Long-term neuropsychological, neuroanatomical, and life outcome in hippocampal amnesia

Abstract

Focal bilateral hippocampal damage typically causes severe and selective amnesia for new declarative information (facts and events), a cognitive deficit that greatly impacts the ability to live a normal, fully independent life. We describe the case of 1846, a 48-year-old woman with profound hippocampal amnesia following status epilepticus and an associated anoxic episode at age 30. Patient 1846 has undergone extensive neuropsychological testing on many occasions over the 18 years since her injury, and we present data indicating that her memory impairment has remained severe and stable during that time. New, high-resolution, structural MRI studies of 1846's brain reveal substantial bilateral hippocampal atrophy resembling that of other well-known amnesic patients. In spite of severe amnesia 1846 lives a full and mostly independent adult life, facilitated by an extensive social support network of family and friends. Her case provides an example of a rare and unlikely positive outcome in the face of severe memory problems.

Figure 1

Three-dimensional tracing-based models of hippocampus, amygdala, and the ventricular system in 1846 and a healthy age- and sex-matched comparison participant, 3608. In panels A–D, the whole-brain volume is presented in gray, portions of the ventricular system within our scan volume in translucent blue, amygdala in translucent red, and hippocampus in solid green. E illustrates the extent of the high-resolution scan. Panels B and D illustrate healthy structures in 3608. The size and extent of the hippocampus is normal bilaterally. Panels A and C model the same structures in patient 1846. While the hippocampus is diminished bilaterally, right hippocampus is somewhat less atrophied than left.

Figure 2

Anatomy of 1846 and healthy comparison 3608 based on high-resolution T2-weighted structural MRI scans. Panel A uses three-dimensional models of traced structures from 1846 (see Fig. 1) and planar sections to illustrate the location of the slices shown in panels BD. In panel B, sagittal sections reveal the extensive atrophy of 1846's left hippocampus along its entire length (left column). The right hippocampus is less compromised (right column). In panel C, successive coronal sections illustrate hippocampal anatomy of the anterior hippocampal head (top row), the posterior hippocampal head at the uncal apex (middle row), and the hippocampal body caudal to the uncal apex (bottom row). At bottom right, 3608's right hippocampus contains enough detail for identification of several hippocampal subfields. In panel D, axial sections reveal the severe atrophy of 1846's left hippocampus and the corresponding enlargement of the inferior horns of the lateral ventricles. Common abbreviations for panels BD: A, anterior; P, posterior; R, right; L, left; h, hippocampus; hh, hippocampal head; hb, hippocampal body; ht, hippocampal tail; a, amygdala; v, inferior horn of the lateral ventricle; mb, mammillary body/bodies; sub, subiculum; ca1, cornu ammonis-1; dg/ca4, dentate gyrus and cornu ammonis-4; fim, alveus/fimbria.