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Jonathan E. Martin, Markus Bookland, Douglas Moote, and Catherine Cebulla

OBJECTIVE

Grabb’s line—the perpendicular distance from the basion-C2 line (pB-C2)—is a widely used radiographic measurement with significant clinical implications in patients with a complex Chiari malformation. Rigorous demonstration of the reproducibility of this measurement has not previously been reported. The authors report a standardized measurement technique with excellent inter- and intrarater reliability on T1-weighted sagittal MRI.

METHODS

The authors developed a standardized measurement technique that included specifications of midline slice selection, landmark and reference line definitions, and measurement technique on T1-weighted sagittal images. Twenty MR images were reviewed by 2 pediatric neurosurgeons, 1 pediatric radiologist, and 1 undergraduate student. Measurements were performed using the technique specified on 2 separate occasions. Intrarater and interrater reliabilities were calculated using the intraclass correlation coefficient.

RESULTS

A combined interrater reliability of 0.879 was achieved for the pB-C2, and 0.916 for the clival-canal angle, another measure of interest in patients with complex Chiari malformations. Intrarater reliability for these measurements exceeded 0.858 for all 4 reviewers.

CONCLUSIONS

Grabb’s line—the pB-C2—can be measured with excellent reliability using a standardized measurement protocol. Individual clinicians and collaborative databases should consider using validated measurement techniques to guide clinical decision making in patients with craniocervical junction pathology.

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Wesley Hsu, Khan W. Li, Markus Bookland, and George I. Jallo

In the early 1920s, Walter E. Dandy began translating the field of endoscopy to neurosurgery. In the ensuing years, Dandy, who would become known as the “Father of Neuroendoscopy,” applied his own ingenuity in combination with guidance from prominent medical contemporaries in the development of the early neuroendoscope. This paper reviews his contributions to the early evolution of this growing and important field of neurosurgery.

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Markus Bookland, Eileen Gillan, Xianyuan Song, and Antonina Kolmakova

OBJECTIVE

Micro RNAs (miRNAs) in peripheral biofluids (e.g., blood, saliva, urine) have been investigated as potential sources of diagnostic and prognostic information for a variety of tumor types, including pediatric brain tumors. While significant predictive associations have been identified between unique serum miRNA concentrations and some pediatric brain tumors, it is unclear whether serum miRNA abnormalities in pediatric brain tumor patients are representative of miRNA alterations in the tumor tissue compartment or whether they represent host tissue reactions to the presence of a brain tumor. The authors sought to identify whether serum miRNA changes in pediatric brain tumor patient sera could be explained by miRNA alterations within their tumors.

METHODS

Matched serum and tissue samples were taken from a cohort of pediatric brain tumor patients (juvenile pilocytic astrocytoma [JPA] = 3, medulloblastoma = 4, ependymoma = 3), and unmatched control samples (n = 5) were acquired from control pediatric patients without oncological diagnoses. Extracted RNAs were tested within an array of 84 miRNAs previously noted to be relevant in a variety of brain tumors.

RESULTS

miR-26a-5p correlated strongly in JPA patients within both the serum and tumor tissue samples (R2 = 0.951, p = 0.046), and serum levels were highly predictive of JPA (area under the curve = 0.751, p = 0.027). No other miRNAs that were significantly correlated between biological compartments were significantly associated with brain tumor type. In total, 15 of 84 tested miRNAs in JPA patients, 14 of 84 tested miRNAs in ependymoma patients, and 4 of 84 tested miRNAs in medulloblastoma patients were significantly, positively correlated between serum and tumor tissue compartments (R2 > 0.950, p < 0.05).

CONCLUSIONS

The majority of miRNA changes in pediatric brain tumor patient sera that are significantly associated with the presence of a brain tumor do not correlate with brain tumor miRNA expression levels. This suggests that peripheral miRNA changes within pediatric brain tumor patients likely derive from tissues other than the tumors themselves.

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Jonathan E. Martin, Thomas Manning, Markus Bookland, and Charles Castiglione

OBJECTIVE

Minimally invasive (MI) synostectomy with postoperative helmet orthosis is increasingly used in the management of sagittal craniosynostosis. Although the MI technique reduces or eliminates the need for access to the lateral skull surface, the modified prone/sphinx position remains popular. The authors present their initial experience with supine positioning for MI sagittal synostectomy.

METHODS

The authors used supine positioning with the head turned laterally on a horseshoe head holder in 5 consecutive patients undergoing MI sagittal synostectomy.

RESULTS

Resection of the sagittal suture from the anterior to posterior fontanel was accomplished in all patients. Surgical time averaged 70 minutes. No patient required transfusion. The posttreatment cephalic index averaged 83%.

CONCLUSIONS

Initial experience with supine positioning for MI sagittal synostectomy suggests that the technique can be used as an alternative to the modified prone position, with the potential to reduce anesthetic risk in these patients.

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Markus J. Bookland, Vishad Sukul, and Patrick J. Connolly

Object

Ventriculitis related to external ventricular drain (EVD) placement is a significant source of morbidity in neurological intensive care patients. Current rates of EVD-related infections range from 2% to 45% in the literature. The authors sought to determine if a 2-octyl cyanoacrylate adhesive would result in lower infection rate than standard semiocclusive dressings.

Methods

The authors tracked ventriculitis rates via CSF cultures among 259 patients whose EVD sites were dressed with sterile semiocclusive dressings and underwent routine sterile dressing exchanges every 48 hours. They analyzed data obtained in an additional 113 patients whose EVD sites were dressed one time with a surgical adhesive, 2-octyl cyanoacrylate.

Results

Ventriculitis rate in patients with standard bioocclusive dressings and wound care was 15.1%, whereas that in patients with a 2-octyl cyanoacrylate dressing was 3.54% (p = 0.002). Staphylococcus genus accounted for 79.5% of instances of ventriculitis among patients with bioocclusive dressings and routine wound care, whereas it accounted for 25.0% of the instances of ventriculitis among patients with a liquid polymer sealant dressing. A 90% reduction in Staphylococcus infection completely accounts for the observed effect (p = 0.04).

Conclusions

The one-time application of 2-octyl cyanoacrylate to EVD wounds and exit sites provided superior protection against EVD-related ventriculitis compared to conventional EVD-site wound care. Likely this protection results from a barrier to the entry of gram-positive skin flora along the EVD exit tract. The results should be validated in a randomized trial.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, and Timothy F. Witham

Object.

Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column.

Methods.

Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 μL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 μL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL-1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed.

Results.

There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups.

Conclusions.

These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

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Markus J. Bookland, Edward S. Ahn, Petronella Stoltz, and Jonathan E. Martin

OBJECTIVE

The authors sought to evaluate the accuracy of a novel telehealth-compatible diagnostic software system for identifying craniosynostosis within a newborn (< 1 year old) population. Agreement with gold standard craniometric diagnostics was also assessed.

METHODS

Cranial shape classification software accuracy was compared to that of blinded craniofacial specialists using a data set of open-source (n = 40) and retrospectively collected newborn orthogonal top-down cranial images, with or without additional facial views (n = 339), culled between April 1, 2008, and February 29, 2020. Based on image quality, midface visibility, and visibility of the cranial equator, 351 image sets were deemed acceptable. Accuracy, sensitivity, and specificity were calculated for the software versus specialist classification. Software agreement with optical craniometrics was assessed with intraclass correlation coefficients.

RESULTS

The cranial shape classification software had an accuracy of 93.3% (95% CI 86.8–98.8; p < 0.001), with a sensitivity of 92.0% and specificity of 94.3%. Intraclass correlation coefficients for measurements of the cephalic index and cranial vault asymmetry index compared to optical measurements were 0.95 (95% CI 0.84–0.98; p < 0.001) and 0.67 (95% CI 0.24–0.88; p = 0.003), respectively.

CONCLUSIONS

These results support the use of image processing–based neonatal cranial deformity classification software for remote screening of nonsyndromic craniosynostosis in a newborn population and as a substitute for optical scanner– or CT-based craniometrics. This work has implications that suggest the potential for the development of software for a mobile platform that would allow for screening by telemedicine or in a primary care setting.

Open access

David S. Hersh, William A. Lambert, Markus J. Bookland, and Jonathan E. Martin

Surgical options for metopic craniosynostosis include the traditional open approach or a minimally invasive approach that typically involves an endoscopy-assisted strip craniectomy. The minimally invasive approach has been associated with less blood loss and operative time, a lower transfusion rate, and a shorter length of stay. Additionally, it is more cost-effective than open reconstruction, despite the need for a postoperative cranial orthosis and multiple follow-up visits. The authors describe a variation of the minimally invasive approach using a lighted retractor to perform a strip craniectomy of the metopic suture in a 2-month-old patient with metopic craniosynostosis.

The video can be found here: https://vimeo.com/511237503.

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Carlos A. Bagley, Jonathan A. Pindrik, Markus J. Bookland, Joaquin Q. Camara-Quintana, and Benjamin S. Carson

Object

Achondroplasia is the most common hereditary form of dwarfism, and is characterized by short stature, macrocephaly, and a myriad of skeletal abnormalities. In the pediatric population, stenosis and compression at the level of the cervicomedullary junction commonly occurs. The goal in this study was to assess the outcomes in children with achondroplasia who underwent cervicomedullary decompression.

Methods

Forty-three pediatric patients with heterozygous achondroplasia and foramen magnum stenosis underwent 45 cervicomedullary decompressions at the authors’ institution over an 11-year period. After surgical decompression, complete resolution or partial improvement in the preoperative symptoms was observed in all patients. There were no deaths in the treated patients. The surgical morbidity rate was low and usually consisted of a cerebrospinal fluid (CSF) leak in patients in whom the dura mater had been opened (either intentionally or accidentally). This problem was successfully managed in all cases with local measures (wound oversewing) or CSF diversion.

Conclusions

In this review the authors demonstrate that decompression of the cervicomedullary junction in the setting of achondroplasia may be accomplished safely with significant clinical benefit and minimal morbidity.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, Jean-Paul Wolinsky, and Timothy F. Witham

Object

Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases.

Methods

After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animal's death.

Results

Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose.

Conclusions

These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.