Extramotor involvement in ALS: PET studies with the GABA(A) ligand [C-11]flumazenil

We used the benzodiazepine GABAA marker [C-11] flumazenil to study cerebral dysfunction in amyotrophic lateral sclerosis (ALS) with PET. Seventeen non -demented patients with clinically definite or probable ALS were scanned an d statistical parametric maps were derived to localize changes in regional flumazenil volumes of distribution (FMZVD), which correlate closely with re ceptor density (B-max), and the results were compared with those of 17 cont rols. The ALS group showed statistically significant decreases in relative FMZVD in the prefrontal cortex (areas 9 and 10 bilaterally), parietal corte x (area 7 bilaterally), visual association cortex (area 18 bilaterally) and left motor/premotar cortex (including area 4) (P < 0.001). Relative reduct ions in FMZVD were also seen in the left ventrolateral and dorsolateral pre frontal cortex (areas 45, 46 and 47), Broca's area and the right temporal ( area 21) and right visual association carter (area 19), These observations suggest that cerebral dysfunction in ALS involves motor/premotor and extram otor areas, particularly the prefrontal regions.