Diagnostic Considerations
Failure to rule out reversible forms of spinal cord lesions (mechanical cord compression or spinal cord tumor) when considering a diagnosis of hereditary spastic paraplegia (HSP) invites problems.
Conditions to consider in the differential diagnosis of HSP include the following:
- Hereditary motor-sensory neuropathy type 5
- Spondylosis
- Atlantoaxial canal stenosis
- Arteriovenous malformation compressing spinal cord
- Arnold-Chiari syndrome
- Tethered cord
- Neoplasm
- Granuloma
- Spinocerebellar ataxias
- Adrenomyeloneuropathy
- Deficiency of vitamins B-12 and E
- Abetalipoproteinemia
- Mitochondrial disorders
- Human T-cell lymphocytotrophic virus infection
- Toxins
- Stiff-limb syndrome
Differential Diagnoses
- Dopamine-Responsive Dystonia
- HIV Infection and AIDS
- Hydrocephalus
- Krabbe Disease
- Metachromatic Leukodystrophy
- Syphilis
- Syringomyelia
Sawhney IM, Bansal SK, Upadhyay PK, et al. Evoked potentials in hereditary spastic paraplegia. Ital J Neurol Sci. Sep 1993;14(6):425-8. [Medline].
Reid E. Pure hereditary spastic paraplegia. J Med Genet. Jun 1997;34(6):499-503. [Medline]. [Full Text].
Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. Dec 2008;7(12):1127-38. [Medline].
Tarrade A, Fassier C, Courageot S, Charvin D, Vitte J, Peris L. A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet. Dec 15 2006;15(24):3544-58. [Medline].
Sanderson CM, Connell JW, Edwards TL, Bright NA, Duley S, Thompson A. Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. Hum Mol Genet. Jan 15 2006;15(2):307-18. [Medline].
Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. Oct 21 2005;123(2):277-89. [Medline].
Depienne C, Stevanin G, Brice A, et al. Hereditary spastic paraplegias: an update. Curr Opin Neurol. Dec 2007;20(6):674-80. [Medline].
Fink JK. Advances in the hereditary spastic paraplegias. Exp Neurol. Nov 2003;184 Suppl 1:S106-10. [Medline].
Tallaksen CM, Durr A, Brice A. Recent advances in hereditary spastic paraplegia. Curr Opin Neurol. Aug 2001;14(4):457-63. [Medline].
Züchner S. The genetics of hereditary spastic paraplegia and implications for drug therapy. Expert Opin Pharmacother. Jul 2007;8(10):1433-9. [Medline].
Paisan-Ruiz C, Dogu O, Yilmaz A, et al. SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. Neurology. Apr 15 2008;70(16 Pt 2):1384-9. [Medline].
Blackstone C, O'Kane CJ, Reid E. Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. Jan 2011;12(1):31-42. [Medline].
Hazan J, Fonknechten N, Mavel D, et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet. Nov 1999;23(3):296-303. [Medline].
Fink JK, Rainier S. Hereditary spastic paraplegia: spastin phenotype and function. Arch Neurol. Jun 2004;61(6):830-3. [Medline].
Orlacchio A, Patrono C, Gaudiello F, et al. Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4. Neurology. May 20 2008;70(21):1959-66. [Medline].
Tzoulis C, Denora PS, Santorelli FM, et al. Hereditary spastic paraplegia caused by the novel mutation 1047insC in the SPG7 gene. J Neurol. Jun 23 2008;[Medline].
Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. Mar 2007;39(3):366-72. [Medline].
Steinmüller R, Lantigua-Cruz A, Garcia-Garcia R, Kostrzewa M, Steinberger D, Müller U. Evidence of a third locus in X-linked recessive spastic paraplegia. Hum Genet. Aug 1997;100(2):287-9. [Medline].
Fink JK, Heiman-Patterson T, Bird T, et al. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working Group. Neurology. Jun 1996;46(6):1507-14. [Medline].
Hazan J, Lamy C, Melki J, et al. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet. Oct 1993;5(2):163-7. [Medline].
Appleton RE, Farrell K, Dunn HG. 'Pure' and 'complicated' forms of hereditary spastic paraplegia presenting in childhood. Dev Med Child Neurol. Apr 1991;33(4):304-12. [Medline].
Schlipf N, Schüle R, Klimpe S, Karle K, Synofzik M, Schicks J, et al. Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clin Genet. Aug 2011;80(2):148-60. [Medline].
Schady W, Smith CM. Sensory neuropathy in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. Jun 1994;57(6):693-8. [Medline]. [Full Text].
Schady W, Dick JP, Sheard A, Crampton S. Central motor conduction studies in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. Sep 1991;54(9):775-9. [Medline]. [Full Text].

