Epilepsia, 42(Suppl.

6):3, 2001
Blackwell Science, Inc.
International League Against Epilepsy

Special Lecture II

Intractable Epilepsy: Definition and Neurobiology

Jerome Engel, Jr.
UCLA School of Medicine, Los Angeles, California, U.S.A.

epileptic disorders associated with ictal events that represent different pathophysiologic mechanisms, such as
drop attacks and complex partial seizures of limbic origin. A recent study from a major epilepsy center indicated that 2550% of their patients had mesial temporal
lobe epilepsy (MTLE), the form of temporal lobe epilepsy associated with hippocampal sclerosis. MTLE,
therefore, may be the most common form of epilepsy.
MTLE patients are among the most refractory to medical
treatment.
The fundamental mechanisms of seizure generation in
MTLE appear to differ from those of the neocortical or
primary generalized epilepsies, indicating the need for
instituting new approaches to pharmacotherapy of
MTLE. Approximately 80% of MTLE patients can expect to become seizure free after anteromesial temporal
lobectomy, and several other so-called intractable epilepsies also can be treated effectively with surgery. In all
instances, early surgical intervention provides the best
chance of a return to a normal lifestyle. Today, it would
take a lifetime to try every combination of available
AEDs, so exhaustive proof of medical intractability is
impossible. Therefore, it is important to recognize surgically remediable syndromes and the value of timely
surgical intervention.

Approximately 20% of individuals with a diagnosis of

epilepsy have seizures that are not adequately controlled
by antiepileptic drugs (AEDs). Some of these patients
fail to respond because their paroxysmal events are not
epileptic. Others continue to have seizures because an
incorrect treatment plan has been prescribed, because of
either misdiagnosis of seizure type or misinformation
about appropriate therapy. Still other patients fail to
achieve control because of noncompliance with their
medicine regimens. However, a significant number of
patients with medically uncontrolled seizures do not respond to appropriate AED management. These have
been labeled medically intractable.
Many types of epilepsy can be refractory to pharmacotherapy, especially symptomatic disorders, including
certain catastrophic epilepsies of infancy and early childhood, the LennoxGastaut syndrome, and a variety of
localization-related epilepsies. Virtually all AEDs reach
the market after screening against animal models of generalized convulsive and absence seizures. Therefore, it is
not surprising that these drugs are ineffective against
Address correspondence and reprint requests to Dr. J. Engel, Jr. at
Department of Neurology, Reed Neurological Research Center, UCLA
School of Medicine, 710 Westwood Plaza, Los Angeles, CA 900951769, U.S.A.