Drug-Resistant Epilepsy: Workup, EEG, MRI and When to Refer

Drug-resistant epilepsy is confirmed in three steps: correct every seizure trigger, give at least two appropriate antiepileptic drugs at their maximum allowed doses, then investigate with EEG, video EEG and MRI to find out whether the seizures come from a single, removable source. Whether the EEG and MRI agree on that source decides who is a good surgical candidate.

For Dr. Dinesh Rattnani, Senior Director - Neurosurgery, Neuro Critical Care & Spine Surgery, Max Super Speciality Hospital, Noida, India, the workup decides which patients are likely to benefit from epilepsy surgery. An operation on a well-chosen patient, with matching EEG and MRI findings, gives extremely good results. When the tests point in different directions, it becomes difficult to judge exactly what to remove. This article sets out the investigations, what each one shows, how concordance is judged, and when a doctor should refer. The wider pathway, from medical treatment to the three families of surgery, is covered in the complete guide to epilepsy diagnosis and management.

Drug-resistant epilepsy: the definition that opens the door to surgery

Dr. Rattnani labels epilepsy drug-resistant when a patient continues to have seizures despite a minimum of two drugs, each given at its maximum allowed dose. The label is applied only after trigger factors have been excluded and corrected. Stress, lack of sleep, alcohol, hormonal changes, illness, fever, flashing lights, physical exertion and dehydration can all keep seizures going in a patient whose drugs would otherwise work. A patient whose seizures stop once sleep is regularised or alcohol is stopped does not have drug-resistant epilepsy, and does not need a neurosurgeon.

Investigations for drug-resistant epilepsy: EEG, video EEG and MRI

Once epilepsy is diagnosed, an EEG and an MRI of the brain are mandatory, even when the plan is purely medical. Video EEG is added when the standard EEG does not settle the question. Single-photon emission computed tomography (SPECT) and magnetoencephalography (MEG) are needed only very rarely.

EEG: where the discharge comes from

An electroencephalogram (EEG) records the brain's electrical activity through electrodes placed on the scalp. The recording shows where the abnormal discharge is coming from. The brain is mapped into frontal, temporal, parietal and occipital lobes on the right and left, and the recordings are traced to the region where the seizures originate.

Its weakness is time. A routine EEG captures only a short window, while a seizure may not come for two or three days. A normal routine EEG therefore does not mean the patient has no epileptic focus.

Video EEG: recording the seizure itself

Video EEG solves the timing problem. It is an institutional investigation: the patient is admitted and monitored for 24 to 48 hours, with video of the patient and the EEG recorded simultaneously. When a seizure occurs, the team can see exactly what the patient was doing and what was happening in the brain at that moment. This links the clinical pattern of the seizure, its semiology, to its electrical origin.

MRI: finding a structural cause

MRI of the brain looks for a structural abnormality that could be generating the seizures. Many patients have a normal MRI; idiopathic epilepsy, with no structural cause, is the most common type. When the MRI is abnormal, the findings Dr. Rattnani highlights fall into a few groups.

• Mesial temporal sclerosis. The medial part of the temporal lobe becomes sclerosed, effectively scarred, and generates seizures. Dr. Rattnani describes it as a scar from which the epilepsy arises, and patients continue to have frequent seizures until that area is removed. On MRI volumetry, an asymmetry of more than 10% in volume between the right and left hippocampi is a marker he uses. The established imaging features of hippocampal sclerosis are atrophy of the hippocampus with increased signal on T2-weighted and FLAIR sequences and loss of its normal internal structure.
• Neurocysticercosis. Cysts formed in the brain by the larvae of the pork tapeworm, Taenia solium, can act as an irritant focus.
• Tumours. A glioma, meningioma or other brain tumour can cause seizures, particularly when it lies close to the motor cortex.
• Head injury. A contusion, a depressed skull fracture, or a sharp object irritating or eroding the cortex can generate seizures, as can the scar left once an earlier head injury has healed. All of these are sources of cortical irritation.
• Damaged lobes. A temporal, frontal or parietal lobe affected by hypoxic injury (damage from oxygen deprivation), trauma or malignancy can become a seizure source that needs removal.

EEG and MRI concordance: who is a surgical candidate

Concordance means agreement between three things: the seizure semiology, the MRI location and the EEG. Dr. Rattnani's example is straightforward. If the MRI shows an abnormality in the right temporal lobe, and the EEG shows that the seizures originate in the same right temporal lobe, the findings are concordant. Those are very good cases, and the results of surgery in them are extremely good.

The best scenario of all is the patient with drug-resistant epilepsy whose MRI shows right temporal pathology and whose EEG focus is right temporal. That patient can proceed to temporal lobectomy with hippocampectomy or amygdalohippocampectomy. Temporal lobe epilepsy is the most common form of focal epilepsy in adults and the most common indication for epilepsy surgery, and Dr. Rattnani describes these patients as good responders.

When the findings disagree

Discordance is where the difficulty lies. The MRI may show a subtle abnormality on the right while the EEG focus comes from the left, or the EEG may point to the parietal, occipital or frontal lobe rather than the temporal lobe. When MRI and EEG do not correlate, it becomes difficult to judge exactly what to remove.

For these patients, Dr. Rattnani relies on electrocorticography during surgery: recording directly from the surface of the exposed brain and resecting until the epileptic discharges disappear. The technique, and how it guides the extent of resection, is described in types of epilepsy surgery: temporal lobectomy, disconnection and brain stimulation.

When the MRI is normal

A completely normal MRI changes the surgical picture. Resection remains possible when video EEG, functional imaging such as PET or SPECT, or intracranial EEG localises a single focus, but the chance of seizure freedom is lower than in lesional epilepsy. For many such patients, the surgical option is neuromodulation, through vagal nerve stimulation or deep brain stimulation. Disconnection by corpus callosotomy can occasionally be used for atonic seizures, to stop their spread, but it is mostly not done. For a patient with a normal MRI, medical management must be pursued fully first.

When to refer epilepsy to a neurosurgeon

Referring doctors, particularly where investigations are limited, need a simple rule. Dr. Rattnani gives one.

1. Investigate at diagnosis. Once epilepsy is diagnosed, obtain an EEG and an MRI of the brain, even if the plan is medical.
2. If the MRI is normal, treat medically. Continue the standard antiepileptic drugs, dosed by body weight in children, using up to two or three drugs at maximal doses. Most patients will respond.
3. Refer when medication fails. If the patient continues to have seizures despite two or three drugs, that is the time to refer.
4. Refer early when the MRI shows a lesion. If the MRI shows an abnormality such as mesial temporal sclerosis, a tumour, neurocysticercosis or a post-traumatic scar, the patient may be a candidate for resective surgery and should be seen by a neurosurgeon.

There is no rush to operate on a patient whose seizures are controlled. Dr. Rattnani's position is that if medical management controls the epilepsy, the patient does not need him. If medical management fails, or if there is an abnormality in the brain, surgery should be considered.

Age and timing

Teenagers can undergo epilepsy surgery. Medical management is still tried first, and the same definition of drug resistance applies.

What the investigations predict

The workup does more than select patients; it sets expectations. Concordant temporal lobe cases carry the best outlook. Discordant cases need intraoperative mapping and carry more uncertainty. Patients with a normal MRI are directed towards neuromodulation, where the aim is to reduce seizures rather than remove their source.

A careful workup therefore answers three questions before anyone enters the operating theatre: is the epilepsy genuinely drug-resistant, is there a single source, and can it be removed safely. The answers to the questions doctors asked about candidacy and medication during the session are collected in the live discussion with Dr. Rattnani.