Abstract
Cortical hyperexcitability is an established clinical feature present in the earliest stages of disease onset in ALS and can be used to detect subclinical upper motor neuron dysfunction. The abnormality is believed to reflect an underlying glutamate-induced excitotoxicity implicated in disease pathogenesis and linked to functional motor impairment. While a large body of TMS and MRS research have independently documented the disease signature of ALS, their association remains to be investigated.
Objectives Characterize the relationship between cortical motor hyperexcitability and metabolite abnormalities.
Examine asymmetry differences in hemispheric cortical motor integrity.
Methods 32 non-familial ALS patients and 17 age-education matched healthy controls were recruited. All participants received an MRI scan (3T GE MR750; 32-channel head coil) and single-voxel 1H-MRS (PRESS) data was sequentially acquired from the hand region of the left and right motor cortices. All patients underwent TMS to determine presence of cortical hyperexcitability based on SICI threshold (≤ 5.5).
Results As a whole, ALS patients demonstrated a consistent reduction in NAA/Cr in the left (p=0.02) and right (p=0.01) hand region, without evidence of hemispheric imbalance relative to controls. Patients with cortical hyperexcitability, however, demonstrated significantly higher levels of Glu/Cr and NAA/Cr across both hemispheres (p values < 0.05), relative to patients with a normal SICI. Interestingly, patients with a normal SICI demonstrated a significantly higher degree of hemispheric NAA/Cr imbalance (p=0.04).
Conclusions Cortical excitability is associated with a consistent pattern of metabolite abnormality across cortical hemispheres underlying hand motor function in ALS.
