Andrew Jea

Moyamoya Syndrome Associated With Down Syndrome: Outcome After Surgical Revascularization

Objectives. This study was undertaken to describe the clinical, radiologic, and angiographic features of moyamoya syndrome in a surgical series of children and adults with Down syndrome. We wished to define the features of moyamoya syndrome associated with Down syndrome and to determine the results of surgical revascularization among these patients at early and late follow-up times. Methods. We reviewed the clinical, radiologic, and angiographic records of all patients with moyamoya syndrome associated with Down syndrome, as a subset of a previously reported, consecutive series of patients who underwent cerebral revascularization surgery with a standardized surgical procedure, pial synangiosis, between January 1, 1985, and June 30, 2004. Results. Of 181 patients with moyamoya syndrome from the initial series who were treated surgically during the study period, 16 patients had Down syndrome (10 female patients and 6 male patients). The average age at onset was 9.3 years (range: 1–29 years); the average age at the time of surgery was 9.8 years (range: 2–29 years). Although the presenting symptoms were transient ischemic attacks for 10 patients and strokes for 6 patients, computed tomographic and/or MRI scans demonstrated bilateral infarctions for 9 patients and unilateral infarctions for 6, with only 1 patient having no imaging evidence of a previous stroke. No cases presented with intracerebral hemorrhage. Preoperative angiography showed the presence of bilateral moyamoya syndrome changes for all patients, including posterior circulation involvement for 8 patients. Surgical treatment included pial synangiosis for all patients, although 1 patient underwent a superficial temporal artery-middle cerebral artery bypass in the contralateral hemisphere. Surgical complications included symptomatic subdural hematomas requiring evacuation, at 48 days and 54 days postoperatively (2 cases), seizures (2 cases), and strokes within 30 days after surgery, at 1 day and 7 days postoperatively (2 cases). Late clinical and radiologic follow-up data (average: 67.6 months; range: 6–146 months) demonstrated no worsening in neurologic status for any patient except for 1 patient who developed a seizure disorder with associated chronic hypocalcemia; she was totally dependent at the 10-year follow-up evaluation, despite no evidence of new infarction since her surgery. There was no clinical or radiologic evidence of new infarction for any patient in late follow-up evaluations. Postoperative angiography, conducted 1 year after surgery for 11 patients, revealed radiologic evidence of good to excellent cerebral revascularization in 85% of the surgically treated hemispheres. Patients were maintained on lifetime aspirin therapy. Conclusions. The clinical, radiologic, and angiographic features of moyamoya syndrome associated with Down syndrome seem comparable to those of primary moyamoya disease. Cerebral revascularization surgery with the pial synangiosis technique seems to confer long-lasting protection against additional strokes in this patient population. The presence of moyamoya syndrome should be considered in the evaluation of patients with Down syndrome who present with transient ischemic attack-like symptoms.

Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors.

Importance Whole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown. Objective To characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors. Design Unselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic childrens hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record. Main Outcomes and Measures Clinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations. Results Of the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%). Conclusions and Relevance Tumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors.

Accurate placement of cerebrospinal fluid shunt ventricular catheters with real-time ultrasound guidance in older children without patent fontanelles

The authors present a technique in which real-time ultrasound monitoring is used to aid the insertion of cerebrospinal fluid (CSF) shunt ventricular catheters in children without patent fontanelles. Experience with the technique is reviewed. Intraoperative ultrasound is used to identify the compartments of the lateral ventricles and the choroid plexus prior to catheter insertion. Distance and trajectory to the best location for the hole-bearing segment of the catheter are determined and the catheter is inserted while real-time ultrasound monitoring is performed. Ten pediatric patients without open fontanelles underwent CSF shunt placement with the aid of transcranial ultrasound guidance between July and December 2006. After enlarging an occipital or frontal bur hole to a diameter of 2 cm to accommodate a small-footprint ultrasound probe, a ventricular catheter was carefully advanced into the frontal or occipital horn of the lateral ventricle while continuous ultrasound monitoring was performed. All catheters were inserted with a single pass through the brain. The final position of the ventricular catheter was visualized using intraoperative ultrasound. Postoperative computed tomography scans revealed all ventricular catheters placed accurately into the intended compartment of the ventricular system (for example, frontal horn or trigone). No procedure-related complications were noted. Real-time transcranial ultrasound monitoring through an enlarged bur hole is a feasible, safe, and effective technique for the placement of ventricular catheters in pediatric patients without a patent fontanelle.

USE OF AXIAL AND SUBAXIAL TRANSLAMINAR SCREW FIXATION IN THE MANAGEMENT OF UPPER CERVICAL SPINAL INSTABILITY IN A SERIES OF 7 CHILDREN

OBJECTIVEThe management of upper cervical spinal instability in children continues to represent a technical challenge. Traditionally, a number of wiring techniques followed by halo orthosis have been applied; however, they have been associated with a high rate of nonunion and poor tolerance for the halo. Alternatively, C1–C2 transarticular screws and C2 pars/pedicle screws allow more rigid fixation, but they are technically demanding and associated with vertebral artery injuries. Recently, C2 translaminar screws have been added to the armamentarium of the pediatric spine surgeon as a technically simple and biomechanically efficient method of fixation. However, subaxial translaminar screws have not been described in the pediatric population. We describe our experience with axial and subaxial translaminar screws in 7 pediatric patients. METHODSSeven pediatric patients with the diagnosis of upper cervical spinal instability required surgical fixation (age, 19 months–14 years; sex, 4 boys and 3 girls; follow-up, 4–21 months; etiology, trauma [3 patients], os odontoideum/os terminale [2 patients], hypoplastic dens [2 patients]). All patients underwent axial and/or subaxial translaminar screw insertion. Iliac crest bone graft was used for fusion in 4 patients; bone morphogenic protein and cancellous morselized allograft was used for fusion in 3 patients. A rigid cervical collar was applied for 12 weeks postoperatively in all cases. No intraoperative image guidance was used for insertion of the translaminar screws. RESULTSAll patients had a postoperative computed tomographic scan. Two patients underwent placement of bilateral crossing C2 translaminar screws. Two patients had subaxial translaminar screw placement at C3 and the upper thoracic spine, respectively. Hybrid constructs (a C2 translaminar screw combined with a C2 pars screw) were incorporated in 3 patients. No patients were found to have a breach of the ventral laminar cortex. All patients achieved solid fusion. One patient had a perioperative complication: prolonged dysphagia probably related to C1 lateral mass screw insertion rather than C2 translaminar screw placement. CONCLUSIONTo our knowledge, this report represents the only series of pediatric patients treated with axial and subaxial translaminar screws. This series shows that axial and subaxial translaminar screw fixation is a viable option for upper cervical spinal fusion in children. The technique is safe and results in adequate fixation with high fusion rates and minimal complications.

Routine use of recombinant human bone morphogenetic protein-2 in posterior fusions of the pediatric spine: safety profile and efficacy in the early postoperative period.

BACKGROUND:Previous studies using recombinant human bone morphogenetic protein-2 (rhBMP-2) in the adult lumbar spine have shown consistently good results. There have been no pediatric case series. OBJECTIVE:To determine the safety and efficacy of rhBMP-2 use in posterior instrumented fusions of the pediatric population. METHODS:A retrospective review of 19 consecutive pediatric patients who underwent posterior occiptocervical, cervical, thoracic, lumbar, or lumbosacral spine fusion from October 1, 2007, to June 30, 2008, at Texas Childrens Hospital was performed. The average age was approximately 12 years old (range, 9 months to 20 years). The minimum follow-up was 17 months (average of 19 months, range: 17–25 months), with computed tomography (CT) evaluation and grading of fusion by an independent radiologist at 3 months after surgery. RESULTS:The average CT grade was 3, indicating bilateral bridging bone. No pseudoarthroses or loss of correction was identified clinically or radiographically at 3 months and latest follow-up. There was one complication of bony overgrowth and restenosis of the spinal canal necessitating reoperation, and two superficial wound infections. There were no deep wound infections. CONCLUSION:Early outcomes using rhBMP-2 in the pediatric population show that it is a safe and efficacious adjunct to posterior spine fusions of the occipitocervical, cervical, thoracic, lumbar, and lumbosacral spine. It dependably results in the development of stable bridging bone at 3 months after surgery with good maintenance of correction and stability in long-term follow-up. Lessons learned from the case of unexpected bony overgrowth are discussed.

Biocompatibility of pristine graphene for neuronal interface: Laboratory investigation

OBJECT Graphene possesses unique electrical, physical, and chemical properties that may offer significant potential as a bioscaffold for neuronal regeneration after spinal cord injury. The purpose of this investigation was to establish the in vitro biocompatibility of pristine graphene for interface with primary rat cortical neurons. METHODS Graphene films were prepared by chemical vapor deposition on a copper foil catalytic substrate and subsequent apposition on bare Permanox plastic polymer dishes. Rat neuronal cell culture was grown on graphene-coated surfaces, and cell growth and attachment were compared with those on uncoated and poly-d-lysine (PDL)-coated controls; the latter surface is highly favorable for neuronal attachment and growth. Live/dead cell analysis was conducted with flow cytometry using ethidium homodimer-1 and calcein AM dyes. Lactate dehydrogenase (LDH) levels-indicative of cytotoxicity-were measured as markers of cell death. Phase contrast microscopy of active cell culture was conducted to assess neuronal attachment and morphology. RESULTS Statistically significant differences in the percentage of live or dead neurons were noted between graphene and PDL surfaces, as well as between the PDL-coated and bare surfaces, but there was little difference in cell viability between graphene-coated and bare surfaces. There were significantly lower LDH levels in the graphene-coated samples compared with the uncoated ones, indicating that graphene was not more cytotoxic than the bare control surface. According to phase contrast microscopy, neurons attached to the graphene-coated surface and were able to elaborate long, neuritic processes suggestive of normal neuronal metabolism and morphology. CONCLUSIONS Further use of graphene as a bioscaffold will require surface modification that enhances hydrophilicity to increase cellular attachment and growth. Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical applications.

Equivalence of fusion rates after rigid internal fixation of the occiput to C-2 with or without C-1 instrumentation

OBJECT The object of this study was to assess a multiinstitutional experience with pediatric occipitocervical constructs to determine whether a difference exists between the fusion and complication rates of constructs with or without direct C-1 instrumentation. METHODS Seventy-seven cases of occiput-C2 instrumentation and fusion, performed at 9 childrens hospitals, were retrospectively analyzed. Entry criteria included atlantooccipital instability with or without atlantoaxial instability. Any case involving subaxial instability was excluded. Constructs were divided into 3 groups based on the characteristics of the anchoring spinal instrumentation: Group 1, C-2 instrumentation; Group 2, C-1 and C-2 instrumentation without transarticular screw (TAS) placement; and Group 3, any TAS placement. Groups were compared based on rates of fusion and perioperative complications. RESULTS Group 1 consisted of 16 patients (20.8%) and had a 100% rate of radiographically demonstrated fusion. Group 2 included 22 patients (28.6%), and a 100% fusion rate was achieved, although 2 cases were lost to follow-up before documented fusion. Group 3 included 39 patients (50.6%) and demonstrated a 100% radiographic fusion rate. Complication rates were 12.5, 13.7, and 5.1%, respectively. There were 3 vertebral artery injuries, 1 (4.5%) in Group 2 and 2 (5.1%) in Group 3. CONCLUSIONS High fusion rates and low complication rates were achieved with each configuration examined. There was no difference in fusion rates between the group without (Group 1) and those with (Groups 2 and 3) C-1 instrumentation. These findings indicated that in the pediatric population, excellent occipitocervical fusion rates can be accomplished without directly instrumenting C-1.

Incorporation of C-1 lateral mass screws in occipitocervical and atlantoaxial fusions for children 8 years of age or younger

The authors describe the novel use of C-1 lateral mass screws in four children 8 years of age or younger, in whom occipitocervical or atlantoaxial fusion was performed for trauma or os odontoideum. The authors retrospectively reviewed the demographics and procedural data of four children, ranging in age from 2 to 8 years, who required and underwent surgical fixation. Although C1-2 screw/rod constructs involving individual C-1 lateral mass screws and C-2 pars interarticularis or pedicle screws have been widely applied in adults, only C1-2 transarticular screw fixation has been reported in children less than 8 years of age. This report demonstrates the successful results of rigid occipitocervical and atlantoaxial fusion in four children in whom C-1 lateral mass screws were placed as part of a screw/rod construct. There was one instance of a vertebral artery injury, and the lessons learned from this complication are discussed.

Publication patterns of oral and poster presentations at the annual meetings of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons

OBJECT National and international meetings, such as the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS) meetings, provide a central location for the gathering and dissemination of research. The purpose of this study was to determine the publication rates of both oral and poster presentations at CNS and AANS meetings in peer-reviewed journals. METHODS The authors reviewed all accepted abstracts, presented as either oral or poster presentations, at the CNS and AANS meetings from 2003 to 2005. This information was then used to search PubMed to determine the rate of publication of the abstracts presented at the meetings. Abstracts were considered published if the data presented at the meeting was identical to that in the publication. RESULTS The overall publication rate was 32.48% (1243 of 3827 abstracts). On average, 41.28% of oral presentations and 29.03% of poster presentations were eventually published. Of those studies eventually published, 98.71% were published within 5 years of presentation at the meeting. Published abstracts were published most frequently in the Journal of Neurosurgery and Neurosurgery. CONCLUSIONS Approximately one-third of all presentations at the annual CNS and AANS meetings will be published in peer-reviewed, MEDLINE-indexed journals. These meetings are excellent forums for neurosurgical practitioners to be exposed to current research. Oral presentations have a significantly higher rate of eventual publication compared with poster presentations, reflecting their higher quality. The Journal of Neurosurgery and Neurosurgery have been the main outlets of neurosurgical research from these meetings.

Prospective surveillance of complications in a pediatric neurosurgery unit: Clinical article

OBJECT Complications of specific pediatric neurosurgical procedures are well recognized. However, focused surveillance on a specific neurosurgical unit, for all procedures, may lead to better understanding of the most important complications, and allow targeted strategies for quality improvement. METHODS The authors prospectively recorded the morbidity and mortality events at a large pediatric neurosurgical unit over a 2-year period. Morbidity was defined as any significant adverse outcome or death (for obstructive shunt failure, within 30 days). Multiple and unrelated complications in the same patient were recorded as separate events. RESULTS There were 1082 surgical procedures performed during the evaluation period. One hundred seventy-seven complications (16.4%) occurred in 147 patients. By procedure, the most common complications occurred in vascular surgery (41.7%) and brain tumor surgery (27.9%). The most common complications were CSF leakage (31 cases), a new neurological deficit (27 cases), early shunt or endoscopic third ventriculostomy obstruction (27 cases), and shunt infection (24 cases). Meningitis occurred in 19 cases: in 58% of shunt infections, 13% of CSF leaks, and 10% of wound infections. Sixty-four percent of adverse events required a second procedure, most commonly an external ventricular drain placement or shunt revision. CONCLUSIONS Complications in pediatric neurosurgical procedures are common, result in significant morbidity, and more than half the time require a repeat surgical procedure. Targeted strategies to prevent common complications, such as shunt infections or CSF leaks, might significantly reduce this burden.