Lateral Lumbar Interbody Fusion at L4-5: A Morphometric Analysis of Psoas Anatomy and Cage Placement.

BACKGROUND: The ventral elevation (VE) of the psoas from the vertebral column as seen on axial magnetic resonance imaging has been suggested as a preclusion of a safe working zone for lateral lumbar interbody fusion (LLIF) at L4-5. However, no quantitative study has been conducted to verify this. METHODS: L4-5 LLIF was attempted using 22-mm wider cages whenever feasible over 18-mm standard cages in a consecutive series of 62 patients. The degree of VE of the psoas measured from the anterior border of the L5 endplate and the anteroposterior cage position measured from the posterior vertebral border to the center of the cage normalized to the anteroposterior width of the L5 endplate were recorded on axial images. RESULTS: LLIF was successfully performed in all cases despite 18 patients (29%) harboring elevated psoas. Standard cage was applied in 25 (40%) patients due to nerve proximity. Wider cage was applied equally frequent in both elevated (56%) and nonelevated groups (60%, P = 0.78). The mean cage position was found to be 0.54 ± 0.10 (standard deviation) and no difference was detected between the elevated (0.54 ± 0.11) and nonelevated (0.53 ± 0.10, P = 0.78) groups. Multivariate analyses and receiver operating characteristic analysis demonstrated that VE displayed low performance in predicting the choice of cages. CONCLUSIONS: LLIF is feasible in patients with ventrally elevated psoas, and the choice of cages does not appear to be influenced by the location of the psoas. Relying on the rising psoas sign on magnetic resonance imaging as a case selection criterion may unjustly exclude patients from LLIF.

Effects of FOXM1 inhibition and ionizing radiation on melanoma cells.

Metastatic melanoma can be highly refractory to conventional radiotherapy and chemotherapy but combinatorial-targeted therapeutics are showing greater promise on improving treatment efficacy. Previous studies have shown that knockdown of Forkhead box M1 (FOXM1) can sensitize various tumor types to radiation-induced cell death. The effect of combining radiation with a small molecule FOXM1 inhibitor, Siomycin A, on growth, death and migration of a metastatic melanoma cell line (SK-MEL-28) that overexpresses this pleiotropic cell cycle regulator was investigated. Siomycin A (SIOA) was found to be a strong inducer of apoptosis, and inhibitor of proliferation and migration in a scratch wound assay in this cell line. Induction of apoptosis occurred at concentrations >1 µM in association with reductions in the constitutive FOXM1 and anti-apoptotic B-cell lymphoma 2 protein levels found in these cells. Single doses of ionizing radiation (0-40 Gy) delivered by linear accelerator caused inhibition of growth and migration without significant induction of cell death. Pretreatment with SIOA did not increase the sensitivity of this melanoma cell line to radiation as observed in other tumor types. These data confirm that as a single agent, SIOA is an effective inducer of cell death and inhibitor of migration in metastatic melanoma cells expressing constitutive FOXM1. In combination with radiation, SIOA pre-treatment, however, may not be of added benefit.

Custom-Made Titanium 3-Dimensional Printed Interbody Cages for Treatment of Osteoporotic Fracture-Related Spinal Deformity.

BACKGROUND: Advances in minimally invasive interbody fusion have greatly enhanced surgeons' capability to correct adult spinal deformity with reduced morbidity. However, the feasibility of such approaches is limited in patients with previous osteoporotic fractures as the resultant vertebral deformity renders the end plate geometry incongruous with conventional interbody implants. Current 3-dimensional (3D) printing technology offers a novel solution by fabricating custom-made implants tailored to individual anatomy. We present the results of a patient with osteoporotic lumbar fractures treated by such technology. CASE DESCRIPTION: A 74-year-old woman, with previous osteoporotic fractures at L2 and L3 resulting in concave deformity of the end plates, presented with intractable radiculopathy secondary to lateral recess and foraminal stenosis (L2-3 and L3-4). A minimally invasive lateral lumbar interbody fusion at L2-3 and L3-4 was considered favorable, but due to the associated vertebral collapse, off-the-shelf implants were not compatible with patient anatomy. In silico simulation based on preoperative computed tomography (CT) imaging was thus conducted to design customized cages to cater for the depressed recipient end plates and vertebral loss. The design was converted to implantable titanium cages through 3D additive manufacturing. At surgery, a tight fit between the implants and the targeted disk space was achieved. Postoperative CT scan confirmed excellent implant-end plate matching and restoration of lost disk space. The patient began to ambulate from postoperative day 1 and at 6-month follow-up resolution of radicular symptoms and CT evidence of interbody fusion were recorded. CONCLUSIONS: 3D-printed custom-made interbody cages can help overcome the difficulties in deformity correction secondary to osteoporotic fractures.

Lateral lumbar interbody fusion at the lumbosacral junction.

Due to the obstruction of the iliac crest and the retroperitoneal vessels, lateral lumbar interbody fusion (LLIF) is generally considered contraindicated at the lumbosacral junction (LSJ). In particular the 'rise' of the psoas from the vertebral column in the lower lumbar segments has been associated with significant overlap of the lumbar plexus with the vertebral body and exclusion of a safe transpsoas entry. However in selected individuals anatomical variations may help circumvent the difficulties and the anatomical corridor posterior to the lumbar plexus may provide an alternative to the conventional anterior approach. Currently there is a dearth of information in informing the feasibility. We therefore reviewed the records of three patients in whom LLIF was successfully conducted at the LSJ. The patients' spinopelvic parameters and psoas anatomy were analysed by whole spine standing X-rays and MRI respectively. Intraoperative findings and postoperative outcome were examined. We found that in keeping with published morphometric data, low pelvic incidence (40-50°) appeared associated with 'low-lying' iliac crests which had facilitated lateral access to the LSJ in all cases. Patients with scoliosis provided added advantage when the concave side of the curve was utilised for the approach. A very high 'rising' psoas was found conducive to a novel posterior surgical corridor. No significant neurovascular sequelae were noted. In conclusion, LLIF can be safely performed at the LSJ in selected cases. To our knowledge this is the first report to describe the possibility of a safe LLIF working zone posterior to the lumbar plexus.

A radiographic analysis of cage positioning in lateral transpsoas lumbar interbody fusion.

Direct Lumbar Interbody Fusion (DLIF) and eXtreme Lateral Interbody Fusion (XLIF) are the most common surgical platforms available for performing transpsoas spinal fusion but no study has been carried out to compare them. We evaluated 21 DLIF and 22 XLIF cage positions by measuring the distance between the posterior vertebral border and the centre of the cage normalised to the midsagittal length of the inferior end plate. We found that DLIF cages were significantly more anteriorly located than XLIF (0.65 vs 0.52, p = 0.001) at L4-5, suggesting that XLIF would permit implantation of wider cages than DLIF.

Direct Tubular Lumbar Microdiscectomy for Far Lateral Disc Herniation: A Modified Approach.

OBJECTIVE: The concept of minimally invasive tubular discectomy is based on precise placement of the retractor over the surgical target to minimize collateral tissue trauma. For far lateral disc herniation, the junction between the pars and the transverse process has generally been adopted as the target for facilitating early nerve root exposure; however, this may limit access to the disc space and increase the risks of iatrogenic neuralgia. An alternative approach to help address these issues involving docking the retractor caudally directly over the disc space with the aid of a microscope is here proposed. The purpose of this study was to evaluate the safety and efficacy of such an approach. METHODS: Nineteen patients in whom the modified approach was performed over a 35-month period were identified. Direct access to the disc space was attained by directing the retractor against the lateral margin of the facet joint and following the inferior transverse process medially towards the foramen with minimal exposure of the nerve root. Clinical outcomes were assessed by the Oswestry Disability Index, visual analogue scale scores for leg and back pain, Short Form 36 physical functioning (SF36-PF) and bodily pain (SF36-BP) scores and sciatica bothersomeness and frequency indexes (SBI & SFI) and obtained from a prospective patient database. Follow-up data in the first 6 months were compared with preoperative baseline data. RESULTS: All procedures were successfully completed with the modified approach. Contained disc herniation without sequestrated fragments was found in all but four cases. No perioperative complications or reoperation were recorded and no postoperative dysesthesia was noted. Clinically significant reductions in mean Oswestry Disability Index (32; 95% CI, 21-43) and visual analogue scale scores for leg pain (38 mm; 95% CI, 23-54 mm) and back pain (35 mm; 95% CI, 21-48 mm) scores were noted in the first 6 months. Significant improvements in SF36-PF (40; 95% CI, 30-51) and SF36-BP (35; 95% CI, 26-43), SBI (9; 95% CI, 6-11) and SFI (11; 95% CI, 8-13) were also recorded. CONCLUSIONS: A modified direct tubular approach is safe and effective for treating far lateral lumbar disc herniation. Our early results suggest that this approach helps safeguard adequate decompression and reduce the risk of postoperative dysesthesia.

Microscopic tubular discectomy for far lateral lumbar disc herniation.

Microscopic tubular discectomy (MTD) reduces muscle trauma associated with treatment of far lateral lumbar disc herniation (FLDH), but data from randomised controlled studies concerning its efficacy on posterolateral disc herniation, has failed to demonstrate its superiority over standard open techniques. Importantly concerns have been raised that it may be inferior in terms of relief of leg and back pain. Although several FLDH series show that MTD can deliver excellent outcomes, the volume of literature in this field has remained small and evidence based on health-related quality of life (HRQOL) measures, scarce. In this study we therefore evaluated the role of MTD for FLDH through analysing multiple HRQOL scores collected in a prospective database. We identified 24 patients who underwent MTD through a caudal approach, targeting directly the disc space to minimise traction on the dorsal root ganglion implicated in causing iatrogenic neuralgia. With a mean follow-up of 9.2months, the improvement in Oswestry Disability Index and Short Form 36 physical functioning and bodily pain scores was 32, (95% confidence interval [CI]: 21-43), 40 (95% CI: 30-51) and 35 (95% CI: 26-43) respectively. The improvement on the Visual Analogue Scale was 38mm (95% CI: 23-54) and 35mm (95% CI: 21-48) for leg pain and back pain respectively. There was no postoperative neuralgia noted and no reoperation required. Our data demonstrated clinically meaningful treatment effects and compare favourably with HRQOL surgical outcomes established for posterolateral disc herniation, supporting MTD as a valid treatment option for FLDH.

Glioblastoma multiforme formation and EMT: role of FoxM1 transcription factor.

Glioblastoma multiforme (GBM) is one of the most malignant cancers in human brain. The prognosis of GBM is extremely poor because it is resistant to radiotherapy and chemotherapy. Improving understanding of the tumor biology brings some new hope to the treatment of GBM. In this review, we discuss the evidence that FoxM1 promotes the development and progression of GBM by regulating key factors involved in cell proliferation, epithelial to mesenchymal transition (EMT), invasion, angiogenesis and upregulating Wnt/ß-catenin signalling. Our recent experimental findings are also summarized to prove that FoxM1 is a novel therapeutic target against GBM.

Current strategies in the surgical management of cerebral metastases: an evidence-based review.

Metastatic tumours are the most common form of cerebral neoplasm, occurring in up to 40% of patients with systemic cancer. Although the presence of metastatic disease portends limited survival, aggressive management of cerebral metastases is vital to preventing death from neurological causes and prolonging functional independence. Due to advancement in neurosurgical techniques and the advent of stereotactic radiosurgery as a non-operative alternative, current decision making for selecting the appropriate local treatment often results in clinical equipoise. In addition, the traditional blanket application of whole brain radiation has come under scrutiny as new evidence regarding the deleterious neurocognitive effects of ionizing radiation emerges. The completion of a series of randomized studies comparing the efficacy of surgery, radiosurgery, whole brain radiotherapy and various combined approaches for cerebral metastases in recent years has shed important light on addressing some of these issues. The focus of this review is to summarize the key findings and outline a practical approach for the management of cerebral metastases.

Cerebral metastases from malignant melanoma: current treatment strategies, advances in novel therapeutics and future directions.

Of all primary cancers in humans, melanoma has the highest propensity to metastasize to the brain. The prognosis of patients with this disease is extremely poor. Due to its radioresistance and poor response to existing chemotherapeutic regimes, no treatment options other than surgical extirpation, when feasible, have been shown to be effective. An understanding of the underlying tumor biology therefore remains the cornerstone of offering new hope in the treatment. In this review, we comment on the current treatment strategies for melanoma brain metastases and summarize some recent experimental findings from our laboratory with potential for the development of target specific antitumor therapies.

Suppression of visual cortical evoked responses following deprivation of pattern vision in adult mice.

The effect of visual loss on the adult neocortex can have significant impact on the success of a visual implant. Recent research has shown that the adult neocortex retains substantial plasticity following a disruption to its afferent input. The result of these changes may hamper the development of a visual prosthesis if visual sensation cannot be effectively restored by stimulation of the surviving elements of the visual pathway. In order to evaluate further the visual performance of the mammalian adult brain following visual loss, especially the dominant form of blindness in humans, namely loss of pattern vision, we examined the cortical evoked potential of adult mice following 7, 30 and 120 days of visual deprivation via bilateral eyelid suture. Cortical potentials were elicited with a flash visual stimulus or by electrical stimulation of the retina. We found that after 7 days deprivation there was a potentiation of the evoked response while at 30 and 120 days deprivation the visual evoked responses were significantly reduced. Increasing the visual stimulus intensity reduced the effects. The electrical evoked potential demonstrated a corresponding reduction in stimulus threshold at 7 days and a corresponding rise (40-50%) after 30 and 120 days. These findings suggest that the adult brain exhibited significant experience-dependent modifications following visual loss, and the impact depended on the duration of deprivation. Such reduction in visual responsiveness, especially with electrical activation, will need to be taken into account in the development of a visual implant.

Radical resection of focal brainstem gliomas: is it worth doing?

OBJECTIVES: Despite revolutionary technical advancement in neuroimaging and operative neurosurgery, surgical extirpation of focal brainstem glioma (BSG) remains steeped in controversy. In this study, we evaluated our senior author's (CT) surgical experience in radically treating these tumours in children to determine the safety and efficacy of such approach. MATERIALS AND METHODS: Thirty-four consecutive patients aged between 3 and 16 years who underwent endoscope-assisted microsurgery for focal BSG with the intent of radial resection from 1999 to 2005 were evaluated. The clinical outcome at 6 months and long-term survival were analysed. CONCLUSION: Thirty-one patients had >90% tumour resection and the remainder had >50%. There was no perioperative mortality. The average follow-up was 46 months. Twenty-three patients (74%) harboured low-grade gliomas, whilst the remainder (26%) had high-grade gliomas. Kaplan-Meier survival analysis revealed marked difference in the 5-year survival rates between the two groups (100% vs 33%). Multivariate analysis demonstrated that the degree of tumour resection was not associated with poor outcome at 6 months. This series underscores the benefits of surgical resection for focal BSG. Radical resection can be achieved in a majority of patients with favourable outcome regardless of tumour pathology.

Toxicology of the retina: advances in understanding the defence mechanisms and pathogenesis of drug- and light-induced retinopathy.

The neurosensory retina is a highly specialized sense organ that is subjected to constant exposure of systemic toxins, oxidative stress and focused light rays. Important advances have been made in recent decades in unravelling a myriad of defence mechanisms against such insults and consequently in improving the understanding of the principles underlying various drug- and light-induced disease processes. To defend against circulating toxins, the retina possesses a specialized blood-retinal barrier (BRB) that tightly regulates the transport of substances across the functional boundaries of the retina at the retinal capillaries and the retinal pigmented epithelium. An endogenous cytochrome p450 system is strategically located within the retina to neutralize agents that can diffuse through the BRB. The biooxidation effect of light is prevented by a wide array of unique antioxidant mechanisms in the retina. Nonetheless, pathological processes may evolve when these different lines of defence are overwhelmed by various xenobiotics, environmental agents such as cigarette smoke and excessive light exposure, particularly of short wavelength high frequency blue light and ultraviolet light. Latest research using transgenic models has revealed novel apoptotic pathways implicated in acute phototoxicity, in particular blue light damage, and provides important clues for further understanding the risks of high-frequency light exposure to human retinopathy. This review article summarizes the basic scientific principles of these different defence mechanisms and discuss the implications in pathophysiology and treatment.

In vivo evaluation of an episcleral multielectrode array for stimulation of the retina with reduced retinal ganglion cell mass.

A visual prosthesis is an experimental device designed to activate residual functional neurons in the visual pathway to generate artificial vision for blind patients. Specifically, for photoreceptor disease, a microelectrode array applied to the surface of the sclera could potentially serve to stimulate the remaining interneurons in the retina to produce topographically mapped visual percepts. However, of those neurons spared in the disease process, the retinal ganglion cells (RGC), which represent the final output neurons of the retina, can be markedly reduced in number. Using an albino rabbit model with RGC deficits, acute recording of cortical electrical evoked potential was performed to ascertain whether such a stimulation strategy is feasible. By analyzing the strength-duration curve (current threshold vs. pulse duration) and cortical activation profiles, our results prove that bioelectrically safe and spatially differentiated stimulation of the retina is feasible notwithstanding the condition of markedly reduced RGC counts.

Visual cortical potentials of the mouse evoked by electrical stimulation of the retina.

An electrical evoked potential (EEP) of the visual system is a summed electrical record of the visual cortex in response to electrical stimulation of the retina. It is the primary method in the assessment of a visual prosthesis which targets at restoring vision to individuals with disease of the outer retina. However despite marked enthusiasm in the fabrication of such devices, little is known about the feasibility of such devices with the visually deprived brain. Recent research in visual plasticity has demonstrated that the adult brain retains marked plasticity following visual deafferentation. The deprived visual cortex may be recruited to process other sensory modality in a cross-modal manner, thus vitiating its capacity to process restored visual input. In this regard, the mouse benefited with a wealth of mutant models and transgenic technology may help to unravel many of the underlying mechanisms of neuroplasticity and provide novel avenues to manipulate such changes. Nevertheless, the feasibility of recording EEP in the mouse has not been established to date. In this study we successfully established a noninvasive technique for stimulation and recording mouse EEP. The approach provides a tool for not only investigating the plastic changes in visual processing following deafferentation but also longitudinal and live data collection for in vivo evaluation of a prosthetic device.

Influence of callosal transfer on visual cortical evoked response and the implication in the development of a visual prosthesis.

BACKGROUND: The development of a visual prosthesis has been limited by an incomplete understanding of functional changes of the visual cortex accompanying deafferentation. In particular, the role of the corpus callosum in modulating these changes has not been fully evaluated. Recent experimental evidence suggests that through synaptic modulation, short-term (4-5 days) visual deafferentation can induce plastic changes in the visual cortex, leading to adaptive enhancement of residual visual input. We therefore investigated whether a compensatory rerouting of visual information can occur via the indirect transcallosal linkage after deafferentation and the influence of this interhemispheric communication on the visual evoked response of each hemisphere. METHODS: In albino rabbits, misrouting of uncrossed optic fibres reduces ipsilateral input to a negligible degree. We thus took advantage of this congenital anomaly to model unilateral cortical and ocular deafferentation by eliminating visual input from one eye and recorded the visual evoked potential (VEP) from the intact eye. RESULTS: In keeping with the chiasmal anomaly, no VEP was elicited from the hemisphere ipsilateral to the intact eye. This remained unchanged following unilateral visual deafferentation. The amplitude and latency of the VEP in the fellow hemisphere, however, were significantly decreased in the deafferented animals. CONCLUSION: Our data suggest that callosal linkage does not contribute to visual evoked responses and this is not changed after short-term deafferentation. The decrease in amplitude and latency of evoked responses in the hemisphere ipsilateral to the treated eye, however, confirms the facilitatory role of callosal transfer. This observation highlights the importance of bicortical stimulation in the future design of a cortical visual prosthesis.

Spinal cord infarction complicating acute hydrocephalus secondary to a colloid cyst of the third ventricle. Case report.

Occipital lobe infarction secondary to tentorial herniation is a rare but well-recognized complication of posterior cerebral artery interruption during acute hydrocephalus; however, a similar event in which tonsillar herniation leads to symptomatic occlusion of the anterior spinal arteries (ASAs) has not been reported. The authors present the case of a third ventricular colloid cyst in a previously healthy 24-year-old man who presented with symptoms and signs of critically raised intracranial pressure. He subsequently survived the ictus of insults following emergency external cerebrospinal fluid drainage and definitive resection of the colloid cyst, but he sustained occipital lobe and spinal cord infarction despite the absence of systematic hypotension. The presence of watershed cervicothoracic cord infarction on magnetic resonance imaging suggested that the most likely causes were compromise of ASAs during the period of acute hydrocephalus and the accompanying downward brain herniation. To the authors' knowledge, this is the first report to provide evidence that acute hydrocephalus may lead to ASA syndrome.

Neurolysis for meralgia paresthetica: an operative series of 45 cases.

BACKGROUND: Failure of symptom relief after neurolysis for meralgia paresthetica (MP) is reported frequently, yet systematic outcome analysis is limited in the modern literature. The present operative series of 45 cases aims to address this issue. METHODS: From 1996 to 2000, all patients who had neurolysis for MP by our senior author were enrolled in the study. Nerve entrapment was confirmed preoperatively by electrophysiological studies or a positive response to local anesthetic and steroid injection. Attention to the anatomical variability of the lateral femoral cutaneous nerve was made during nerve exploration. Decompression of the nerve was performed at the level of the iliac fascia, the inguinal ligament, and the fascia of the thigh distally. The outcome of surgery was assessed 6 weeks after the procedure followed by 3 monthly intervals if symptoms persisted. Telephone interviews were conducted to assess long-term results. RESULTS: Forty-five decompressive procedures were performed in 42 patients over the 5-year period. The average duration of symptoms was 31 (2.5-180) months. All patients were followed for an average of 4.1 years. Complete and partial symptom improvements were noted in 33 (73%) and 9 (20%) cases, respectively. No recurrence was reported. Analysis of clinical variables demonstrated that the duration of symptoms preoperatively did not affect the rate of complete symptom relief, but obese patients (body mass index > 30) was 6 times more likely to have (odds ratio 6.16, P = 0.04) incomplete relief after surgery at long-term follow-up. CONCLUSION: High success rate was recorded in our series of 45 cases. Prolonged duration of symptoms did not preclude favorable outcome but obesity had a negative association with good outcome.