Frontal dysfunctions of ALS-PBP patients in relation to their bulbar symptoms and rCBF decline

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by progressive degeneration of spinal and bulbar motor neurons. However up to 50% ALS patients may also have cognitive dysfunction which has not been fully examined. Methods: 35 ALS patients [23 patients presenting with limb-type ALS (ALS-limb) and 12 patients presenting with primary bulbar palsy (PBP)-type ALS (ALS-PBP)] and 5 Spinal and Bulbar Muscular Atrophy (SBMA) patients have participated. To assess cognitive function mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), and frontal assessment battery (FAB) were performed. Additionally the time to complete card flipping with a computerized touch panel-type screening test was also examined. To investigate regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) using a ^99mTc labeled ethyl cysteinate dimer (^99mTc-ECD) were performed. Statistical image analysis was performed using the easy Z-score imaging system (eZIS). Results: HDS-R and FAB scores were significantly lower in the ALS-PBP group than in age- and gender-matched control subjects or ALS-limb groups (p < 0.01). The time to complete card flipping was significantly longer in the ALS-PBP group than in the control and ALS-limb groups (p < 0.01). Although MMSE, HDS-R and FAB scores and the time to complete card flipping had no correlation with ALS functional rating scale-revised (ALSFRS-R) or Norris-limb scale scores, FAB score (r = 0.63, p < 0.01) and the time to complete card flipping (r = - 0.66, p < 0.01) were strongly correlated with Norris-bulbar score. The eZIS showed that rCBF of the frontal lobe was more severely declined in ALS-PBP patients than in ALS-limb patients (p < 0.05). Conclusion: These results suggest a selective decline of frontal cerebral functions in the ALS-PBP group in relation to their bulbar symptoms and rCBF decline.