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Benjamin S. Carson, Carol S. James, Craig A. VanderKolk and Michael Guarnieri

Lambdoid craniosynostosis has been regarded as one of the least common categories of premature fusion of the cranial sutures, yet reports have suggested the incidence may be increasing. To guide treatment decisions, the authors describe a set of rules based on radiographic indicators and clinical assessment in the child. Experience suggests that children can have abnormal-appearing cranial sutures with normal neurological status and normal-appearing sutures with neurological deficits or marked cerebral compression. Early evaluation and follow-up treatment is essential for children with suspected craniosynostosis.

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John Aryanpur, Orest Hurko, Clair Francomano, Henry Wang and Benjamin Carson

✓ The congenital osseous abnormalities associated with achondroplasia include stenosis of the foramen magnum and the upper cervical spinal canal. In the pediatric achondroplastic patient, such stenosis may lead to cervicomedullary compression with serious sequelae, including paresis, hypertonia, delayed motor milestones, and respiratory compromise. Using a standardized protocol the authors have treated 15 young achondroplastic patients with documented cervicomedullary compression by craniocervical decompression and duroplasty. Following this procedure, significant improvement in presenting neurological or respiratory complaints was noted in all patients. The mortality rate in this series was zero. The major cause of morbidity associated with this procedure was perioperative cerebrospinal fluid (CSF) leakage from the surgical wound, presumably related to coexisting abnormalities of CSF dynamics. This problem was successfully managed by temporary or, when necessary, permanent CSF diversion procedures. It is concluded that craniocervical decompression is an effective and safe treatment for young achondroplastic patients with cervicomedullary compression.

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Jeffery Meadows, Michael Kraut, Michael Guarnieri, Raymond I. Haroun and Benjamin S. Carson

Object. Chiari Type I malformation (CMI) is a congenital disorder recognized by caudal displacement of the cerebellar tonsils through the foramen magnum and into the cervical canal. Frequently, associated findings include abnormalities of nearby bony and neural elements as well as syringomyelia. Cerebellar tonsillar ectopia is generally considered pathological when greater than 5 mm below the foramen magnum. However, asymptomatic tonsillar ectopia is an increasingly recognized phenomenon, the significance of which is poorly understood.

Methods. The authors retrospectively reviewed the records of all brain magnetic resonance (MR) images obtained at our hospital over a 43-month period in an attempt to ascertain the relative prevalence and MR imaging characteristics of asymptomatic CMIs. Of 22,591 patients who underwent MR imaging of the head and cervical spine, 175 were found to have CMIs with tonsillar herniation extending more than 5 mm below the foramen magnum. Of these, 25 (14%) were found to be clinically asymptomatic. The average extent of ectopia in this population was 11.4 ± 4.86 mm, and was significantly associated with a smaller cisterna magna. Syringomyelia and osseous anomalies were found in only one asymptomatic patient.

Conclusions. The authors suggest that the isolated finding of tonsillar herniation is of limited prognostic utility and must be considered in the context of all available clinical and radiographic data. Strategies for treating patients with asymptomatic CMIs are discussed.

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Andleeb Khan, George I. Jallo, Ya J. Liu, Benjamin S. Carson Sr. and Michael Guarnieri

Object. The aim of this study was to investigate the optimal delivery rates of chemotherapy for the treatment of central nervous system tumors and to determine whether local delivery can lower toxicity profiles and increase target concentrations of chemotherapy.

Methods. The authors used two brain tumor models in rats. Slow (1 µl/hour) and fast (10 µl/hour) pumps were used to deliver chemotherapy—carboplatin, doxorubicin, and a high-molecular-weight transferrin-doxorubicin conjugate to the brains of normal rats and rats previously injected with F98 or 9L rat brain tumor cells. Brains were cut in 1-mm sections rostral and caudal from the infusion point. Slices were analyzed for doxorubicin and platinum by fluorescence and atomic absorption, respectively.

In the normal tissues, the volume of drug distribution is generally greater at the faster flow rate. In abnormal tissues, distribution is similar at slow and fast infusion rates for low-molecular-weight drugs and greater at slow rates for a high-molecular-weight targeted toxin.

Conclusions. After local administration the distribution of chemotherapy appears to be significantly influenced by tumor metabolism. Additional studies are needed to determine the optimal delivery rates for the interaction of the drug with the targeted tumor.

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James Lee, George I. Jallo, Michael Guarnieri, Benjamin S. Carson Sr. and Margret B. Penno

Object

Survival rates for high-grade brainstem tumors are approximately 10% and optimal therapy has yet to be determined. Development of a satisfactory brainstem tumor model is necessary for testing new therapeutic paradigms that may prolong survival. The authors report the technique, functional progression, radiological appearance, and histopathological features of a novel brainstem tumor model in rats.

Methods

Thirty female Fischer 344 rats were randomized (10 animals/group) to receive an injection of either 3 μl of 9L gliosarcoma cells (100,000 cells), 3 μl of F98 glioma cells (100,000 cells), or 3 μl of medium (Dulbecco modified Eagle medium) into the pontine tegmentum of the brainstem. Using a cannulated guide screw system implanted in the skull of the animal, rats in each group were injected at coordinates 1.4 mm to the right of the sagittal and 1 mm anterior to the lambdoid sutures, at a depth of 7 mm from the dura mater. The angle of the syringe during injection was anteflexed 5° from the vertical. Postoperatively, the rats were evaluated for neurological deficits by using an automated rotarod test. High-resolution [18F]fluorodeoxyglucose–positron emission tomography (FDG-PET) fused with computerized tomography (CT) scans were acquired pre- and postoperatively through the onset of hemiparesis and correlated accordingly. Kaplan–Meier curves were generated for survival and disease progression, and brains were processed postmortem for histopathological investigation.

The 9L and F98 tumor cells grew in 95% of the animals in which they were injected and resulted in a statistically significant mean onset of hemiparesis of 16.5 ± 0.56 days (p = 0.001, log-rank test), compared with animals in the control group, which had no neurological deficits by Day 45. The FDG-PET studies coregistered with CT scans demonstrated space-occupying brainstem lesions, and this finding was confirmed by histological studies. Animals in the control group showed no functional, radiological, or pathological signs of tumor.

Conclusions

Progression to hemiparesis was consistent in all tumor-injected animals, with predictable onset of symptoms occurring approximately 17 days postsurgery. The histopathological and radiological characteristics of the 9L and F98 brainstem tumors were comparable to those of aggressive primary human brainstem tumors. Establishment of this animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of these lesions.

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Matthias Ringkamp, Matthew Wooten, Benjamin S. Carson Sr., Michael Lim, Timothy Hartke and Michael Guarnieri

OBJECT

Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model.

METHODS

This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion.

RESULTS

Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement.

CONCLUSIONS

Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

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Benjamin S. Carson, Jon D. Weingart, Michael Guarnieri and Paul G. Fisher

✓ This 9-year-old boy with a history of behavioral problems and worsening psychosis responded initially to treatment with haloperidol. However, a magnetic resonance image obtained as part of his psychiatric evaluation revealed an anterior third ventricle tumor and mild-to-moderate hydrocephalus. The resected tumor was found on pathological examination to be a choroid plexus papilloma. The patient had an uneventful postoperative course and remained free of psychosis or mood disorder at 1-year follow-up examination.

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Yukio Ikeda, Benjamin S. Carson, Jeremy A. Lauer and Donlin M. Long

✓ To determine if dexamethasone administered by osmotic pump directly to brain tumors would control peritumoral edema and at the same time suppress tumor growth and prolong survival, the authors studied experimental brain tumors produced in 102 rabbits by implanting VX2 carcinoma cells. Of these, 58 animals were separated into three treatment groups: Group 1 included 15 untreated rabbits; Group 2 included 18 rabbits treated with systemic dexamethasone (4 mg/kg/day); and Group 3 included 25 rabbits treated with local dexamethasone (0.24 mg/day) delivered by osmotic pump. Systemic or local dexamethasone was administered from Day 3 or Day 7 after tumor implantation, and animals were sacrificed on Day 13. A survival study was performed with 44 rabbits separated into the same treatment groups, beginning drug delivery on Day 7. Brain water content in the white matter of sacrificed animals was measured by the specific gravity method. The length and width of the brain tumors in all animals were measured and the tumor volume estimated. Findings showed that systemic and local dexamethasone administered from Day 3 or Day 7 was associated with a significant (5% level) inhibition of tumor volume as well as a mean reduction of brain edema in most tested sites. Systemic and local dexamethasone therapy also resulted in a significant (5% level) increase in survival time relative to the untreated group. These short-term results suggest that locally delivered dexamethasone may constitute a clinically important therapeutic modality.