Dementia in SPG4 hereditary spastic paraplegia : Clinical, genetic, and neuropathologic evidence

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Title: Dementia in SPG4 hereditary spastic paraplegia : Clinical, genetic, and neuropathologic evidence
Authors: Murphy, S.
Gorman, B.
Beetz, C.
Byrne, P.
Dytko, Malgorzata
McMonagle, P.
Kinsella, K.
Hutchinson, Michael
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Date: 4-Aug-2009
Abstract: Background: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder.Objective: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed.Methods: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed.Results: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter.Conclusion: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene. Neurology (R) 2009; 73: 378-384
Type of material: Journal Article
Publisher: Wolters Kluwer
Copyright (published version): 2009 American Academy of Neurology
Keywords: Hereditary spastic paraparesisDementia
DOI: 10.1212/WNL.0b013e3181b04c6c
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection

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