Search PubMed⌕ Search

Biomedical subjects

Michael G Fehlings

Publications and source records attributed to Michael G Fehlings.

At least 37 records · Page 2Linked to original sources
PubMed2005

Multi-modality neurophysiological monitoring during surgery for adult tethered cord syndrome.

During complex microneurosurgery performed in patients with tethered cord syndrome, the conus medullaris and the roots that innervate the lower limbs, bladder and bowel are potentially exposed to damage. The aim of multimodality intraoperative monitoring (IOM) is to reduce the risk of inadvertent injury of neural tissue. We simultaneously record tibial nerve somatosensory evoked potentials (SSEPs) from the scalp and free run electromyography (EMG) of limb muscles supplied by L2 to S2 roots, anal and urethral sphincters. We also identify critical neural structures in the operative field, including the conus and exiting nerve roots, with a nerve stimulator to evoke EMG. SSEPs assess the sensory pathways mainly mediated by the S1 roots. Continuous EMG provides the surgeon with immediate auditory feedback resulting from irritative discharges triggered by manipulation of nerve fibres. Microstimulation can distinguish the filum terminale, scar tissue and invasive tumors from functional neural tissue, thus minimizing the risk of iatrogenic injury. Overall multimodality IOM proves a valuable adjunct to microneurosurgery of the lumbosacral spine.

Adult↗
PubMed2005

A new classification of thoracolumbar injuries: the importance of injury morphology, the integrity of the posterior ligamentous complex, and neurologic status.

STUDY DESIGN: A new proposed classification system for thoracolumbar (TL) spine injuries, including injury severity assessment, designed to assist in clinical management. OBJECTIVE: To devise a practical, yet comprehensive, classification system for TL injuries that assists in clinical decision-making in terms of the need for operative versus nonoperative care and surgical treatment approach in unstable injury patterns. SUMMARY OF BACKGROUND DATA: The most appropriate classification of traumatic TL spine injuries remains controversial. Systems currently in use can be cumbersome and difficult to apply. None of the published classification schemata is constructed to aid with decisions in clinical management. METHODS: Clinical spine trauma specialists from a variety of institutions around the world were canvassed with respect to information they deemed pivotal in the communication of TL spine trauma and the clinical decision-making process. Traditional injury patterns were reviewed and reconsidered in light of these essential characteristics. An initial validation process to determine the reliability and validity of an earlier version of this system was also undertaken. RESULTS: A new classification system called the Thoracolumbar Injury Classification and Severity Score (TLICS) was devised based on three injury characteristics: 1) morphology of injury determined by radiographic appearance, 2) integrity of the posterior ligamentous complex, and 3) neurologic status of the patient. A composite injury severity score was calculated from these characteristics stratifying patients into surgical and nonsurgical treatment groups. Finally, a methodology was developed to determine the optimum operative approach for surgical injury patterns. CONCLUSIONS: Although there will always be limitations to any cataloging system, the TLICS reflects accepted features cited in the literature important in predicting spinal stability, future deformity, and progressive neurologic compromise. This classification system is intended to be easy to apply and to facilitate clinical decision-making as a practical alternative to cumbersome classification systems already in use. The TLICS may improve communication between spine trauma physicians and the education of residents and fellows. Further studies are underway to determine the reliability and validity of this tool.

Humans↗
PubMed2005

Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation.

Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation.

Animals↗
PubMed2005

Thoracolumbar injury classification and severity score: a new paradigm for the treatment of thoracolumbar spine trauma.

BACKGROUND: Contemporary understanding of the biomechanics, natural history, and methods of treating thoracolumbar spine injuries continues to evolve. Current classification schemes of these injuries, however, can be either too simplified or overly complex for clinical use. METHODS: The Spine Trauma Group was given a survey to identify similarities in treatment algorithms for common thoracolumbar injuries, as well as to identify characteristics of injury that played a key role in the decision-making process. RESULTS: Based on the survey, the Spine Trauma Group has developed a classification system and an injury severity score (thoracolumbar injury classification and severity score, or TLICS), which may facilitate communication between physicians and serve as a guideline for treating these injuries. The classification system is based on the morphology of the injury, integrity of the posterior ligamentous complex, and neurological status of the patient. Points are assigned for each category, and the final total points suggest a possible treatment option. CONCLUSIONS: The usefulness of this new system will have to be proven in future studies investigating inter- and intraobserver reliability, as well as long-term outcome studies for operative and nonoperative treatment methods.

Algorithms↗
PubMed2005

Structural and functional alterations of spinal cord axons in adult Long Evans Shaker (LES) dysmyelinated rats.

Abnormal formation or loss of myelin is a distinguishing feature of many neurological disorders and contributes to the pathobiology of neurotrauma. In this study we characterize the functional and molecular changes in CNS white matter in Long Evans Shaker (LES) rats. These rats have a spontaneous mutation of the gene encoding myelin basic protein which results in severe dysmyelination of the central nervous system (CNS), providing a unique model for demyelinating/dysmyelinating disorders. To date, the functional and molecular changes in CNS white matter in this model are not well understood. We have used in vivo somatosensory evoked potential (SSEP), in vitro compound action potential (CAP) recording in isolated dorsal columns, confocal immunohistochemistry, Western blotting and real-time PCR to examine the electrophysiological, molecular and cellular changes in spinal cord white matter in LES rats. We observed that dysmyelination is associated with dispersed labeling of Kv1.1 and Kv1.2 K+ channel subunits, as well as Caspr, a protein normally confined to paranodes, along the LES rat spinal cord axons. Abnormal electrophysiological properties including attenuation of CAP amplitude and conduction velocity, high frequency conduction failure and enhanced sensitivity to K+ channel blockers 4-aminopyridine and dendrotoxin-I were observed in spinal cord axons from LES rats. Our results in LES rats clarify some of the key molecular, cellular and functional consequences of dysmyelination and myelin-axon interactions. Further understanding of these issues in this model could provide critical insights for neurological disorders characterized by demyelination.

Action Potentials↗
PubMed2005

The role and timing of early decompression for cervical spinal cord injury: update with a review of recent clinical evidence.

It remains controversial whether early decompression following spinal cord injury conveys a benefit in neurological outcome. The goal of this paper is to provide evidence-based recommendations regarding spinal cord decompression in patients with acute spinal cord injury. We performed a Medline search of experimental and clinical studies reporting on the effect of decompression on neurological outcome following spinal cord injury. Animal studies consistently show that neurological recovery is enhanced by early decompression. One randomized controlled trial showed no benefit to early (<72 h) decompression, however, several recent prospective series suggest that early decompression (<12 h) can be performed safely and may improve neurological outcomes. A recent meta-analysis showed that early decompression (<24 h) resulted in statistically better outcomes compared to both delayed decompression and conservative management. Currently, there are no standards regarding the role and timing of decompression in acute spinal cord injury. We recommend urgent decompression of bilateral locked facets in patients with incomplete tetraplegia or in patients with spinal cord injury experiencing neurological deterioration. Urgent decompression in acute cervical spinal cord injury remains a reasonable practice option and can be performed safely.

Acute Disease↗
PubMed2005

Current status of clinical trials for acute spinal cord injury.

Acute spinal cord injury (ASCI) occurs as a result of physical disruption of spinal cord axons through the epicenter of injury leading to deficits in motor, sensory, and autonomic function. This is a debilitating neurological disorder common in young adults that often requires life-long therapy and rehabilitative care, placing a significant burden on our healthcare system. While no cure exists, research has identified various pharmacological compounds that specifically antagonize primary and secondary mechanisms contributing to the etiology of ASCI. Several compounds including methylprednisolone (MPSS), GM-1 ganglio-side, thyrotropin releasing hormone (TRH), nimodipine, and gacyclidine have been tested in prospective randomized clinical trials of ASCI. MPSS and GM-1 ganglioside have shown evidence of modest benefits. Clearly trials of improved neuroprotective agents are required. Promising potential therapies for ASCI include riluzole, minocycline, erythropoietin, and the fusogen polyethylene glycol, as well as mild hypothermia.

Clinical Trials as Topic↗
PubMed2005

The effects of gender on clinical and neurological outcomes after acute cervical spinal cord injury.

The potential clinical relevance of gender on clinical and neurological outcome after spinal cord injury (SCI) has received little attention. In order to address this issue, we examined all consecutive cases of acute traumatic cervical SCI admitted to our institution from 1998 to 2000. There were 38 males (ages 17-89 years, mean of 51.6) and 17 females (ages 18-84 years, mean of 63.2). Both groups were comparable regarding level (C1 to C7) and severity of SCI (ASIA A to D) at admission. Age differences between the groups approached significance (p = 0.057), and thus this factor was treated as a covariate in the analysis. Co-morbidities were as frequent in men (86.8%) as in women (76.5%). The therapeutic approaches, length-of-stay in the acute care unit, mortality, and discharge disposition were similar in men and women. During hospitalization, 44.7% of men and 52.9% of women developed post-SCI secondary complications without any significant gender-related differences. Both groups showed a similar incidence of infections, cardiovascular complications, thromboembolism, and pressure sores. Univariate analysis revealed a trend for higher incidence of psychiatric complications (p = 0.054) and deep venous thrombosis (p = 0.092) in women, which was confirmed by multivariate analysis. Neurological outcome was not correlated with gender. A similar number of males and females (42.1%, 47.1%) showed evidence of neurological recovery as revealed by an improvement in ASIA scores. Moreover, 18.4% of males and 29.4% of females recovered to ASIA E status. Our data suggest a shift in the demographics of acute SCI with an increasing incidence in elderly women. Although neurological outcomes were not significantly related to gender, we observed a trend for higher rates of reactive depression and deep venous thrombosis in women. These issues may be of key clinical importance in developing improved management protocols for SCI so as to maximize functional recovery and quality-of-life.

Acute Disease↗
PubMed2005

Surgical treatment of cervical myeloradiculopathy associated with movement disorders: indications, technique, and clinical outcome.

OBJECTIVE: Movement disorders may be associated with advanced cervical myeloradiculopathy, which represents a major management challenge. We report on eight patients with movement disorders causing progressive cervical myeloradiculopathy who were treated successfully by cervical decompression and reconstruction. RESULTS: The mean age of our patients was 44 years with a male/female ratio of 3:1. The average duration of symptoms prior to presentation was 10 months. The most common levels decompressed and reconstructed were C3-C4 and C4-C5. Six cases showed improvement, and two cases showed stabilization of neurologic status at a mean follow-up of 21 months. Our management strategy and results are interpreted in the context of a systematic review of the literature in which 78 cases are reported. CONCLUSIONS: Movement disorders cause premature cervical spondylosis most commonly involving the C3-C4 and C4-C5 levels. Ventral pathology with kyphotic angulation requires corpectomy or discectomy with or without posterior decompression and reconstruction. Decompression should always be combined with segmental internal fixation. Perioperative use of botulinum toxin and halo vest immobilization can increase the rate of clinical success but requires vigilance to minimize complications. Laminectomy with lateral mass fixation may be used successfully in the absence of kyphotic deformity.

Adult↗
PubMed2005

Complete cord injury.

Explore the source record for details and available documents.

Clinical Trials, Phase I as Topic↗
PubMed2005

The thoracolumbar injury severity score: a proposed treatment algorithm.

OBJECTIVE: Significant controversy exists regarding the optimal management of thoracolumbar injuries. This is in part due to the lack of understanding of the natural history of various injury subtypes and the absence of a universally accepted classification scheme that facilitates communication among care providers and assists in directing treatment. The Spine Trauma Study Group has developed an injury severity score based on three major variables: the mechanism of injury determined by radiographic appearance, the integrity of the posterior ligamentous complex, and the neurologic status of the patient. By systematically assigning specific point values within each category based on the severity of injury, a final severity score may be generated that can be used to help direct treatment. The goal of this work is to present a proposal of a detailed treatment algorithm to assist in the nonoperative or operative management of thoracolumbar injuries. METHODS: A detailed review of the world's spinal literature was performed to ascertain predictors of instability following thoracolumbar trauma. With use of known biomechanical and clinical outcome measures, an arbitrary assignment of point values to various injury descriptors was performed. The assessment of the validity of the severity score was compared retrospectively with a variety of selected cases representing the typical injury patterns under the three major injury groups: compression, translational/rotational, and distraction injuries. CONCLUSIONS: The proposed treatment algorithm is an attempt to assist physicians using best-evidence medicine in managing thoracolumbar spinal injuries. The final point flow chart with graduated treatment recommendations is only preliminary and needs to be validated through prospective cohort analysis. In addition, the importance of the chosen variables determining spinal stability must also be verified.

Algorithms↗
PubMed2004

Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN.

The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid and protein phosphatase. We report here that PTEN physically associates with the NR1 and NR2B subunits of NMDA receptors (NMDARs) in rat hippocampus. Downregulating the protein expression of PTEN inhibits the function of extrasynaptic NMDARs and decreases NMDAR surface expression, suggesting a crucial role for endogenous PTEN in the modulation of NMDAR-mediated neuronal function. Reducing PTEN expression also enhances Akt/Bad phosphorylation in hippocampal neurons. Importantly, suppressing lipid and protein phosphatase activity of PTEN, respectively, activates Akt and inhibits extrasynaptic NMDAR activity and thereby protects against ischemic neuronal death in vitro and in vivo. Thus, our study reveals a dual neuroprotective mechanism by which Akt/Bad and extrasynaptic NMDARs are regulated via downregulation of two distinct PTEN phosphatase activities and present the possibility of PTEN as a potential therapeutic target for stroke treatment.

Animals↗
PubMed2004

Similarities and differences in the treatment of spine trauma between surgical specialties and location of practice.

STUDY DESIGN: Questionnaires administered to practicing orthopedic and neurosurgical spine surgeons from various regions of the United States and abroad. OBJECTIVES: To determine similarities and differences in the treatment of spinal trauma. SUMMARY OF BACKGROUND DATA: Spinal trauma is generally referred to subspecialists of orthopedic or neurosurgical training. Prior studies have suggested that there is significant variability in the management of such injuries. METHODS: Questionnaires based on eight clinical scenarios of commonly encountered cervical, thoracic, and lumbar injuries were administered to 35 experienced spinal surgeons. Surgeons completed profile information and answered approximately one dozen questions for each case. Data were analyzed with SPSS software to determine the levels of agreement and characteristics of respondents that might account for a lack of agreement on particular aspects of management. RESULTS: Of the 35 surgeons completing the questionnaire, 63% were orthopedists, 37% were neurosurgeons, and 80% had been in practice for more than 5 years. Considerable agreement was found in the majority of clinical decisions, including whether or not to operate and the timing of surgery. Of the differences noted, neurosurgeons were more likely to obtain a MRI, and orthopedists were more likely to use autograft as a sole graft material. Physicians from abroad were, in general, more likely to operate and to use an anterior approach during surgery than physicians from the northeastern United States. CONCLUSIONS: More commonalities were identified in the management of spinal trauma than previously reported. When found, variability in opinion was related to professional and regional differences.

Adult↗
PubMed2004

Real-time continuous intraoperative electromyographic and somatosensory evoked potential recordings in spinal surgery: correlation of clinical and electrophysiologic findings in a prospective, consecutive series of 213 cases.

STUDY DESIGN: Retrospective analysis of a prospectively accrued series of 213 consecutive patients who underwent intraoperative neurophysiologic monitoring with electromyography and somatosensory-evoked potentials during thoracolumbar spine surgery. OBJECTIVES: To study the incidence of significant intraoperative electrophysiologic changes and new postoperative neurologic deficits. SUMMARY OF BACKGROUND DATA: Continuous intraoperative electromyography and somatosensory-evoked potentials are frequently used in spinal surgery to prevent neural injury. However, only limited data are available on the sensitivity, specificity, and predictive values of intraoperative electrophysiologic changes with regard to the occurrence of new postoperative neurologic deficits. METHODS: We examined data on patients who underwent intraoperative monitoring with continuous lower limb electromyography and somatosensory-evoked potentials. The analysis focused on the correlation of intraoperative electrophysiologic changes with the development of new neurologic deficits. RESULTS: A total of 213 patients underwent surgery on a total of 378 levels; 32.4% underwent an instrumented fusion. Significant electromyograph activation was observed in 77.5% of the patients and significant somatosensory-evoked potential changes in 6.6%. Fourteen patients (6.6%) had new postoperative neurologic symptoms. Of those, all had significant electromyograph activation, but only 4 had significant somatosensory-evoked potential changes. Intraoperative electromyograph activation had a sensitivity of 100% and a specificity of 23.7% for the detection of a new postoperative neurologic deficit. Somatosensory-evoked potentials had a sensitivity of 28.6% and specificity of 94.7%. CONCLUSIONS: Intraoperative electromyographic activation has a high sensitivity for the detection of a newpostoperative neurologic deficit but a low specificity. In contrast, somatosensory-evoked potentials have low sensitivity but high specificity. Combined intraoperative neurophysiologic monitoring with electromyography and somatosensory-evoked potentials is helpful for predicting and possibly preventing neurologic injury during thoracolumbar spine surgery.

Adolescent↗
PubMed2004

Confocal imaging of changes in glial calcium dynamics and homeostasis after mechanical injury in rat spinal cord white matter.

Periaxonal glia play an important role in maintaining axonal function in white matter. However, little is known about the changes that occur in glial cells in situ immediately after traumatic injury. We used fluo-3 and confocal microscopy to examine the effects of localized (<0.5 mm) mechanical trauma on intracellular calcium (Ca(i)(2+)) levels in glial cells in a mature rat spinal cord white matter preparation in vitro. At the injury site, the glial Ca(i)(2+) signal increased by 300-400% within 5 min and then irreversibly declined indicating cell lysis and death. In glial cells at sites adjacent to the injury (1.5-2 mm from epicenter), Ca(i)(2+) levels peaked at 10-15 min, and thereafter declined but remained significantly above rest levels. At distal sites (6-9 mm), Ca(i)(2+) levels rose and declined even slower, peaking at 80-90 min. Injury in zero calcium dampened Ca(i)(2+) responses, indicating a role for calcium influx in the generation and propagation of the injury-induced Ca(i)(2+) signal. By 50-80 min post-injury, surviving glial cells demonstrated an enhanced ability to withstand supraphysiological Ca(i)(2+) loads induced by the calcium ionophore A-23187. Glial fibrillary acidic protein (GFAP) and CNPase immunolabeling determined that the glial cells imaged with fluo-3 included both astrocytes and oligodendrocytes. These data provide the first direct evidence that the effects of localized mechanical trauma include a glial calcium signal that can spread along white matter tracts for up to 9 mm within less than 3 h. The results further show that trauma can enhance calcium regulation in surviving glial cells in the acute post-injury period.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2004

The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration.

Following an initial impact after spinal cord injury (SCI), there is a cascade of downstream events termed 'secondary injury', which culminate in progressive degenerative events in the spinal cord. These secondary injury mechanisms include, but are not limited to, ischemia, inflammation, free radical-induced cell death, glutamate excitotoxicity, cytoskeletal degradation and induction of extrinsic and intrinsic apoptotic pathways. There is emerging evidence that glutamate excitotoxicity plays a key role not only in neuronal cell death but also in delayed posttraumatic spinal cord white matter degeneration. Importantly however, the differences in cellular composition and expression of specific types of glutamate receptors in grey versus white matter require a compartmentalized approach to understand the mechanisms of secondary injury after SCI. This review examines mechanisms of secondary white matter injury with particular emphasis on glutamate excitotoxicity and the potential link of this mechanism to apoptosis. Recent studies have provided new insights into the mechanisms of glutamate release and its potential targets, as well as the downstream pathways associated with glutamate receptor activation in specific types of cells. Evidence from molecular and functional expression of glutamatergic AMPA receptors in white matter glia (and possibly axons), the protective effects of AMPA/kainate antagonists in posttraumatic white matter axonal function, and the vulnerability of oligodendrocytes to excitotoxic cell death suggest that glutamate excitotoxicity is associated with oligodendrocyte apoptosis. The latter mechanism appears key to glutamatergic white matter degeneration after SCI and may represent an attractive therapeutic target.

Apoptosis↗
PubMed2004

Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma.

After spinal cord injury (SCI), surviving white matter axons display axonal dysfunction associated with demyelination and altered K+ channel activity. To clarify the molecular basis of posttraumatic axonal pathophysiology after SCI, we investigated the changes in expression and distribution of the axonal K+ channel subunits Kv1.1 and Kv1.2 in spinal cord white matter after in vivo SCI in the rat. Using Western blot analysis, we found an increased expression of Kv1.1 and Kv1.2 at 2 and 6 weeks after SCI. By real-time PCR we observed an increase in Kv1.1 and Kv1.2 mRNA levels 1 day after SCI, which persisted until 6 weeks. Confocal immunohistochemistry showed a markedly dispersed labelling of Kv1.1 and Kv1.2 along the injured axons, in contrast to the tight localization of these channels to the juxtaparanodes of noninjured axons. This redistribution of Kv1.1 and Kv1.2 occurred as early as 1 h postinjury along some injured axons, and persisted at 6 weeks postinjury. In parallel with the redistribution of Kv1.1 and 1.2, contactin-associated protein (Caspr), which is normally confined to a paranodal location, also displayed a more diffuse distribution along the injured spinal cord axons. Our results suggest that the increased expression of Kv1.1 and Kv1.2 proteins is transcriptionally regulated. In contrast, the redistribution of the axonal K+ channel subunits occurs very early postinjury and probably reflects a disruption of the juxtaparanodal axonal region due to physical trauma, as shown by altered localization of Caspr.

Actins↗