Mesial Temporal Sclerosis

Mesial temporal sclerosis (hippocampal sclerosis) is the commonest pathology in drug resistant temporal lobe epilepsy, with neuronal loss and gliosis in the hippocampus, amygdala and parahippocampal gyrus. It follows an initial precipitating injury (prolonged febrile seizures, infection, head injury, hypoxia) in early childhood in many cases, after a latent period of years. It accounts for 30 to 50% of surgical epilepsy cases.

Pathophysiology. Selective loss of hilar and CA1 and CA3 neurons causes mossy fibre sprouting, network reorganisation and hyperexcitability.

Focal seizures with a rising epigastric sensation, fear, déjà vu, olfactory or gustatory aura, followed by impaired awareness with oral automatisms, staring and dystonic posturing of the contralateral arm, and postictal confusion and aphasia (dominant side). Secondary generalisation occurs. Memory impairment and depression are common. Seizures are often drug resistant.

Red flags.

• Status epilepticus or seizure clusters.
• Seizures despite two appropriate antiseizure drugs.
• Progressive memory loss.

MRI epilepsy sequences (thin coronal T2 and FLAIR sequences perpendicular to the hippocampal axis) shows hippocampal atrophy with increased T2 or FLAIR signal and loss of internal structure. Video EEG shows anterior temporal spikes and rhythmic temporal theta onset. Neuropsychological testing (verbal memory with left sided disease). FDG-PET (temporal hypometabolism), and intracranial EEG in discordant cases. Wada test or functional MRI for language and memory lateralisation.

Differential diagnosis.

• Other temporal lesions (tumour, cortical dysplasia, cavernoma).
• Autoimmune limbic encephalitis, post-ictal hippocampal oedema and psychogenic non-epileptic seizures.
• Syncope and panic attacks.

Antiseizure drugs. Carbamazepine 200 mg twice daily, increased to 400 to 600 mg twice daily (or oxcarbazepine or lamotrigine), with levetiracetam, lacosamide, topiramate or clobazam as add on at usual doses. About 30 to 40% remain drug resistant.

Surgery. Referral for presurgical evaluation after failure of two drugs. Anterior temporal lobectomy with amygdalohippocampectomy gives seizure freedom in 60 to 80% (compared with under 10% with continued medical therapy). Selective amygdalohippocampectomy, laser interstitial thermal therapy and stereotactic radiosurgery are alternatives. Risks include verbal memory decline (dominant side), visual field defect (superior quadrantanopia) and mood change.

Neuromodulation. Responsive neurostimulation, vagus nerve stimulation or deep brain stimulation of the anterior thalamic nucleus when surgery is not possible.

Psychosocial. Treat depression and anxiety, cognitive rehabilitation and driving advice.

Monitoring. Seizure diary, drug levels, bone health and mood.

Referral and escalation. Refer to a full epilepsy centre.