Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis.

Brain magnetic resonance imaging (MRI) and an extensive battery of neuropsychological tests exploring frontal functions, short and long-term memory, visuo-spatial skills, attention and language were applied to 14 patients with primary progressive multiple sclerosis (PPMS) and 17 patients with secondary progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of physical disability, but cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01). Patients with SPMS had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02) horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02), parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes. Patients with SPMS and neuropsychological deficits had higher non-periventricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005). Our results indicate that both neuropsychological and brain MRI abnormalities are more extensive in patients with SPMS. Since physical disability was similar for both groups, disability in PPMS may be predominantly due to spinal cord involvement.

Influence of clinical variables on neuropsychological performance in multiple sclerosis.

The effects of age, educational level, duration and course of the disease, physical disability and mood status on several cognitive functions (short- and long-term memory, frontal functions, attention, language and visuospatial skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton Depression Rating Scale (HDRS) scores and a secondary progressive disease course significantly influenced neuropsychological performance. Factorial analysis revealed that indexes of (1) frontal function impairment, (2) long-term verbal memory and language function impairment, and (3) visuospatial short- and long-term memory and visuoperceptive function impairment accounted for 85% of the variance in neuropsychological performance. Only the first factor was significantly related to the presence of depressive symptomatology, as assessed by the HDRS. These results indicate that both the course of the disease and the presence of affective disorders must be taken into account when evaluating the natural history of cognitive impairment in MS and suggest that depressive symptomatology and cognitive dysfunction in MS are related to the involvement of at least partially overlapping anatomofunctional circuits.

Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis.

We evaluated the correlations between cognitive impairment, clinical and brain magnetic resonance imaging (MRI) findings in 100 patients with multiple sclerosis (MS). The performance on one or more neuropsychological tests was abnormal in 47% of the 64 patients who completed the entire neuropsychological battery; the cognitive impairment was mild in 14 (22%) and severe in 16 (25%). Performance on any single neuropsychological test was unrelated to clinical parameters (age, duration of the disease, disability). The neuropsychological performance of relapsing-remitting patients was better than in patients with a chronic-progressive disease. The mean scores for almost all the neuropsychological tests were significantly lower in patients with severe ventricular dilatation and corpus callosum atrophy than in patients in whom these structures were little affected. Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of cortical sulci and total lesional scores. Our data support the contention that the involvement of pathways that are critical for a given cognitive process as well as the progression of the axonal degeneration and sclerosis seem to play important roles in the pathophysiology of cognitive dysfunction in MS.