The prevalence of cognitive dysfunction in the estonian population of the hereditary spastic paraplegia


The hereditary spastic paraplegias (HSPs) are neu-rodegenerative disorders of the motor system. The information about the prevalence of the cognitive dysfunction in HSP is inconsistent. The aim of the study was to describe the prevalence of cognitive dysfunction and the cognitive profiles of persons with HSP (pwHSP) compared to healthy controls. Subjects. Participating in the cognition study were 48 persons with HSP from the epidemiological study and 48 healthy controls. Of those with HSP, 81% (39/48) had pure and 19% (9/48) had complex forms. Among pwHSP, 20.8% (10/48) had pathogenic and 14.6% (7/48) had non-pathogenic mutations in the SPAST gene. There were no mutations detected in 31 persons with the SPAST gene. Methods. Neuropsychological test battery, MMSE Results. The results of the neuropsychological tests were significantly lower in persons with HSP than in the controls (Bonferroni correction, p < 0.00625). There were statistically significant differences in subtests measuring consistent long term retrieval (p < 0.001), later recall (p = 0.004) in verbal memory and symbol digit modalities (p = 0.0015). Five persons with HSP had an MMSE score of 24 or less. Conclusions. Our results demonstrate that cognitive dysfunction is present in 16.7 to 33.3% of persons with HSP, depending on the criteria applied. There was cognitive dysfunction in 30% of persons with a known pathogenic mutation in the SPAST gene. The most frequently damaged functions in HSP are consistent long term retrieval and later recall in verbal memory and symbol digit modalities tests that discriminate between controls and pwHSP with dysfunction (1.5 SD) in three or more domains. Dementia in HSP is rare.

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Vahter, L. , Braschinsky, M. , Haldre, S. , Kool, P. , Talvik, T. and Gross-Paju, K. (2012) The prevalence of cognitive dysfunction in the estonian population of the hereditary spastic paraplegia. World Journal of Neuroscience, 2, 91-97. doi: 10.4236/wjns.2012.22013.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Harding, A.E. (1983) Classification of the hereditary ataxias and paraplegias. Lancet, 21, 1151-1155. doi:10.1016/S0140-6736(83)92879-9
[2] Okuda, B., Iwamoto, Y. and Tachibana, H. (2002) Hereditary spastic paraplegia with thin corpus callosum and cataract: A clinical description of two siblings. Acta Neurologica Scandinavica, 106, 222-224. doi:10.1034/j.1600-0404.2002.01210.x
[3] Iwabuchi, K., Yagishita, S., Amano, N. and Kosaka, K. (1991) A new type of complicated form of hereditary spastic paraplegia showing mental deterioration, quadriplegia with muscular atrophy, sensory disturbance, extrapyramidal disorders, and epilepsy. Rinsho Shinkeigaku, 31, 945-952.
[4] Okubo, S., Ueda, M., Kamiya, T., Mizumura, S., Terashi, A. and Katayama, Y. (2000) Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum. Acta Neurologica Scandinavica, 102, 196-199. doi:10.1034/j.1600-0404.2000.102003196.x
[5] Maruta, K. and Kondo, I. (2001) A family of hereditary spastic paraplegia with dementia, ataxia, and dystonia. Rinsho Shinkeigaku, 41, 683-690.
[6] Uttner, I., Baumgartner, A., Sperfeld, A.D. and Kassubek, J. (2007) Cognitive performance in pure and complicated hereditary spastic paraparesis: A neuropsychological and neuroimaging study. Neuroscience Letters, 419, 158-161. doi:10.1016/j.neulet.2007.04.031
[7] Byrne, P.C., Webb, S., McSweeney, F., Burke, T., Hutchinson, M., and Parfrey, N.A. (1998) Linkage of AD HSP and cognitive impairment to chromosome 2p: haplotype and phenotype analysis indicates variable expression and low or delayed penetrance. European Journal of Human Genetics, 6, 275-282. doi:10.1038/sj.ejhg.5200185
[8] Murphy, S., Gorman, G., Beetz, C., Byrne, P., Dytko, M., McMonagle, P., Kinsella, K., Farrell, M. and Hutchinson, M. (2009) Dementia in SPG4 hereditary spastic paraplegia: Clinical, genetic, and neuropathologic evidence. Neurology, 73, 378-384. doi:10.1212/WNL.0b013e3181b04c6c
[9] Byrne, P.C., McMonagle, P., Webb, S.F., Fitzgerald, B., Parfrey, N.A. and Hutchinson M. (2000) Age-related cognitive decline in hereditary spastic paraparesis linked to chromosome 2p. Neurology, 54, 1510-1517.
[10] Tallaksen, C.M., Guichart-Gomez, E., Verpillat, P., Hahn-Barma, V., Ruberg, M., Fontaine, B., Brice, A., Dubois, B. and Durr, A. (2003) Subtle cognitive impairment but no dementia in patients with spastin mutations. Archives of Neurology, 60, 1113-1118. doi:10.1001/archneur.60.8.1113
[11] Valentino, P., Cerasa, A., Chiriaco, C., Nisticò, R., Pirritano, D., Gioia, M., Lanza, P., Canino, M., Del Giudice, F., Gallo, O., Condino, F., Torchia, G. and Quattrone, A. (2009) Cognitive deficits in multiple sclerosis patients with cerebellar symptoms. Multiple Sclerosis Journal, 15, 854-859. doi:10.1177/1352458509104589
[12] Amato, M.P., Ponziani, G., Siracusa, G. and Sorbi, S. (2001) Cognitive dysfunction in early-onset multiple sclerosis: A reappraisal after 10 years. Archive of Neurology, 58, 1602-1606. doi:10.1001/archneur.58.10.1602
[13] Patti, F., Amato, M.P., Trojano, M., Bastianello, S., Tola, M.R., Goretti, B., Caniatti, L., Di Monte, E., Ferrazza, P., Brescia Morra, V., Lo Fermo, S., Picconi, O., Luccichenti, G. and COGIMUS Study Group. (2009) Cognitive impairment and its relation with disease measures in mildly disabled patients with relapsing-remitting multiple sclerosis: baseline results from the Cognitive Impairment in Multiple Sclerosis (COGIMUS) study. Multiple Sclerosis Journal, 15, 779-788. doi:10.1177/1352458509105544
[14] Webb, S., Patterson, V. and Hutchinson, M. (1997) Two families with autosomal recessive spastic paraplegia, pigmented maculopathy and dementia. Journal of Neurology, Neurosurgery & Psychiatry, 63, 628-632. doi:10.1136/jnnp.63.5.628
[15] Webb, S. and Hutchinson, M. (1998) Cognitive impairment in families with pure autosomal dominant hereditary spastic paraparesis. Brain, 121, 923-929. doi:10.1093/brain/121.5.923
[16] Reid, E., Grayson, C., Rubinsztein, D.C., Rogers, M. and Rubinsztein, J.S. (1999) Subclinical cognitive impairment in autosomal dominant “pure” hereditary spastic paraplegia. Journal of Medical Genetics, 36, 797-798.
[17] McMonagle, P., Byrne, P. and Hutchinson, M. (2004) Further evidence of dementia in SPG4-linked autosomal dominant hereditary spastic paraplegia. Neurology, 62, 407-410.
[18] Lizcano-Gil, L.A., Garcia-Cruz, D., del Pilar Bernal-Beltran, M. and Hernandez, A. (1997) Association of late onset spastic paraparesis and dementia: Probably an autosomal dominant form of complicated paraplegia. American Journal of Medical Genetics, 68, 1-6. doi:10.1002/(SICI)1096-8628(19970110)68:1<1::AID-AJMG1>3.0.CO;2-V
[19] Rao, S.M. and the Cognitive Function Study Group of the National Multiple Sclerosis Society. (1990) A manual for brief repeatable battery of the neuropsychological tests in multiple sclerosis. Medical College of Wisconsin, Milwaukee, WI.
[20] Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) Mini-mental state: A practical method for grading the state of patients for the clinician. Journal of Psychiatric Research, 12, 189-198. doi:10.1016/0022-3956(75)90026-6
[21] Braschinsky, M., Tamm, R., Beetz, C. Sachez-Ferrero, E., Raukas, E., Lüüs, S.M., Gross-Paju, K., Boillot, C., Canzian, F., Metspalu, A. and Haldre, S. (2010) Unique spectrum of SPAST variants in Estonian HSP patients: Presence of benign missense changes but lack of exonic rearrangements. BMC Neurology, 9, 10-17.
[22] Braschinsky, M., Lüüs, S.-M., Gross-Paju, K. and Haldre, S. (2009) The prevalence of hereditary spastic paraplegia and the occurence of SPG4 mutations in Estonia. Neuroepidemiology, 32, 89-93. doi:10.1159/000177033

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