Robert E. Elliott

Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: Long-term outcomes and predictors of response

OBJECTIVE The goal of this study was to assess the efficacy and safety of vagus nerve stimulation in a consecutive series of adults and children with treatment-resistant epilepsy (TRE). METHODS In this retrospective review of a prospectively created database of 436 consecutive patients who underwent vagus nerve stimulator implantation for TRE between November 1997 and April 2008, there were 220 (50.5%) females and 216 (49.5%) males ranging in age from 1 to 76 years at the time of implantation (mean: 29.0 ± 16.5). Thirty-three patients (7.6%) in the primary implantation group had inadequate follow-up (<3 months from implantation) and three patients had early device removal because of infection and were excluded from seizure control outcome analyses. RESULTS Duration of vagus nerve stimulation treatment varied from 10 days to 11 years (mean: 4.94 years). Mean seizure frequency significantly improved following implantation (mean reduction: 55.8%, P<0.0001). Seizure control ≥ 90% was achieved in 90 patients (22.5%), ≥ 75% seizure control in 162 patients (40.5%), ≥ 50% improvement in 255 patients (63.75%), and <50% improvement in 145 patients (36.25%). Permanent injury to the vagus nerve occurred in 2.8% of patients. CONCLUSION Vagus nerve stimulation is a safe and effective palliative treatment option for focal and generalized TRE in adults and children. When used in conjunction with a multidisciplinary and multimodality treatment regimen including aggressive antiepileptic drug regimens and epilepsy surgery when appropriate, more than 60% of patients with TRE experienced at least a 50% reduction in seizure burden. Good results were seen in patients with non-U.S. Food and Drug Administration-approved indications. Prospective, randomized trials are needed for patients with generalized epilepsies and for younger children to potentially expand the number of patients who may benefit from this palliative treatment.

Surgical Management of Craniopharyngiomas in Children: Meta-analysis and Comparison of Transcranial and Transsphenoidal Approaches

BACKGROUND:Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas. OBJECTIVE:We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid. METHODS:Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria. RESULTS:Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages. CONCLUSION:Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification.

Outcome comparison of atlantoaxial fusion with transarticular screws and screw-rod constructs: meta-analysis and review of literature.

Study Design: Literature review and meta-analysis. Objective: To compare clinical and radiographic outcomes of patients treated with transarticular screws (TASs) and screw-rod constructs (SRCs) for posterior atlantoaxial fusion. Background: Modern techniques for C1–C2 fusions include Magerl and Seeman’s TAS and SRC using C1 lateral mass screws and C2 pars/pedicle screws as described by Goel and Laheri and later modified by Harms and Melcher. Materials and Methods: Online databases were searched for English-language articles between 1986 and April 2011 describing posterior atlantoaxial instrumentation with C1–C2 TAS or SRC. Forty-five studies (2073 patients) treated with TAS and 24 studies (1073 patients) treated with SRC fulfilled inclusion criteria. Standard and formal meta-analysis techniques were used to compare the outcomes. Results: All studies provided class III evidence. There were no differences in 30-day mortality (0.8% vs. 0.6%) or neurological injury (0.2% vs. 0%). There was a higher incidence of vertebral artery injury [4.1% (95% confidence interval (CI), 2.8%–5.4%) vs. 2.0% (95% CI, 1.1%–3.4%); P=0.02] and malpositioned screws [7.1% (95% CI, 5.7%–8.8%) vs. 2.4% (95% CI, 1.1%–4.1%); P<0.001] and a slightly lower rate of fusion with the TAS technique [97.5% (95% CI, 95.9%–98.5%) vs. 94.6% (95% CI, 92.6%–96.1%); P<0.001]. Conclusions: TAS and SRC are safe and effective treatment options for C1–C2 instability but require a thorough knowledge of atlantoaxial anatomy for successful insertion of screws. Slightly higher rates of fusion and less risk of injury to the vertebral artery during screw placement were observed with the SRC technique. However, differences in graft material and techniques were noted. Prospective, randomized studies with validated radiographic and clinical outcome metrics are necessary for proper comparison of these techniques.

Craniopharyngioma Clinical Status Scale: a standardized metric of preoperative function and posttreatment outcome

OBJECT Controversy persists concerning the optimal treatment of craniopharyngiomas in children, and no standard outcome metric exists for comparison across treatment modalities, nor is there one that adequately reflects the multisystem dysfunction that may arise. METHODS The authors retrospectively analyzed the records of 86 consecutive children who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. Excluding 3 perioperative deaths and 3 patients with inadequate follow-up, 80 children (34 girls and 46 boys; mean age 9.56 years; mean follow-up 9.6 years) composed the study group (53 primary and 27 previously treated/recurrent tumors). Building on existing classification schemes proposed by De Vile for hypothalamic dysfunction and Wen for overall functional outcome, the authors devised a more nuanced classification system (Craniopharyngioma Clinical Status Scale [CCSS]) that assesses outcome across 5 axes, including neurological examination, visual status, pituitary function, hypothalamic dysfunction, and educational/occupational status at last follow-up (there is a 4-tiered grading scale in each domain, with increasing values reflecting greater dysfunction). RESULTS There was a significant increase in pituitary dysfunction following treatment-consistent with the high rates of diabetes insipidus and hypopituitarism common to the surgical management of craniopharyngiomas-and less dramatic deterioration in hypothalamic function or cognitive domains. Significant improvement in vision was also demonstrated, with no significant overall change in neurological status. Preoperative CCSS scores predicted postoperative outcome better than clinical characteristics like patient age, sex, tumor size, and the location or presence of hydrocephalus. CONCLUSIONS Preoperative CCSS scores predicted outcome with higher accuracy than clinical or imaging characteristics. In lieu of randomized trials, the CCSS may provide a useful outcome assessment tool for comparison across treatment paradigms and surgical approaches. Long-term follow-up is critical to the analysis of outcomes of craniopharyngioma treatment, given the often-delayed sequelae of all therapies and the high recurrence rates of these tumors.

Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous sclerosis complex

OBJECT Tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder resulting in hamartomas of several organs. Cortical tubers are the most prominent brain lesions in TSC. Treatment-resistant epilepsy often develops early in life in patients with TSC and is associated with severe intellectual and behavioral impairments. Seizures may remit following epilepsy surgery in selected cases, yet it remains unclear whether the tuber or the perituberal cortex is the source of seizure onset. In this study, the authors reviewed the onset of seizures in patients in whom depth electrodes had been placed within or adjacent to cortical tubers. METHODS After obtaining institutional review board approval, the authors retrospectively reviewed data from 12 pediatric patients with multifocal TSC and treatment-resistant epilepsy who had undergone invasive intracranial electroencephalographic monitoring. Tubers were identified on postimplantation MRI, and all depth electrodes were located. Depth electrode contacts were classified visually as either tuber/perituberal cortex or nontuber/nonperituberal cortex. Board-certified clinical neurophysiologists reviewed the seizures to identify all electrodes involved in the ictal onset. RESULTS Among 309 recorded seizures, 104 unique ictal onset patterns were identified. Of the 11 patients with electrodes recording in a tuber, 9 had seizure onsets involving the tuber. Similarly, of the 9 patients with perituberal recording electrodes, 7 had perituberal ictal onsets. Overall, there was no difference in the percentage of contacts involved in seizure onset between the tuber and perituberal cortex. In a subset of 7 patients in whom at least 1 depth electrode contact was within the tuber and 1 was in the perituberal cortex, there was no difference between the percentage of tuber and perituberal onsets. CONCLUSIONS Findings demonstrated heterogeneity in the ictal onset patterns as well as involvement of the tuber and perituberal cortex within and between patients. Although the data are limited by the restricted region(s) sampled with intracranial electrodes, they do suggest that cortical hyperexcitability in TSC may derive from the tuber or surrounding cortex.

Role of diffusion tensor imaging in resection of thalamic juvenile pilocytic astrocytoma

OBJECT The choice of surgical approach during resection of a thalamic juvenile pilocytic astrocytoma (JPA) is dictated by the location of the displaced normal thalamus and posterior limb of the internal capsule (PLIC). Diffusion tensor (DT) imaging and white matter tractography can identify the location of the PLIC in relation to the tumor and may be useful in planning the operative trajectory. METHODS Diffusion tensor imaging was used to localize the PLIC on preoperative MR imaging in 6 children undergoing resection of thalamic JPAs. After review of the standard T2-weighted MR imaging sequences, the anticipated position of the PLIC was determined. This result was compared with the location of the PLIC determined by a blinded radiologist with the use of DT imaging. The utility of DT imaging in determining the surgical approach to a thalamic JPA, degree of resection, and neurological outcomes were all evaluated. RESULTS Diffusion tensor imaging confirmed the expected location of the PLIC as approximated on conventional T2-weighted images in all 6 cases. In 1 patient in particular, unexpected medial deviation of the PLIC was identified, and this proved useful in tailoring the approach to a more lateral trajectory. Gross-total resection of all cystic and solid tumor components was confirmed on postoperative imaging in all cases. All patients experienced mild to moderate worsening of neurological status immediately following resection, but 4 of 6 patients were back to their preoperative baseline at 6-month follow-up. CONCLUSIONS Diffusion tensor imaging and white matter tractography successfully identified the white matter fibers emanating from the precentral gyrus within the PLIC in children with thalamic JPAs prior to surgery. Diffusion tensor imaging served as a valuable tool for stereotactic planning of operative approaches to thalamic JPAs. Localizing the position of the PLIC helped minimize potential neurological morbidity and facilitated gross-total resection.

The Prevalence of the Ponticulus Posticus (Arcuate Foramen) and Its Importance in the Goel-Harms Procedure: Meta-Analysis and Review of the Literature

OBJECTIVE We reviewed published radiographic and cadaver series describing the incidence of the anatomical anomaly ponticulus posticus and discuss its relevance to C1 lateral mass screw (C1LMS) insertion. METHODS Online databases were searched for English-language articles describing the presence of ponticulus posticus in cadaver and radiographic studies. Forty-four reports describing 21,789 patients (n = 15,542) or bony/cadaver specimens (n = 6247) fulfilled inclusion criteria. Meta-analysis techniques were applied to estimate the prevalence of this anomaly. RESULTS The overall prevalence of ponticulus posticus was 16.7%. The anomaly was identified in 18.8% of cadaver, 17.2% of computed tomographic, and 16.6% on radiographic studies. The anomaly composed a complete foramen in 9.3% of patients and was partial/incomplete in 8.7%. It was present bilaterally in 5.4% of cases and unilateral in 7.6%. There was no significant difference in prevalence between males (15.8%) and females (14.6%). Review of that literature demonstrated a dramatic increase in the number of patients treated with C1LMS through the posterior arch since first described in 2002, necessitating recognition of this anomaly when performing the Goel-Harms procedure. CONCLUSION The atlantal anomaly ponticulus posticus is not rare, occurring in 16.7% of patients in radiographic and cadaver studies. This anomaly may give the false impression that the posterior arch of the atlas is of adequate size to accommodate a C1LMS and may lead to inadvertent vertebral artery injury. Careful assessment via preoperative multiplanar computed tomographic imaging should be performed before consideration of C1LMS implantation.

C2 nerve root sectioning in posterior C1-2 instrumented fusions.

OBJECTIVE To analyze qualitatively C2 nerve dysfunction after its transection in C1-2 posterolateral instrumented fusions. METHODS From 2002-2010, 20 consecutive patients underwent posterolateral instrumented fusions using C1 lateral mass and C2 pars or pedicle screws, mainly for type 2 dens fractures. Screws were placed under lateral fluoroscopic guidance using standard techniques. Bilateral C2 nerve roots were coagulated and transected in all patients. Mean follow-up was 30.7 months and consisted of clinical and radiographic examinations, telephone interviews, and mailed visual analogue scale (VAS) questionnaires assessing C2 nerve dysfunction. RESULTS One patient was lost to follow-up after the initial postoperative visit. Fusion was evident in all patients with 12 months of follow-up and two of three patients with <12 months of follow-up. There were no instances of unintended neurologic deficits, vascular injury, cerebrospinal fluid (CSF) leak, or hardware malfunction or malposition. By the 2-week or 6-week office visit, 4 of 20 patients complained of sensory disturbance, and 2 had paresthesias in the C2 distribution. After longer follow-up, one additional patient developed mild sensory symptoms. Quality of life was adversely affected in only one patient. No patient developed neuropathic pain at any time after C2 sectioning. CONCLUSIONS This study is the first series to describe C2 nerve function after posterior atlantoaxial instrumented fusion in adults of all ages. Sacrifice of the C2 nerve root increases fusion surface, allows for better preparation and decortication of the atlantoaxial joint, improves visualization for screw placement, and decreases blood loss and operative time without major clinical consequences.

Atlantoaxial Fusion with Screw-Rod Constructs: Meta-Analysis and Review of Literature

OBJECTIVE To review published series describing C1-2 posterior instrumented fusions and summarize clinical and radiographic outcomes of patients treated with screw-rod constructs (SRC). METHODS Online databases were searched for English-language articles published between 1991 and April 2011 describing posterior atlantoaxial instrumentation with C1-2 SRC. There were 24 studies including 1073 patients treated with SRC that fulfilled inclusion criteria. Meta-analysis techniques were used to compare outcomes. RESULTS All studies provided class III evidence. The 30-day perioperative mortality rate was 0.6%, and neurologic injury occurred in two patients with vertebral artery injury (VAI) from screw malpositions (0.2%). The incidence of clinically significant screw malpositions was 2.4% (confidence interval [CI], 1.1%-4.1%), the incidence of VAI was 2.0% (CI, 1.1%-3.4%), and the rate of fusion with the SRC technique was 97.5% (CI, 95.9%-98.5%). CONCLUSIONS SRC is a safe and effective treatment option for C1-2 instability. The low but nonzero incidence of screw malposition and VAI emphasizes the necessity of having a thorough knowledge of atlantoaxial anatomy for successful insertion of screws.

Successful surgical treatment of craniopharyngioma in very young children

OBJECT Given the potential morbidity of cranial irradiation in young children, the risk-benefit analysis of limited surgery plus irradiation versus radical resection may favor the latter strategy. The purpose of this study was to assess the oncological, endocrinological, and functional outcomes of patients 5 years of age and younger who underwent radical resection of craniopharyngiomas. METHODS Between 1991 and 2008, 19 children age < or = 5 years were diagnosed with a craniopharyngioma and underwent radical resection by the senior author (J.H.W.). Data were retrospectively collected on these 19 patients (11 males, 8 females; mean age 3.2 years) to assess the efficacy and impact of surgical treatment. RESULTS Eighteen (95%) of 19 patients underwent gross-total resection (GTR) confirmed by intraoperative inspection and postoperative imaging. There was no operative death and 18 of (95%) 19 patients were alive at a mean follow-up of 9.4 years (median 8.3 years). Six patients (31%) had a total of 7 tumor recurrences treated by repeat GTR in 5 patients and Gamma knife surgery in 1 patient. No patient required conventional, fractionated radiation therapy. Disease control was achieved surgically in 17 (89.5%) patients and with surgery and Gamma knife surgery in 1 patient, yielding an overall rate of disease control of 95% without the use of conventional radiotherapy. New-onset diabetes insipidus occurred in 50% of patients. Vision worsened in 1 patient, and there was no long-term neurological morbidity. CONCLUSIONS In this retrospective series, children aged < or = 5 years with craniopharyngiomas can have excellent outcomes with minimal morbidity after radical resection by an experienced surgeon. Disease control in this population can be successfully achieved with GTR alone in the majority of cases, avoiding the detrimental effects of radiotherapy in this vulnerable population.