{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:29:57Z","timestamp":1791350997078,"version":"4.3.1"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,7,9]],"date-time":"2004-07-09T00:00:00Z","timestamp":1089331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>Hereditary spastic paraplegia (HSP) comprises a group of inherited neurodegenerative disorders with the shared characteristics of progressive weakness and spasticity predominantly affecting the lower limbs. Limited pathological accounts have described a \u2018dying back\u2019 axonal degeneration in this disease. However, the distribution and extent of axonal loss has not been elucidated in a quantitative way. We have studied <jats:italic>post\u2010mortem<\/jats:italic> material from six HSP patients and 32 controls in detail. The population of axons was examined quantitatively in the corticospinal tracts from the medulla to the lumbar spinal cord and the sensory tracts from the lumbar to upper cervical spinal cord. Myelin and axon\u2010stained sections were employed to estimate the notional area and axonal density, respectively, of both tracts. Our results indicate that in the corticospinal tracts there is a significant reduction in area and axonal density at all levels investigated in HSP compared to controls. In the corticospinal tracts, the ratio of medulla and lumbar total axonal number was significantly greater in HSP cases compared to controls suggesting more pronounced axonal loss in the distal neuraxis in HSP than in controls. The sensory tracts in HSP, in contrast, showed a significant reduction in area and axonal density only in the upper regions of the spinal cord. Similar to the corticospinal tracts, the ratio of lumbar and upper cervical cord total axonal number in the sensory tracts was increased in HSP cases compared to controls. These findings are consistent with a length\u2010dependent \u2018dying back\u2019 axonopathy. Nerve fibre loss was not size\u2010selective with both small and large diameter fibres affected. In HSP, axonal loss is widespread and symmetrical and its extent tract\u2010specific. The characterization of the nature of axonal loss in HSP, where this is a primary phenomenon, may help the interpretation of axonal loss in conditions such as multiple sclerosis where the sequence of events is less clear.<\/jats:p>","DOI":"10.1111\/j.1365-2990.2004.00587.x","type":"journal-article","created":{"date-parts":[[2004,11,15]],"date-time":"2004-11-15T19:20:49Z","timestamp":1100546449000},"page":"576-584","source":"Crossref","is-referenced-by-count":175,"title":["The extent of axonal loss in the long tracts in hereditary spastic paraplegia"],"prefix":"10.1111","volume":"30","author":[{"given":"G. C.","family":"DeLuca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. C.","family":"Ebers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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