Regional hippocampal atrophy in multiple sclerosis

Abstract

Gray matter brain structures, including deep nuclei and the cerebral cortex, are affected significantly and early in the course of multiple sclerosis and these changes may not be directly related to demyelinating white matter lesions. The hippocampus is an archicortical structure that is critical for memory functions and is especially sensitive to multiple insults including inflammation. We used high-resolution MR imaging at 3.0 T to measure hippocampal volumes in relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients and controls. We found that both groups of MS patients had hippocampal atrophy and that this volume loss was in excess of global brain atrophy. Subregional analysis revealed selective volume loss in the cornu ammonis (CA) 1 region of the hippocampus in RRMS with further worsening of CA1 loss and extension into other CA regions in SPMS. Hippocampal atrophy was not correlated with T2-lesion volumes, and right and left hippocampi were affected equally. Volume loss in the hippocampus and subregions was correlated with worsening performance on word-list learning, a task requiring memory encoding, but not with performance on the Paced Auditory Serial Addition Task (PASAT), a test of information processing speed. Our findings provide evidence for selective and progressive hippocampal atrophy in MS localized initially to the CA1 subregion that is associated with deficits in memory encoding and retrieval. The underlying histopathological substrate for this selective, symmetric and disproportionate regional hippocampal vulnerability remains speculative at this time. Further understanding of this process could provide targets for therapeutic interventions including neuroprotective treatments.

Distinct and common cerebral activation changes during mental time travel in relapsing-remitting multiple sclerosis patients

“…Cognitive impairment is a common feature in MS and disturbances are mainly observed in anterograde memory (verbal and visual modalities), information processing speed, attention, working memory, vi-suospatial abilities and executive functioning (Chiaravalloti and DeLuca 2008). From a neurological standpoint, several neuroimaging studies carried out in MS patients have demonstrated that structures such as the frontal cortex (Benedict et al 2002;Bendfeldt et al 2009) and the hippocampus (Sicotte et al 2008;Hulst et al 2012), which are essential in the AM and EFT core network, are frequently damaged.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Thalamic atrophy has been linked with fatigue and cognitive impairment [89,90], but the effect of DMAs on thalamic volume or function has not been assessed. The hippocampus is an archicortical gray matter structure that is impacted by MS and related to cognitive impairment [91]. Pathological studies show demyelination and neuronal loss throughout the hippocampal formation [92,93].…”

Neuropsychologist

“…16 A recent study showed a correlation between volume loss in the CA1 region of the hippocampus and reduced performance on a verbal-learning task in a group of RRMS patients. 17 Across different disease courses, people with MS often show reduced or impaired performance relative to age-matched controls. 2 Individuals with a progressive course typically do not perform as well as those with a relapsing-remitting course, but less consistent findings regarding cognitive abilities have emerged in comparisons of those with secondary progressive MS (SPMS) versus primary progressive MS (PPMS).…”