Wetjen, Nicholas M.

Abstract BACKGROUND: Medically intractable epilepsy involving drop attacks can be difficult to manage and negatively affect quality of life. Most studies investigating the effect of corpus callosotomy (CC) on seizures have been limited, focusing on the pediatric population or drop seizures alone, with little attention to other factors influencing seizure outcome. OBJECTIVE: To assess seizure outcomes after CC in adults and children. METHODS: Retrospective analysis was performed on all patients who underwent CC (anterior two thirds, 1- or 2-stage complete) at our institution between 1990 and 2011. Change in frequency after CC was assessed for drop seizures and other seizure types. Multiple factors were evaluated for impact on seizure outcome. RESULTS: Fifty patients met inclusion criteria. The median age was 1.5 years at seizure onset and 17 years at time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage complete in 17, and 2-stage complete in 5. All 3 groups experienced a significant decrease in drop seizures (P < .001, P < .001, and P = .020, respectively), with 40% experiencing complete resolution, and 64% dropping at least 1 frequency category. Other seizure types significantly decreased in anterior two-thirds CC and 1-stage complete (P = .0035, P = .001, respectively). Younger age at surgery correlated with better seizure outcomes (P = .043). CONCLUSION: CC for medically refractory generalizing epilepsy is effective for both drop seizures and other seizure types. CC should be considered soon after a patient has been deemed medically refractory because earlier age at surgery results in lower risk and better outcome.

Purpose Children with multiple hereditary exostoses (MHE) have numerous osteochondromas, with the most prominent lesions typically over the appendicular skeleton. A recent report noted a high rate of intracanal lesions in this patient population and recommended preventative spinal screening with magnetic resonance imaging (MRI) or computed tomography (CT). We sought to evaluate the prevalence of spinal stenosis from intracanal osteochondromas at our pediatric orthopedic center in order to evaluate if routine screening is warranted. Methods All pediatric patients treated for MHE were retrospectively identified. Records were reviewed to determine demographics, previous orthopedic surgery, and indication and results of axial spine imaging (CT or MRI). Imaging studies were reviewed to evaluate the presence of intracanal and compressive spinal lesions. Results Between 1990 and 2011, axial imaging was performed in nine patients with MHE due to concerns of pain, weakness, and/or dizziness. These patients had moderate disease involvement, with a mean of 4.9 previous orthopedic surgeries to address skeletal osteochondromas. Two patients with MHE had cervical spinal stenosis secondary to intracanal osteochondromas. Both children successfully underwent spinal decompression. Thus, of our MHE population undergoing axial imaging, 22 % were noted to have intracanal lesions. Conclusions Our experience reveals a >20 % rate of compressive intracanal osteochondromas in MHE patients undergoing spinal imaging. These two patients represent 5 % of the MHE patients treated at our center. These lesions may be slow growing, and significant consequences can occur if not identified promptly. Thus, we confer that routine axial screening of the spinal canal may be warranted in these children.

Purpose. To investigate EEG and SPECT in the surgical outcome of patients with normal MRI (nonlesional) and extratemporal lobe epilepsy. Methods. We retrospectively identified 41 consecutive patients with nonlesional extratemporal epilepsy who underwent epilepsy surgery between 1997 and 2007. The history, noninvasive diagnostic studies (scalp EEG, MRI, and SPECT) and intracranial EEG (iEEG) monitoring was reviewed. Scalp and iEEG ictal onset patterns were defined. The association of preoperative studies and postoperative seizure freedom was analyzed using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard. Results. Thirty-six of 41 patients had adequate information with a minimum of 1-year followup. Favorable surgical outcome was identified in 49% of patients at 1 year, and 35% at 4-year. On scalp EEG, an ictal onset pattern consisting of focal beta-frequency discharge (>13–125 Hz) was associated with favorable surgical outcome (P=0.02). Similarly, a focal fast-frequency oscillation (>13–125 Hz) on iEEG at ictal onset was associated with favorable outcome (P=0.03). Discussion. A focal fast-frequency discharge at ictal onset identifies nonlesional MRI, extratemporal epilepsy patients likely to have a favorable outcome after resective epilepsy surgery.

Object Patients with normal MR imaging (nonlesional) findings and medically refractory extratemporal epilepsy make up a disproportionate number of nonexcellent outcomes after epilepsy surgery. In this paper, the authors investigated the usefulness of intracranial electroencephalography (iEEG) in the identification of surgical candidates. Methods Between 1992 and 2002, 51 consecutive patients with normal MR imaging findings and extratemporal epilepsy underwent intracranial electrode monitoring. The implantation of intracranial electrodes was determined by seizure semiology, interictal and ictal scalp EEG, SPECT, and in some patients PET studies. The demographics of patients at the time of surgery, lobar localization of electrode implantation, duration of follow-up, and Engel outcome score were abstracted from the Mayo Rochester Epilepsy Surgery Database. A blinded independent review of the iEEG records was conducted for this study. Results Thirty-one (61%) of the 51 patients who underwent iEEG ultimately underwent resection for their epilepsy. For 28 (90.3%) of the 31 patients who had epilepsy surgery, adequate information regarding follow-up (> 1 year), seizure frequency, and iEEG recordings was available. Twenty-six (92.9%) of 28 patients had frontal lobe resections, and 2 had parietal lobe resections. The most common iEEG pattern at seizure onset in the surgically treated group was a focal high-frequency discharge (in 15 [53.6%] of 28 patients). Ten (35.7%) of the 28 surgically treated patients were seizure free. Fourteen (50%) had Engel Class I outcomes, and overall, 17 (60.7%) had significant improvement (Engel Class I and IIAB with ≥80% seizure reduction). Focal high-frequency oscillation at seizure onset was associated with Engel Class I surgical outcome (12 [85.7%] of 14 patients, p = 0.02), and it was uncommon in the nonexcellent outcome group (3 [21.4%] of 14 patients). Conclusions A focal high-frequency oscillation (> 20 Hz) at seizure onset on iEEG may identify patients with nonlesional extratemporal epilepsy who are likely to have an Engel Class I outcome after epilepsy surgery. The prospect of excellent outcome in nonlesional extratemporal lobe epilepsy prior to intracranial monitoring is poor (14 [27.5%] of 51 patients). However, iEEG can further stratify patients and help identify those with a greater likelihood of Engel Class I outcome after surgery.

Object To better understand syrinx pathophysiology, the authors performed a prospective study in which they used findings from serial clinical and magnetic resonance (MR) imaging examinations performed before and after craniocervical decompression to establish the time course of syrinx narrowing. Methods Serial clinical examinations and cervical MR imaging were performed in 29 consecutive patients with Chiari malformation Type I (CM-I) and syringomyelia before surgery, 1 week, and 3–6 months after surgery, and then annually. Time to narrowing of the syrinx (> 50% decrease in maximal anteroposterior diameter) following surgery was calculated using the Kaplan–Meier method. Results All syringes decreased in diameter and length (number of segments) on MR images at 3–6 months, 1 year, and 2 years or later. The syrinx diameter decreased from 6.9 ± 2.1 mm (mean ± standard deviation) preoperatively to < 1.5 mm at last evaluation (p < 0.0001). The median time to syrinx narrowing was 3.6 months following CM-I decompression (95% confidence interval 3.0–6.5 months). After surgery 94% of patients had improved symptoms, but symptoms resolved incompletely in 68% of patients; 52 and 59% of patients had residual dysesthesias and sensory loss, respectively. Clinical improvement occurred before partial or complete disappearance of the syrinx on MR images. Patient age, duration of symptoms, sex, preoperative syrinx diameter, and length of syrinx were unrelated to time to syrinx narrowing. Conclusions Most patients improve after decompression for CM-I, but many have residual symptoms. Syringes may continue to diminish for months to years after surgical decompression. A collapsed syrinx (absence of distention of the spinal cord) indicates that the pathophysiology has been reversed by treatment regardless of the completeness of elimination of the cavity on MR images.

Object The aim of this study was to determine whether ictal single-photon emission computed tomography (SPECT) is useful in localizing the site of seizure onset in patients in whom surgery for intractable epilepsy failed and who are being considered for repeated surgery. Methods Subtraction ictal SPECT coregistered to magnetic resonance imaging (SISCOM) studies were retrospectively analyzed in 58 patients who were being evaluated for possible repeated resection for intractable partial epilepsy between January 1, 1996, and October 31, 1999. All patients had persistent seizures subsequent to an initial resection and underwent another excision. The SISCOM-demonstrated abnormalities were classified as concordant, discordant, or indeterminate, compared with the localization of the epileptogenic zone revealed on video electroencephalography monitoring. The ability of SISCOM to predict operative outcome was also determined in patients who had undergone repeated surgical procedures. The SISCOM studies revealed a localized hyperperfused alteration in 46 (79%) of 58 patients. Forty-one (89%) of these 46 patients had a SISCOM-demonstrated alteration in the hemisphere of the previous epilepsy surgery. Imaging changes in 33 (72%) of the 46 patients were at the site of the previous focal cortical resection. Eight (17%) of the 46 had SISCOM-demonstrated abnormalities remote from the lobe in which surgery had been performed but in the ipsilateral hemisphere. The hyperperfusion focus was in the contralateral hemisphere in the remaining five patients (11%). The site of the epileptogenic zone was concordant with the SISCOM focus in 32 (70%) of 46 patients. Twenty-six patients underwent repeated resection and were followed up for a mean of 44 months thereafter; 11 of these patients (42%) had a significant reduction in seizure tendency. Only five patients (19%) were seizure free. Ten (50%) of 20 patients with a concordant SISCOM focus compared with none (0%) of three patients with a discordant focus had a favorable surgical outcome (p = 0.23). Conclusions The SISCOM method might be useful in the evaluation of, and the surgical planning for, patients with intractable partial epilepsy in whom previous resective treatment has failed and who are being considered for reoperation.

Object The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx–region combination according to an immunoreactive score. Across all three measures—that is, staining intensity, percentage of positively stained cells, and immunoreactive score—Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p < 0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p < 0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.