Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis.

Abstract

SUMMARY Regional cerebral oxygen utilisation (rCMRO2), oxygen extraction (rOER), blood flow (rCBF), and blood volume (rCBV) have been determined for fifteen patients with multiple sclerosis in remission using positron emission tomography (PET). Cerebral oxygen utilisation and blood flow were significantly reduced in both white matter and peripheral cortical grey matter in the multiple sclerosis patients compared to a group of normal controls. No evidence of regional cerebral ischaemia in the multiple sclerosis group was found. Lowest levels of cerebral oxygen utilisation were found in patients with cerebral atrophy, and in patients in whom a significant fall in present full-scale IQ from estimated pre-morbid levels had occurred. No correlation was found between rCMRO2 values and severity of locomotor dysfunction or clinical disease duration.The primary pathology of multiple sclerosis consists of plaques of demyelination distributed about the central nervous system.' 2 These plaques range from 1 mm-4 cm in size and initially form as perivenular sleeves of demyelination.3 The lesions contain macrophages, lymphocytes and plasma cells and characteristically consist of breakdown of the myelin sheath with axonal sparing.4 Occasionally Wallerian degeneration of the axon is seen. The plaques tend to be symmetrically distributed with a prediliction for the spinal cord, cerebellum, and periventricular regions. At necropsy, however, numerous plaques may be found in clinically silent areas of central white and cortical grey matter.5Gyldensted has reviewed 110 CT brain scans of multiple sclerosis patients and found a 36% incidence of intracerebral plaques and a 79% incidence of generalised central white matter atrophy and/or widening of the cortical sulCi.6 Forty five per cent of his group had evidence of generalised cerebral atrophy in the absence of demonstrable focal plaques. It is likely that a higher incidence of plaques would have been found had brain scans been performed with a nuclear magnetic resonance (NMR) rather than a CT scanner.7

Perfusion Magnetic Resonance Imaging Correlates of Neuropsychological Impairment in Multiple Sclerosis

“…This is in line with the findings of previous studies using PET and singlephoton emission computed tomography (Blinkenberg et al, 2000;Brooks et al, 1984;Lycke et al, 1993;Paulesu et al, 1996;Pozzilli et al, 1991;Roelcke et al, 1997), which have demonstrated a generalized coupled reduction in both cerebral oxygen utilization and blood flow in patients with established MS. Hypoperfusion was reported in both WM and GM and correlated with cognitive impairment rather than with locomotor disability, thus reiterating that the EDSS is heavily weighted toward locomotor disability and that the cerebral functional system is of limited sensitivity. Most PET and single-photon emission computed tomography studies, however, investigated only patients affected by RR-MS and, with very few exceptions (Paulesu et al, 1996;Pozzilli et al, 1991), cognition was assessed using the mini mental status scale or the cerebral functional system of the EDSS.…”

Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency: The Neuroimaging Perspective

“…23 However, an SWI study at 3T demonstrated a significantly reduced visibility of the venous vasculature in the periventricular white matter (WM) of patients with RRMS. 24 In line with previous positron-emission tomography studies, which showed a reduction of oxygen use and extensive hypometabolism in the GM and normal-appearing (NA) WM of patients with MS, 25,26 this reduced visibility and volume of the cerebral venous system, reflecting a decreased venous blood deoxyhemoglobin concentration, can be interpreted as a result of a decreased oxygen extraction in the diseased MS tissue. On the contrary, occlusion of the venous vasculature should lead to an intracranial venous engorgement (increased visibility and volume) and enhancement of susceptibility effects, due to increased oxygen extraction.…”

Quantitative Oxygen Extraction Fraction from 7-Tesla MRI Phase: Reproducibility and Application in Multiple Sclerosis

“…This finding is consistent with positron emission tomography studies that found no regional distribution to metabolic abnormalities in MS, and posited that cerebral metabolic hypoactivity in the disease may reflect autoimmune changes in the brain independent of focal, visible lesions. 5,13 These diffuse OEF changes may also explain the excellent intraobserver (COV = 2.1%), interobserver (COV = 5.2%), and scan-rescan (COV = 5.9%) agreement of mean cortical OEF values in controls and patients, even though vessels were selected independently for all reproducibility analyses.…”

“…Initial studies on brain oxygen consumption in MS performed using 15 O positron emission tomography showed reductions of absolute cerebral blood flow and cerebral oxygen metabolism in both gray matter (GM) and white matter (WM). 5,13 Similarly, MRI observations of decreased T 2 * relaxation rate in frontal normal-appearing WM 14 and reduced visibility of periventricular veins on susceptibility-weighted images 15 indicate decreased oxygen extraction in MS. T 2 *-weighted imaging at 7 T has also revealed vascular alterations (reduced periventricular venous density) in patients that are consistent with widespread hemodynamic and metabolic changes related to the disease. 16 In a previous study, Ge et al 17 applied T2-relaxation-under-spin-tagging MRI to directly measure absolute OEF in the sagittal sinus of patients with relapsing-remitting MS (RRMS) with MRI.…”