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Potential role of stem cells for neuropathic pain disorders

Sudhakar Vadivelu, Matthew Willsey, Daniel J. Curry, and John W. McDonald III

Chronic neuropathic pain is a debilitating disease process associated with several medical disorders. Different from pain caused by inflammation, neuropathic pain is a diffuse pain disorder often found to be recalcitrant to the limited medical treatments available. Intractable nerve pain may benefit from other therapies capable of longer-lasting pain coverage or greater efficacy. A growing number of reports have emerged suggesting a role for stem cells as a cellular delivery source with neuroprotective agents opposing the effects of nerve damage. Here, the authors review the current experimental therapies examining the use of stem cells for the treatment of neuropathic pain disorders.

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Preservation of microelectrode recordings with non–GABAergic drugs during deep brain stimulator placement in children

Technical note

Helena Karlberg Hippard, Mehernoor Watcha, Amber J. Stocco, and Daniel Curry

Object

Deep brain stimulation (DBS) has become accepted therapy for intractable dystonia and other movement disorders. The accurate placement of DBS electrodes into the globus pallidus internus is assisted by unimpaired microelectrode recordings (MERs). Many anesthetic and sedative drugs interfere with MERs, requiring the patient to be awake for target localization and neurological testing during the procedure. In this study, a novel anesthetic technique was investigated in pediatric DBS to preserve MERs.

Methods

In this paper, the authors describe a sedative/anesthetic technique using ketamine, remifentanil, dexmedetomidine, and nicardipine in 6 pediatric patients, in whom the avoidance of GABAergic stimulating drugs permitted excellent surgical conditions with no detrimental effects on intraoperative MERs. The quality of the MERs, and the frequency of its use in making electrode placement decisions, was reviewed.

Results

All 6 patients had good-quality MERs. The data were of sufficient quality to make a total of 9 trajectory adjustments.

Conclusions

Microelectrode recordings in pediatric DBS can be preserved with a combination of dexmedetomidine and ketamine, remifentanil, and nicardipine. This preservation of MERs is particularly crucial in electrode placement in children.

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Surgical outcome for focal cortical dysplasia: an analysis of recent surgical series

A review

Joshua J. Chern, Akash J. Patel, Andrew Jea, Daniel J. Curry, and Youssef G. Comair

Object

Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy and is at times treatable by resection. The now widespread use of MR imaging and recent advancement of functional imaging have increased the number of patients undergoing surgical treatment for FCD. The objective of this review is to critically examine and to provide a summary of surgical series on FCD published since 2000.

Methods

Studies concerning surgery for FCD were identified from MEDLINE and references of selected articles and book chapters. Data from these included studies were summarized and analyzed to identify factors correlated with seizure outcome.

Results

Sixteen studies were identified, and 469 patients met our selection criteria. Seizure-free outcome at 1-year postoperatively was achieved in 59.7% of the patients. Children and adults were equally likely to benefit from the surgery. Complete resection (OR 13.7, 95% CI 6.68–28.1; p < 0.0001) and temporal location (OR 2.15, 95% CI 1.26–3.69; p = 0.0073) were two positive prognostic indicators of seizure-free outcome. Utilization of invasive monitoring did not affect the chance of seizure remission, but firm conclusions could not be drawn because patients were not randomized.

Conclusions

The advancement of modern imaging has transformed the process of surgical candidate selection for partial epilepsy due to FCD. Patients from recent surgical series were more homogeneous in their clinical presentations and might represent FCD as an independent pathological entity. This likely explained the improved surgical outcome for this group of patients. These reports also documented the increased utilization of functional imaging, but their efficacy needs to be verified with further studies.

Free access

Magnetic resonance–guided laser interstitial thermal therapy for pediatric periventricular nodular heterotopia-related epilepsy

Vijay M. Ravindra, Sungho Lee, David Gonda, Ilana Patino, Lucia Ruggieri, Daniel S. Ikeda, and Daniel J. Curry

OBJECTIVE

Periventricular nodular heterotopia (PVNH) is a result of disrupted neuronal migration from the ventricular system and can be a rare cause of refractory focal epilepsy. The goal of this case series was to describe the treatment of pediatric PVNH-related epilepsy with MR-guided laser interstitial thermal ablation.

METHODS

Patients treated at a single institution with MR-guided laser interstitial thermal therapy (MRgLITT) for PVNH-related epilepsy were identified. Preoperative and postoperative seizure outcomes and procedural information were evaluated.

RESULTS

Five children with PVNH treated with MRgLITT were reviewed; 1 child was treated twice. Three patients were female; the median age was 10.9 years. Five of 6 treatments were preceded by stereoelectroencephalography phase II monitoring. Three children experienced unilateral PVNH, and 2 had bilateral seizures. The median number of seizures recorded during phase II monitoring was 2; the median number of ablation targets was 2 (range 1–4). All patients experienced a decrease in seizure frequency; 4 patients (80%) had an Engel class ≤ III at the last follow-up (range I–IV). One child experienced right hemianopia posttreatment.

CONCLUSIONS

This case series investigation has illustrated a novel, minimally invasive approach for treating pediatric PVNH-related epilepsy. Further study of this technique with comparison with other surgical techniques is warranted.

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Periosteal chondroma of the pediatric cervical spine

Case report

Daniel K. Fahim, Keyne K. Johnson, William E. Whitehead, Daniel J. Curry, Thomas G. Luerssen, and Andrew Jea

Periosteal chondromas located in the spine are rare. The authors document an even more infrequent occurrence of a recurrent periosteal chondroma in the cervical spine of a 6-year-old boy. During the operation, a giant (> 7 cm in diameter) periosteal chondroma with involvement of the C-5 and C-6 vertebral bodies was resected. The vertebral column was reconstructed with anterior-posterior instrumentation. The pathological examination revealed that the tumor consisted of chondroid tissue with typical chondrocytes, confirming the diagnosis of periosteal chondroma.

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Computed tomography morphometric analysis for axial and subaxial translaminar screw placement in the pediatric cervical spine

Clinical article

Joshua J. Chern, Roukoz B. Chamoun, William E. Whitehead, Daniel J. Curry, Thomas G. Luerssen, and Andrew Jea

Object

The 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, C1–2 transarticular screws and C-2 pars/pedicle screws allow more rigid fixation, but their placement is technically demanding and associated with vertebral artery injuries. Recently, C-2 translaminar screws have been added to the armamentarium of the pediatric spine surgeon as a technically simple and biomechanically efficient means of fixation. However, the use of subaxial translaminar screws have not been described in the general pediatric population. There are no published data that describe the anatomical considerations and potential limitations of this technique in the pediatric population.

Methods

The cervical vertebrae of 69 pediatric patients were studied on CT scans. Laminar height and thickness were measured. Statistical analysis was performed using unpaired Student t-tests (p < 0.05) and linear regression analysis.

Results

The mean laminar heights at C-2, C-3, C-4, C-5, C-6, and C-7, respectively, were 9.76 ± 2.22 mm, 8.22 ± 2.24 mm, 8.09 ± 2.38 mm, 8.51 ± 2.34 mm, 9.30 ± 2.54 mm, and 11.65 ± 2.65 mm. Mean laminar thickness at C-2, C-3, C-4, C-5, C-6, and C-7, respectively, were 5.07 ± 1.07 mm, 2.67 ± 0.79 mm, 2.18 ± 0.73 mm, 2.04 ± 0.60 mm, 2.52 ± 0.66 mm, and 3.84 ± 0.96 mm. In 50.7% of C-2 laminae, the anatomy could accept at least 1 translaminar screw (laminar thickness ≥ 4 mm).

Conclusions

Overall, the anatomy in 30.4% of patients younger than 16 years old could accept bilateral C-2 translaminar screws. However, the anatomy of the subaxial cervical spine only rarely could accept translaminar screws. This study establishes anatomical guidelines to allow for accurate and safe screw selection and insertion. Preoperative planning with thin-cut CT and sagittal reconstruction is essential for safe screw placement using this technique.

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Pneumothorax complicating “in-out-in” thoracic pedicle screw placement for kyphotic deformity correction in a child

Case report

Ashwin Viswanathan, Katherine Relyea, William E. Whitehead, Daniel J. Curry, Thomas G. Luerssen, and Andrew Jea

The authors describe a rare case of pneumothorax as a complication of thoracic pedicle screw placement in an 11-year-old girl undergoing posterior segmental instrumentation for a kyphotic deformity. Spontaneous pneumothorax after posterior fusion for adolescent idiopathic scoliosis has been reported in the orthopedic literature; however, to the best of the authors' knowledge, pneumothorax directly related to pedicle screw placement for spinal deformity has not been previously described. The authors discuss the anatomical and technical aspects leading to this complication and the lessons learned from it.

Full access

A standardized protocol to reduce pediatric baclofen pump infections: a quality improvement initiative

Virendra R. Desai, Jeffrey S. Raskin, Arvind Mohan, JoWinsyl Montojo, Valentina Briceño, Daniel J. Curry, and Sandi Lam

OBJECTIVE

Intrathecal baclofen pumps are generally placed in children for the treatment of spasticity and dystonia. Use of implants in this pediatric population with comorbidities is reported to have a high risk of complications and infections. With the aim of reducing baclofen pump–related infections, a quality improvement project was instituted at the authors’ institution.

METHODS

A workflow paradigm unique to baclofen pump implantation aimed at decreasing implant-related infections was implemented. All baclofen pump operations performed at the authors’ institution between August 2012 and June 2016 were reviewed. An infection prevention protocol was created and implemented in August 2014 based on a literature review and the consensus opinion of the pediatric neurosurgeons in the group. Compliance with the prevention bundle was tracked. Case outcomes before and after implementation of the protocol with a minimum of 3 months of follow-up were retrospectively reviewed. Univariate and multivariate analyses were performed to assess the association of the steps in the prevention bundle with infection and complication outcomes.

RESULTS

A total of 128 baclofen pump surgeries were performed (64 preprotocol and 64 postprotocol). The patient age range was 3 to 27 years. The overall compliance rate with the infection prevention bundle was 82%. The pre- and postimplementation infection rates were 12.5% and 6.3%, respectively (p = 0.225). The total pre- and postimplementation complication rates were 23.4% and 9.4%, respectively (p = 0.032). The absolute and relative risk reductions for infections were 6.3% (95% CI 3.8%–16.3%) and 50%, respectively; for complications, the absolute and relative risk reductions were 14.1% (95% CI 1.5%–26.7%) and 60%, respectively.

CONCLUSIONS

The total complication rate following intrathecal baclofen pump surgery was significantly lower after implementation of the quality improvement protocol. This study is an example of using checklist standardization to diminish special cause variability.

Open access

Bow hunter syndrome in rheumatoid arthritis: illustrative case

Brian P. Curry, Vijay M. Ravindra, Jason H. Boulter, Chris J. Neal, and Daniel S. Ikeda

BACKGROUND

Rheumatoid arthritis (RA) frequently features degeneration and instability of the cervical spine. Rarely, this degeneration manifests as symptoms of bow hunter syndrome (BHS), a dynamic cause of vertebrobasilar insufficiency.

OBSERVATIONS

The authors reviewed the literature for cases of RA associated with BHS and present a case of a man with erosive RA with intermittent syncopal episodes attributable to BHS as a result of severe extrinsic left atlantooccipital vertebral artery compression from RA-associated cranial settling. A 72-year-old man with RA-associated cervical spine disease who experienced gradual, progressive functional decline was referred to a neurosurgery clinic for evaluation. He also experienced intermittent syncopal events and vertiginous symptoms with position changes and head turning. Vascular imaging demonstrated severe left vertebral artery compression between the posterior arch of C1 and the occiput as a result of RA-associated cranial settling. He underwent left C1 hemilaminectomy and C1–4 posterior cervical fusion with subsequent resolution of his syncope and vertiginous symptoms.

LESSONS

This is an unusual case of BHS caused by cranial settling as a result of RA. RA-associated cervical spine disease may rarely present as symptoms of vascular insufficiency. Clinicians should consider the possibility, though rare, of cervical spine involvement in patients with RA experiencing symptoms consistent with vertebral basilar insufficiency.

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Magnesium and experimental vasospasm

R. Loch Macdonald, Daniel J. Curry, Yasuo Aihara, Zhen-Du Zhang, Babak S. Jahromi, and Reza Yassari

Object. Interest has developed in the use of magnesium (Mg++) as a neuroprotectant and antivasospastic agent. Magnesium may increase cerebral blood flow (CBF) and reduce the contraction of cerebral arteries caused by various stimuli. In this study the authors tested the hypothesis that a continuous intravenous infusion of Mg++ reduces cerebral vasospasm after experimental subarachnoid hemorrhage (SAH).

Methods. A dose-finding study was conducted in five monkeys (Macaca fascicularis) to determine what doses of intravenous MgSO4 elevate the cerebrospinal fluid (CSF) concentrations of Mg++ to vasoactive levels and to determine what effects these doses have on the diameters of cerebral arteries, as shown angiographically. After a standard dose of MgSO4 had been selected it was then administered in a randomized, controlled, blinded study to 10 monkeys (five animals/group) with SAH, beginning on Day 0 and continuing for 7 days, at which time angiography was repeated. A 0.086-g/kg bolus of MgSO4 followed by an infusion of 0.028 g/kg/day MgSO4 significantly elevated serum and CSF levels of Mg++ (five monkeys). Magnesium sulfate significantly elevated the serum level of total Mg++ from a control value of 0.83 ± 0.04 mmol/L to 2.42 ± 1.01 mmol/L on Day 7 and raised the CSF level from 1.3 ± 0.04 mmol/L to 1.76 ± 0.14 mmol/L. There was no angiographic evidence of any effect of MgSO4 on normal cerebral arteries. After SAH, the vasospasm in the middle cerebral artery was not significantly reduced (46 ± 8% in the MgSO4-treated group compared with 35 ± 6% in the placebo [vehicle]-treated group, p > 0.05, unpaired t-test).

Conclusions. Magnesium sulfate did not significantly reduce cerebral vasospasm after SAH in the doses tested. An investigation of SAH is warranted mainly to test whether a benefit can be achieved by neuroprotection or by augmentation of CBF by dilation of small vessels and/or collateral pathways.