Temporal epilepsy associated with hippocampal focal cortical dysplasia

Abstract

Background:

Focal cortical dysplasia (FCD) is a congenital abnormality of the cerebral cortex and a common cause of epilepsy. However, FCD in the hippocampus is rare.

Case Description:

A 30-year-old woman was admitted to the hospital because of seizures. Brain magnetic resonance imaging showed focal cortical thickening of the right medial temporal lobe cortex. The patient underwent a right-sided anteromedial temporal lobectomy. Pathologic examination showed disorganized cortical gray matter tissue with large dysmorphic cortical neurons, supporting a FCD diagnosis. The histological findings of hippocampal sclerosis were not found.

Conclusion:

The present case is a rare case of dysmorphic neurons without histological findings of sclerosis in the hippocampus reported. Recognizing more hippocampal FCD-related epilepsy cases is essential to better understanding the condition.

INTRODUCTION

Focal cortical dysplasia (FCD), which was first described by Taylor et al., in 1971, is a congenital abnormality of the cerebral cortex characterized by deranged neurons in white matter, dyslamination, and abnormal balloon cells.[9] It is the most common cause of refractory epilepsy in children.[3] The FCD has been classified into 3 types, and FCD type I, associated with hippocampal sclerosis (HS), is classified as type IIIA.[7] Epilepsy is the main symptom of dysplasia, and occurs at any age, but mostly in childhood.[4] FCD may be present at any part of the brain and may be multifocal.[2] However, FCD in the hippocampus has rarely been reported.[8] Here, we report a 30-year-old patient who suffered from temporal epilepsy associated with FCD at the right hippocampus.

CASE REPORT

A 30-year-old woman was admitted to our hospital with an exacerbation of seizures. She had her first seizure episode when she was 15 years old, 1 week after having a head trauma without traumatic brain injuries, and had suffered from epilepsy since childhood. Using witnesses’ reports, her episodes could be classified as focal, motor (myoclonic) onset with impaired awareness seizures. She had received a variety of anti-epileptic medical regimens, with the most recent being a combination of Topamax 75 mg, Depakine 500 mg, and Piracetam 800 mg daily. Neurological examination revealed no localizing signs.

Brain magnetic resonance imaging (MRI) showed focal cortical thickening of the right medial temporal lobe cortex, accompanied by a decrease in the N-acetylaspartate/Creatine (NAA/Cre) ratio on the magnetic resonance spectroscopy [Figure 1]. A 2-day video electroencephalogram (EEG) showed frequent unilateral right anterior temporal spikes with phase reversals at F8 and T2 during both wakefulness and sleep [Figure 2]. Despite complete antiseizure medication withdrawal before admission, no clinical seizures were captured. Given the concordance between interictal discharges and MRI findings, ictal recordings were deemed unnecessary in mesial temporal epilepsy. A diagnosis of FCD of the right temporal lobe was made, and the patient underwent right-sided anteromedial temporal lobectomy and amygdalohippocampectomy. The postoperative course was noncomplicated. Her seizures have been well-controlled (Engel IB) with oral antiepileptic drugs since the surgery, with a follow-up of 12 months.

Figure 1:

(A). T2W flair axial slice, Focal cortical thickening of the right medial temporal lobe cortex (red arrow) compared to the left medial temporal lobe (yellow arrow). These images are suggestive of focal cortical dysplasia type Ia. (B-1). T2w coronal oblique through the right hippocampus (red arrow) and the left one (yellow arrow); (B-2). T2w flair coronal oblique of the right medial temporal lobe (red arrow) and the left one (yellow arrow); (B-3). DIR-3D thin slice, coronal oblique reconstruction of the right medial temporal lobe (red arrow) and the left one (yellow arrow). (C1–C2). T1_Space_Inversion Recovery sequence, reconstructed through the right hippocampal region (red arrow) and the left one (yellow arrow) on the Sagittal plane. (D1-D2). A decrease in the NAA/Cre ratio in the left medial temporal lobe (4.5 on D-1 image in comparison with 7.1 on D-2 image) on the MRS. NAA/Cre: N-acetylaspartate/Creatine, MRS: Magnetic resonance spectroscopy, DIR: Double inversion recovery

Figure 2:

(A) Scalp electroencephalogram recordings demonstrated frequent right anterior temporal spikes with phase reversals at F8 and T2, observed during both wakefulness and .(B). Frequent right anterior temporal spikes with phase reversal at F8 and T2 during sleep. The recordings were obtained using a high-pass filter of 1 Hz and a low-pass filter of 70 Hz.

Pathologic examination of the three resected specimens that were of the amygdala, head of the hippocampus, and body of the hippocampus origins was performed. Hematoxylin and eosin staining showed a disorganized cortical gray matter tissue with large dysmorphic cortical neurons, and immunohistochemical study with synaptophysin demonstrated a strong positive staining in cytoplasm of dysmorphic cortical neurons that supports the diagnosis of FCD type IIA [Figures 3 and 4]. The presence of synaptophysin positivity in the hippocampal head and body indicates preserved neurons, thereby ruling out HS and gliosis in the present case [Figure 5].

Figure 3:

(A) IIA pattern: Marked by the presence of large dysmorphic neuronal cells in the cortex (arrows) (HE ×40). (B) Strong cytoplasmic expression of synaptophysin in dysmorphic neurons (arrows) (IHC staining ×40). HE: Hematoxylin and eosin stain, IHC: Immunohistochemistry

Figure 4:

(A) Head of hippocampus with dentate gyrus and dysmorphic neurons in CA4 (HE×4), (B). Dysmorphic neurons in CA4 (HE×40). HE: Hematoxylin and eosin.

Figure 5:

Body of hippocampus with background and dysmorphic neurons positive for Synaptophysin (IHC staining × 40), thereby excluding hippocampal sclerosis and gliosis. IHC: Immunohistochemistry.

DISCUSSION

The classification of FCD was based on the histological changes. According to the most recent classification given by the International League Against Epilepsy in 2022, FCDs with altered cortical lamination have been classified into type I, those with neuronal cell dysmorphism have been classified into type II, and FCDs type I associated with another primary lesion have been classified as type III.[7] A report on the autopsy of patients who suffered from sudden and unexpected death in epilepsy showed the most common locations of FCD were the frontal lobe and the precentral gyrus.[5]

The seizure presentation, EEG characteristics, and MRI of the present case suggested her epileptic zone onset was associated with the lesion located at the right hippocampus. She underwent right anteromedial temporal lobectomy. The histology confirmed a FCD type IIA with disorganized cortical gray matter tissue with dysmorphic cortical neurons, without balloon cells at the hippocampus. The histological findings of HS, such as neuronal loss, gliosis, and granule cell dispersion, were not found in this patient. Five cases of hippocampal dysplasia with balloon cells have been reported in the literature, but histological findings of HS were all present in these four cases.[5,6,10] In a report by da Silva, among 17 cases of mesial temporal sclerosis, dysmorphic neurons were found in the hippocampus in 7 cases.[1] The authors hypothesized that the coexistence of dysmorphic neurons or balloon cells with hippocampus sclerosis might be a developmental disorder.[1,8] To the best of our knowledge, the present case is the first case of dysmorphic neurons without histological findings of sclerosis in the hippocampus that has been reported. We need more similar cases to elucidate the pathophysiological mechanism of FCD in the hippocampus.

CONCLUSION

We report a rare case of refractory epilepsy associated with hippocampal FCD. Recognition of more cases of epilepsy associated with hippocampal FCD is essential for further understanding of this pathology.

Ethical approval:

Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.

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