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Neuroradiology

, Volume 47, Issue 10, pp 730–734 | Cite as

Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia

  • P. Hedera
  • O. P. Eldevik
  • P. Maly
  • S. Rainier
  • J. K. FinkEmail author
Diagnostic Neuroradiology

Abstract

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity. HSP pathology involves axonal degeneration that is most pronounced in the terminal segments of the longest descending (pyramidal) and ascending (dorsal columns) tracts. In this study, we compared spinal cord magnetic resonance imaging (MRI) in 13 HSP patients with four different types of autosomal dominant hereditary spastic paraplegia (SPG3A, SPG4, SPG6, and SPG8) with age-matched control subjects. The cross-section area of HSP subjects at cervical level C2 was 59.42±12.57 mm2 and at thoracic level T9 was 28.58±5.25 mm2. Both of these values were less than in the healthy controls (p<0.001). The degree of cord atrophy was more prominent in patients with SPG6 and SPG8 who had signs of severe cord atrophy (47.60±6.58 mm2 at C2, 21.40±2.4 mm2 at T9) than in subjects with SPG3 and SPG4 (66.0±8.94 mm2 at C2, p<0.02; 31.75±2.76 mm2 at T9, p<0.001). These observations indicate that spinal cord atrophy is a common finding in the four genetic types of HSP. Spinal cord atrophy was more severe in SPG6 and SPG8 HSP subjects than in other types of HSP we studied. This may suggest a different disease mechanism with more prominent axonal degeneration in these two types of HSP when compared with HSP due to spastin and atlastin mutations.

Keywords

Magnetic resonance imaging Hereditary spastic paraplegia Atrophy Spastin Atlastin 

Notes

Acknowledgements

P.H. is supported by NIH K08NS42743. J.K.F. is supported by NIH R01NS33645, NIH R01NS38713, and the VA Merit Review Award. S.R. is supported by a grant from the University of Michigan Institute of Gerontology.

References

  1. 1.
    Fink JK (2002) Hereditary spastic paraplegia. In: Rimoin DL, Pyeritz RE, Connor JM, Korf BR (eds) Emery and Rimoin’s principles and practice of medical genetics, 4th edn. Harcourt, London, pp 3124–3145Google Scholar
  2. 2.
    Fink JK (2003) The hereditary spastic paraplegias: nine genes and counting. Arch Neurol 60:1045–1049CrossRefPubMedGoogle Scholar
  3. 3.
    Fink JK, Heiman-Patterson T, Bird T, Cambi F, Dubé M-P, Figlewicz DA, Haines JL et al (1996) Hereditary spastic paraplegia: advances in genetic research. Neurology 46:1507–1514PubMedGoogle Scholar
  4. 4.
    Hazan J, Fonknechten N, Mavel D et al (1999) Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet 23:296–303CrossRefPubMedGoogle Scholar
  5. 5.
    Zhao X, Alvarado D, Rainier S et al (2001) Mutations in a novel GTPase cause autosomal dominant hereditary spastic paraplegia. Nat Genet 29:326–331CrossRefPubMedGoogle Scholar
  6. 6.
    Hansen JJ, Durr A, Cournu-Rebeix I et al (2002) Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet 70:1328–1332CrossRefPubMedGoogle Scholar
  7. 7.
    Reid E, Kloos M, Ashley-Koch A et al (2002) A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet 71:189–194CrossRefGoogle Scholar
  8. 8.
    Rainier S, Chai J-H, Tokarz D, Nicholls RD, Fink JK (2003) NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet 273:967–971CrossRefGoogle Scholar
  9. 9.
    Schwarz GA (1952) Hereditary (familial) spastic paraplegia. Arch Neurol Psychiatry 68:655–682Google Scholar
  10. 10.
    Sack GH, Huether CA, Garg N (1978) Familial spastic paraplegia: clinical and pathological studies in a large kindred. Johns Hopkins Med J 143:117–121PubMedGoogle Scholar
  11. 11.
    White KD, Ince PG, Lusher M et al (2000) Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation. Neurology 51:89–94Google Scholar
  12. 12.
    Dürr A, Brice A, Serdaru M et al (1994) The phenotype of pure autosomal dominant spastic paraplegia. Neurology 44:1274–1277PubMedGoogle Scholar
  13. 13.
    Krabbe K, Nielsen JE, Fallentin E, Fenger K, Herning M (1997) MRI of autosomal dominant pure spastic paraplegia. Neuroradiology 39:724–727CrossRefPubMedGoogle Scholar
  14. 14.
    Nielsen JE, Krabbe K, Jennum P et al (1998) Autosomal dominant pure spastic paraplegia: a clinical, paraclinical and genetic study. J Neurol Neurosurg Psychiatry 64:61–66PubMedGoogle Scholar
  15. 15.
    Hedera P, DiMauro S, Bonilla E et al (1999) Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q. Neurology 53:44–50CrossRefPubMedGoogle Scholar
  16. 16.
    Hedera P, Rainer S, Alvarado D et al (1999) Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. Am J Hum Genet 64:563–569CrossRefPubMedGoogle Scholar
  17. 17.
    Lathrop GM, Lalouel JM, Julier C, Ott J (1985) Multipoint linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet 37:482–498PubMedGoogle Scholar
  18. 18.
    Rauch RA, Jinkins JR (1994) Analysis of cross-sectional area measurements of the corpus callosum adjusted for brain size in male and female subjects from childhood to adulthood. Behav Brain Res 64:65–78CrossRefPubMedGoogle Scholar
  19. 19.
    Fink JK, Sharp GB, Lange BM et al (1995) Autosomal dominant, familial spastic paraplegia, type I: clinical and genetic analysis of a large North American family. Neurology 45:325–331PubMedGoogle Scholar
  20. 20.
    Hentati A, Deng HX, Zhai H et al (2000) Novel mutations in spastin gene and absence of correlation with age at onset of symptoms. Neurology 55:1388–1390PubMedGoogle Scholar
  21. 21.
    Shibasaki Y, Tanaka H, Iwabuchi K et al (2000) Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13–15. Ann Neurol 48:108–112CrossRefPubMedGoogle Scholar
  22. 22.
    Okubo S, Ueda M, Kamiya T, Mizumura S, Terashi A, Katayama Y (2000) Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum. Acta Neurol Scand 102:196–199CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • P. Hedera
    • 1
    • 4
  • O. P. Eldevik
    • 2
  • P. Maly
    • 2
  • S. Rainier
    • 1
  • J. K. Fink
    • 1
    • 3
    Email author
  1. 1.Department of NeurologyThe University of MichiganAnn ArborUSA
  2. 2.Department of RadiologyThe University of MichiganAnn ArborUSA
  3. 3. Geriatric Research Education and Clinical CenterAnn Arbor Veterans Affairs Medical CenterAnn ArborUSA
  4. 4.Department of NeurologyVanderbilt UniversityNashvilleUSA

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