Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is recognised by the International League Against Epilepsy as an aetiology-specific epilepsy syndrome.

It is more specific than simply having temporal lobe epilepsy or an MRI showing hippocampal sclerosis. The diagnosis requires a characteristic mesial temporal seizure pattern together with MRI-confirmed hippocampal sclerosis.

Why this is a syndrome

The ILAE syndrome framework identifies recurring combinations of seizure type, imaging, EEG and clinical features that have implications for diagnosis, prognosis and treatment.

MTLE-HS is unusual among adult focal epilepsies because a specific structural cause—hippocampal sclerosis—is mandatory for the syndrome diagnosis.

What is hippocampal sclerosis?

Hippocampal sclerosis is a pattern of neuronal loss and gliosis affecting the hippocampus.

MRI may show hippocampal volume loss, abnormal internal architecture and increased signal on appropriate sequences.

It may be unilateral or bilateral.

Mandatory seizure pattern

Seizures are focal aware or focal impaired-awareness seizures whose earliest symptoms are referable to mesial temporal networks.

Typical features can include:

an epigastric rising sensation;
déjà vu or jamais vu;
sudden fear;
autonomic sensations;
olfactory or gustatory phenomena;
behavioural arrest;
impaired awareness;
oral or manual automatisms.

Seizures can spread

Mesial temporal seizures can spread beyond the temporal lobe and may evolve to focal-to-bilateral tonic-clonic seizures.

MRI is required for the ILAE syndrome diagnosis

ILAE diagnostic criteria require MRI evidence of hippocampal sclerosis.

This separates MTLE-HS from MRI-negative mesial temporal epilepsy and from temporal lobe epilepsy caused by tumours, focal cortical dysplasia, vascular lesions or other abnormalities.

EEG

Interictal EEG commonly shows temporal epileptiform abnormalities, but an ictal EEG recording is not mandatory when the clinical and imaging criteria are otherwise convincing.

Repeated absence of temporal EEG abnormalities should prompt caution and reconsideration of the diagnosis.

Age at onset

The syndrome can begin in childhood or adulthood.

Onset before two years of age is an alert feature in the ILAE criteria rather than the expected presentation.

What causes hippocampal sclerosis?

There is no single pathway.

A 2026 scoping review describes interacting genetic, developmental, immune and acquired mechanisms. Febrile status epilepticus, inflammation and other early brain insults have been studied, but not everyone with MTLE-HS has an identifiable preceding event.

Febrile status epilepticus

The long-term FEBSTAT study found that acute hippocampal T2 hyperintensity after febrile status epilepticus predicted later hippocampal sclerosis and increased risk of mesial temporal epilepsy.

This does not mean ordinary childhood febrile seizures usually cause MTLE-HS.

Memory and cognition

The hippocampus is central to memory formation.

People with MTLE-HS may therefore have memory difficulties caused by the underlying pathology, recurrent seizures, medication effects or the wider temporal network.

The pattern often differs between dominant and non-dominant temporal involvement.

Psychiatric comorbidity

Anxiety, depression and other psychiatric symptoms are common in temporal lobe epilepsy and should be assessed independently rather than treated as merely a reaction to seizures.

Drug resistance

MTLE-HS is frequently drug resistant.

If two appropriate and tolerated antiseizure medication schedules fail to produce sustained seizure freedom, referral to a comprehensive epilepsy-surgery service should not be delayed.

Surgery

MTLE-HS is one of the best-established surgically treatable focal epilepsies.

Possible procedures include anterior temporal lobectomy, selective amygdalohippocampectomy and, in selected centres, laser interstitial thermal therapy.

Why presurgical testing still matters

Even when hippocampal sclerosis is visible, surgery is not based on MRI alone.

Seizure semiology, video-EEG, neuropsychology and sometimes PET, fMRI, Wada testing or SEEG are used to confirm that the epileptogenic network and functional risks are sufficiently understood.

Memory risk after surgery

Removing or ablating a hippocampus can affect memory, especially when the operated hippocampus retains useful function.

Presurgical neuropsychological assessment is therefore central to counselling.

Not every hippocampal abnormality is MTLE-HS

Hippocampal atrophy can occur for other reasons, and MRI abnormalities need to be interpreted alongside the seizure phenotype.

Likewise, temporal seizures without MRI-confirmed hippocampal sclerosis do not meet the ILAE MTLE-HS syndrome definition.

The central point

MTLE-HS is a specifically defined aetiology-linked epilepsy syndrome: characteristic mesial temporal seizures plus MRI-confirmed hippocampal sclerosis. Its importance lies partly in the high risk of drug resistance and the possibility of effective surgical treatment.

Sources

Evidence checked: September 2026.