Revisiting retrosplenial amnesia: Injury of the crus of the fornix following splenial hemorrhage – A 3D magnetic resonance imaging case report

INTRODUCTION

The retrosplenial cortex, located posterior to the splenium of the corpus callosum and corresponding to Brodmann areas 29 and 30, forms a distinct cortical component of the Papez circuit.^[1] Directly beneath the splenium lies the crus of the fornix (FxCr), the principal efferent pathway of the hippocampus, and a key subcortical component of the circuit.^[2] Because these structures abut the splenium within a narrow anatomical corridor, lesions involving the splenium have the potential to disrupt multiple adjoining components of the Papez circuit, including the retrosplenial cortex and the FxCr, resulting in significant episodic memory impairment.

Clinically, retrosplenial amnesia has been used to describe a syndrome characterized by severe anterograde episodic memory impairment, often accompanied by topographical disorientation, in the absence of widespread cognitive dysfunction, typically associated with lesions at or around the splenium of the corpus callosum.^[3-5] In the classical single-case report by Valenstein et al., this amnestic syndrome followed a left-sided splenial hemorrhage with ventricular rupture, in which ipsilateral retrosplenial cortex involvement was suspected based on chronic-phase magnetic resonance imaging (MRI) available at the time. In that context, dysfunction of the retrosplenial cortex was considered a primary mechanism underlying the memory disturbance.^[4] However, Valenstein et al. also noted that involvement of the forniceal pathway could not be excluded using the imaging techniques available at the time. Because subtle forniceal injury is difficult to detect on conventional MRI, its potential contribution to amnestic syndromes was not directly assessable.^[4]

Subsequent advances in high-resolution three-dimensional imaging have demonstrated that post-operative amnesia following anterior communicating artery aneurysm surgery, previously described as “basal forebrain amnesia”, may in fact result from unrecognized injury to the fornix, particularly the columns of the fornix.^[6,7] These observations underscore the value of high-resolution 3D MRI for directly visualizing forniceal injury and for clarifying the anatomical substrates of amnestic syndromes that were previously difficult to localize.

A similar reappraisal may therefore be warranted for retrosplenial amnesia. Given the close anatomical relationship between the splenium and the forniceal pathway, injury to the FxCr running immediately beneath the splenium may represent an unrecognized but clinically relevant contributor to memory impairment in patients with splenial-region lesions.

Here, we report a patient who developed severe anterograde amnesia following a splenial hemorrhage with ventricular rupture. High-resolution 3D MRI with multiplanar reconstruction in the chronic phase demonstrated focal disruption of the left FxCr immediately beneath the lesion, providing direct structural evidence of FxCr involvement. This case highlights the importance of systematically evaluating forniceal integrity, particularly the FxCr, in patients with splenial or retrosplenial lesions presenting with amnesia.

CASE REPORT

A left-handed young adult man collapsed while exercising at home and was transported to a local hospital, where he regained consciousness without focal neurological deficits. Non-contrast computed tomography (CT) revealed an acute hematoma centered in the splenium with left-dominant intraventricular extension [Figure 1A and B]. Subsequent axial and near–mid-sagittal T2-weighted MRI confirmed that the lesion was confined to the splenium of the corpus callosum, without definite extension into the cingulate gyrus or retrosplenial region [Figure 1C and D]. Diffusion-weighted imaging showed faint hyperintensity in the left hippocampus, and fluid-attenuated inversion recovery (FLAIR) demonstrated subtle swelling and mild hyperintensity in the same region [Figure 2]. Arterial spin labeling (ASL) additionally revealed relative hyperperfusion. Digital subtraction angiography revealed no vascular abnormality such as arteriovenous malformation or aneurysm. In retrospect, these findings appear more consistent with transient physiological disturbance within the Papez circuit than with structural hippocampal injury. At this stage, however, no definitive lesion that could later account for the patient’s amnestic syndrome was identified.

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Figure 1:

A left-handed 29-year-old man collapsed while exercising at home and was transported to a local hospital, where head computed tomography (CT) revealed an acute splenial hemorrhage. (A and B) Non-contrast CT shows an acute hematoma centered in the splenium of the corpus callosum with left-dominant intraventricular extension (arrow). (C) Acute phase axial T2-weighted magnetic resonance imaging (MRI) reveals a focal lesion in the splenial region (arrow), corresponding to the hemorrhagic site, with intraventricular extension into both lateral ventricles. (D) A slightly left paramedian, near–mid-sagittal T2-weighted MRI demonstrates that the hematoma is confined to the splenium of the corpus callosum (arrow), with no definite extension into the posterior cingulate cortex or the retrosplenial cortex.

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Figure 2:

A left-handed 29-year-old man, acute-phase magnetic resonance imaging (MRI) demonstrating transient hippocampal abnormalities. (A) Diffusion-weighted imaging shows faint hyperintensity in the left hippocampus (arrow). (B) fluid-attenuated inversion recovery imaging reveals subtle swelling and mild hyperintensity in the corresponding region (arrow). (C and D) Arterial spin-labeling perfusion images, co-registered to the anatomical images, demonstrate relative hyperperfusion of the left hippocampus (arrows). These abnormalities resolved on follow-up MRI, suggesting transient physiological changes within the hippocampus rather than a persistent structural injury.

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Although he became fully alert shortly after admission, the patient began to show prominent anterograde memory impairment, characterized by rapid forgetting and repeated questioning. These symptoms persisted and interfered with daily activities, and he was referred to another institution for further evaluation approximately 2 months after onset. At referral, he was fully alert and oriented, with normal neurological examination findings. Screening cognitive tests showed only mild reductions (MMSE 26; MoCA-J 22), whereas a comprehensive neuropsychological assessment revealed markedly impaired episodic memory with relatively preserved non-memory functions [Table 1]. Testing with the Wechsler Memory Scale–Revised,^[8] the Wechsler Adult Intelligence Scale–Third Edition, the Rey Auditory Verbal Learning Test, and the Rey–Osterrieth Complex Figure Test showed a consistent pattern of severely impaired delayed recall with relatively preserved recognition memory and non-memory domains [Table 1] No callosal disconnection signs, such as tactile afignomia, intermanual conflict, or tachistoscopic visual field dissociation, were observed. Nevertheless, the patient and his family reported persistent new-learning difficulties.

Because the etiology of the amnestic syndrome remained unclear despite repeated evaluations with conventional MRI sequences, high-resolution 3D MRI was obtained 6 months after onset, with particular attention to the fornix as a potential source of impairment. 3D imaging was performed on a 3.0-T scanner (MAGNETOM Trio Tim, Siemens Healthineers, Erlangen, Germany). The protocol included a 3D T1-weighted sequence acquired in the sagittal plane using magnetization-prepared rapid gradient-echo (MPRAGE; TR/TE = 2000/2.98 ms; matrix = 240 × 256; slice thickness = 1.0 mm) and a 3D T2-weighted sequence acquired in the sagittal plane using sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE; TR/TE = 3600/363 ms; matrix = 222 × 224; slice thickness = 0.5 mm). Both datasets were evaluated using multiplanar reconstruction. Axial images parallel to the anterior commissure–posterior commissure line and orthogonal coronal images were primarily used for assessment of the forniceal pathway.

Multiplanar reconstruction of the 3D datasets demonstrated focal thinning and discontinuity of the left FxCr immediately beneath the splenial lesion [Figure 3A-E], a finding that had not been appreciable on conventional two-dimensional imaging. The hemorrhagic lesion within the left splenium had evolved into a focal scar, whereas no definite scar formation or structural abnormality was identified in the retrosplenial region. In addition, both hippocampi appeared structurally intact on follow-up imaging. Notably, coronal reconstruction of 3D at the level of the mammillary bodies demonstrated relative flattening and volume loss of the left mammillary body compared with the contralateral side, consistent with secondary atrophy [Figure 3F]. Taken together, these findings support the interpretation that disruption of the FxCr, rather than intrinsic hippocampal damage or a retrosplenial cortex lesion, played a central role in the patient’s persistent anterograde amnesia.

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Figure 3:

A left-handed 29-year-old man, Focal disruption of the left forniceal crus on 3D magnetic resonance imaging (MRI) in the chronic phase. (A and B) Axial multiplanar reconstruction images of the high-resolution 3D T1-weighted MRI obtained in the chronic phase (6 months after hemorrhage onset) demonstrate focal discontinuity of the left forniceal crus (FxCr, arrows). (C) Sagittal 3D T1-weighted MRI shows the scarred chronic splenial hemorrhagic lesion (white arrow) located directly above the disrupted left FxCr (yellow arrows), highlighting their close anatomical proximity and the vulnerability of the FxCr to secondary injury from splenial hemorrhage. (D) Coronal multiplanar reconstruction image of the high-resolution 3D T1-weighted MRI demonstrates focal discontinuity of the left FxCr (arrows). (E) Coronal 3D T2-weighted MRI shows a corresponding defect along the expected trajectory of the left FxCr (arrow). (F) Coronal 3D T1-weighted MRI at the level of the mammillary bodies shows relative flattening and volume loss of the left mammillary body compared with the contralateral side, consistent with atrophy (arrowhead).

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I-123 IMP single photon emission computed tomography (SPECT) in the 3 months after the onset revealed hypoperfusion in the left hippocampus and the left anterior and posterior cingulate, as well as in the left basal forebrain, but no significant hyperperfusion in the retrosplenial region. eZIS-based Z-score maps confirmed significant reductions relative to the age-matched database [Figure 4].^[9] These findings indicate that injury to the FxCr resulted in both functional downstream disturbance of the Papez circuit and impaired hippocampal–basal forebrain connectivity, each mediated by the forniceal pathway.

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Figure 4:

A left-handed 29-year-old man, I-123 IMP single photon emission computed tomography (SPECT) showing hypoperfusion in hippocampus, cingulate gyrus, and basal forebrain on the left. Coronal (A) and mid-sagittal (B) views of I-123 IMP SPECT obtained in the chronic phase (3 months after hemorrhage onset) demonstrate relative hypoperfusion in the medial temporal lobe, cingulate gyrus, and basal forebrain on the left. (C and D) Corresponding eZIS-based Z-score maps (blue areas; arrows) highlight regions where regional cerebral blood flow is significantly lower than the age-matched normal database, indicating marked reductions in perfusion within the left hippocampus (arrow in C) and the cingulate gyrus (arrows in D). In addition, hypoperfusion is observed in the left basal forebrain (short arrow in D), a region anatomically and functionally connected to the hippocampus through the forniceal pathway. In contrast, the retrosplenial region (asterisk in D) does not show a significant reduction in cerebral blood flow. These findings are concordant with Papez circuit dysfunction secondary to forniceal disconnection and provide functional evidence that parallels the structural abnormalities detected on high-resolution 3D magnetic resonance imaging.

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During follow-up, the patient noted gradual improvement in daily memory. Neuropsychological testing at 6 and 10 months showed partial recovery, especially in delayed recall, although mild episodic memory deficits persisted. Non-memory domains remained stable and within the average range throughout the course, further supporting the selective nature of the amnestic syndrome.

DISCUSSION

Reappraising “retrosplenial amnesia”

The concept of “retrosplenial amnesia” was originally based on a single-case report by Valenstein et al., in which severe amnesia followed a splenial hemorrhage adjacent to the retrosplenial cortex, and retrosplenial cortical dysfunction was considered the primary mechanism [Figure 5A].^[4] In the present case, although the lesion was similarly located near the retrosplenial cortex, high-resolution 3D MRI demonstrated no definite structural involvement of the retrosplenial cortex in either the acute or chronic phase. Instead, focal disruption of the left FxCr was clearly identified immediately beneath the splenium [Figure 5B]. This anatomical dissociation between preserved retrosplenial cortex and disrupted FxCr provides direct structural evidence that challenges the classical interpretation of retrosplenial amnesia.

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Figure 5:

Schematic representation of the Papez circuit highlighting two anatomical components that abut the splenium of the corpus callosum and are relevant to memory disturbance in splenial-region lesions. A schematic illustration of the Papez circuit, including the hippocampus (Hp), parahippocampal gyrus (PHG), forniceal pathway (crus of the fornix: FxCr; body: FxB; column: FxCo), mammillary bodies (MB), mammillothalamic tract (MTT), anterior thalamic nucleus (A), thalamus (Th) and cingulate gyrus (CiG). (Panel A) Schematic representation of the traditional concept of “retrosplenial amnesia,” in which memory impairment has been attributed primarily to injury of the retrosplenial cortex (RSC, black cross) adjacent to the splenium. (Panel B) Schematic representation of the present case, in which severe anterograde amnesia is attributed to the structural disconnection of the FxCr (FxCr; red cross) immediately beneath the splenium of the corpus callosum. This disconnection interrupts the hippocampal output pathway within the Papez circuit, providing a mechanistic explanation for the patient’s episodic memory impairment. Together, these schematics illustrate how lesions within the compact anatomical corridor surrounding the splenium may give rise to amnestic syndromes through distinct anatomical substrates. The present case supports FxCr disconnection, rather than retrosplenial cortical injury, as the critical mechanism underlying the patient’s amnesia. RSC: Retrosplenial cortex.

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CONCLUSION

This case provides contemporary evidence refining the classical observation that severe amnesia can follow splenial hemorrhage. Using high-resolution 3D MRI, we directly demonstrated focal structural disruption of the FxCr immediately beneath the splenium, identifying forniceal disconnection as the primary anatomical substrate underlying the patient’s anterograde amnesia. This finding suggests that amnestic syndromes associated with splenial lesions may, in some cases, be better explained by forniceal pathway injury rather than by retrosplenial cortical dysfunction. High-resolution 3D MRI thus provides critical diagnostic value by enabling direct assessment of the fornix, and systematic evaluation of forniceal integrity, particularly the FxCr, should be incorporated into the assessment of patients with splenial pathology presenting with memory impairment.