Selective affection of hippocampal CA-1 neurons in patients with transient global amnesia without long-term sequelae

Abstract

The aetiology, pathomechanisms and anatomical correlates of transient global amnesia (TGA) still remain obscure. Recently, focal MR-signal diffusion-weighted imaging (DWI) changes in the hippocampus have been described in patients with TGA, but the exact localization, long term outcome and pathophysiological nature of these lesions still remain unknown. The topography and time course of hippocampal DWI lesions in 41 TGA patients was studied using serial 3 T high-resolution MR-imaging and correlated to clinical and neuropsychometric results. Of these, 29 patients showed 36 DWI lesions with corresponding T(2) lesions in the hippocampus within a time window of 48 h after onset. Almost all lesions (94%; 34/36) were selectively found in the CA-1 sector (Sommer sector) of the hippocampal cornu ammonis. Most DWI lesions (8/10) were already detectable in the peri-acute phase <6 h after onset of symptoms. A follow-up study 4-6 months after the episode did not show evidence for residual structural sequelae of these lesions (n = 20/20). A venous MR angiography of the intracranial dural sinus showed an asymmetric venous drainage in 21/24 (88%) patients. In 11/16 (69%) patients with unilateral lesions, the asymmetry corresponded to the side of the DWI lesion. Significant episodic verbal memory deficits in the acute phase (n = 14/18) were associated with lesions of the dominant hemisphere while impairment of visuospatial memory was associated with lesions of the non-dominant hemisphere. Persistent neuropsychological sequelae were not detected 4-6 months after the episode (n = 16). This is the first prospective study combining high-resolution imaging and neuropsychometry analysing the detailed functional anatomy and outcome of hippocampal DWI/T(2) lesions in TGA supporting the view the TGA being a benign transient disorder. The TGA can be considered a model for a focal transient perturbation of memory circuits in the temporo-mesial region.

Optimal Diffusion-Weighted Imaging Protocol for Lesion Detection in Transient Global Amnesia

“…In recent published studies, 9,11 which included Ͼ30 patients with TGA, multiple lesions were found in only 17, approximately 19% of the patients. We think that the higher incidence of multiple lesions in our study is due to the combined use of higher bvalues and thin section thicknesses.…”

“…Most of the previous DWI studies of TGA were conducted by using a section thickness of 5 mm and a b-value of 1000, except a recent study by Bartsch et al, 11 in which a 3-mm section thickness was used. However, no comparison of lesion detection rates at different section thicknesses was conducted in their study.…”

“…6 Recent diffusion-weighted imaging (DWI) studies have indicated the presence of focal hyperintensities involving the hippocampus in TGA. [7][8][9][10][11] The lesions detected by DWI are small and punctate (1-3 mm) and located within the lateral portion of the hippocampus. 9,11,12 Since Strupp et al 13 first detected hyperintense lesions in the hippocampus in TGA by using DWI, the frequency of lesions detected on DWI has been reported in a range of 0%-84%.…”

“…[7][8][9][10][11] The lesions detected by DWI are small and punctate (1-3 mm) and located within the lateral portion of the hippocampus. 9,11,12 Since Strupp et al 13 first detected hyperintense lesions in the hippocampus in TGA by using DWI, the frequency of lesions detected on DWI has been reported in a range of 0%-84%. 9,10,14,15 According to a recent study, this discrepancy in detection rates appears to be attributable to the different timing of imaging from the onset of symptoms.…”

High-Resolution Diffusion-Weighted Imaging Increases Lesion Detectability in Patients with Transient Global Amnesia

“…Because TGA lesions are susceptible to the partial volume averaging effect, due to their small size (1-3 mm) and subtle diffusion restriction during the first day of symptom onset, a higher-resolution DWI seems preferable for detecting smaller lesions at the early stage. 7,9 Prior to our study, Bartsch et al 22 performed DWI at 3T using the smallest voxel size (1.7 ϫ 0.9 ϫ 3 mm in x-, y-, and z-axis ϭ 4.7 mm 3 ), with lesion detectability of 70% within 72 hours after symptom onset. The high-resolution DWI in our study had an even smaller voxel size (1 ϫ 1 ϫ 2 mm ϭ 2 mm 3 ) compared with those of previous studies (4.7-14 mm 3 ), 9,17,22 and achieved lesion detectability of 52% at the first visit and 81% 2-4 days after symptom onset.…”