What is mesial temporal sclerosis?

What is Mesial Temporal Sclerosis?

Mesial temporal sclerosis (MTS), also known as hippocampal sclerosis or Ammon horn sclerosis, is a pathological condition characterized by specific patterns of neuronal loss and gliosis in the medial temporal lobe structures, particularly the hippocampus, and represents the most common cause of medically intractable temporal lobe epilepsy in adults. 1, 2

Pathological Features

MTS demonstrates a characteristic pattern of neuronal damage with specific regional vulnerability:

• The CA1/prosubiculum region is universally affected (100% of cases), representing the most severely damaged area 3
• The CA4 region shows involvement in 41% of cases, while the dentate gyrus demonstrates focal severe damage in 44% of patients 3
• Neuronal loss is accompanied by reactive gliosis throughout the affected hippocampal structures 1
• White matter neuronal heterotopia occurs in 93% of cases, representing a common associated finding 3
• Coexistent cortical dysplasia is present in approximately 24% of patients with MTS, though this does not appear to affect clinical presentation or surgical outcomes 3

Clinical Presentation

MTS manifests as a distinctive clinical syndrome with recognizable temporal evolution:

The typical disease course includes:

• Early prolonged febrile seizures in childhood, followed by a latent period 2
• Seizure onset in mid-to-late childhood, with initial auras that may occur in isolation 2
• Periods of remission during adolescence or early adulthood, before progression to drug-resistant epilepsy 2

Seizure characteristics are highly stereotyped:

• Seizures develop gradually over 1-2 minutes with partial awareness at onset, lasting 2-10 minutes total 2
• Auras are common, featuring visceral, autonomic, psycho-affective, or experiential components 2
• Loss of consciousness occurs after initial awareness, accompanied by motionless stare and automatisms (oro-alimentary, vocal, or gestural) 2
• Contralateral dystonic posturing is a typical motor manifestation 2
• Dysphasia is frequent when the dominant hemisphere is affected, often prolonged into the postictal period 2

Diagnostic Approach

MRI is the initial imaging investigation of choice, using thin coronal slices through the suspected seizure origin area, demonstrating 84% sensitivity compared to CT's 62% 4, 5:

• The hallmark finding is unilateral (or asymmetrical) hippocampal volume loss with increased T2 signal on coronal sequences 2
• Coronal slices must be ≤5mm thick with no gap for optimal detection 6

When MRI is normal or shows nonspecific findings:

• FDG-PET demonstrates glucose hypometabolism in the antero-mesial temporal region extending to the pole and lateral temporal lobe, with 63-67% sensitivity 4, 2
• Ictal SPECT shows hyperperfusion of the epileptogenic region during seizures, while interictal SPECT typically demonstrates hypoperfusion 7, 4
• SISCOM (Subtraction Ictal SPECT Co-registered to MRI) improves sensitivity and specificity of seizure-related perfusion network detection, with >90% localization sensitivity in temporal lobe seizures 7, 4

Interictal EEG findings:

• Anterior or mid-temporal spikes/sharp waves ipsilateral to the focus, combined with non-epileptiform regional slowing 2
• Bilateral changes may occur but typically predominate ipsilaterally 2

Ictal EEG demonstrates:

• Rhythmic temporal alpha or theta activity within 30 seconds of clinical onset 2

Prognosis and Medical Management

Contrary to common assumptions, not all patients with MTS are medically intractable:

• 25% of patients achieve complete seizure control with appropriate antiepileptic medication 6
• 38% remain intractable despite aggressive polytherapy, while 37% achieve ≥50% seizure reduction 6
• Among treatment-naïve patients, 31% become seizure-free with initial therapy 6

Poor prognostic factors for medical control include:

• Younger age at seizure onset correlates with worse medical responsiveness 6
• History of febrile convulsions predicts poorer seizure control 6
• Epileptiform discharges on EEG are associated with reduced medication effectiveness 6

The standard trial of medical management is typically 2 years, though earlier surgical consideration is appropriate when multiple appropriate antiepileptic drugs fail to establish control 4, 5

Surgical Management

Complete surgical resection of the epileptogenic region is the treatment of choice for medically refractory MTS 4, 5:

• Extended resection (temporal lobectomy) demonstrates superior seizure outcomes compared to lesionectomy alone 4, 5
• Complete removal of the epileptogenic zone is critical for optimal seizure control 4, 5
• Concordance between multiple diagnostic modalities (MRI, EEG, PET, SPECT) predicts better surgical outcomes 4, 5
• 93% of patients in one series achieved seizure freedom or significant improvement postoperatively, including all patients with coexistent cortical dysplasia 3

Critical surgical considerations:

• Incomplete resection significantly increases seizure recurrence risk and need for reoperation 4, 5
• Duration of epilepsy prior to resection does not affect surgical outcome, arguing against delaying surgery once medical intractability is established 4, 5
• Contralateral thalamic hypometabolism on imaging predicts poorer surgical outcomes compared to ipsilateral involvement 4

Pathophysiology and Disease Progression

MTS may represent a progressive disease driven by uncontrolled inflammation 8:

• A self-propagating cycle of inflammation, blood-brain barrier damage, and seizures may drive disease progression 8
• This inflammatory mechanism offers potential therapeutic targets for preventing progression or interrupting epileptogenesis 8