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  • Author or Editor: David F. Kallmes x
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Huy M. Do, Mary E. Jensen, William F. Marx and David F. Kallmes

The authors report the clinical symptoms and response to therapy of a series of patients who presented with subacute or chronic back pain due to vertebral osteonecrosis (Kümmell's spondylitis) and who underwent percutaneous vertebroplasty.

The authors performed a retrospective chart review of a series of 95 patients in whom 149 painful, nonneoplastic compression fractures were demonstrated and who were treated with percutaneous transpediculate polymethylmethacrylate (PMMA) vertebroplasty. In six of these patients there was evidence of vertebral osteonecrosis, as evidenced by the presence of an intravertebral vacuum cleft on radiography or by intravertebral fluid on magnetic resonance (MR) imaging. Clinical and radiological findings on presentation were noted. Technical aspects of the vertebroplasty technique were compiled. Response to therapy, defined as qualitative change in pain severity and change in level of activity, was noted immediately following the procedure and at various periods on follow-up reviews.

One man and five women, who ranged in age from 72 to 90 years (mean 81 years), were treated. Each patient had one compression fracture. The fractures were at T-11 (one patient), L-1 (two patients), L-3 (two patients), and L-4 (one patient). The pain pattern was described as severe and localized to the affected vertebra, and sometimes radiated along either flank. Pain duration ranged from 2 to 12 weeks, and the pain was refractory to conservative therapy that consisted of bedrest, analgesics, and external bracing. At the time of treatment, all patients were bedridden because of severe back pain. In all patients either plain radiographic or computerized tomography evidence of intravertebral vacuum cleft or MR imaging evidence of vertebral fluid collection consistent with avascular necrosis of the vertebral body was demonstrated. Four patients underwent bilateral transpediculate vertebroplasty, and two patients underwent unilateral transpediculate vertebroplasty. The fracture cavities were specifically targeted for PMMA injection. Additional fortification of the osteoporotic vertebral body trabeculae was also performed when feasible. "Cavitygrams" or intraosseous venograms with gentle contrast injection were obtained prior to application of cement mixture. In all patients subjective improvement in pain and increased mobility were demonstrated posttreatment. The follow-up period ranged from 4 to 24 hours after treatment. Two patients made additional office visits at 1 and 3 months, respectively.

Patients presenting with vertebral osteonecrosis (Kümmell's spondylitis) often suffer from local paraspinous or referred pain. When performing vertebroplasty on these patients, confirmation of entry into the fracture cavities with contrast-enhanced "cavitygrams" should be performed prior to injection of PMMA cement. The response to vertebroplasty with regard to amelioration of pain and improved mobility is encouraging.

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Ross C. Puffer, David J. Daniels, David F. Kallmes, Harry J. Cloft and Giuseppe Lanzino

Object

The authors conducted a study to review their experience with tentorial dural arteriovenous fistulas (DAVFs) treated with transarterial endovascular embolization in which Onyx was used.

Methods

The authors reviewed prospectively collected data in 9 patients with tentorial DAVFs treated with Onyx embolization between 2008 and 2011. Information reviewed included clinical presentation, angiographic features, treatment, and clinical and radiologically documented outcome. Clinical follow-up was available in every patient. Radiological follow-up studies were available in 8 of 9 patients (mean follow-up 4.6 months).

Results

Six of 9 patients had complete angiographic obliteration (in 5 this was confirmed by a follow-up angiogram obtained 3–6 months later), and 2 patients had near-complete obliteration (faint filling of the venous drainage in the late venous phase). One patient had partial obliteration and required surgical disconnection. In all patients with complete obliteration, transarterial embolization was performed through the posterior branch of the middle meningeal artery. There were no procedural complications, and no morbidity or mortality resulted from Onyx embolization.

Conclusions

Transarterial Onyx embolization is a valid, effective, and safe alternative to surgical disconnection in many patients with tentorial DAVFs. The presence of an adequate posterior branch of the middle meningeal artery is critical to achieve a microcatheter position distal enough to increase the likelihood of complete obliteration.

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Tord D. Alden, Gerald R. Hankins, Elisa J. Beres, David F. Kallmes and Gregory A. Helm

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type-5 adenovirus with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with a universal promoter and ß-galactosidase (ß-gal) gene (Ad-ß-gal) was used as a control. Seven and one-half microliters of virus was injected percutaneously and paraspinally at the lumbosacral junction in three groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad-ß-gal on the left, and 3) Ad-ß-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12 weeks, the animals were killed for histological inspection. Ectopic bone formation was seen both on three-dimensional CT reconstruction and histologically in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. This study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.

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Ioannis Loumiotis, Robert D. Brown Jr., Roanna Vine, Harry J. Cloft, David F. Kallmes and Giuseppe Lanzino

Object

The management of incidental small unruptured intracranial aneurysms (UIAs) is controversial and many factors need to be considered in the decision-making process. The authors describe a large consecutive series of patients harboring small incidental intracranial aneurysms. Treatment strategy, natural history, complications, and short-term outcomes are presented.

Methods

Between January 2008 and May 2011, the authors prospectively evaluated 212 patients with 272 small (< 10-mm) incidental aneurysms. Treatment recommendations (observation, endovascular treatment, or surgery), complications of treatment, and short-term outcomes were assessed.

Results

Recommended treatment consisted of observation in 125 patients, endovascular embolization in 64, and surgery in 18. Six patients were excluded from further analysis because they underwent treatment elsewhere. In the observation group, at a mean follow-up of 16.7 months, only 1 patient was moved to the embolization group. Seven (6%) of the 125 patients in the observation group died of causes unrelated to aneurysm. Sixty-five patients underwent 69 embolization procedures. The periprocedural permanent morbidity and mortality rates in patients undergoing endovascular treatment were 1.5% and 1.5%, respectively (overall morbidity and mortality rate 3.0%). In the surgery group no periprocedural complications were observed, although 1 patient did not return to her previous occupation. No aneurysmal rupture was documented in any of the 3 treatment groups during the follow-up period.

Conclusions

A cautious and individualized approach to incidental UIAs is of utmost importance for formulation of a safe and effective treatment algorithm. Invasive treatment (either endovascular or surgery) can be considered in selected younger patients, certain “higher-risk” locations, expanding aneurysms, patients with a family history of aneurysmal hemorrhage, and in those who cannot live their lives knowing that they harbor the UIA. Although the complication rate of invasive treatment is very low, it is not negligible. The study confirms that small incidental UIAs deemed to be not in need of treatment have a very benign short-term natural history, which makes observation a reasonable approach in selected patients.

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Gregory A. Helm, Jin Zhong Li, Tord D. Alden, Sarah A. Hudson, Elisa J. Beres, Mary Cunningham, Mark M. Mikkelsen, Debra D. Pittman, Kelvin M. Kerns and David F. Kallmes

Object

Bone morphogenetic proteins (BMPs) are involved in the growth and development of many tissues, but it is their role in skeletal development and their unique ability to induce ectopic and orthotopic osteogenesis that has attracted the greatest interest. Expression of the BMP-13 gene has been shown to be predominantly localized to hypertrophic chondrocytes in regions of endochondral bone formation during development, as well as in mature articular cartilage in the adult. In addition, the application of BMP-13 on a collagen carrier induces neotendon/ligament formation when delivered subcutaneously or intramuscularly in rodents. The aim of the present study was to determine the histological and ultrastructural changes that occur after the intramuscular injection of a first-generation BMP-13 adenoviral vector.

Methods

Athymic nude rats were injected with 3.75 × 1010 plaque-forming unit adenovirus (Ad)-BMP-13 or Ad-β-galactosidase in the thigh musculature, and the regions examined using light and electron microscopy at various time points between 2 and 100 days postinjection. As early as 2 days after injection of Ad-BMP-13, progenitor cells were observed infiltrating between the transduced muscle fibers. These cells subsequently proliferated, differentiated, and secreted large amounts of collagenous extracellular matrix. By 100 days postinjection, the induced tissue had the histological and ultrastructural appearance of neotendon/ligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the induced tissue. A short-term bromodeoxyuri-dine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection.

Conclusions

The results of this study suggest that in the future the use of the BMP-13 gene may have therapeutic utility for the healing of tendon and ligament tears and avulsion injuries.