Surgery For Epilepsy: Stratifying Outcome in Patients With Hippocampal Sclerosis

Abstract & Commentary

Synopsis: Epilepsy duration is the most important predictor for long-term surgical outcome.

Source: Jansky J et al. Temporal lobe Epilepsy With Hippocampal Sclerosis: Predictors For Long-Term Surgical Outcome. Brain. 2005;128:395-404.

Surgery for medication-resistant seizures is an increasingly utilized treatment option. Temporal lobectomy (either en bloc or tailored) is the most common surgical procedure in cases of idiopathic epilepsy involving complex partial seizures (with and without secondary generalization) of temporal lobe onset. Hippocampal sclerosis (HS) is identified in most of these cases, either by pre-operative MRI scan or microscopic analysis of resected tissue. While the presence of HS statistically predicts a favorable surgical outcome, it is clear that HS, as currently defined, is not the sole determinant of surgical outcome. Different patients can have disparate post-operative seizure frequencies, despite the fact that hippocampal pathology is essentially identical.

Jansky and colleagues posed the question of what other factors may play a role in determining surgical outcome in patients operated on for HS, as the apparent cause of their seizures. Specifically, they analyzed 171 surgical patients from the epilepsy surgery center located in Bielefeld, Germany. All patients had undergone a pre-surgical evaluation including video-EEG to localize ictal onset. All had HS by MRI scan and had undergone temporal lobectomy. Seizure-free outcome was assessed at 6 months and 2, 3, and 5 years after surgery. Not all patients were available for the full follow-up period.

Surgical outcome was correlated relative to the following clinical parameters: age at operation, gender, age at epilepsy onset, duration of epilepsy, history of febrile seizures, seizure frequency, presence of secondary generalized tonic-clonic seizures (GTCs), frequency of secondary GTCs, history of status epilepticus, ictal limb dystonia, post-ictal aphasia, unilateral interictal discharges, presence of contralateral ictal electrographic patterns, and standard en bloc temporal lobectory versus tailored resection. No other structural abnormalities were analyzed, save that patients with bilateral HS or other dual pathology were excluded from analysis.

In a multivariate analysis of the longer term outcomes, Jansky et al found the following factors to be independent predictors of poor outcome: at 2 years- secondary GTCs and ictal dystonia; at 3 years-ictal dystonia along with longer epilepsy duration; at 5 years-longer epilepsy duration (P = 0.003).

Commentary

While there are methodological considerations that confound definitive analysis (eg, lack of homogeneity in the post-operative use of anti-epileptic drugs), these results are important because they again support the concept that earlier surgical treatment provides the greatest benefit in terms of long-term seizure freedom in the medically intractable epilepsy population (N Engl J Med. 2001;345:311-318).

The fact that the prognosis for 2-year outcome is influenced by the presence of secondary GTCs and ictal limb dystonia, may reflect the fact these phenomena result from electrographic ictal spread. This, in turn, could lead to the generation of new ictal foci. Unfortunately, since there are no data presented regarding the outcome of patients at 5 years who had had negative outcomes at 2 years, we do not know whether new foci exist and, if they do, whether they persist (leading to poor 5-5year outcome). Alternatively, new ictal foci may eventually extinguish (ie, running down is a term used to describe patients who have a more gradual reduction in seizure frequency for months to years post-operatively), which may be due to lack of reinforcement from the excised ictal focus.

We continue to await the results of the NIH-sponsored prospective study comparing best medical treatment vs early epilepsy surgery. Until then, with supporting evidence from multiple sources, we will continue to make early referrals for at least pre-surgical evaluation. — Andy Dean

Dr. Dean, Assistant Professor of Neurology and Neuroscience; Director of the Epilepsy Monitoring Unit, Department of Neurology, New York Presbyterian Hospital Cornell Campus, is Assistant Editor of Neurology Alert.