoencephalopathy with spheroids. Acta Psychiatr Scand Suppl 314:1–65PubMedGoogle Scholar
  2. 2.
    Yazawa I, Nakano I, Yamada H, Oda M (1997) Long tract degeneration in familial sudanophilic leukodystrophy with prominent spheroids. J Neurol Sci 147(2):185–191PubMedCrossRefGoogle Scholar
  3. 3.
    van der Knaap MS, Naidu S, Kleinschmidt-Demasters BK, Kamphorst W, Weinstein HC (2000) Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. Neurology 54(2):463–468PubMedCrossRefGoogle Scholar
  4. 4.
    Hancock N, Poon M, Taylor B, McLean C (2003) Hereditary diffuse leucoencephalopathy with spheroids. J Neurol Neurosurg Psychiatry 74(9):1345–1347PubMedCrossRefGoogle Scholar
  5. 5.
    Marotti JD, Tobias S, Fratkin JD, Powers JM, Rhodes CH (2004) Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature. Acta Neuropathol 107(6):481–488PubMedCrossRefGoogle Scholar
  6. 6.
    Terada S, Ishizu H, Yokota O, Ishihara T, Nakashima H, Kugo A, Tanaka Y, Nakashima T, Nakashima Y, Kuroda S (2004) An autopsy case of hereditary diffuse leukoencephalopathy with spheroids, clinically suspected of Alzheimer’s disease. Acta Neuropathol 108(6):538–545PubMedCrossRefGoogle Scholar
  7. 7.
    Baba Y, Ghetti B, Baker MC, Uitti RJ, Hutton ML, Yamaguchi K, Bird T, Lin W, DeLucia MW, Dickson DW et al (2006) Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred. Acta Neuropathol 111(4):300–311PubMedCrossRefGoogle Scholar
  8. 8.
    Itoh K, Shiga K, Shimizu K, Muranishi M, Nakagawa M, Fushiki S (2006) Autosomal dominant leukodystrophy with axonal spheroids and pigmented glia: clinical and neuropathological characteristics. Acta Neuropathol 111(1):39–45PubMedCrossRefGoogle Scholar
  9. 9.
    Van Gerpen JA, Wider C, Broderick DF, Dickson DW, Brown LA, Wszolek ZK (2008) Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids. Neurology 71(12):925–929PubMedCrossRefGoogle Scholar
  10. 10.
    Freeman SH, Hyman BT, Sims KB, Hedley-Whyte ET, Vossough A, Frosch MP, Schmahmann JD (2009) Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol 19(1):39–47Google Scholar
  11. 11.
    Goodman LE, Dickson DW (1995) Nonhereditary diffuse leucepahlopathy with spheroids presenting as early-onset rapidly progressive dementia. J Neuropathol Exp Neurol 54:471CrossRefGoogle Scholar
  12. 12.
    Yamashita M, Yamamoto T (2002) Neuroaxonal leukoencephalopathy with axonal spheroids. Eur Neurol 48(1):20–25PubMedCrossRefGoogle Scholar
  13. 13.
    Mascalchi M, Gavazzi C, Morbin M, Giaccone G, Arnetoli G, Zappoli R, Bugiani O (2006) CT and MR imaging of neuroaxonal leukodystrophy presenting as early-onset frontal dementia. AJNR Am J Neuroradiol 27(5):1037–1039PubMedGoogle Scholar
  14. 14.
    Browne L, Sweeney BJ, Farrell MA (2003) Late-onset neuroaxonal leucoencephalopathy with spheroids and vascular amyloid. Eur Neurol 50(2):85–90PubMedCrossRefGoogle Scholar
  15. 15.
    Moro-de-Casillas ML, Cohen ML, Riley DE (2004) Leucoencephalopathy with neuroaxonal spheroids (LENAS) presenting as the cerebellar subtype of multiple system atrophy. J Neurol Neurosurg Psychiatry 75(7):1070–1072PubMedCrossRefGoogle Scholar
  16. 16.
    Keegan BM, Giannini C, Parisi JE, Lucchinetti CF, Boeve BF, Josephs KA (2008) Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS. Neurology 70(13 Pt 2):1128–1133PubMedGoogle Scholar
  17. 17.
    Levin N, Soffer D, Biran I, Gomori JM, Bocher M, Blumen SC, Abramsky O, Segal R, Lossos A (2008) Leukoencephalopathy with neuroaxonal spheroids presenting as frontotemporal dementia. Isr Med Assoc J 10(5):386–387PubMedGoogle Scholar
  18. 18.
    Lyon G, Fattal-Valevski A, Kolodny EH (2006) Leukodystrophies: clinical and genetic aspects. Top Magn Reson Imaging 17(4):219–242PubMedCrossRefGoogle Scholar
  19. 19.
    Ali ZS, Van Der Voorn JP, Powers JM (2007) A comparative morphologic analysis of adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia—a role for oxidative damage. J Neuropathol Exp Neurol 66(7):660–672PubMedCrossRefGoogle Scholar
  20. 20.
    Wider C, Van Gerpen JA, DeArmond S, Shuster EA, Dickson DW, Wszolek ZK (2009) Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity? Neurology 72(22):1953–1959PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • A. Maues De Paula
    • 1
  • B. Michel
    • 2
  • D. W. Dickson
    • 3
  • Z. K. Wszolek
    • 4
  • J. F. Pellissier
    • 1
  1. 1.Service d’Anatomie Pathologique et Neuropathologie du Pr Figarella-BrangerCentre Hospitalier Universitaire La TimoneMarseille Cedex 05France
  2. 2.Unité de Neurologie Comportementale, Hôpital Sainte-MargueriteMarseilleFrance
  3. 3.Department of NeuropathologyMayo ClinicJacksonvilleUSA
  4. 4.Department of NeurologyMayo ClinicJacksonvilleUSA

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