Understanding memory impairment in multiple sclerosis contributions of macro and micro-structural alterations in the thalamus and hippocampus

Background: Memory impairment is common in multiple sclerosis and is associated with abnormalities of the thalamus and hippocampus. These structures are intricately linked through functional memory networks. To date, studies have considered the thalamus and hippocampus in isolation however it seems likely that memory impairment is generated through a process of retrograde synaptic degeneration in these functional networks. Studies that incorporate neuropsychology and neuroimaging may be first step to further understanding this association. Objective: To elucidate the contributions of structural alterations of the hippocampus and thalamus to memory impairment in patients with relapsing remitting multiple sclerosis (RRMS). Methods: 28 patients with RRMS and 29 age, sex and education-matched controls were enrolled. Each participant underwent a battery of neuropsychological assessments and brain magnetic resonance imaging (MRI). Episodic memory was assessed with the Brief Visuospatial Memory Test - Revised. 3DT1, 3D FLAIR and diffusion MRI sequences were acquired on a 3T GE MRI scanner. Normalised whole brain volume was assessed with SIENAX/FSL. The thalamus and hippocampus were segmented using FIRST/FSL, and normalised volumes and mean diffusivity (MD) measured. Results: Patients with RRMS were impaired on episodic memory tasks compared to controls (p < 0.05). Total thalamic volume was reduced in the RRMS group compared to controls (p < 0.005) and correlated with episodic memory impairment (r = 0.357, p < 0.01). Thalamic MD was increased in RRMS compared to controls (p < 0.005) and correlated with episodic memory impairments (r = -0.259, p < 0.05). Hippocampal volumes did not differ between groups. Hippocampal MD was significantly higher in patients than controls (p < 0.05), however this did not correlate with memory scores. Conclusion: Episodic memory impairment in RRMS was associated with macro and micro-structural changes within the thalamus. Although hippocampal microstructural changes were present in the patient group, these findings were not correlated with memory impairment. This suggests that thalamic involvement in RRMS may occur earlier in the disease course and future studies should determine if dysfunction in memory networks are mediated by thalamic involvement. Furthermore, the extended memory network including the anterior cingulate cortex and mammillary bodies should be examined, in addition to the integrity of the connecting white matter tracts.