BOSTON—The concentration of GABA in the sensorimotor cortex and in the hippocampus is decreased significantly in patients with secondary progressive multiple sclerosis (MS), compared with healthy individuals, according to research described at the 2014 Joint ACTRIMS–ECTRIMS Meeting. The decreased concentration in the sensorimotor cortex is associated with impaired motor performance.
The reduced GABA levels likely reflect pathologic changes that result from neuronal loss and may indicate a decrease in synaptic density, said Niamh Cawley, MRCPI, Clinical Research Associate at University College London.
Niamh Cawley, MRCPI
Clinical and Cognitive Assessments
For their investigation, Dr. Cawley and colleagues enrolled patients with secondary progressive MS and an Expanded Disability Status Scale (EDSS) score of between 4 and 6.5. Patients taking medications that alter the GABAnergic system were excluded from the study. The researchers recruited healthy controls as a comparison group.
The investigators performed cognitive assessments that examined attention and information processing speed, executive function, working memory, and visual and verbal memory. Clinical assessments included EDSS, the Nine-Hole Peg Test, the Timed Walk Test, grip strength of the right upper limb, muscle strength of the right upper and lower limbs, and vibration sensation of the right upper and lower limbs. Brain images were obtained with a 3-T scanner.
The researchers used a general linear model to compare differences in metabolite concentration between patients and controls, while adjusting for age, gender, and gray matter fraction within the spectroscopic voxel. A linear regression model enabled Dr. Cawley’s group to examine the relationships between cognitive and clinical scores and GABA concentrations. Data were adjusted for age, gender, gray matter fraction, and gray matter lesions within the spectroscopic voxel.
GABA Was Decreased in Two Brain Regions
Data were analyzed for 30 patients and 17 controls. Patients’ median EDSS score was 6. Patients performed significantly worse than controls on grip strength, muscle strength, the Nine-Hole Peg Test, and vibration sensation. Patients also performed significantly worse on digit span and immediate and delayed verbal recall.
The investigators found a significant decrease in the concentration of GABA in the sensorimotor cortex and in the hippocampus in patients, compared with controls. They did not observe a significant difference in the concentration of GABA in the prefrontal cortex. Data analysis revealed a significant positive correlation between the concentration of GABA in the sensorimotor cortex and scores on the Nine-Hole Peg Test, as well as grip strength and muscle strength. No significant correlation was seen between the concentration of GABA in the prefrontal cortex or the hippocampus and any cognitive assessments.
Although the current results are consistent with a previous post mortem investigation that demonstrated reduced presynaptic and postsynaptic GABA neurotransmission in patients with progressive MS, the findings diverge from those of Bhattacharyya et al, who found an inverse correlation between scores obtained on the Nine-Hole Peg Test and concentration of GABA in the sensorimotor cortex among patients with relapsing-remitting MS. “Our findings in patients with progressive disease are likely to reflect the loss of the compensatory mechanisms associated with plasticity due to this neuronal loss,” said Dr. Cawley. She plans to follow the patients over time to monitor GABA changes in the three brain regions, as well as to examine the association between GABA levels and functional changes.
—Erik Greb