Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism.

OBJECTIVE: To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS. METHODS: MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach. RESULTS: A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS. CONCLUSIONS: Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

Healthy aging, memory subsystems and regional cerebral oxygen consumption.

The present study was designed to search for concomitant age-related changes in memory subsystems, defined according to current structural theories, and resting oxygen consumption in selected brain regions. We have investigated a sample of subjects between 20 and 68 years of age and strictly screened for their good health. We applied in the same subjects a battery of neuropsychological tests selected to investigate several memory subsystems, and high-resolution positron imaging with stereotaxic localization to study a purposely limited number of cerebral structures, selected on a priori hypotheses to match the different memory subsystems. Our results showed significant age-related changes in performance on some tests, consistent with the literature, including an increase in semantic memory and a decrease in both working memory (central executive system) and verbal episodic and explicit memory. There was also an age-related linear decrease in global brain oxygen consumption which regionally reached statistical significance for the neocortical areas and the left thalamus. There was a limited number of significant, age-independent correlations between the raw psychometric test scores and resting regional oxidative metabolism. Consistent with our present understanding of the functional anatomy of memory, the Associate Learning scores (verbal episodic and explicit memory) were positively correlated with left hippocampal and thalamic metabolism. The positive relationships found between right hippocampal metabolism and performance in the Associate Learning and the Brown-Peterson tests were less expected but would be consistent with findings from recent PET activation studies. The results from this investigation are discussed in the light of current knowledge concerning the neuropsychology and the neurobiology of both aging and memory.

Right frontal cortex hypometabolism in transient global amnesia. A PET study.

A 60-year-old lady with previous hypertension was studied with PET in the acute (early recovery) phase of an otherwise typical episode of transient global amnesia (TGA). Follow-up over > 1 year was uneventful, and delayed CT scans and MRI showed no brain damage. No medical cause was disclosed despite extensive work-up. The PET study revealed a matched reduction in cerebral blood flow and oxygen consumption over the entire lateral frontal cortex on the right side, with an associated, less significant reduction in ipsilateral thalamic and lentiform nucleus metabolism, but sparing the hippocampal area. These changes, which had resolved at a repeat PET study 3 months later, suggest right prefrontal metabolic depression, possibly secondary to thalamic dysfunction, as the underlying mechanism for TGA in this case, consistent with the emerging involvement of the prefrontal cortex in strategies or control of memory traces retrieval. Thus, in analogy with permanent amnesia, TGA may be a core syndrome with several possible foci of dysfunction along the neuronal networks that subserve explicit memory. In the future, combined PET neuropsychological assessment in the acute stage of TGA may prove useful in defining distinct neuropsychological-topographical subtypes of this intriguing clinical entity.