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Dennis G. Vollmer and Nathan E. Simmons

The transthoracic approach to herniated thoracic discs is an important procedure in the management of these uncommonly encountered lesions. Whereas posterior and posterolateral microsurgical approaches and thoracoscopic procedures have been widely advocated in the recent neurosurgical literature, the transthoracic operation continues to offer significant advantages in appropriately selected cases. The authors discuss the preoperative considerations, relevant anatomical structures, and surgical technique.

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Gregory A. Helm, Nathan E. Simmons, Charles G. diPierro and Neal F. Kassell

✓ Several types of adjustable clamp have been widely utilized to gradually occlude the carotid artery for the treatment of various intracranial vascular lesions. A fairly large number of patients, many of whom have not been adequately followed, have these clamps still in place. The authors report two patients, initially treated with a Crutchfield clamp for an intracranial aneurysm, in whom carotid artery system revascularization occurred through the clamp many years later, leading to continued filling of the aneurysm. Recommendations are given on monitoring patients with Crutchfield clamps in order to minimize long-term complications.

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George J. Kaptain, Nathan E. Simmons, Robert E. Replogle and Louis Pobereskin

Object. The authors undertook a study to explore the predisposing risk factors, frequency of occurrence, and clinical implications of kyphosis following laminectomy for cervical spondylotic myelopathy (CSM).

Methods. Preoperative radiological studies were available in 46 patients with CSM who had undergone laminectomy. Records were reviewed to obtain demographic data and operative reports. Preoperative radiographs were assessed to determine spinal alignment. In a follow-up interview the authors established clinical outcome and patient satisfaction. Postoperative cervical alignment and mobility was also determined by assessing lateral neutral, flexion, and extension x-ray films.

Preoperatively, the cervical spine was shown to be kyphotic in four (9%) of 46, straight in 20 (43%) of 46, and lordotic in 22 (48%) of 46 patients. Nine (21%) of 42 patients with either straight or lordotic alignment demonstrated in the preoperative period developed kyphosis after surgery. Kyphosis developed in six (30%) of 20 patients in whom straight spinal alignment was demonstrated preoperatively and in only three (14%) of 22 patients in whom lordosis was found preoperatively. Clinically, 13 (29%) of 45 patients improved and 19 (42%) of 45 remained unchanged after an average 4-year follow-up period; 36 (80%) patients believed that their surgery was successful (one patient, who was mentally retarded, could not respond to the follow-up questionnaire). Spinal alignment was not predictive of outcome; cervical mobility as demonstrated on flexion and extension, however, correlated with improved functional performance (p = 0.005).

Conclusions. Kyphosis may develop in up to 21% of patients who have undergone laminectomy for CSM. Progression of the deformity appears to be more than twice as likely if preoperative radiological studies demonstrate a straight spine. In this study, clinical outcome did not correlate with either pre- or postoperative sagittal alignment.

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W. Jeffrey Elias, Nathan E. Simmons, George J. Kaptain, James B. Chadduck and Richard Whitehill

Object. The authors reviewed their series of patients to quantify clinical and radiographic complications in those who underwent a posterior lumbar interbody fusion (PLIF) procedure in which a threaded interbody cage (TIC) was implanted.

Methods. Sixty-seven patients underwent a posterior lumbar interbody fusion procedure in which a TIC was used. The authors excluded patients who underwent procedures in which other instrumentation was used or a nondorsal approach was performed. Fifteen percent of the cases (10 patients) were complicated by laceration of the dura. In three cases, bilateral implantation could not be performed. The average blood loss was 670 ml for all cases, and blood transfusion was required in 25% of the cases (17 patients). The rate of minor wound complication was 4.5% (three patients). One patient died. The average period of hospitalization was 4.25 days.

Twenty-eight patients (42%) experienced significant low-back pain 3 months postoperatively, and in 10 (15%) of these cases it persisted beyond 1 year. In 10 patients postoperative radiculopathy was demonstrated, and magnetic resonance imaging revealed epidural fibrosis in six patients, arachnoiditis in one, and a recurrent disc herniation in one. One patient incurred a permanent motor deficit with sexual dysfunction. Pseudarthrosis was suggested radiographically with evidence of motion on lateral flexion—extension radiographs (10 cases), lucencies around the implants (seven cases), and posterior migration of the cage (two cases).

Additional procedures (in 14 patients) consisted primarily of transverse process fusion with pedicle screw and plate augmentation for persistent back pain and radiographically demonstrated signs of spinal instability. In two patients with radiculopathy, migration of the TIC required that it be removed. Graft material that extruded from one implant necessitated its removal. In one patient scarectomy was performed.

Conclusions. Our high incidence of TIC-related complications in PLIF is inconsistent with that reported in previous studies.

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Nathan E. Simmons, Tord D. Alden, Michael O. Thorner and Edward R. Laws Jr.

Object. Transsphenoidal surgery remains the optimal treatment for Cushing disease, but the definitions of surgical cure and failure remain debatable. In this study the authors evaluated serum cortisol levels in patients before and after they underwent transsphenoidal surgery to elucidate the patterns of cortisol decrease and the optimal time and criteria for determining surgically induced remission.

Methods. Twenty-seven patients were evaluated throughout an 8-month period. Serum cortisol levels were obtained before surgery and at 6-hour intervals postoperatively. No exogenous steroid medications were administered until after cortisol sampling was discontinued, following diagnosis of remission.

Twenty-one (78%) of 27 cases were labeled initial surgically induced remissions. Twenty-two (81%) of 27 cases were deemed surgically induced remissions at follow-up examination. Following surgery, initial remissions and failures demonstrated divergent patterns of cortisol levels. No patient whose condition was deemed an initial surgically induced remission has experienced definitive relapse of disease since discharge. One patient whose condition was initially deemed a surgical failure, eventually was found to exhibit surgically induced remission without further intervention.

Conclusions. Given such findings, exogenous steroid medications do not appear to be required for patients until after the determination of remission. During the 1st postoperative day, there is a time period during which serum cortisol values significantly differ between the categories of surgically induced remissions and surgical failures. Surgically induced remissions were identified when postoperative values of cortisol were lower than preoperative midnight levels and when absolute values of cortisol were less than 10 µg/dl. In a small proportion of patients remission on a delayed basis may also be demonstrated. These data allow for a simple and rapid determination of postoperative remission in patients undergoing transsphenoidal surgery for Cushing disease.

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Neal F. Kassell, Gregory Helm, Nathan Simmons, C. Douglas Phillips and Wayne S. Cail

✓ Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 12 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Eight patients had marked angiographic reversal of the arterial narrowing following papaverine infusion, four of whom showed dramatic reversal of profound neurological deficits. Two patients deteriorated clinically 5 days after the initially successful papaverine infusions. In both, repeat angiography demonstrated severe recurrent vasospasm, which was partially reversed with a second intra-arterial papaverine treatment. Two patients developed focal neurological deficits during papaverine infusion, which resolved spontaneously over several hours after cessation of the intra-arterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than was spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over 1 hour seemed to be an adequate and safe dose to effect these angiographic and clinical improvements.

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Kimon Bekelis, Ann-Christine Duhaime, Symeon Missios, Clifford Belden and Nathan Simmons

In cadaveric studies and recently in one adult patient the occipital condyle has been studied as an option to allow bone purchase by fixation devices. In the current case the authors describe the use of occipital condyle screws in a child undergoing occipitocervical fixation. To the best of the authors' knowledge this case is the first reported instance of this technique in a pediatric patient.

This girl had a history of posterior fossa decompression for Chiari malformation Type I when she was 22 months of age. When she was 6 years old she presented with neck pain on flexion and extension of her head. Magnetic resonance imaging in flexion and extension revealed occipitocervical instability. She underwent an occiput to C-2 posterior arthrodesis with bilateral screw placement in the occipital condyles, C-2 lamina, and C-1 lateral masses. Postoperatively, she was neurologically intact. Computed tomography demonstrated a stable construct, and her cervical pain had resolved on follow-up.

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Kimon Bekelis, Joanna S. Kerley-Hamilton, Amy Teegarden, Craig R. Tomlinson, Rachael Kuintzle, Nathan Simmons, Robert J. Singer, David W. Roberts, Manolis Kellis and David A. Hendrix

OBJECTIVE

The molecular mechanisms behind cerebral aneurysm formation and rupture remain poorly understood. In the past decade, microRNAs (miRNAs) have been shown to be key regulators in a host of biological processes. They are noncoding RNA molecules, approximately 21 nucleotides long, that posttranscriptionally inhibit mRNAs by attenuating protein translation and promoting mRNA degradation. The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled.

METHODS

A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets.

RESULTS

Overall, 7 unruptured cerebral aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143–5p (fold change −11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms.

CONCLUSIONS

This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed.

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Camilo E. Fadul, Andrew L. Kominsky, Louise P. Meyer, Linda S. Kingman, William B. Kinlaw, C. Harker Rhodes, Clifford J. Eskey and Nathan E. Simmons

✓Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma.

One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone–secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy.

Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

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Charles G. diPierro, Gregory A. Helm, Christopher I. Shaffrey, James B. Chadduck, Scott L. Henson, Jacek M. Malik, Thomas A. Szabo, Nathan E. Simmons and John A. Jane

✓ A new surgical technique for the treatment of lumbar spinal stenosis features extensive unilateral decompression with undercutting of the spinous process and, to preserve stability, uses contralateral autologous bone fusion of the spinous processes, laminae, and facets. The operation was performed in 29 patients over a 19-month period ending in December of 1991. All individuals had been unresponsive to conservative treatment and presented with low-back pain in addition to signs and symptoms consistent with neurogenic claudication or radiculopathy. Nine had undergone previous lumbar decompressive surgery. The minimum and mean postoperative follow-up times were 2 and 2 1/2 years, respectively. The mean patient age was 64 years; only two patients were younger than 50 years of age.

Of the patients with neurogenic claudication, 69% reported complete pain relief at follow-up review. Of those with radicular symptoms, 41% had complete relief and 23% had mild residual pain that was rated 3 or less on a pain—functionality scale of 0 to 10. For the entire sample, this surgery decreased pain from 9.2 to 3.3 (p < 0.0001) on the scale. Sixty-nine percent of patients were satisfied with surgery. Low-back pain was significantly relieved in 62% of all patients (p < 0.0001). Low-back pain relief correlated negatively with number of levels decompressed (p < 0.05). To assess fusion, follow-up flexion/extension radiographs were obtained, and no motion was detected at the surgically treated levels in any patient.

The results suggest that this decompression procedure safely and successfully treats not only the radicular symptoms caused by lateral stenosis but also the neurogenic claudication symptoms associated with central stenosis. In addition, the procedure, by using contralateral autologous bone fusion along the laminae and spinous processes, can preserve stability without instrumentation.