title: Reduced regional cerebral blood flow in SPG4-linked hereditary spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) linked to the spastic gait gene 4 (SPG4) is controversial, as the "pure" form traditionally has been considered confined to the long axons of the spinal cord. However, recent immunolabeling experiments have demonstrated extensive Spastin expression in the cortex and striatum. This could indicate a more widespread neuropathology from mutations in the SPG4 gene than previously assumed. The aim of this study was therefore to ascertain the extent of cerebral involvement in SPG4 linked HSP by neuropsychological examination and measurement of the regional cerebral blood flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using Statistical Parametric Mapping (SPM 99). Neuropsychological assessment was performed using established and nationally validated tests (RH Basic Battery). Compared to healthy controls, the patient group had significantly decreased rCBF in the left fronto-temporal cortex (P<0.05), and more extensive changes were observed in a separate analysis of the most disabled individuals. The neuropsychological assessment revealed only significantly impaired recognition memory for faces. In summary, the findings support cerebral pathology in SPG4-linked HSP, although the decreased rCBF in fronto-temporal cortex was not associated with severe cognitive impairment.
authors.affiliation: The Neurobiology Research Unit, N 9201, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Kristin H
authors.initials: KH
authors.lastname: Scheuer
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Katja
authors.initials: K
authors.lastname: Krabbe
authors.forename: Carina
authors.initials: C
authors.lastname: Simonsen
authors.forename: Pernille
authors.initials: P
authors.lastname: Koefoed
authors.forename: Sven A
authors.initials: SA
authors.lastname: Sørensen
authors.forename: Anders
authors.initials: A
authors.lastname: Gade
authors.forename: Olaf B
authors.initials: OB
authors.lastname: Paulson
authors.forename: Ian
authors.initials: I
authors.lastname: Law
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D008040:Genetic Linkage / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010103:Oxygen Isotopes / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D012039:Regional Blood Flow / Q000502:physiology*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000074181:Spastin
chemical_list: D010103:Oxygen Isotopes; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human