Chasing language through the brain: Successive parallel networks.

OBJECTIVE: To describe the spatio-temporal dynamics and interactions during linguistic and memory tasks. METHODS: Event-related electrocorticographic (ECoG) spectral patterns obtained during cognitive tasks from 26 epilepsy patients (aged: 9-60 y) were analyzed in order to examine the spatio-temporal patterns of activation of cortical language areas. ECoGs (1024 Hz/channel) were recorded from 1567 subdural electrodes and 510 depth electrodes chronically implanted over or within the frontal, parietal, occipital and/or temporal lobes as part of their surgical work-up for intractable seizures. Six language/memory tasks were performed, which required responding verbally to auditory or visual word stimuli. Detailed analysis of electrode locations allowed combining results across patients. RESULTS: Transient increases in induced ECoG gamma power (70-100 Hz) were observed in response to hearing words (central superior temporal gyrus), reading text and naming pictures (occipital and fusiform cortex) and speaking (pre-central, post-central and sub-central cortex). CONCLUSIONS: Between these activations there was widespread spatial divergence followed by convergence of gamma activity that reliably identified cortical areas associated with task-specific processes. SIGNIFICANCE: The combined dataset supports the concept of functionally-specific locally parallel language networks that are widely distributed, partially interacting in succession to serve the cognitive and behavioral demands of the tasks.

Postmortem investigation of a human cortical visual prosthesis that was implanted for 36 years.

Objective: Postmortem analysis of the brain from a blind human subject who had a cortical visual prosthesis implanted for 36 years (Dobelle 2000 Asaio J. 46 3­9) Approach: This provided insight into the design requirements for a successful human cortical visual prosthesis by revealing, (a) unexpected rotation of the electrode array 25 to 40 degrees away from the midsagittal plane, thought to be due to the torque of the connecting cable, (b) degradation of the platinum electrodes, and (c) only partial coverage of the primary visual cortex by the rectangular array. The electrode array only overlapped with the anterior 45% of primary visual cortex (identified by the line of Gennari), largely missing the posterior foveal representation of visual cortex. Main results: A significantly greater proportions of electrodes outside of V1 elicited phosphenes than did electrodes within of V1. Histology did not reveal appreciable loss of neurons in cortex that surrounded the migrated array, perhaps due to the very slow rotation of this implant. Significance: This pioneering effort to develop a cortical visual prosthesis suggests that to maximize efficacy, the long-term effects of implanted alien materials on nervous tissue, and vice versa, need to be considered in detail, and that electrode array design considerations need to optimally match the electrodes to the patient's cortical anatomy. Modern pre-implant imaging can help optimize future implants by identifying the location and extent of bridging veins with MRI and even map the location of the V1/V2 border in vivo with PET.

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

BACKGROUND: Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study. OBJECTIVE: To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction. METHODS: We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of -2.5%. RESULTS: We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin. CONCLUSION: TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.

Dural Ectasia in Neurofibromatosis 1: Case Series, Management, and Review.

BACKGROUND: The natural history and management of dural ectasia in Neurofibromatosis 1 (NF1) is still largely unknown. Dural ectasias are one of the common clinical manifestations of NF1; however, the treatment options for dural ectasias remain unstudied. OBJECTIVE: To investigate the natural history, diagnosis, management, and outcome of the largest case series of patients with NF1-associated dural ectasia to date. METHODS: Records from our NF1 clinic were reviewed to identify NF1 patients with computed tomography or magnetic resonance imaging evidence of dural ectasia(s) to determine their clinical course. Demographics, symptoms, radiographic and histopathologic findings, treatment, and clinical course were assessed. RESULTS: Thirty-four of 37 patients were managed without surgery. Of the 18 initially asymptomatic patients, 5 (27.8%) progressed to symptoms attributable to a dural ectasia (onset of 2.7% per patient-year). Three patients required surgical intervention because of extraspinal mass effect. All 3 initially improved but had symptom recurrence within 2 yr. Reoperation involved shunt placement for cerebrospinal fluid (CSF) diversion. On imaging review, 26 (76.5%) of the nonsurgical patients harbored an associated nearby plexiform neurofibroma. Pathology of one surgical case revealed dural infiltration by diffuse neurofibroma. CONCLUSION: Using the largest NF1-associated dural ectasia group to date, we report the first symptom-onset rate for nonsurgical patients. In the few cases requiring surgery for decompression, primary resection, and patching of ectasias failed, subsequently requiring CSF shunting. We demonstrate imaging evidence of nearby plexiform neurofibroma in a majority of cases, which, when combined with histopathology, provides a novel explanation for the formation of dural ectasias.

Outcomes in children undergoing posterior fossa decompression and duraplasty with and without tonsillar reduction for Chiari malformation type I and syringomyelia: a pilot prospective multicenter cohort study.

OBJECTIVE: Despite significant advances in diagnostic and surgical techniques, the surgical management of Chiari malformation type I (CM-I) with associated syringomyelia remains controversial, and the type of surgery performed is surgeon dependent. This study's goal was to determine the feasibility of a prospective, multicenter, cohort study for CM-I/syringomyelia patients and to provide pilot data that compare posterior fossa decompression and duraplasty (PFDD) with and without tonsillar reduction. METHODS: Participating centers prospectively enrolled children suffering from both CM-I and syringomyelia who were scheduled to undergo surgical decompression. Clinical data were entered into a database preoperatively and at 1-2 weeks, 3-6 months, and 1 year postoperatively. MR images were evaluated by 3 independent, blinded teams of neurosurgeons and neuroradiologists. The primary endpoint was improvement or resolution of the syrinx. RESULTS: Eight clinical sites were chosen based on the results of a published questionnaire intended to remove geographic and surgeon bias. Data from 68 patients were analyzed after exclusions, and complete clinical and imaging records were obtained for 55 and 58 individuals, respectively. There was strong agreement among the 3 radiology teams, and there was no difference in patient demographics among sites, surgeons, or surgery types. Tonsillar reduction was not associated with > 50% syrinx improvement (RR = 1.22, p = 0.39) or any syrinx improvement (RR = 1.00, p = 0.99). There were no surgical complications. CONCLUSIONS: This study demonstrated the feasibility of a prospective, multicenter surgical trial in CM-I/syringomyelia and provides pilot data indicating no discernible difference in 1-year outcomes between PFDD with and without tonsillar reduction, with power calculations for larger future studies. In addition, the study revealed important technical factors to consider when setting up future trials. The long-term sequelae of tonsillar reduction have not been addressed and would be an important consideration in future investigations.

Neurocognitive Functioning in Unoperated Adults with Chiari Malformation Type I.

OBJECTIVE: Adults with Chiari malformation type 1 (CM1) often report cognitive impairment. This cross-sectional study investigates the cognitive and emotional functioning of a sample of adults with CM1 who presented for neurosurgical evaluation prior to intervention. METHODS: A total of 36 participants (18 patients with CM1 and 18 healthy control subjects) completed a comprehensive neurocognitive battery of tests. RESULTS: Demographic variables (sex, age, handedness, and education) were not statistically significant between the groups. Measures of gross cognition (Mini-Mental State Examination and Repeatable Battery for the Assessment of Neuropsychological Status) were statistically significant between the groups. On a more focused assessment of neurocognitive abilities, the CM1 group performed significantly worse on measures of learning, memory, fluency, and figural copy. A high rate of clinical depression was seen in the CM1 group; however, this did not correlate with cognitive performance. CONCLUSIONS: The CM1 group displayed subtle learning, semantic fluency, and complex construction difficulties compared with healthy control subjects. Although not correlated with cognition, adults with CM1 are at high risk for clinical depression.

Prevalence of Psychiatric Diagnoses in Pediatric Chiari Malformation Type 1.

This cross-sectional study investigates the prevalence and risks for psychiatric diagnoses in a large cohort of children with Chiari malformation type 1 (CM1) presenting for neurosurgical evaluation. Children between the ages of 6 and 17 years who were evaluated and diagnosed with CM1 at a neurosurgery clinic were identified. Eighty-six participants were recruited for this study with an average age of 11 years. Parents of participants completed a pediatric medical history questionnaire and a semistructured interview regarding the child's psychiatric, developmental, medical, and family history. A review of medical records was completed to complement interview data. Elevated rates of psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD) (22.1%), anxiety (12.8%), and depression (10.5%), were identified in the study population when compared to published norms in the general population documented by the American Psychiatric Association in 2013. In addition, elevated rates of psychiatric diagnoses in first-degree relatives of study participants were also identified. A 2-step binary logistic regression analysis revealed that maternal complications during pregnancy (Wald = 6.52, p = 0.01) increased the risk of a psychiatric diagnosis 9-fold. Premature birth (Wald = 6.79, p = 0.01) also significantly predicted a psychiatric diagnosis amongst participants. The current findings suggest a high prevalence of psychiatric illness in children with CM1. Pregnancy complications were associated with a high risk of a psychiatric diagnosis. Early CNS developmental disturbance may explain this relationship. Prematurity only slightly improved the prediction model. Limitations and future directions are discussed, including the cross-sectional nature of the present study, possible self-selection bias, and the importance of future investigation of other causative and/or associative factors of CM1, such as cognitive, psychiatric, and medical influences on health status.

Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency.

BACKGROUND: The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes. METHODS: Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed. RESULTS: Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism. CONCLUSIONS: Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.

Magnetic resonance imaging in the prone position and the diagnosis of tethered spinal cord.

OBJECTIVE Tethered cord syndrome (TCS) is a neurosurgical disorder with varied clinical manifestations believed to result from vascular compromise due to stretch forces on the spinal cord. Conventional supine MRI findings may include a low-lying conus medullaris, thickened or fat-infiltrated filum terminale, or lipoma; however, imaging sensitivity and specificity for tethered cord can be low. The purpose of this study was to evaluate the utility of prone MRI in the diagnosis of tethered and retethered spinal cord. METHODS Medical records were reviewed in 41 patients who underwent surgical release of tethered cord and in whom preoperative prone MRI sequences were available. Patients were divided into Group 1 (new TCS diagnosis) and Group 2 (recurrent TCS after previous untethering). Absolute conus ventral motion and motion as a percentage of canal width between supine and prone positions was measured in these 2 groups via sagittal T2-weighted sequences; these groups were compared with 30 consecutive patients (Group 3) who were classified as the normal control group. RESULTS The mean ventral motion was as follows: Group 1 (absolute: 0.5 ± 0.5 mm [range 0-2.4 mm]; canal percentage: 3.7% ± 3.9% [range 0%-16.3%]); Group 2 (absolute: 0.4 ± 0.7 mm [range 0-2.6 mm]; canal percentage: 2.2% ± 3.7% [range 0%-14.0%]); and Group 3 (absolute: 3.4 ± 1.3 mm [range 1.4-5.6 mm]; canal percentage: 22.0% ± 7.2% [range 10.5%-36.1%]). Whereas 38/41 surgically treated patients with TCS had diminished (< 10% canal width) ventral motion on preoperative MRI, 30/30 controls had > 10% canal width motion. Sensitivity and specificity were thereby calculated as 92.7% and 100%, respectively. CONCLUSIONS In the present series, prone imaging is found to be a sensitive and specific tool, and the authors believe it may have a role as supportive evidence in the diagnosis of tethered and retethered spinal cord.

Transcardiac migration of ventriculoperitoneal shunt requiring open cardiac surgery: case report and review of the literature.

INTRODUCTION: Cardiac migration of ventriculoperitoneal (VP) shunts has been reported, with most easily removed or shortened via a cervical incision. We present a review of the literature, highlighting our unique case with significant scarring requiring open, on-pump, cardiac surgery for removal of migrated distal tubing. CASE PRESENTATION: A 7-year-old boy underwent VP shunt insertion for hydrocephalus secondary to intracranial astrocytoma. He presented at age 17 with evidence of right heart strain, associated with the distal shunt catheter proximally migrated into his heart and pulmonary arteries. Due to his delayed presentation, the catheter was knotted and partially immobilized by scar formation, finally requiring open-heart surgery to remove the catheter. CONCLUSIONS: A multi-disciplinary evaluation with endovascular, neurosurgery, and cardiothoracic surgery may be the safest approach, especially in those patients with knotting on preoperative imaging.

In situ repair of vagus nerve stimulator lead damage: technical note.

Vagus nerve stimulators (VNSs) are currently an accepted treatment for intractable epilepsy not amenable to ablative surgery. Battery death and lead damage are the main reasons for reoperation in patients with VNSs. In general, any damage to the lead requires revision surgery to remove the helical electrodes from the vagus nerve and replace the electrode array and wire. The electrodes are typically scarred and difficult to remove from the vagus nerve without injury. The authors describe 6 patients with VNSs who presented with low lead impedance on diagnostic testing, leading to the intraoperative finding of lead insulation disruption, or who were found incidentally at the time of implantable pulse generator battery replacement to have a tear in the outer insulation of the electrode wire. Instead of replacement, the wire insulation was repaired and reinforced in situ, leading to normal impedance testing. All 6 devices remained functional over a follow-up period of up to 87 months, with 2 of the 6 patients having a relatively shorter follow-up of only 12 months. This technique, applicable in a subset of patients with VNSs requiring lead exploration, obviates the need for lead replacement with its attendant risks.

Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex.

High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (n = 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales.

Parent-Reported Executive Dysfunction in Children and Adolescents with Chiari Malformation Type 1.

BACKGROUND: Children with Chiari malformation type 1 (CM1) have increasingly presented to neurosurgery clinics. Limited research relating to the cognitive dysfunction experienced by this population has been completed. In adults, inhibition problems and executive dysfunction have been documented. METHODS: Seventy-seven parental reports of children with CM1 were included in the study. Parents completed questions on a scale rating daily executive functioning as well as reporting on common neurological symptoms. RESULTS: The sample consisted of 41 males and 36 females with a mean age of 133.57 ± 42.18 months. Thirty-eight subjects had had decompression surgery. The most common neurological symptoms included: headache (69%), a history of pain (31%) and gait disturbance (20%). One third of the sample demonstrated overall executive functioning impairment, with working memory elevations being most prevalent (44%). Depression, gender, age and decompression surgery were not related to executive dysfunction. CONCLUSIONS: The parental report of executive dysfunction in children with CM1 was higher than the standardized healthy sample. Metacognitive problems, especially working memory and initiation problems were most prevalent. A quick parental rating scale identifying children with executive dysfunction may be beneficial for neurosurgeons and assist with referrals for a more comprehensive neuropsychological assessment.

MRI Findings After Surgery for Chiari Malformation Type I.

OBJECTIVE: Surgery plays an important role in the management of Chiari I malformation. The purpose of this article is to review expected and unexpected MRI findings after the various types of surgery performed during the treatment of Chiari I malformation and associated abnormalities. CONCLUSION: Familiarity with optimal MRI techniques and findings is important when evaluating postoperative changes after treatment of Chiari I malformation.

A ten-year review of myelodysplastic defect management and use of a novel closure technique with V-Y crescentic rotation advancement flaps.

The reconstructive goals for myelodysplastic defects are to provide a multilayered, tension-free and well-vascularized closure to prevent cerebrospinal fluid leakage, wound infection or breakdown and to optimize neurologic outcomes. We reviewed our ten-year experience with myelodysplastic defects and our preferred technique for large defects utilizing paraspinous flaps followed by V-Y crescentic rotation advancement flaps. A retrospective chart review was performed on all myelodysplastic defects closed at the University of Chicago Medicine from 2002 to 2012. Twenty-three patients were treated: eight were closed using V-Y crescentic rotation advancement flaps, eight primarily, two with transposition flaps and five with bilateral latissimus dorsi and gluteus maximus myocutaneous flaps. Patient defect characteristics, reconstructive details, follow up time, and wound complications were analyzed. The primary closure group included eight patients. There was one minor complication and two major complications that required debridement and plastic surgery consultation in this group. The transposition group included two patients and had no wound healing issues. The latissimus and gluteus myocutaneous group included five patients and had one minor wound healing issues. The V-Y crescentic group included eight patients. There were four minor wound breakdowns in the lateral donor sites and one major wound complication involving a CSF leak, meningitis and wound breakdown that required debridement. The groups were stratified by size, <5 cm and >5 cm, and further analyzed. Bilateral V-Y crescentic rotation advancement flap is a useful option when confronted with large myelodysplastic defects. It provides a multilayer, tension-free wound closure and spares the gluteus maximus and latissimus dorsi muscle groups.

Is pelvic plexus nerve documentation feasible during robotic assisted laparoscopic ureteral reimplantation with extravesical approach?

PURPOSE: Urinary retention is a known complication of using an extravesical approach for ureteral reimplantation, especially in bilateral cases. The etiology may be secondary damage to pelvic nerves during ureteral dissection. Recent literature suggests that it is possible to visually identify these nerves during a robotic assisted laparoscopic approach. We performed an exploratory study to identify and document them in pediatric patients by means of electrophysiologic recordings. MATERIAL AND METHODS: Seven consecutive patients undergoing robotic assisted laparoscopic ureteral reimplantation with extravesical approach were prospectively enrolled in the study. Following dissection of the ureter below the level of vas deferens in male and the uterine artery in female, staying close to the adventitia and approaching the ureterovesical junction, the fibers as described in human cadaveric studies were identified dorsomedial to the ureter and preserved. Stimulating and recording electrodes were passed through to record post-synaptic compound muscle action potentials of the bladder. RESULTS: Even though the nerve fibers were visually identified, we were unable to consistently and reproducibly record compound muscle action potentials after stimulation of putative pelvic plexus fibers at the distal ureter, despite modulation in stimulation intensity, pulse characteristics, signal recording sensitivity and stimulator probe variation. CONCLUSIONS: In this pilot study, the inconsistent findings raise questions about the exact location of the neurovascular bundle, nature of bladder smooth muscle electrophysiology and the appropriate methodology of evaluation. This may provide a reason to reexamine the intraoperatively expected location of pelvic plexus nerve fibers.

Intrapleural migration of a spinal catheter in a patient with arachnoiditis and extensive epidural scarring after tethered cord release: a case report and review of literature.

OBJECTIVE: The objective of this study was to report a case of new onset refractory pain from intrapleural migration of a spinal catheter five months after the implantation of an intrathecal drug delivery system (IDDS). MATERIALS AND METHODS: A 57-year-old man had intractable pain because of multiple intradural spinal explorations for tethered cord release. His pain was effectively treated with intrathecal morphine via an IDDS. Five months after the implantation, the patient developed return of the original pain more than two weeks after intrapleural migration of the intrathecal catheter. RESULTS: The migration was documented by computed tomography, and repositioning of the catheter rendered the patient comfortable. The gradual onset of pain may have been due to decreasing delivery of drug to the cerebrospinal fluid as the catheter tip migrated further away from the dura. To our knowledge, this complication has not been reported in the literature. CONCLUSION: Physicians and nursing staff that place and manage an IDDS should be aware of this complication.

A large pelvic mass in a 39-year-old man.

Schwannomas are encapsulated, usually benign, tumors composed of well-differentiated Schwann cells, arising from the neural sheath of peripheral nerves. The most common type of benign schwannoma is the acoustic neuroma arising from the eighth cranial nerve. Retroperitoneal schwannomas account for 0.5-3% of the retroperitoneal tumors in most series. We present a case of a 39-year-old man with a pelvic mass, arising from a sacral nerve root, diagnosed as a schwannoma.