Brain Circuitry of Consciousness: A Review of Current Models and a Novel Synergistic Model With Clinical Application.

How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple "three-strikes" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.

Combined Anterior-Posterior Decompression and Fusion for Cervical Spondylotic Myelopathy.

We conducted a study to evaluate the operative details, perioperative complications, and short-term outcomes associated with combined anterior-posterior decompression and fusion (CAPDF) for treating cervical spondylotic myelopathy (CSM). We retrospectively reviewed the charts of 21 patients who underwent CAPDF at our institution. Pertinent information, including demographics, surgery indication, perioperative complications, operative time, levels fused (and number of levels fused) anteriorly and posteriorly, estimated blood loss, and length of stay, was gathered. Outpatient follow-up data were available for 20 of the 21 patients, and postoperative neurologic status was evaluated with Nurick grades as well as by subjective means. Mean age was 62.1 years (range, 44-79 years). Of the 21 patients, 9 were female, and 12 were male. Before surgery, all patients had a diagnosis of CSM of varying degree. Mean number of levels fused was 2 (range, 1-3) anteriorly and 3 (range, 1-4) posteriorly. Mean operative time, which included patient repositioning, was 4 hours 55 minutes (range, 3:04-6:22). Mean estimated blood loss was 131 mL (range, 55-278 mL), and mean length of stay was 5 days (range, 2-10 days). The most commonly encountered complication was dysphagia (28.6%, 6/21). Neither neurologic instability nor mortality was observed after surgery. Neurologic status was subjectively improved for 19 patients and unimproved for 1 patient; no patient's neurologic status was worse. Mean Nurick grade was 1.9 before surgery and 1.1 after surgery (mean difference, 0.80; P < .001), at a mean follow-up of 96 days (range, 51-149 days). When indicated, CAPDF is an efficient and effective treatment for CSM. This study found the procedure to be associated with minor complications, no new neurologic deficits, and high levels of neurologic improvement. The positive short-term outcomes and low rate of long-term complications in our study, combined with data from previous comparative studies, suggest that same-day surgery is superior to staged surgery.

Hemostasis in endoscopic endonasal skull base surgery using the Aquamantys bipolar sealer: Technical note.

BACKGROUND: A major challenge during endoscopic transsphenoidal surgery is adequate intraoperative hemostasis. The Aquamantys® is a relatively new bipolar sealing device which uses radiofrequency energy and saline. This promotes hemostasis while decreasing charring and thermal spread. In this paper, we describe our experience with the Aquamantys® Mini EVS 3.4 Epidural Vein Sealer Bipolar Electrocautery System (Medtronic Advanced Energy, Portsmouth, NH, USA) during endoscopic surgery for tumors of the skull base with particular attention to ergonomic benefits and technical nuances. METHODS: We conducted a retrospective review of all patients undergoing endoscopic surgery for skull base tumors from September 2012 to June 2016 at our institution. All procedures used the Aquamantys® system. 45 cases were identified. RESULTS: Successful hemostasis was achieved in all cases with an average estimated blood loss (EBL) of 46mL (Range 10-250). There were no intraoperative complications. The single-shaft design allowed for excellent manipulation compared to pistol-grip bipolar forceps. The thermal energy provided excellent radial coverage without extensive penetration into viable pituitary tissue. CONCLUSION: To our knowledge, this is the largest series documenting the use of the Aquamantys® system in skull base surgery. The device is easily mobile and highly effective within the endonasal corridor and should be a tool in the repertoire of the endoneurosurgeon. Randomized control trials would be useful in comparing EBL between the Aquamantys® and standard bipolar electrocautery.

Superion(®) InterSpinous Spacer for treatment of moderate degenerative lumbar spinal stenosis: durable three-year results of a randomized controlled trial.

PURPOSE: This report provides the 3-year clinical outcomes from the randomized, controlled US Food and Drug Administration Investigational Device Exemption trial of the Superion(®) for the treatment of moderate degenerative lumbar spinal stenosis. PATIENTS AND METHODS: The Superion(®) was evaluated in the treatment of subjects aged 45 years or older suffering from symptoms of intermittent neurogenic claudication, secondary to a confirmed diagnosis of moderate degenerative lumbar spinal stenosis at one or two contiguous levels from L1 to L5. Patients were treated between June 2008 and December 2011 at 31 investigational sites. Three hundred ninety-one subjects were included in the randomized study group consisting of 190 Superion(®) and 201 X-STOP(®) control subjects. The primary composite endpoint was individual patient success based on four components: improvement in two of three domains of the Zurich Claudication Questionnaire, no reoperations at the index level, no major implant/procedure-related complications, and no clinically significant confounding treatments. RESULTS: At 3 years, the proportion of subjects achieving the primary composite endpoint was greater for Superion(®) (63/120, 52.5%) than for X-STOP(®) (49/129, 38.0%) (P=0.023) and the corresponding success rates exceeded 80% for each of the individual components of the primary endpoint in the Superion(®) group (range: 81%-91%). Improvements in back and leg pain severity as well as back- and disease-specific functional outcomes were also maintained through 36 months. CONCLUSION: The 3-year outcomes from this randomized controlled trial demonstrate durable clinical improvement consistently across all clinical outcomes for the Superion(®) in the treatment of patients with moderate degenerative lumbar spinal stenosis.

Intraspinal psammomatous melanotic schwannoma not associated with Carney complex: case report.

The authors present a case of intraspinal malignant psammomatous melanotic schwannoma (PMS) not associated with Carney complex and review all reported cases not associated with this syndrome. The focus of this review paper is on the characteristics of the malignant progression of PMS. A 54-year-old man had a history of squamous cell carcinoma of the neck and tonsillar carcinoma. The patient's serial CT scanning study showed a mass in the left C-5 foramen. On presentation he was neurologically intact. After 18 months, the patient developed radiating pain down the left arm with decreased sensation. MRI of the cervical spine showed an enhancing 2.1 × 1.5 × 1.9-cm mass in the left C5-6 foramen. A C5-6 hemilaminectomy was performed with gross-total removal of the tumor. At 3 months postoperatively, the patient developed new-onset pain and weakness. MRI showed a dumbbell-shaped mass in the left C-7 foramen. MRI of the pelvis showed a 1.4 × 1.0-cm lesion on the right ischium and a 1.1 × 2.8-cm lesion on the right inferior pubic ramus. Anterior cervical discectomy of C5-6 and C6-7 with corpectomy of C-6 with subtotal resection of the tumor was completed. PMS should not be considered a benign tumor because in 41.1% of patients, including the patient in this report, the tumor progresses to malignancy. Long-term follow-up is needed in these patients. New surgical treatment plans should be considered.

Superion interspinous process spacer for intermittent neurogenic claudication secondary to moderate lumbar spinal stenosis: two-year results from a randomized controlled FDA-IDE pivotal trial.

STUDY DESIGN: Prospective, multicenter, randomized, controlled, investigational device exemption noninferiority trial. OBJECTIVE: To determine 2-year outcomes in patients with intermittent neurogenic claudication secondary to moderate lumbar spinal stenosis (LSS) who were treated with the Superion interspinous process spacer. SUMMARY OF BACKGROUND DATA: Interspinous spacers are a less-invasive treatment alternative compared with surgical decompression for patients with LSS unresponsive to conservative care. High-quality comparative data with these devices are lacking. METHODS: Patients presenting with intermittent neurogenic claudication secondary to moderate LSS who failed at least 6 months of nonsurgical management were randomly allocated to treatment with the Superion spacer or a control spacer (X-Stop) and followed for 2 years. RESULTS: A total of 391 randomized patients were implanted with Superion (n = 190) or control (n = 201) spacers at 29 sites in the United States between August 2008 and December 2011. Implants were successfully implanted in 99.5% of patients with Superion and 99.0% of control patients. The primary composite endpoint of this study was met, which demonstrated that the Superion spacer was noninferior to the X-Stop spacer. Leg pain, the predominant patient complaint, decreased in severity by 70% during 2 years in each group. Most (77%) patients achieved leg pain clinical success (improvement ≥20 mm) at 2 years. Back pain clinical success (improvement ≥20 mm) was 68%, with no differences between groups. Oswestry Disability Index clinical success (≥15% point improvement) was achieved in 65% of patients. The rates of complications and reoperations were similar between groups. CONCLUSION: The Superion interspinous process spacer relieves symptoms of intermittent neurogenic claudication secondary to moderate LSS in the majority of patients through 2 years. LEVEL OF EVIDENCE: 2.

Report from a quality assurance program on patients undergoing the MILD procedure.

OBJECTIVES: To characterize trends in pain and functional outcomes and identify risk factors in patients with lumbar spinal stenosis (LSS) and neurogenic claudication undergoing the "Minimally Invasive Lumbar Decompression" (MILD) procedure. DESIGN: Retrospective observational cohort study. SETTING: Academic multidisciplinary pain center at Stony Brook Medicine. SUBJECTS: Patients undergoing the MILD procedure from October 2010 to November 2012. METHODS: De-identified perioperative, pain and function related data for 50 patients undergoing MILD were extracted from the Center for Pain Management's quality assessment database. Data included numerical rating scale (NRS), symptom severity and physical function (Zurich Claudication Questionnaire), functional status (Oswestry Disability Index [ODI]), pain interference scores (National Institutes of Health Patient-Reported Outcomes Measurement Information System [PROMIS]), and patients' self-reported low back and lower extremity pain distribution. RESULTS: No MILD patient incurred procedure-related complications. Average NRS scores decreased postoperatively and 64.3% of patients reported less pain at 3 months. Clinically meaningful functional ODI improvements of at least 20% from baseline were present in 25% of the patients at 6 months. Preliminary analysis of changes in PROMIS scores at 3 months revealed that pre-MILD "severe" lumbar canal stenosis may be associated with high risk of "no improvement." No such impact was observed for NRS or ODI outcomes. CONCLUSION: Overall, pain is reduced and functional status improved in LSS patients following the MILD procedure at 3 and 6 months. Given the small sample size, it is not yet possible to identify patient subgroups at risk for "no improvement." Continued follow-up of longer-term outcomes appears warranted to develop evidence-based patient selection criteria.

Rupture of a craniopharyngioma cyst following trauma: a case report.

There have been only 20 reported cases of non-surgical rupture of a craniopharyngioma cyst, with only 3 cases secondary to trauma. Here we present a rare case of temporary shrinkage of a cystic craniopharyngioma following head trauma. After a motor vehicle accident in May 2001, a 61-year old woman began to have blurred vision and headaches. Magnetic resonance imaging (MRI) of the head revealed a primarily cystic mass measuring approximately two centimeters, involving the sellar and suprasellar area with compression of the pituitary. Visual field testing showed a left hemianopsia and the patient was referred for surgical evaluation. Transsphenoidal drainage of the cystic lesion in November 2001 provided histologic confirmation of the craniopharyngioma. Post-operative MRI showed cyst reduction and visual fields improved. Late in 2002, the patient again experienced progressive visual loss. Repeat MRI revealed a recurrent cystic craniopharyngioma, now measuring approximately three centimeters with subfrontal and parasellar extension and compression of the optic chiasm. A bifrontal surgical approach was advocated; however, prior to the scheduled surgery, the patient sustained a fall with trauma to the head. Following this event she experienced dramatic improvement in her headache and vision and repeat MRI showed the cystic lesion to be significantly decreased in size. Spontaneous rupture of craniopharyngioma cysts is uncommon but has been reported with increasing frequency. It is, however, exceedingly rare for a cyst to rupture following trauma.

Conservative management of acoustic neuroma: a meta-analysis and proposed treatment algorithm.

OBJECTIVES/HYPOTHESES: Conservative management is a viable treatment alternative for acoustic neuroma. Using previous studies to provide evidence-based support, we have attempted to more clearly define the role of conservative management. STUDY DESIGN: Retrospective review of literature and patient charts. METHODS: Published studies on conservative management of acoustic neuroma were found using a key word search through PubMed in addition to the bibliographies of these selected studies. A spreadsheet was made to tabulate the selection criteria for conservative management, duration and frequency of follow-up, patient demographics, initial tumor size and rate of growth, change in hearing status, and the need for definitive treatment. RESULTS: A total of 21 studies comprising 1,345 patients were included in our meta-analysis. The average length of follow-up these studies was 3.2 years. The average initial tumor size was 11.8 mm (n = 900); 43% of 1,244 acoustic neuromas showed growth, whereas 57% showed either no growth or tumor regression. The average growth rate was 1.9 mm/year in 793 individuals. Hearing loss occurred in 51% of 347 individuals. In 15 studies, 20.0% of 1,001 individuals eventually failed conservative management. CONCLUSIONS: Our meta-analysis supports the role of conservative management of acoustic neuromas in properly selected patients on the basis of a slow overall rate of growth and a substantial incidence of no growth. However, the lack of predictive factors, the relatively short duration of follow-up, and the variability of inclusion criteria underscore the need for continued collection of long-term data. An algorithm for acoustic neuroma management is proposed based on initial tumor size, patient age, and hearing status.

Osteogenic sarcoma of the sella after radiation treatment of a pituitary adenoma.

OBJECTIVE: To report an uncommon case of osteogenic sarcoma of the sella turcica after radiation treatment of a pituitary adenoma. METHODS: We present the clinical history, physical findings, laboratory data, imaging studies, and pathologic findings in a patient found to have osteogenic sarcoma of the sella after radiation therapy for a nonfunctioning pituitary adenoma. RESULTS: Six years after transsphenoidal resection and postoperative fractionated radiation therapy for a nonfunctioning pituitary adenoma that extended to the cavernous sinus, a 45-year-old man presented with a sinus infection, diplopia, and ophthalmoplegia of the right eye. A computed tomographic scan of the head showed a mass in the sella with involvement of the optic chiasm and right cavernous sinus. Transsphenoidal resection and debulking of the tumor revealed an osteogenic sarcoma. The patient was discharged from the hospital with residual diplopia and ophthalmoplegia. He was treated with levothyroxine, testosterone, and hydrocortisone. Six weeks later, the patient was readmitted after he was found unresponsive, and computed tomographic scans disclosed a massive cerebrovascular accident. He died a few days later. CONCLUSION: Osteogenic sarcoma is a rare, late complication of radiation treatment of pituitary adenoma. Although radiotherapy remains an effective adjunctive treatment in patients with pituitary adenomas, particularly those with residual or recurrent tumor, potential complications must be acknowledged.