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Murphy, Seán
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Murphy, Seán
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Murphy, Seán
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- PublicationDementia in SPG4 hereditary spastic paraplegia : Clinical, genetic, and neuropathologic evidence(Wolters Kluwer, 2009-08-04)
; ; ; ; ; ; ; 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: 378-384760Scopus© Citations 45 - PublicationA Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke(Wolters Kluwer, 2020-01-17)
; ; ; ; ; ; ; ; ; ; ; ; ; Background and Purpose— In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods— We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0–5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2–2.99 g/mL, 1 point; SUVmax 3–3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%–69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results— In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5], P<0.001; C statistic 0.77 [95% CI, 0.67–0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58–12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39], P=0.004). Conclusions— The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.329Scopus© Citations 36