Faculty Bibliography

Epilepsy surgery is an effective treatment for properly selected patients with intractable seizures. However, many patients with medically intractable epilepsy are not excellent candidates for surgical resection of the epileptogenic zone. Due to recent advances in computer technology and bioengineering, several novel techniques are receiving increasing interest for their role in the care of people with epilepsy. Neuromodulation is an emerging surgical option to be used when conventional resective surgery is not indicated. We review the indications and expected outcomes of neuromodulatory treatments currently available for the treatment of refractory epilepsy, i.e., vagus nerve stimulation, deep brain stimulation, stereotactic radiosurgery, and multiple subpial transections.

The characterization of a seizure as generalized or focal onset depends on a basic knowledge of the underlying pathophysiology. Recently, an uncommon phenomenon in generalized epilepsy-evolution of seizures from generalized to focal followed by secondary generalization-was reported for the first time. We describe a 15-year-old boy, initially classified as having partial epilepsy, who had a typical absence seizure that became focal with second secondary generalization (double generalization). On the basis of these findings his epilepsy was classified as juvenile absence epilepsy and his treatment was changed, resulting in seizure freedom. This is the first report of this unusual electroclinical evolution in a patient with juvenile absence epilepsy. The recognition of this particular pattern allows correct classification and impacts both treatment and prognosis.

Since its advent during the mid-twentieth century, radiosurgery has undergone a steady evolution. Gamma Knife and linear accelerator based systems using rigid frames preceded the development of frameless devices. The present report describes the development of microbeam radiosurgery, a technique which uses submillimetric beams of radiation to treat disease. Typically, the technique is employed using parallel arrays of beams delivered via a high-fluence synchrotron source. Beam widths between 20 and 950 mum have been used with the majority of studies utilizing beam widths less than 100 mum. In addition to its high precision, the technique allows users to take advantage of two unique properties of microbeams. The first is a remarkable tolerance of healthy tissue to microbeams delivered at doses up to several hundred grays, while at the same time, tumors are highly susceptible to the lethal effects of microbeams. Together, these findings allow for a "preferential tumoricidal effect" beyond the typical dose-volume relationship. Although only used in animal experiments so far, we explore the hypothetical clinical role of microbeam radiosurgery which may be feasible in the near future. In addition to the treatment of traditional radiosurgery targets such as malignancies and vascular malformations, microbeams may allow the non-invasive treatment of functional disease such as movement disorders, epilepsy, and mental illness.

The tissue-sparing effect of parallel, thin (narrower than 100 microm) synchrotron-generated X-ray planar beams (microbeams) in healthy tissues including the central nervous system (CNS) is known since early 1990 s. This, together with a remarkable preferential tumoricidal effect of such beam arrays observed at high doses, has been the basis for labeling the method microbeam radiation therapy (MRT). Recent studies showed that beams as thick as 0.68 mm ("thick microbeams") retain part of their sparing effect in the rat's CNS, and that two such orthogonal microbeams arrays can be interlaced to produce an unsegmented field at the target, thus producing focal targeting. We measured the half-value layer (HVL) of our 120-keV median-energy beam in water phantoms, and we irradiated stereotactically bis acrylamide nitrogen gelatin (BANG)-gel-filled phantoms, including one containing a human skull, with interlaced microbeams and imaged them with MRI. A 43-mm water HVL resulted, together with an adequately large peak-to-valley ratio of the microbeams' three-dimensional dose distribution in the vicinity of the 20 mm x 20 mm x 20 mm target deep into the skull. Furthermore, the 80-20% dose fall off was a fraction of a millimeter as predicted by Monte Carlo simulations. We conclude that clinical MRT will benefit from the use of higher beam energies than those used here, although the current energy could serve certain neurosurgical applications. Furthermore, thick microbeams particularly when interlaced present some advantages over thin microbeams in that they allow the use of higher beam energies and they could conceivably be implemented with high power orthovoltage X-ray tubes.

Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors. We report on the results of multimodality IONM during 18 cases in which a TIVA regimen incorporating dexmedetomidine (Precedex, Hespira, Lake Forest, IL) was used. Monitoring techniques included sensory (SSEP) and motor evoked potentials (MEP), as well as pedicle screw stimulation. SSEPs were maintained within an acceptable range of baseline amplitude (50%) and latency (10%), and MEPs remained elicitable throughout each case. We therefore found that the anesthetic regimen did not significantly interfere with any of the monitoring modalities used and conclude that IONM in the presence of dexmedetomidine is feasible under appropriate conditions.

Sixty adult comprehensive epilepsy center patients were given a simple writing task to complete. The essays were scored using four unique scales: Subject--whether the writing concentrated on physical or emotional aspects of the seizures; Focus-how much of the essay was on task; Ratio--a measure of detail; Word--total word count. Among the findings, patients with nonepileptic events (n=28) tended to write essays containing both physical and emotional components (P=0.058), whereas those with partial seizures (n=28) did not (P=0.006). Essays concentrating on emotional aspects increased the likelihood of a diagnosis of partial seizures (P=0.059). The variance of Ratio was higher in those without nonepileptic events than in those with nonepileptic events (P=0.0003), whereas it was higher in the group with partial seizures than in the group without partial seizures (P=0.000008). This study suggests unique features associated with the writing of patients with epilepsy and those with nonepileptic events.

Radiosurgery is an emerging therapeutic approach for the treatment of medically intractable epileptogenic foci. A favourable seizure outcome was first reported in studies of the effects of radiosurgery in the treatment of arteriovenous malformations and tumours. Radiosurgery has since been applied to the treatment of complex partial seizures with mesial-temporal-lobe onset. Nearly simultaneously, experimental evidence supporting the usefulness of radiosurgery to improve or abolish seizures has confirmed that stereotactic irradiation can preferentially affect epileptogenic versus normal cortex. Further work is clearly needed, but this technique might become an important approach in the management of mesial-temporal and extratemporal epilepsy, especially if refractory seizures arise from eloquent cortex or surgically challenging regions of brain.