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Gregory A. Helm, Jonas M. Sheehan, Jason P. Sheehan, John A. Jane Jr., Charles G. diPierro, Nathan E. Simmons, George T. Gillies, David F. Kallmes and Thomas M. Sweeney

✓ Autologous bone grafts are currently considered “gold standard” material for achieving long-term spinal arthrodesis. The present study was performed to determine whether demineralized bone matrix (DBM), type I collagen gels, or bone morphogenetic protein-2 (BMP-2) can improve autologous bone spinal fusions. Using a unilateral decompression—contralateral fusion technique in dogs, each of these materials was added to an autologous bone graft. Volumetric analysis, histological analysis, and biomechanical testing were performed to assess the effectiveness of each material. The DBM had an inhibitory effect on solid bone fusion of the spine, whereas the type I collagen gels improved the bony interface between the graft and the host spine. The BMP-2 strongly enhanced the amount of bone deposition at the fusion site and increased the number of intervertebral levels that were solidly fused. This study strongly supports the use of BMP-2 as an additive to autologous bone grafts in spine stabilization.

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Clival encephalocele

Case illustration

George J. Kaptain, David A. Vincent, Jason P. Sheehan and Edward R. Laws Jr.

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Jonas M. Sheehan, Mary L. Vance, Jason P. Sheehan, Dilantha B. Ellegala and Edward R. Laws Jr.

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.

Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.

Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.

Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

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George J. Kaptain, Jason P. Sheehan and Neal F. Kassell

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Intramedullary spinal cysticercosis

Case report and review of the literature

Jason P. Sheehan, Jonas Sheehan, M. Beatriz Lopes and John A. Jane Sr.

Cysticercosis is the most common parasitic infection of the central nervous system. It infrequently affects the spine, but when it does, it can present with symptoms similar to other more common spinal diseases. The authors present a case of isolated intramedullary cysticercosis of the cervical spine and review the literature.

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Jason P. Sheehan, Gregory A. Helm, Jonas M. Sheehan and John A. Jane Sr.

Lumbar spinal stenosis can be effectively treated by performing an extensive ipsilateral spinal decompression, including a partial pediculotomy, and contralateral posterior bone fusion. Infrequently, complications can arise following radical decompression to alleviate symptoms of stenosis, and one such complication is a pedicle fracture. Three reports of pedicle fractures following extensive spinal decompression and contralateral posterior fusion are detailed. This complication is emphasized, and interventions are discussed.

Three patients presented with symptoms attributable to lumbar stenosis; they were initially treated with an ipsilateral decompression, achieved in part, through a partial pediculotomy followed by contralateral autologous bone fusion. Initially, all three patients improved postoperatively; however, they later developed neurological symptoms ipsilateral to the side of spinal decompression. Computerized tomography scanning demonstrated pedicle fractures on the decompressed side. This complication has not yet been reported in association with decompression and fusion for lumbar stenosis.

Two of the patients developed leg pain necessitating reoperation whereas the third experienced only mild transient symptoms. The fractured pedicle was removed in one patient; laminar and spinous process fusion was performed again. Another patient underwent a total laminectomy, removal of the fractured pedicle, and bilateral transverse process fusion. Reoperation yielded satisfactory outcomes. The third patient's symptoms resolved without intervention.

Pedicle fractures are a potential complication of extensive lumbar decompression and contralateral posterior fusion. Loading forces from the facets or transverse processes are possibly the cause of such fractures. Removal of the fractured pedicle, additional decompression, and enhanced bone fusion are recommended when the symptoms warrant surgical intervention.

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Jason P. Sheehan, Jonas M. Sheehan, M. Beatriz Lopes and John A. Jane Sr.

✓ Diastematomyelia is a rare entity in which some portion of the spinal cord is split into two by a midline septum. Most cases occur in childhood, but some develop in adulthood. A variety of concurrent spinal anomalies may be found in patients with diastematomyelia.

The authors describe a 38-year-old right-handed woman who presented with a 7-month history of lower-extremity pain and weakness on the right side. She denied recent trauma or illness. Sensorimotor deficits, hyperreflexia, and a positive Babinski reflex in the right lower extremity were demonstrated on examination.

Neuroimaging revealed diastematomyelia extending from T-1 to T-3, an expanded right hemicord from T-2 to T-4, and a C6–7 syrinx. The patient underwent T1–3 total laminectomies, resection of the septum, untethering of the cord, and excision of the hemicord lesion. The hemicord mass was determined to be an intramedullary epidermoid cyst; on microscopic evaluation the diastematomyelia cleft was shown to contain fibroadipose connective tissue with nerve twigs and ganglion cells. Postoperatively, the right lower-extremity pain, weakness, and sensory deficits improved.

Diastematomyelia can present after a long, relatively asymptomatic period and should be kept in the differential diagnosis for radiculopathy, myelopathy, tethered cord syndrome, or cauda equina syndrome. Numerous spinal lesions can be found in conjunction with diastematomyelia. To the authors' knowledge, this is the first case in which a thoracic epidermoid cyst and cervical syrinx occurred concurrently with an upper thoracic diastematomyelia. Thorough neuraxis radiographic evaluation and surgical treatment are usually indicated.

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Jason P. Sheehan, Ming-Hsi Sun, Douglas Kondziolka, John Flickinger and L. Dade Lunsford

Object. Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non—small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival.

Methods. A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival.

The overall median patient survival time was 15 months (range 1–116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time.

Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis.

Conclusions. Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.

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Jason P. Sheehan, Douglas Kondziolka, John Flickinger and L. Dade Lunsford

Object. Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas.

Methods. A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm.

Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size.

Conclusions. Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

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Jason P. Sheehan, Jonas M. Sheehan, Howard Seeherman, Mark Quigg and Gregory A. Helm

Object. The goal of this study was to evaluate the safety and efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in cranial applications.

Methods. Critical-sized calvarial defects were created bilaterally in four rhesus monkeys, and bilateral rectangular bone flaps were created in six others. Control and rhBMP-2—treated sides were randomly chosen for each animal, and an absorbable collagen sponge was used to deliver the growth factor. Over a 6-month period postoperatively, the animals were serially evaluated for bone healing and adverse BMP-related consequences by using the following methods: computerized tomography (CT) scanning, magnetic resonance (MR) imaging, electroencephalography, histological investigations, and cerebrospinal fluid (CSF) analysis.

The critical-sized defects for the rhBMP-2—treated and control sides attained 71 ± 12% and 28 ± 11% closure, respectively (four animals; p = 0.04). The CT scans demonstrated that the bone flaps treated with rhBMP-2 had complete osteointegration in five of six animals, whereas scans of the untreated bone flaps demonstrated uniformly poor osteointegration with the intact skull. Histological analysis confirmed well-formed bridges of bone on the rhBMP-2—treated sides. No epileptogenic activity was detected in any of the animals, and MR imaging revealed no evidence of adverse effects on the brain parenchyma. Meningitic irritation was not found on postoperative CSF sample analysis.

Conclusions. Treatment of bone flaps and critical-sized cranial defects with rhBMP-2 leads to improved bone formation and osteointegration in nonhuman primates. Initial evaluation of rhBMP-2 appears to indicate a good safety profile for use in cranial procedures in primates.