Challenges of Epilepsy Surgery in an Infant with a Hemispheric Syndrome: Case Study

By Elaine Wyllie, MD

Presentation

Kevin (a pseudonym) was brought by family to Cleveland Clinic at age 6.5 months for a third opinion on management of his seizure disorder, which first emerged at age 5 months in the setting of epidermal nevus syndrome. Other features of the condition included mild right hemihypertrophy, right linear alopecia, a midline facial nevus, linear hyperpigmentation on the right limbs and trunk, and mild coarctation of the aorta.

Six weeks before the visit, he developed seizures which escalated quickly to 10 to 100 epileptic spasms a day. His parents also noted that he was not moving his right arm and leg as much as the left. Since the most common brain malformation associated with epidermal nevus syndrome is hemimegalencephaly, a corresponding left hemispheric epilepsy syndrome was deemed most likely.

Video EEG revealed diffuse hypsarrhythmia with abundant spikes from multiple regions of both hemispheres, as well as nonlocalized EEG seizures during most of the spasms. However, the right posterior temporo-occipital region seemed disproportionately involved in the epileptogenic process. Interictal EEG often showed rhythmic periodic lateralized epileptiform discharge (PLED)-like runs of spikes and sharp waves from the right temporo-occipital region, and subclinical EEG seizures were also recorded from those areas. See Figure 1, which presents five EEGs in slideshow format.

Slide 1/5

MRI scan and PET imaging were available from age 5 months (see Figure 2, which presents four images in slideshow format).

The MRI showed the following on T2 sequences:

• An enlarged right temporal lobe with indistinct gray-white differentiation, indicating malformation of cortical development in this area (Figure 2A)
• Abnormal myelination of the right visual tracts, which becomes apparent upon comparison with the normal visual tracts on the left (Figure 2B)
• Indistinct gray-white differentiation in the right pre- and post-central gyri, appreciable upon comparison with same regions on the left (Figure 2C)

PET scan showed hypometabolism that was most pronounced in right temporo-occipital regions, with more intact and symmetrical metabolism in the frontal regions (Figure 2D).

Slide 1/4

At 6.5 months of age, he was being treated with phenobarbital and “medical” marijuana. He previously had been given oxcarbazepine and zonisamide without success.

Clinical consideration 1: Is he ready for surgery?

Two therapy approaches were discussed by the Cleveland Clinic Epilepsy Center team and presented to the family, as follows:

• Try additional medications. Kevin had had seizures for only a short duration, and had undergone relatively few drug trials. The family was reluctant to try ACTH, which can cause hypertension, glucosuria, cardiomegaly (of particular concern with his preexisting coarctation of the aorta) and immune suppression. They were also concerned about trying vigabatrin because of its associated risk for retinal toxicity, which could complicate future postoperative visual outcome.
• Go straight to surgery. Surgery promised the potential to stop the spasms as soon as possible, thereby maximizing Kevin’s developmental potential. However, his small size (6.8 kg) and young age elevated his surgical risk. The mild aortic coarctation was also an issue, but testing showed no obstruction and his cardiologist approved him for epilepsy surgery if needed.

The parents felt that epilepsy surgery was the best path. They had researched this extensively prior to consultation at Cleveland Clinic, and requested to proceed.

Clinical consideration 2: How extensive a surgery?

One of the following two courses could be taken:

• Right hemispherectomy could be justified because of the likelihood of hemispheric cortical dysplasia based on the underlying epidermal nevus syndrome. This option offered the greatest likelihood of a seizure-free outcome but would lead to permanent left hemiparesis.
• Right temporo-occipital resection could also be justified based on the presence of some localized temporo-occipital findings on video EEG, MRI and PET. This option would spare motor function but may entail a greater risk for postoperative seizure recurrence.

Both centers where Kevin had been evaluated previously recommended hemispherectomy. The Cleveland Clinic team recommended the more conservative option, leaving open the possibility that a second procedure might be needed in the future.

Surgery and outcome

Kevin underwent a right temporo-occipital resection (Figure 3). Histology revealed cortical dysplasia, classified as International League Against Epilepsy (ILAE) type 1c. Findings included linear arrangements of neurons in the cortex and a loss of layer 2, with rare malpositioned neurons high in the cortex (Figure 4).

Figure 3

Figure 4

On days 1 to 4 following resection, Kevin had seizures in the form of subtle spasms. These abated spontaneously, and since then he has had no further seizures. After 16 months, EEG was normal and he was successfully weaned off all antiepileptic medications.

At his most recent appointment at 5.5 years of age, Kevin remained seizure-free, and his right hemi-neglect had resolved completely. He was developmentally appropriate and doing well in kindergarten.

Key takeaways

Kevin’s case illustrates the following important issues in an infant with an underlying condition that is usually hemispheric.

Consider focality.It’s worth keeping in mind that even with a hemispheric neurological syndrome, the epilepsy process may be more localized. Clues to focality include:

• A single predominant EEG spike and seizure focus
• A regional area of greatest MRI abnormality
• Regional hypometabolism on PET

Fixed hemiparesis and reversible hemi-neglect are difficult to distinguish in infancy. This fact makes motor-sparing surgery a favorable option when feasible, as it provides the opportunity for a functional motor deficit to resolve when the seizures are stopped.

In the immediate postoperative period, seizures may be self-limiting. Research has shown that patients may experience long-term seizure-free outcome despite some seizure recurrences in the first few weeks after surgery.

Early surgery may increase the chance for favorable seizure and developmental outcome. Had the family chosen trying the medical option first, we would have strongly encouraged them to not let the trial last more than a few months without success. There is some evidence to indicate that the longer epilepsy is left uncontrolled, the more likely it is to become fixed — and unfixable. Another reason to consider early surgery is plasticity in the developing brain, which affords opportunity for improved neurological outcome.

In this case, an excellent outcome resulted from a controversial decision to choose a more conservative surgical approach. It is important not to forget what’s possible when dealing with epilepsy in the developing brain.

Dr. Wyllie, Professor of Neurology at Cleveland Clinic Lerner College of Medicine, is a pediatric epilepsy specialist at Cleveland Clinic.