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Qiuqian Wu and Jason H. Huang

OBJECTIVE

Lumbar intervertebral disc degeneration, an age-related process, is a major cause of low-back pain. Although low-back pain is a very common clinical problem in the aging population, no effective treatment is available, largely owing to lack of understanding of the molecular mechanisms underlying disc degeneration. The goal of this study was to characterize how ectopic expression of Smurf2 driven by the collagen Type II alpha 1 (Col2a1) promoter alters disc cell phenotype and associated cellular events, matrix synthesis, and gene expression during disc degeneration in mice.

METHODS

To characterize how ectopic expression of Smurf2 in Col2a1-promoter working cells affects the disc degeneration process, the authors performed histological and immunohistochemical analysis of lumbar spine specimens harvested from wild-type (WT) and Col2a1-Smurf2 transgenic mice at various ages (n ≥ 6 in each age group). To elucidate the molecular mechanism underlying Smurf2-mediated disc degeneration, the authors isolated cells from WT and Col2a1-Smurf2 transgenic lumbar intervertebral discs and performed Western blot and real-time RT-PCR (reverse transcription polymerase chain reaction) to examine the protein and mRNA levels of interesting targets.

RESULTS

The authors demonstrated that approximately 30% of WT mice at 10–12 months of age had started to show disc degeneration and that the disc degeneration process was accelerated by 3–6 months in Col2a1-Smurf2 transgenic mice. Chondrocyte-like cell proliferation, maturation, and fibrotic tissue formation in the inner annulus were often accompanied by fibroblast-to-chondrocyte differentiation in the outer annulus in transgenic discs. The chondrocyte-like cells in transgenic discs expressed higher levels of connective tissue growth factor (CTGF) than were expressed in WT counterparts.

CONCLUSIONS

The findings that ectopic expression of Smurf2 driven by the Col2a1 promoter accelerated disc degeneration in Col2a1-Smurf2 transgenic mice, and that higher levels of CTGF protein and mRNA were present in Col2a1-Smurf2 transgenic discs, indicate that Smurf2 accelerates disc degeneration via upregulation of CTGF.

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Je Yeong Sone, Douglas Kondziolka, Jason H. Huang and Uzma Samadani

Helmets are one of the earliest and most enduring methods of personal protection in human civilization. Although primarily developed for combat purposes in ancient times, modern helmets have become highly diversified to sports, recreation, and transportation. History and the scientific literature exhibit that helmets continue to be the primary and most effective prevention method against traumatic brain injury (TBI), which presents high mortality and morbidity rates in the US. The neurosurgical and neurotrauma literature on helmets and TBI indicate that helmets provide effectual protection against moderate to severe head trauma resulting in severe disability or death. However, there is a dearth of scientific data on helmet efficacy against concussion in both civilian and military aspects. The objective of this literature review was to explore the historical evolution of helmets, consider the effectiveness of helmets in protecting against severe intracranial injuries, and examine recent evidence on helmet efficacy against concussion. It was also the goal of this report to emphasize the need for more research on helmet efficacy with improved experimental design and quantitative standardization of assessments for concussion and TBI, and to promote expanded involvement of neurosurgery in studying the quantitative diagnostics of concussion and TBI. Recent evidence summarized by this literature review suggests that helmeted patients do not have better relative clinical outcome and protection against concussion than unhelmeted patients.

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Fei Song, Yuanzheng Hou, Guochen Sun, Xiaolei Chen, Bainan Xu, Jason H. Huang and Jun Zhang

OBJECTIVE

Preoperative determination of the facial nerve (FN) course is essential to preserving its function. Neither regular preoperative imaging examination nor intraoperative electrophysiological monitoring is able to determine the exact position of the FN. The diffusion tensor imaging–based fiber tracking (DTI-FT) technique has been widely used for the preoperative noninvasive visualization of the neural fasciculus in the white matter of brain. However, further studies are required to establish its role in the preoperative visualization of the FN in acoustic neuroma surgery. The object of this study is to evaluate the feasibility of using DTI-FT to visualize the FN.

METHODS

Data from 15 patients with acoustic neuromas were collected using 3-T MRI. The visualized FN course and its position relative to the tumors were determined using DTI-FT with 3D Slicer software. The preoperative visualization results of FN tracking were verified using microscopic observation and electrophysiological monitoring during microsurgery.

RESULTS

Preoperative visualization of the FN using DTI-FT was observed in 93.3% of the patients. However, in 92.9% of the patients, the FN visualization results were consistent with the actual surgery.

CONCLUSIONS

DTI-FT, in combination with intraoperative FN electrophysiological monitoring, demonstrated improved FN preservation in patients with acoustic neuroma. FN visualization mainly included the facial-vestibular nerve complex of the FN and vestibular nerve.

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Yu-Hua Huang, Tao-Chen Lee, Tsung-Han Lee, Chen-Chieh Liao, Jason Sheehan and Aij-Lie Kwan

Object

Decompressive craniectomy is a life-saving measure for patients who have sustained traumatic brain injury (TBI), but patients undergoing this procedure may still die during an early phase of head injury. The aim of this study was to investigate the incidence, causes, and risk factors of 30-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy.

Methods

The authors included 201 head-injured patients undergoing decompressive craniectomy in this 3-year retrospective study. The main outcome evaluated was 30-day mortality in patients who had undergone craniectomy after TBI. Demographic and clinical data, including information on death, were obtained for subsequent analysis. The authors identified differences between survivors and nonsurvivors in terms of clinical parameters; multivariate logistic regression was used to adjust for independent risk factors of short-term death.

Results

The 30-day mortality rate was 26.4% in traumatically brain-injured patients undergoing decompressive craniectomy. The majority of deaths following decompression resulted from uncontrollable brain swelling and extensive brain infarction, which accounted for 79.2% of mortality. In the multivariate logistic regression mode, the 2 independent risk factors for 30-day mortality were age (OR 1.035 [95% CI 1.006–1.064]; p = 0.018) and Glasgow Coma Scale (GCS) score before decompressive craniectomy (OR 0.769 [95% CI 0.597–0.990]; p = 0.041).

Conclusions

There is a high 30-day mortality rate in traumatically brain-injured patients undergoing decompressive craniectomy. Most of the deaths are attributed to ongoing brain damage, even after decompression. Risk factors of short-term death, including age and preoperative GCS score, are important in patient selection for decompressive craniectomy, and these factors should be considered together to ensure the highest chance of surviving TBI.

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Radek Kolecki, Vikalpa Dammavalam, Abdullah Bin Zahid, Molly Hubbard, Osamah Choudhry, Marleen Reyes, ByoungJun Han, Tom Wang, Paraskevi Vivian Papas, Aylin Adem, Emily North, David T. Gilbertson, Douglas Kondziolka, Jason H. Huang, Paul P. Huang and Uzma Samadani

OBJECTIVE

The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip.

METHODS

Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP.

RESULTS

Eye tracking was performed at ICP levels ranging from −3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and ≥ 12 mm Hg was 0.798. To discriminate an ICP < 15 from ≥ 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from ≥ 20 mm Hg the AUC was 0.889.

CONCLUSIONS

Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

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Jason H. Huang, Eric L. Zager, Jun Zhang, Robert F. Groff IV, Bryan J. Pfister, Akiva S. Cohen, M. Sean Grady, Eileen Maloney-Wilensky and Douglas H. Smith

Object

Although neuron transplantation to repair the nervous system has shown promise in animal models, there are few practical sources of viable neurons for clinical application and insufficient approaches to bridge extensive nerve damage in patients. Therefore, the authors sought a clinically relevant source of neurons that could be engineered into transplantable nervous tissue constructs. The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture.

Methods

Cervical DRGs were harvested from 16 live patients following elective ganglionectomies, and thoracic DRGs were harvested from 4 organ donor patients. Following harvest, the DRGs were digested in a dispase–collagenase treatment to dissociate neurons for culture. In addition, dissociated human DRG neurons were placed in a specially designed axon expansion chamber that induces continuous mechanical tension on axon fascicles spanning 2 populations of neurons originally plated ∼ 100 μm apart.

Results

The adult human DRG neurons, positively identified by neuronal markers, survived at least 3 months in culture while maintaining the ability to generate action potentials. Stretch-growth of axon fascicles in the expansion chamber occurred at the rate of 1 mm/day to a length of 1 cm, creating the first engineered living human nervous tissue constructs.

Conclusions

These data demonstrate the promise of adult human DRG neurons as an alternative transplant material due to their availability, viability, and capacity to be engineered. Also, these data show the feasibility of harvesting DRGs from living patients as a source of neurons for autologous transplant as well as from organ donors to serve as an allograft source of neurons.

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Hung-Chuan Pan, Jason Sheehan, Chuan-Fu Huang, Meei-Ling Sheu, Dar-Yu Yang and Wen-Ta Chiu

Object

Gamma Knife surgery (GKS) is an important part of the neurosurgical armamentarium for treatment of patients with trigeminal neuralgia (TN) and is regarded as the first-line treatment in patients with TN who have serious medical comorbidities. In this study, the authors investigated the efficacy of GKS on TN in patients with serious medical comorbidities.

Methods

Between May 2004 and September 2007, 52 severely ill patients who also had TN with Barrow Neurological Institute (BNI) facial pain scores of IV or V were entered into this study. The patients' medical records and imaging findings were reviewed by an anesthesiologist and neurosurgeons to determine whether GKS was a reasonable approach to palliate the patient's pain. All patients underwent GKS, in which a maximum dose of 80 Gy was targeted to the trigeminal nerve with or without plugging to keep the dose received by the brainstem at less than 16 Gy. After treatment, every patient had clinical follow-up every 1–3 months and filled out questionnaires designed to assess BNI facial pain and numbness scores, visual analog scale scores, and 36-Item Short Form Health Survey (SF-36) scores every 3 months until the end of the study. Statistical analysis was performed to find favorable prognostic factors related to pain relief and changes in quality of life.

Results

The median age of the patients was 71 years, and the male/female ratio was 30:22. The median follow-up period was 54 months (at least 2 years). All patients had a positive initial response to GKS, with BNI facial pain scores at least 1 point less than respective pre-GKS scores. Three patients (5.7%) obtained BNI facial pain Score I. Twenty-three patients (44.2%) experienced pain recurrence at a median follow-up of 33 months. One patient suffered from angina and required time in an intensive care unit; another patient had bleeding from a pin wound that required suturing. Alterations in BNI scores were highly correlated to visual analog scale scores (R2 = 0.978). In both univariate and multivariate analyses, a decreased BNI facial pain score at different time points was significantly (p < 0.05) related to younger patient age, no previous treatment, evidence of vessel compression on MR imaging, time of first GKS ≤ 24 months, physical function (SF-36), role limitation due to a physical problem (SF-36), role limitation due to an emotional problem (SF-36), mental health (SF-36), social functioning (SF-36), bodily pain (SF-36), and general health (SF-36), but was not related to vitality (SF-36). Five patients (9.6%) experienced facial numbness at a mean of 13.2 ± 3.1 months after GKS (4 patients with BNI facial numbness Score II and 1 with BNI facial numbness Score III). Post-GKS MR imaging changes, including focal contrast enhancement or T2-weighted signal alterations, were identified in 3 patients (5.7%).

Conclusions

Gamma Knife surgery produced significant pain relief in severely ill patients who had TN without causing appreciable morbidity. The effect of reduced pain significantly paralleled an improvement in SF-36 quality-of-life indices.

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Uzma Samadani, Sameer Farooq, Robert Ritlop, Floyd Warren, Marleen Reyes, Elizabeth Lamm, Anastasia Alex, Elena Nehrbass, Radek Kolecki, Michael Jureller, Julia Schneider, Agnes Chen, Chen Shi, Neil Mendhiratta, Jason H. Huang, Meng Qian, Roy Kwak, Artem Mikheev, Henry Rusinek, Ajax George, Robert Fergus, Douglas Kondziolka, Paul P. Huang and R. Theodore Smith

OBJECT

Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect.

METHODS

The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects.

RESULTS

In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases.

CONCLUSIONS

This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

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Darryl Lau, Cecilia L. Dalle Ore, Phiroz E. Tarapore, Michael Huang, Geoffrey Manley, Vineeta Singh, Praveen V. Mummaneni, Michael Beattie, Jacqueline Bresnahan, Adam R. Ferguson, Jason F. Talbott, William Whetstone and Sanjay S. Dhall

OBJECTIVE

The elderly are a growing subpopulation within traumatic spinal cord injury (SCI) patients. Studies have reported high morbidity and mortality rates in elderly patients who undergo surgery for SCI. In this study, the authors compare the perioperative outcomes of surgically managed elderly SCI patients with those of a younger cohort and those reported in the literature.

METHODS

Data on a consecutive series of adult traumatic SCI patients surgically managed at a single institution in the period from 2007 to 2017 were retrospectively reviewed. The cohort was divided into two groups based on age: younger than 70 years and 70 years or older. Assessed outcomes included complications, in-hospital mortality, intensive care unit (ICU) stay, hospital length of stay (LOS), disposition, and neurological status.

RESULTS

A total of 106 patients were included in the study: 83 young and 23 elderly. The two groups were similar in terms of imaging features (cord hemorrhage and fracture), operative technique, and American Spinal Injury Association Impairment Scale (AIS) grade. The elderly had a significantly higher proportion of cervical SCIs (95.7% vs 71.1%, p = 0.047). There were no significant differences between the young and the elderly in terms of the ICU stay (13.1 vs 13.3 days, respectively, p = 0.948) and hospital LOS (23.3 vs 21.7 days, p = 0.793). Elderly patients experienced significantly higher complication (73.9% vs 43.4%, p = 0.010) and mortality (13.0% vs 1.2%, p = 0.008) rates; in other words, the elderly patients had 1.7 times and 10.8 times the rate of complications and mortality, respectively, than the younger patients. No elderly patients were discharged home (0.0% vs 18.1%, p = 0.029). Discharge AIS grade and AIS grade change were similar between the groups.

CONCLUSIONS

Elderly patients had higher complication and mortality rates than those in younger patients and were less likely to be discharged home. However, it does seem that mortality rates have improved compared to those in prior historical reports.

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Dale Ding, Robert M. Starke, Hideyuki Kano, David Mathieu, Paul P. Huang, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients.

METHODS

The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs.

RESULTS

A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001).

CONCLUSIONS

Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.