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Alexander A. Khalessi, Bryan C. Oh and Michael Y. Wang

✓ In the following literature review the authors consider the available evidence for the medical management of patients with ankylosing spondylitis (AS), and they critically assess current treatment guidelines. Medical therapy for axial disease in AS emphasizes improvement in patients' pain and overall function. First-line treatments include individualized physical therapy and nonsteroidal antiinflammatory drugs (NSAIDs) in conjunction with gastroprotective therapy. After an adequate trial of therapy with two NSAIDs exceeding 3 months or limited by medication toxicity, the patient may undergo tumor necrosis factor–α blockade therapy. Response should occur within 6–12 weeks, and patients must undergo tuberculosis screening. Evidence does not currently support the use of disease modifying antirheumatic drugs, corticosteroids, or radiotherapy in AS.

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Dunbar Alcindor, Michael Y. Oh, Susan Baser, Cindy Angle, Boyle C. Cheng and Donald Whiting

The authors report the case of DYT1-positive primary generalized dystonia refractory to medical management that was successfully treated with continuous deep brain stimulation of the internal segment of the globus pallidus. Prior studies have shown that neuromusculoskeletal deficits can remain permanent if early surgical intervention is not undertaken. The authors report prolonged efficacy and safety over a 10-year period in a 28-year-old man.

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Predictors of survival in patients with prostate cancer and spinal metastasis

Presented at the 2009 Joint Spine Section Meeting 

Dan Michael Drzymalski, William K. Oh, Lillian Werner, Meredith M. Regan, Philip Kantoff and Sagun Tuli

Object

Prostate cancer is the second most common malignancy to cause death in men, with metastases to the spine being the most common site of metastatic burden. A retrospective observational study was performed to determine survival of patients in whom spinal metastasis from prostate cancer had been diagnosed.

Methods

The patient population was obtained from the Prostate Clinical Research Information System (CRIS) at the Dana-Farber Cancer Institute. Patients were observed over a period of 19 years, between June 1990 and April 2009. Clinical covariates were studied in their relationship to overall survival, the primary outcome, by using the Kaplan-Meier method and Cox regression.

Results

Of a total of 9010 patients in the Prostate CRIS database, 333 were identified as having developed spinal metastases. The median overall survival after diagnosis of spinal metastasis was 24 months (95% CI 21–28 months). The estimated 1-year overall survival was 73% (95% CI 67%–77%). In 85% of patients, at least 1 additional site of metastasis was documented. Among 28 patients who had no additional sites of metastases, the median survival was 55.9 months, whereas an increasing burden of disease was associated with shorter survival (p = 0.0001). The association was observed regardless of whether the metastatic burden was characterized as the presence of additional (nonspinal) bone metastasis, the presence of additional nonbone metastasis, or as the number of concomitant metastatic sites (all p = 0.0001). In multivariate analysis, a higher prostate-specific antigen level at the diagnosis of spinal metastasis, a longer duration between the diagnosis of prostate cancer and spinal metastasis, and the presence of additional metastasis at the time of diagnosis of spinal metastasis (all p = 0.0001) were independently associated with a shorter overall survival.

Conclusions

The results of this study are important for oncologists, neurosurgeons, and primary care physicians who have patients with prostate cancer that metastasizes to the spine, because these results can be used to form a prognosis and guide the physician in making appropriate decisions regarding the patient's treatment. Future work should include building a predictive model that accurately determines survival in patients with metastatic disease, because this would guide the physician in devising the most appropriate treatment plan for each patient.

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Michael C. Oh and Manish K. Aghi

The authors' object in this paper was to review the definition, epidemiology, biology, resistance mechanisms, and treatment options for dopamine agonist–resistant prolactinomas (DARPs).

Prolactinomas are relatively unique among primary brain tumors in that medical treatment alone using dopamine agonists carries a high probability of disease control or even radiographic and endocrine remission, and thus has replaced surgery as the first line of therapy. Unfortunately, slightly less than 10% of patients with prolactinomas do not experience normalization of their prolactin levels in response to dopamine agonists, and harbor tumors that are resistant to dopamine agonist therapy. A literature review underscores that in male patients these DARPs are more likely to be invasive macroadenomas than dopamine agonist–responsive prolactinomas and that they are also more angiogenic, more proliferative, and more likely to exhibit cellular atypia. Estrogen receptor antagonists and temozolomide are the most commonly applied medical therapies in cases in which resection and radiosurgery have not induced remission of the hyperprolactinemia.

Dopamine agonist–resistant prolactinomas exhibit aggressive behavior and tend to be large, invasive, hyperangiogenic tumors with high mitotic indices, which makes their management via surgery, radiosurgery, or alternative medical therapies challenging, thus underscoring the need for novel medical therapies or treatment regimens that target these lesions.

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Mitchel Seruya, Albert K. Oh, Michael J. Boyajian, Jeffrey C. Posnick and Robert F. Keating

Object

Patients with delayed presentation of isolated sagittal synostosis (ISS) pose unique surgical challenges. Intracranial hypertension can be missed in the absence of overt findings. Here, an algorithm is presented for the elucidation of intracranial hypertension and approaches to surgical treatment during calvarial reconstruction.

Methods

Patients with delayed presentation (age > 15 months) of ISS between 1997 and 2009 were identified. Symptoms, signs, and radiological evidence of intracranial hypertension were noted. Intraoperative management included calvarial reconstruction in conjunction with ventriculostomy for intracranial pressure (ICP) monitoring and CSF drainage in the setting of suspected intracranial hypertension.

Results

Seventeen patients underwent calvarial reconstruction for delayed presentation of ISS. The mean surgical age was 40.5 months (16.2–82.9 months), and the average follow-up was 34.2 months (0.6–92.2 months). Eleven patients with subtle findings of intracranial hypertension underwent ICP monitoring during calvarial reconstruction. The mean opening ICP was 23.5 cm H2O (16.5–29.5 cm H2O), and the mean closing ICP was 7.0 cm H2O (3.5–17.0 cm H2O). Nine (81.8%) of 11 monitored patients demonstrated intracranial hypertension (ICP ≥ 20 cm H2O); the other 2 had borderline increased ICP. Perioperative morbidity was 5.9%, with 1 patient medically treated for transient, new-onset intracranial hypertension. The postoperative Whitaker category was I in 94.1% of patients, II in 5.9%, and III/IV in 0%. There were no reoperations or deaths.

Conclusions

In this consecutive series, 11 of 17 patients with delayed presentation of ISS underwent ICP monitoring during calvarial reconstruction as a result of subtle clinical findings of intracranial hypertension. Nine (81.8%) of 11 monitored patients demonstrated intracranial hypertension. Calvarial reshaping along with ICP monitoring and CSF drainage facilitated reconstruction and resulted in good outcomes and the resolution of intracranial hypertension.

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Matthew Z. Sun, Michael C. Oh, Michael Safaee, Gurvinder Kaur and Andrew T. Parsa

Avoidance of facial nerve injury is one of the major goals of vestibular schwannoma (VS) surgery because functional deficits of the facial nerve can lead to physical, cosmetic, and psychological consequences for patients. Clinically, facial nerve function is assessed using the House-Brackmann grading scale, which also allows physicians to track the progress of a patient's facial nerve recovery. Because the facial nerve is a peripheral nerve, it has the ability to regenerate, and the extent of its functional recovery depends largely on the location and nature of its injury. In this report, the authors first describe the facial nerve anatomy, the House-Brackmann grading system, and factors known to be predictors of postoperative facial nerve outcome. The mechanisms and pathophysiology of facial nerve injury during VS surgery are then discussed, as well as factors affecting facial nerve regeneration after surgery.

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Michael C. Oh, Eli T. Sayegh, Michael Safaee, Matthew Z. Sun, Gurvinder Kaur, Joseph M. Kim, Derick Aranda, Annette M. Molinaro, Nalin Gupta and Andrew T. Parsa

Object

Ependymoma is a common CNS tumor in children, with spinal cord ependymomas making up 13.1% of all ependymomas in this age group. The clinical features that affect prognosis in pediatric spinal cord ependymomas are not well understood. A comprehensive literature review was performed to determine whether a tumor location along the spinal cord is prognostically significant in children undergoing surgery for spinal cord ependymomas.

Methods

A PubMed search was performed to identify all papers that contained data on patients with spinal cord ependymomas. Only pediatric patients (age < 18 years) who underwent resection with a clearly reported tumor location were included in the analysis. Myxopapillary tumors were excluded from study. Tumor location was subdivided into 6 regions: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus medullaris. Kaplan-Meier survival and Cox regression analyses were performed to determine the effects of tumor location on progression-free survival (PFS) and overall survival (OS).

Results

Fifty-eight patients who underwent resection of spinal cord ependymomas were identified. Ependymomas were located all along the spinal cord but occurred with the highest frequency in the cervical region (29.3%). Progression-free survival was significantly better in patients with tumors arising in the upper portion of the spinal cord (p = 0.031), which remained significant in the multivariate Cox regression analysis (p < 0.05). Moreover, OS was significantly better in patients with upper spinal cord ependymomas than in those harboring ependymomas in the lower spinal cord (p = 0.048).

Conclusions

Although more common in adults, spinal ependymomas can occur anywhere along the spinal cord in the pediatric population; however, tumors occurring in the lower half of the spinal cord carry a worse prognosis with shorter PFS and OS. By comparison, ependymomas in the upper spinal cord recur later and less frequently, with little or no mortality in this patient group.

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Michael C. Oh, Joseph M. Kim, Gurvinder Kaur, Michael Safaee, Matthew Z. Sun, Anahat Singh, Derick Aranda, Annette M. Molinaro and Andrew T. Parsa

Object

Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information.

Methods

A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS).

Results

A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131).

Conclusions

Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor location along the spinal axis is an important prognostic factor.

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Donald M. Whiting, Nestor D. Tomycz, Julian Bailes, Lilian de Jonge, Virgile Lecoultre, Bryan Wilent, Dunbar Alcindor, E. Richard Prostko, Boyle C. Cheng, Cynthia Angle, Diane Cantella, Benjamin B. Whiting, J. Scott Mizes, Kirk W. Finnis, Eric Ravussin and Michael Y. Oh

Object

Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans.

Methods

Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, underwent bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism.

Results

No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber.

Conclusions

Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy.