Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil.
We used the benzodiazepine GABA(A) marker [(11)C] flumazenil to study cerebral dysfunction in amyotrophic lateral sclerosis (ALS) with PET. Seventeen non-demented patients with clinically definite or probable ALS were scanned and statistical parametric maps were derived to localize changes in regional flumazenil volumes of distribution (FMZVD), which correlate closely with receptor density (B(max)), and the results were compared with those of 17 controls. The ALS group showed statistically significant decreases in relative FMZVD in the prefrontal cortex (areas 9 and 10 bilaterally), parietal cortex (area 7 bilaterally), visual association cortex (area 18 bilaterally) and left motor/premotor cortex (including area 4) (P < 0.001). Relative reductions in FMZVD were also seen in the left ventrolateral and dorsolateral prefrontal cortex (areas 45, 46 and 47), Broca's area and the right temporal (area 21) and right visual association cortex (area 19). These observations suggest that cerebral dysfunction in ALS involves motor/premotor and extramotor areas, particularly the prefrontal regions.
Lloyd
C M
CM
Department of Neurology, Guy's, King's and St Thomas' School of Medicine and the Institute of Psychiatry, Medical Research Council Cyclotron Unit, Hammersmith Hospital and Institute of Neurology, London, UK.
Richardson
M P
MP
Brooks
D J
DJ
Al-Chalabi
A
A
Leigh
P N
PN
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005442:Flumazenil; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011963:Receptors, GABA-A / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil