Dynamics of Regional Hippocampal Changes in Clinically Isolated Syndrome

Subregional hippocampal volume changes occur in clinically isolated syndrome with coexisting atrophy in damage-sensitive regions and hypertrophy in the dentate gyrus.

In patients with clinically isolated syndrome, regional hippocampal changes occur, which are modulated by focal white matter lesions, and are more distinct in patients converting to multiple sclerosis, according to a study published in Multiple Sclerosis Journal.

To evaluate the presence of regional changes in hippocampal volume, the associations of these variations to focal white matter lesions, and the prognostic implications for patients with clinically isolated syndrome, investigators recruited 37 patients with clinically isolated syndrome and 14 sex- and age-matched healthy controls. All participants underwent brain MRIs, neurological evaluations, and neuropsychological screenings, including three-dimensional T1-weighted and brain dual-echo scans at baseline, at months 3, 12, and 24. Baseline had to be measured within 2 months of clinical onset.

From month 1 to month 3, participants showed clusters of reduced radial distance progressively extending to the subiculum from the Cornu Ammonis, and these were negatively correlated with T1 and T2 ipsilateral lesion volume. In the right dentate gyrus, increased radial distance appeared after month 3 (P <.05), month 12, and month 24 (P <.001). In the left dentate gyrus, increased radial distance appeared after month 3 and month 24 (P <.001). These showed a positive correlation with lesional measures. Patients converting to multiple sclerosis after month 24 showed more pronounced variations in hippocampal volume, but these did not appear to affect cognitive performance.

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Study investigators concluded that, “despite an apparently preserved hippocampal volume, we observed local atrophy damage in [Cornu Ammonis 1] and subiculum subfields, from the beginning of the disease, confirming the early presence of neurodegenerative mechanisms. Bilateral expansion of the [dentate gyrus] subfield was also observed, which positively correlated with lesion burden and to conversion to [multiple sclerosis], suggesting a possible response to focal [white matter] damage. To better understand and confirm these findings, future studies should try to combine this type of analysis with a quantification of [gray matter] lesions and microstructural hippocampal alterations.”


Cacciaguerra L, Pagani E, Mesaros S, et al. Dynamic volumetric changes of hippocampal subfields in clinically isolated syndrome patients: A 2-year MRI study [published online July 1, 2018]. Mult Scler. doi: 10.1177/1352458518787347