“Unforgettable” – a pictorial essay on anatomy and pathology of the hippocampus

Sulcal remnant cysts and choroidal fissure cysts are benign cerebral cysts that can occasionally be found at the level of the vestigial hippocampal sulcus and the choroid fissure, respectively (Fig. 6). Sulcal remnant cysts are residual cysts resulting from lack of obliteration of the hippocampal sulcus and are, therefore, most commonly localized laterally, at the apex of the hippocampal fold, between the cornu ammonis and dentate gyrus. The aetiology of choroid fissure cysts is less clear. The tela choroidea is a double layer of the pia mater that invaginates through the choroid fissure to reach the lateral ventricles and to form the choroid plexus. Developmental errors may occur anywhere along the choroid fissure at the time of formation of the primitive choroid plexus, thus forming a cyst, which may be of the neuroepithelial or arachnoid type. On MRI, sulcal remnant cysts and choroid fissure cysts are isointense to cerebrospinal fluid and show no contrast enhancement or restricted diffusion. Both lesions are usually asymptomatic and discovered incidentally. Very rarely can choroid fissure cysts become symptomatic due to mass effect on the surrounding structures [9].

Hippocampal calcifications are a frequent incidental finding on CT (Fig. 9). Their prevalence increases with age and they are described in up to 21.7% of the population over 50 years of age. Hippocampal calcifications are not associated with neurodegenerative diseases. Their pathologic significance is unclear, but they most likely reflect the latter stages of vascular fibrosis [12].

The most common cause of medically intractable partial complex epilepsy in adults is mesial temporal sclerosis (MTS). MTS is characterized pathologically by hippocampal gliosis and neuronal loss. The pathophysiology of MTS is not completely understood. One theory is that early or prolonged febrile seizures damage the hippocampus in genetically susceptible patients. However, the difference between cause and effect is not clear, as it is also conceivable that a child may have prolonged febrile seizures due to MTS secondary to a prenatal/perinatal insult or genetic predisposition [13, 14].

Neuronal cell loss and gliosis result in the MRI findings of hippocampal atrophy with increased T2/FLAIR signal intensity (Fig. 10). Other secondary signs can be present such as: (1) loss of the internal architecture of the hippocampus; (2) loss of hippocampal head digitations; and (3) dilatation of the ipsilateral temporal horn. Because of physiologic interconnections between the hippocampus and other parts of the brain, secondary signs can also involve other structures such as: (1) increased signal intensity and/or atrophy of the ipsilateral amygdala; (2) atrophy of the ipsilateral mammillary body; (3) atrophy of the ipsilateral fornix; (4) atrophy of the contralateral cerebellar hemisphere; and (5) atrophy of the ipsilateral entorhinal area [15‐17].

Identification of MTS is important as surgery is often the only treatment option with a good outcome. Regarding the radiological pre-surgical workout, it is important to note that MTS can be bilateral in up to 3–10% of cases although symptomatology may be unilateral [18], and that dual pathology, the existence of a second epileptogenic lesion, can be present in up to 15% of cases (Fig. 11) [19].

Over the past decades, the role of imaging in dementia has shifted from merely excluding possible treatable causes of dementia (e.g. tumour or subdural hematoma) to the identification of certain positive disease markers. In this regard, the mesial temporal atrophy (MTA) score, a radiologic measure for the degree of hippocampal atrophy, has proven to be predictive of progression from mild cognitive impairment to AD [20] and can identify patients with AD with an accuracy and sensitivity of approximately 85% compared to healthy controls [21]. The MTA score is based on four points and takes into account the width of the temporal horn of the lateral ventricle, the width of the choroid fissure and the hippocampal volume (Table 1, Fig. 12) [20]. For subjects younger than 75 years, an MTA score of 2 or more is considered abnormal, while for subjects older than 75 years, an MTA score of 3 or more is considered abnormal [21]. Its usefulness for the distinction of AD from other dementia syndromes is limited however, as MTA not only occurs in AD, but can be seen in other dementia syndromes as well (Fig. 12) [22]. In this regard, it is important to note that the combined visual assessment of mesial temporal atrophy and parietal atrophy has proven to not only increase the sensitivity of MRI in identifying patients with AD, but also increase the specificity of MRI in discriminating AD from other dementia syndromes [23] (Fig. 13; Table 2).

The hippocampus can also be affected by infectious and inflammatory conditions, the best known of which is herpes simplex encephalitis (HSE). HSE is almost always caused by the HSV type 1 virus, except in neonates where type 2 predominates. The precise sequence of events leading to non-neonatal HSE is unclear. It is often assumed that HSE is caused by reactivation of HSV in the trigeminal ganglion. An alternative hypothesis is that HSE is a primary infection rather than virus reactivation, with the olfactory system as the most probable port of entry [24]. This route of infection would better explain the typical distribution of HSE lesions in the limbic system and the insular cortex.

Symptoms reflect the propensity to involve the inferomedial frontal and temporal lobes with acute onset of hallucinations, seizures, personality changes and aphasia. HSE primarily affects neurons, which is reflected by preferential cortical involvement on MRI. On MRI, cortical abnormalities are noted as ill-defined areas of high T2/FLAIR signal intensity, usually beginning unilaterally but progressing to become bilateral. Diffusion restriction is not always present, but can be one of the earliest signs of HSE (Fig. 14) [25, 26]. Gyral enhancement and petechial haemorrhages may also be present (Fig. 15).

HSE has a bad prognosis and quick antiviral treatment is mandatory. The mortality rate of HSE exceeds 70% in patients who had no or incomplete treatment and fewer than 3% of all patients return to normal function after recovering from their illness [27].

On MRI, LE manifests with uni- or bilateral swelling and varying degrees of high T2/FLAIR signal intensity in the mesial temporal lobe. Patchy enhancement and restricted diffusion can be seen. These changes may eventually evolve to medial temporal lobe atrophy and increased T2/FLAIR signal intensity in the hippocampus due to gliosis (Fig. 16). Imaging findings can be subtle early in the course of the disease, however, and can even remain normal in a subset of cases [29].

As discussed earlier, the hippocampus has a complex arterial supply with three hippocampal arteries or groups of arteries supplying the hippocampal head, body and tail. The anterior choroidal artery has a variable contribution to the vascularization of the hippocampal head, which may be preponderant in some cases [1]. Hence, the hippocampal head can be involved in anterior choroidal artery infarctions and the entire hippocampus in posterior cerebral artery infarctions (Figs. 21 and 22) [32]. Of note is that infarction limited to the hippocampus is rare and in acute hippocampal infarction, additional extrahippocampal infarctions in the territory of the anterior choroidal artery or posterior cerebral artery are highly likely [31]. This can be used to differentiate acute ischemic hippocampal infarction from other conditions manifesting with hippocampal diffusion restriction, such as transient global amnesia and seizure-induced abnormalities [32].

Transient global amnesia is a clinical syndrome characterized by acute retrograde amnesia, generally occurring in patients older than 60 years of age and lasting less than 24 hours. Its aetiology is unclear and several hypotheses have been formulated, including arterial thrombo-embolism, venous congestion, epilepsy and migraine. Although the diagnosis is mainly clinical, the detection of uni- or bilateral small punctate foci of diffusion restriction on MR imaging can help to confirm it. On MRI, hippocampal signal abnormalities can be found in up to 85% of patients, depending on the used MRI parameters and the time elapsed from onset (Fig. 23) [33].