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In patients with the frontal variant of frontotemporal lobar degeneration(fv- FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathe tic form) to disinhibition with agitation (disinhibited form). These clinical pr esentations may be related to specific regional cerebral dysfunction and to defi cit in the serotoninergic system. We studied cerebral glucose uptake using 18F- fluorodeoxyglucose and positron emission tomography in 18 patients fulfilling cl inical criteria for fv-FTLD and showing, respectively, an apathetic or disinhib ited behavioral syndrome. In eight of these patients, we also evaluated the 5-h ydroxytryptamine -2A receptor cerebral receptor distribution with [11C]MDL and positron emissi on tomography.We found a reduction of frontal glucose metabolismin the whole gro up of fv-FTLD patients. Apathetic syndrome was associated with a prevalent dorsolateral and frontal medial hypometabolism, whereas the disinh ibited syndrome demonstrated a selective hypometabolism in interconnected limbic structures (the cingulate cortex, hippocampus/amygdala, and accumbens nucleus). The in vivo measurements of [11C]MDL indicated a significant reduction of 5-hy droxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate co rtices.These 18F-fluorodeoxyglucose positron emission tomography changes can be considered as specific functional markers of the different behavioral presentat ions in fv-FTLD. The serotoninergic system dysfunction provides a rationale for therapeutic trials with selective serotonin reuptake inhibitors.
In patients with the frontal variant of frontotemporal lobar degeneration (fv-FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathe tic form) to disinhibition with agitation (disinhibited form). These clinical pr esentations may be related to specific regional cerebral dysfunction and to defi cit in the serotoninergic system. We studied cerebral glucose uptake using 18F-fluorodeoxyglucose and positron emission tomography in 18 patients fulfilling cl inical criteria for fv-FTLD and showing, respectively, an apathetic or disinhib ited behavioral syndrome. these patients, we also evaluate the 5-h ydroxytryptamine -2A receptor cerebral receptor distribution with [11C] MDL and positron emissi on tomography. We found a reduction of frontal glucose metabolismin the whole gro up of fv-FTLD patients. Apathetic syndrome was associated with a prevalent dorsolateral and frontal medial hypometabolism, while the disinh ibited syndrome demonstrated a selective hypometabolism in interconnected limbic structures (the cingulate cortex, hippocampus / amygdala, and accumbens nucleus). The in vivo measurements of [11C] MDL indicate a significant reduction of 5-hy droxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate co rtices These 18F-fluorodeoxyglucose positron emission tomography changes can be considered as specific functional markers of the different behavioral presentations in fv-FTLD. The serotoninergic system dysfunction provides a rationale for therapeutic trials with selective serotonin reuptake inhibitors.