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Treating Complex and Refractory Cases of Epilepsy

September 23, 2020

The UPMC Comprehensive Epilepsy Center

Epilepsy, in its various forms, affects approximately 3.5 million adults and children in the United States (about 1% of the total population), with more than 150,000 newly diagnosed cases occurring each year.

Of these individuals, close to one-third will have uncontrolled or inadequately controlled seizures, having failed two or more medication therapies and thereby falling into the category of drug-resistant epilepsy (DRE). Medication failures can be characterized by a lack of efficacy or inadequate efficacy, intolerable side effects, or adverse reactions.

Patients with epilepsy typically suffer from various comorbidities at higher rates than the general population, and epilepsy patients with DRE are even more susceptible to these comorbidities and seizure-related complications, including injuries, depression or anxiety, sleep disturbances, cognitive impairments, and others.

Sudden unexplained death in epilepsy (SUDEP) is a potential complication for anyone with epilepsy. SUDEP affects approximately 1 in 1,000 adults in the United States each year. Patients classified as having a form of DRE or who otherwise do not have optimal control of their epilepsy have the highest risk of SUDEP. Individuals who experience generalized tonic-clonic seizures have a SUDEP risk that is 10 times higher compared to individuals with other seizure types.

Anto Bagic, MD“Uncontrolled or poorly controlled epilepsy affects every aspect of a patient’s existence. It is a pervasive burden on quality of life and overall health. Uncontrolled or DRE places significant restrictions on an individual’s daily activities and can adversely affect life expectancy, with a high-risk potential for SUDEP. For these and other reasons, it is imperative that patients achieve as close to total freedom from seizures as possible,” says Anto Bagić, MD, PhD, FAES, FACNS, director of the UPMC Comprehensive Epilepsy Center and chief of the Epilepsy Division in the Department of Neurology at the University of Pittsburgh School of Medicine.

When to Refer a Patient for Evaluation by an Epileptologist

Any patient that has failed two different appropriately selected and administered antiseizure medications, regardless of the amount of time they have been on the mediations or the amount of time that has elapsed since their initial diagnosis, should be referred to an epileptologist at a comprehensive epilepsy center for evaluation, testing, and consultation about surgical options.

“While it is not entirely unheard of, individuals that have failed two different drug therapies for their epilepsy and thereby can be classified as having a form of DRE are unlikely to benefit from additional attempts at new medications. The literature is conclusive on this topic – nearly 95% of patients with DRE would or do fail a third attempt at drug therapy to control their seizures,” says Dr. Bagić.

Medications can fail for any number of reasons. They may show a lack of efficacy entirely, or the patient may not be satisfied with their seizure reduction level. Side effects or drug interactions also may make a particular drug therapy intolerable.

A comprehensive patient assessment by an epileptologist and epilepsy surgeon that includes a detailed analysis of the patient’s history and seizure manifestation, neurological examinations, diagnostic imaging, and neurophysiologic evaluations can confirm an initial diagnosis or uncover new findings that may point to potential new treatment modalities or a possible indication for surgical intervention to reduce or eliminate an individual’s seizures.

“The goal we have for every patient is to eliminate their seizures or reduce them to as low a level as possible and restore normalcy of life. This may be through medications alone, surgery to remove a seizure focus, implantation of neuromodulatory devices, or a combination of approaches. Each case is unique, and therefore our assessment and recommended treatment approach will be unique, but always evidence-based and befitting the highest standards of care and the patient’s goals,” says Dr. Bagić.

Why Choose UPMC for Epilepsy Referrals?

The UPMC Comprehensive Epilepsy Center is a high-volume center – one of the busiest programs in the United States – with medical, surgical, and technological capabilities to assess, diagnose, and treat individuals who present with any form along the spectrum of epilepsy. The UPMC Comprehensive Epilepsy Center is accredited by the National Association of Epilepsy Centers (NAEC) and has a level 4 designation, the highest-ranking from the NAEC.

Compassionate and Comprehensive Care for Complex Cases

The guiding philosophy of the UPMC Comprehensive Epilepsy Center is the compassionate and comprehensive care of individuals with epilepsy. Board-certified epileptologists work in close collaboration with neurosurgical colleagues and other team members (neuropsychologists, neuroradiologists, nuclear medicine specialists) to assess patients and develop evidence-based recommendations for care based on the patient's history and diagnosis, imaging and monitoring studies, and their own goals and wishes for care.

Treating patients with DRE must necessarily go beyond only addressing their seizures through medications or surgery. Having epilepsy means much more than just having seizures. The UPMC Comprehensive Epilepsy Center has psychiatrists, neuropsychologists, and social workers embedded in the center to work with patients to address the complications, comorbidities, and challenges associated with epilepsy.

"Patients with DRE whose seizures are not well controlled suffer immensely in every aspect of their lives. Work and social interactions are impaired. They usually cannot drive a car, so their mobility and freedom are impaired, making even doctor visits difficult. We work to understand the complexity and totality of the patient's experience and help them obtain the services and care they need to not only get their epilepsy as controlled as possible but also to thrive to the best of their ability," says Dr. Bagić.

Surgical Expertise

The UPMC Comprehensive Epilepsy Center is home to one of the most advanced neurosurgical programs for epilepsy surgery in the United States. Central to the program’s capabilities and success are its minimally invasive techniques for seizure focus mapping, surgical resection or ablation, and the implantation of various neuromodulation devices.

Dr. Jorge Gonzales-Martinez headshotJorge Gonzalez-Martinez, MD, PhD, is a pioneering figure in minimally invasive and robotic technologies for epilepsy surgery. He is director of the Epilepsy and Movement Disorders Program in the Department of Neurosurgery, and co-director of the UPMC Comprehensive Epilepsy Center alongside Dr. Bagić.

Dr. Gonzalez-Martinez was the first neurosurgeon to bring the use of stereotactic electroencephalography (SEEG) and the use of the ROSA® robotic surgery platform to the United States from Europe, where he trained on their use for epilepsy surgery and seizure mapping. Since adopting the use of SEEG and the ROSA robotic platform, Dr. Gonzalez-Martinez has performed more than 3,000 epilepsy surgeries, which constitutes the largest single-surgeon experience in the United States.

Minimally Invasive Surgical Options at UPMC

The ROSA robot that Dr. Gonzalez-Martinez uses for epilepsy surgery is a stereotactic device that allows for the surgeon's precise placement of SEEG electrodes. The ROSA robot also is deployed for other types of epilepsy surgery, including resections, deep brain stimulation (DBS), responsive neurostimulation (RNS), and laser interstitial thermal therapy (LITT).

SEEG is used to pinpoint and map in three dimensions the areas of the brain where a patient’s seizure activity is focused. Using small electrodes and guidance from the robotic assistant device, SEEG probes are inserted into the brain through the skull using small openings (less than 2.5 mm) instead of larger craniotomies. With guidance from the ROSA robot, the probes can be placed into position with submillimeter accuracy to detect and confirm seizure activity post-procedure in the epilepsy monitoring unit.

"We employ SEEG to confirm our hypotheses regarding a patient's seizure activity location and map the regions in three-dimensions that we will resect or ablate, or use neuromodulation devices to eliminate or reduce a patient's seizure burden. SEEG is not used in a purely exploratory manner. We do not use it for what I like to call 'fishing expeditions,'' says Dr. Gonzalez-Martinez. "Our use of SEEG is done so only after comprehensive evaluations, testing, and the formulation of a hypothesis regarding the patient's epilepsy. The placement of SEEG probes is done using the best evidence available to minimize disturbances to the patient's brain and healthy tissue and reduce potential complications. SEEG is not a panacea for mapping the epileptogenic zone. SEEG is a tool, and like all tools, it must be wielded appropriately and skillfully to obtain optimal results for the patient."

Partners in Collaborative Care

The UPMC Comprehensive Epilepsy Center works in tandem with a patient’s existing neurologist or primary care provider to help patients achieve optimal control of their epilepsy.

"Our goal is to help patients achieve maximal control of their epilepsy using our subspecialty expertise and technological power. We do that alongside and in partnership with the patient's existing care providers. Collaboration is always at the center of our care," says Dr. Bagić.

Patient Referrals and Additional Information

Neurologists or primary care physicians following epilepsy patients who have or likely have a drug-resistant form of epilepsy can discuss patient cases or referrals by contacting the UPMC Comprehensive Epilepsy Center at 833-299-4320. Visit the UPMC Comprehensive Epilepsy Center Website at

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