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Martin Pham, Bradley A. Gross, Bernard R. Bendok, Issam A. Awad and H. Hunt Batjer

The use of radiosurgery for angiographically occult vascular malformations (AOVMs) is a controversial treatment option for those that are surgically inaccessible or located in eloquent brain. To determine the efficacy of this treatment, the authors reviewed the literature reporting hemorrhage rates, seizure control, and radiation-induced morbidity. They found overall hemorrhage rates of 2–6.4%, overall postradiosurgery hemorrhage rates of 1.6–8%, and stratified postradiosurgery hemorrhage rates of 7.3–22.4% in the period immediately to 2 years after treatment; these latter rates declined to 0.8–5.2% > 2 years after treatment. Of 291 patients presenting with seizure across 16 studies, 89 (31%) attained a seizure-free status and 102 (35%) had a reduction in seizure frequency after radiosurgery. Overall radiation-induced morbidity ranged from 2.5 to 59%, with higher complication rates in patients with brainstem lesion locations. Researchers applying mean radiation doses of 15–16.2 Gy to the tumor margin saw both low radiationinduced complication rates (0–9.1%) and adequate hemorrhage control (0.8–5.2% > 2 years after treatment), whereas mean doses ≥ 16.5 Gy were associated with higher total radiation-induced morbidity rates (> 17%). Although the use of stereotactic radiosurgery remains controversial, patients with AOVMs located in surgically inaccessible areas of the brain may benefit from such treatment.

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Shanmukha Srinivas, Arvin R. Wali and Martin H. Pham

OBJECTIVE

Riluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.

METHODS

The PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.

RESULTS

A total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.

CONCLUSIONS

SCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

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Martin H. Pham, Andre M. Jakoi and Patrick C. Hsieh

Lumbar interbody fusion is an important technique for the treatment of degenerative disc disease and degenerative scoliosis. The oblique lumbar interbody fusion (OLIF) establishes a minimally invasive retroperitoneal exposure anterior to the psoas and lumbar plexus. In this video case presentation, the authors demonstrate the techniques of the OLIF at L5–S1 performed on a 69-year-old female with degenerative scoliosis as one component of an overall strategy for her deformity correction.

The video can be found here: https://youtu.be/VMUYWKLAl0g.

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Martin H. Pham, Andre M. Jakoi and Patrick C. Hsieh

Adult deformity patients often require fixation to the sacrum and pelvis for construct stability and improved fusion rates. Although certain sacropelvic fixation techniques can be challenging, the availability of intraoperative navigation has made many of these techniques more feasible. In this video case presentation, the authors demonstrate the techniques of S-1 bicortical screw and S-2-alar-iliac screw fixation under intraoperative navigation in a 67-year-old female. This instrumentation placement was part of an overall T-10–pelvis construct for the correction of adult spinal deformity.

The video can be found here: https://youtu.be/3HZo-80jQr8.

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Shuhan He, Martin H. Pham, Matthew Pease, Gabriel Zada, Steven L. Giannotta, Kai Wang and William J. Mack

Object

A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas.

Methods

The authors performed a review of the current literature to identify the epigenetic modifications associated with the formation and/or progression of meningiomas.

Results

Several epigenomic alterations, mainly pertaining to DNA methylation, have been associated with meningiomas. Hypermethylation of TIMP3 inactivates its tumor suppression activity while CDKN2 (p14[ARF]) and TP73 gene hypermethylation and HIST1H1c upregulation interact with the p53 regulation of cell cycle control. Other factors such as HOX, IGF, WNK2, and TGF-β epigenetic modifications allow either upregulation or downregulation of critical pathways for meningioma development, progression, and recurrence.

Conclusions

Genome-wide methylation profiling demonstrated that global hypomethylation correlates with tumor grades and severity. Identification of additional epigenetic changes, such as histone modification and higher-order chromosomal structure, may allow for a more thorough understanding of tumorigenesis and enable future individualized treatment strategies for meningiomas.

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Christopher J. Stapleton, Martin H. Pham, Frank J. Attenello and Patrick C. Hsieh

Ossification of the posterior longitudinal ligament (OPLL) is a disease of progressive ectopic calcification of the PLL of the spine. It occurs most frequently in the cervical spine, followed by the thoracic spine. The disease was first described in the Japanese population, and the prevalence of OPLL is highest in Japan at a rate of 1.9%–4.3%. Note, however, that OPLL is also seen and is a known cause of cervical myelopathy in other Asian countries and in the white population. Research into the underlying cause of OPLL over the past few decades has shown that it is a multifactorial disease with significant genetic involvement. Genetic studies of OPLL have revealed several gene loci that may be involved in the pathogenesis of this disease. Genes encoding for proteins that process extracellular inorganic phosphate, collagen fibrils, and transcription factors involved in osteoblast and chondrocyte development and differentiation have all been implicated in the pathophysiology of OPLL. In this paper, the authors review current understanding of the genetics and pathophysiology of OPLL.

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Martin H. Pham, Joshua Bakhsheshian, Patrick C. Reid, Ian A. Buchanan, Vance L. Fredrickson and John C. Liu

OBJECTIVE

Freehand placement of C2 instrumentation is technically challenging and has a learning curve due the unique anatomy of the region. This study evaluated the accuracy of C2 pedicle screws placed via the freehand technique by neurosurgical resident trainees.

METHODS

The authors retrospectively reviewed all patients treated at the LAC+USC Medical Center undergoing C2 pedicle screw placement in which the freehand technique was used over a 1-year period, from June 2016 to June 2017; all procedures were performed by neurosurgical residents. Measurements of C2 were obtained from preoperative CT scans, and breach rates were determined from coronal reconstructions on postoperative scans. Severity of breaches reflected the percentage of screw diameter beyond the cortical edge (I = < 25%; II = 26%–50%; III = 51%–75%; IV = 76%–100%).

RESULTS

Neurosurgical residents placed 40 C2 pedicle screws in 24 consecutively treated patients. All screws were placed by or under the guidance of Pham, who is a postgraduate year 7 (PGY-7) neurosurgical resident with attending staff privileges, with a PGY-2 to PGY-4 resident assistant. The authors found an average axial pedicle diameter of 5.8 mm, axial angle of 43.1°, sagittal angle of 23.0°, spinal canal diameter of 25.1 mm, and axial transverse foramen diameter of 5.9 mm. There were 17 screws placed by PGY-2 residents, 7 screws placed by PGY-4 residents, and 16 screws placed by the PGY-7 resident. The average screw length was 26.0 mm, with a screw diameter of 3.5 mm or 4.0 mm. There were 7 total breaches (17.5%), of which 4 were superior (10.0%) and 3 were lateral (7.5%). There were no medial breaches. The breaches were classified as grade I in 3 cases (42.9%), II in 3 cases (42.9%), III in 1 case (14.3%), and IV in no cases. There were 3 breaches that occurred via placement by a PGY-2 resident, 3 breaches by a PGY-4 resident, and 1 breach by the PGY-7 resident. There were no clinical sequelae due to these breaches.

CONCLUSIONS

Freehand placement of C2 pedicle screws can be done safely by neurosurgical residents in early training. When breaches occurred, they tended to be superior in location and related to screw length choice, and no breaches were found to be clinically significant. Controlled exposure to this unique anatomy is especially pertinent in the era of work-hour restrictions.

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Joseph P. Antonios, Ghassan J. Farah, Daniel R. Cleary, Joel R. Martin, Joseph D. Ciacci and Martin H. Pham

Spinal cord injury (SCI) has been associated with a dismal prognosis—recovery is not expected, and the most standard interventions have been temporizing measures that do little to mitigate the extent of damage. While advances in surgical and medical techniques have certainly improved this outlook, limitations in functional recovery continue to impede clinically significant improvements. These limitations are dependent on evolving immunological mechanisms that shape the cellular environment at the site of SCI. In this review, we examine these mechanisms, identify relevant cellular components, and discuss emerging treatments in stem cell grafts and adjuvant immunosuppressants that target these pathways. As the field advances, we expect that stem cell grafts and these adjuvant treatments will significantly shift therapeutic approaches to acute SCI with the potential for more promising outcomes.

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Martin H. Pham, Vivek A. Mehta, Neil N. Patel, Andre M. Jakoi, Patrick C. Hsieh, John C. Liu, Jeffrey C. Wang and Frank L. Acosta

The Dynesys dynamic stabilization system is an alternative to rigid instrumentation and fusion for the treatment of lumbar degenerative disease. Although many outcomes studies have shown good results, currently lacking is a comprehensive report on complications associated with this system, especially in terms of how it compares with reported complication rates of fusion. For the present study, the authors reviewed the literature to find all studies involving the Dynesys dynamic stabilization system that reported complications or adverse events. Twenty-one studies were included for a total of 1166 patients with a mean age of 55.5 years (range 39–71 years) and a mean follow-up period of 33.7 months (range 12.0–81.6 months). Analysis of these studies demonstrated a surgical-site infection rate of 4.3%, pedicle screw loosening rate of 11.7%, pedicle screw fracture rate of 1.6%, and adjacent-segment disease (ASD) rate of 7.0%. Of studies reporting revision surgeries, 11.3% of patients underwent a reoperation. Of patients who developed ASD, 40.6% underwent a reoperation for treatment. The Dynesys dynamic stabilization system appears to have a fairly similar complication-rate profile compared with published literature on lumbar fusion, and is associated with a slightly lower incidence of ASD.

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Martin H. Pham, Frank J. Attenello, Joshua Lucas, Shuhan He, Christopher J. Stapleton and Patrick C. Hsieh

Object

Ossification of the posterior longitudinal ligament (OPLL) can result in significant myelopathy. Surgical treatment for OPLL has been extensively documented in the literature, but less data exist on conservative management of this condition.

Methods

The authors conducted a systematic review to identify all reported cases of OPLL that were conservatively managed without surgery.

Results

The review yielded 11 published studies reporting on a total of 480 patients (range per study 1–359 patients) over a mean follow-up period of 14.6 years (range 0.4–26 years). Of these 480 patients, 348 (72.5%) were without myelopathy on initial presentation, whereas 76 patients (15.8%) had signs of myelopathy; in 56 cases (15.8%), the presence of myelopathy was not specified. The mean aggregate Japanese Orthopaedic Association score on presentation for 111 patients was 15.3. Data available for 330 patients who initially presented without myelopathy showed progression to myelopathy in 55 (16.7%), whereas the other 275 (83.3%) remained progression free. In the 76 patients presenting with myelopathy, 37 (48.7%) showed clinical progression, whereas 39 (51.5%) remained clinically unchanged or improved.

Conclusions

Patients who present without myelopathy have a high chance of remaining progression free. Those who already have signs of myelopathy at presentation may benefit from surgery due to a higher rate of progression over continued follow-up.