Atypical presentation of mesial temporal lobe epilepsy: A case report

INTRODUCTION

Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy, predominantly presenting as sporadic cases. A genetic locus associated with a familial, autosomal dominant MTLE phenotype has also been identified, yet these cases demonstrate a complex inheritance pattern, lacking radiographical evidence of mesial temporal sclerosis.^[1] Childhood febrile seizures are a known risk factor for MTLE development.

MTLE typically presents with focal seizures, often accompanied by auras featuring auditory or gustatory hallucinations, déjà vu, or autonomic symptoms. Seizures with impaired awareness may manifest as behavioral arrest, orofacial automatisms, and postictal confusion.^[2] Rarely, focal seizures progress to generalized tonic-clonic seizures (GTCS), and it is exceedingly uncommon for MTLE to present with GTCS initially.

Hippocampal sclerosis is the most common histopathological finding in drug-resistant MTLE, followed by epilepsy-associated tumors and focal cortical dysplasia. Other rare etiologies include post-herpes simplex virus encephalitis, vascular malformations, and old traumatic or ischemic lesions.^[2,3]

We present a rare case of MTLE with GTCS as the initial presentation, confirmed radiologically. This case is notable for the absence of focal seizures, auras, febrile seizures, and a family history of epilepsy.

CASE REPORT

A 24-year-old male with no significant medical history presented with a complaint of a convulsive episode that occurred the previous day. The episode was characterized by generalized stretching of all four limbs, upward rolling of the eyes, and frothing at the mouth, followed by a ten minute loss of consciousness and subsequent atony. Postictal symptoms included a dull, generalized headache and severe body aches. There was no history of trauma, auditory or visual hallucinations, fever, nausea, or vomiting.

The patient reported three prior episodes of convulsions: One during training and two while on the job. None of these episodes was preceded by auras, altered bowel or bladder habits, or sleep disturbances. He denied any history of childhood febrile seizures, drug intake, or a family history of seizure disorders.

On presentation, his vital signs were stable, with a temperature of 97.5°F, and a systemic examination revealed no abnormalities. An electroencephalogram (EEG) demonstrated mild, non-specific electrophysiological dysfunction localized to the right temporal region. Magnetic resonance imaging (MRI) of the brain showed mild volume loss and hyperintensity in the right hippocampus, consistent with possible mesial temporal sclerosis [Figure 1].

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Figure 1:

Hyperintensity in the right hippocampus.

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The patient was started on oxcarbazepine 300 mg twice daily and clobazam 10 mg at bedtime. During the six months of follow-up, he experienced one breakthrough seizure despite adherence to treatment. A repeat MRI revealed a focal area of cortical thickening with blurring of the gray-white matter junction in the left uncus and amygdala, raising the possibility of a mild malformation in cortical development [Figure 2].

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Figure 2:

Mild cortical malformation.

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DISCUSSION

French et al. highlight the significant correlation between childhood complex febrile seizures and the later development of MTLE. Their study of 67 MTLE patients revealed that habitual seizures typically emerge after the first decade of life, underscoring the potential long-term implications of early-life febrile events.^[4] However, in contrast, our patient lacked a history of febrile seizures or focal seizures, challenging the traditional etiological link and suggesting the need to consider broader diagnostic possibilities in such atypical presentations.

In research by Williamson et al., specific clinical features were identified based on seizure lateralization and focus. Common manifestations included oral automatisms, pupillary dilation, impaired consciousness, and generalized rigidity. Ipsilateral limb automatisms and contralateral dystonia, and postictal hemiparesis were characteristic.^[5] In contrast, our patient exhibited GTCS without preceding focal features or automatisms, further highlighting the unusual presentation of MTLE in this case.

Hippocampal sclerosis, often regarded as the hallmark of MTLE, is thought to result from brain-damaging events such as acute and chronic inflammation, glial cell involvement, and vascular damage, particularly during early life. These insights have expanded therapeutic targets for MTLE. Emerging treatments such as cyclooxygenase-2 inhibitors, rapamycin, and growth hormone secretagogues have shown promise in mitigating brain tissue damage across multiple components.^[6] In our case, the MRI findings of hippocampal hyperintensity and subsequent cortical thickening with blurring of the gray-white junction align with typical imaging features of MTLE. However, the absence of early-life triggers such as febrile seizures or structural damage underscores the complexity of its pathogenesis.

While scalp EEG remains a cornerstone in lateralizing and localizing seizure foci, it may sometimes provide inadequate data, necessitating the use of intracranial electrodes for invasive recording in select cases.^[7] Our patient’s EEG findings of mild non-specific dysfunction in the right temporal region provided limited lateralizing data, emphasizing the diagnostic challenges in such cases. Although MRI is vital in identifying structural abnormalities underlying focal seizures, it may miss subtle changes, leading to false-negative results. Advanced neuroimaging techniques such as 18F-fluorodeoxyglucose positron emission tomography, ictal single-photon emission computed tomography, diffusion MRI, and magnetic resonance spectroscopy (MRS) improve diagnostic accuracy and may complement MRI findings.^[8,9]

MTLE management involves pharmacological and nonpharmacological strategies. First-line treatment includes anti-epileptic drugs (AEDs), but many patients show suboptimal responses, often leading to medical refractoriness. Such cases may require surgical options such as anterior temporal lobectomy or selective amygdalohippocampectomy for favorable outcomes.^[2,9] In our case, the patient was initiated on oxcarbazepine and clobazam, resulting in partial seizure control but with one breakthrough seizure during follow-up, highlighting the potential for pharmacological limitations in similar cases.

Neurostimulation therapies, such as vagus nerve stimulation, responsive neurostimulation, and deep brain stimulation, provide additional treatment options for patients who are ineligible for or decline resective surgery. Furthermore, neurostimulation may be considered for patients experiencing seizure recurrence following surgical intervention.^[2,10] While our case has not yet progressed to surgical consideration, the partial response to AEDs underscores the importance of considering alternative therapeutic strategies, including neurostimulation, if pharmacological control remains inadequate.

This case highlights the unique presentation of MTLE without typical features such as febrile seizures, aura, or focal seizure history, emphasizing the need for heightened clinical vigilance and consideration of atypical presentations. The findings also support a tailored approach, integrating advanced diagnostic tools and emerging therapies to optimize management outcomes.

CONCLUSION

This case underscores the diagnostic complexity and clinical variability of mesial temporal lobe epilepsy (MTLE). Although focal seizures and preceding febrile episodes are hallmark features, our patient presented atypically with generalized tonic-clonic seizures as the initial manifestation, without prior focal symptoms, auras, or significant risk factors. Neuroimaging revealed subtle mesial temporal structural changes, emphasizing the critical role of MRI and advanced modalities in identifying underlying pathologies when initial evaluations appear nonspecific. Despite appropriate anti-epileptic therapy, the occurrence of breakthrough seizures reflects the potential for drug resistance commonly seen in MTLE. In such cases, early consideration of surgical and neurostimulation options is vital for optimizing long-term outcomes. Our report highlights the need for a high index of suspicion, comprehensive imaging, and individualized management strategies in atypical presentations of MTLE.