The clinical indications and added value of obtaining MRI in the acute phase of spinal cord injury (SCI) remain controversial. This review aims to critically evaluate evidence regarding the role of MRI to influence decision-making and outcomes in acute SCI. A systematic review and meta-analysis were performed according to PRISMA methodology to identify studies that address six key questions (KQs) regarding diagnostic accuracy, frequency of abnormal findings, frequency of altered decision-making, optimal timing, and differences in outcomes related to obtaining an MRI in acute SCI. A total of 32 studies were identified that addressed one or more KQs. MRI showed no adverse events in 156 patients (five studies) and frequently identified cord compression (70%, 12 studies), disc herniation (43%, 16 studies), ligamentous injury (39%, 13 studies), and epidural hematoma (10%, two studies), with good diagnostic accuracy (seven comparative studies) except for fracture detection. MRI findings often altered management, including timing of surgery (78%, three studies), decision to operate (36%, 15 studies), and surgical approach (29%, nine studies). MRI may also be useful to determine the need for instrumentation (100%, one study), which levels to decompress (100%, one study), and if reoperation is needed (34%, two studies). The available literature consistently concluded that MRI was useful prior to surgical treatment (13 studies) and after surgery to assess decompression (two studies), but utility before/after closed reduction of cervical dislocations was unclear (three studies). One study showed improved outcomes with an MRI-based protocol but had a high risk of bias. Heterogeneity was high for most findings (I2 > 0.75). MRI is safe and frequently identifies findings alter clinical management in acute SCI, although direct evidence of its impact on outcomes is lacking. MRI should be performed before and after surgery, when feasible, to facilitate improved clinical decision-making. However, further research is needed to determine its optimal timing, effect on outcomes, cost-effectiveness, and utility before and after closed reduction.
Changes in intracellular Ca2+ play a key role in regulating gene expression and developmental changes in oligodendroglial precursor cells (OPCs). However, the mechanisms by which Ca2+ influx in OPCs is controlled remains incompletely understood. Although there are several mechanisms that modulate Ca2+ influx, in many systems the large-conductance, voltage- and Ca2+-activated K+ channel (BK channel) plays an important role in regulating both membrane excitability and intracellular Ca2+ levels. To date, the role of the BK channel in the regulation of intracellular Ca2+ in oligodendroglial lineage cells is unknown. Here we investigated whether cells of the oligodendroglial lineage express BK channels and what potential role they play in regulation of Ca2+ influx in these cells. In oligodendrocytes derived from differentiated adult neural precursor cells (NPCs, obtained from C57bl6 mice) we observed outward currents that were sensitive to the BK channel blocker iberiotoxin (IbTx). Further confirmation of the expression of the BK channel was obtained utilizing other blockers of the BK channel and by confocal immunofluoresence labelling of the BK channel on oligodendroglia. Using Fura-2AM to monitor intracellular Ca2+, it was observed that inhibition of the BK channel during glutamate-induced depolarization led to an additive increase in intracellular Ca2+ levels. Electrophysiological difference currents demonstrated that the expression levels of the BK channel decrease with developmental age. This latter finding was further corroborated via RT-PCR and Western blot analysis. We conclude that the BK channel is involved in regulating Ca2+ influx in OPCs, and may potentially play a role during differentiation of oligodendroglial lineage cells.
Axonal dysfunction after spinal cord injury (SCI) and other types of neurotrauma is associated with demyelination and exposure of juxtaparanodal K + channels. In this study, sucrose gap electrophysiology using selective and nonselective K + channel blockers, confocal immunohistochemistry, and Western blotting were used to study the role of Kv1.1 and Kv1.2 K + channel subunits in dysmyelination-induced spinal cord axonal dysfunction in s hiverer mice, which lack the gene encoding myelin basic protein (MBP) and exhibit incomplete myelin sheath formation on CNS axons. The s hiverer spinal cord axons exhibited smaller amplitude of compound action potentials (CAPs), reduced conduction velocity, reduced excitability, and greater degree of high-frequency conduction failure. The “fast” K + channel blocker 4-aminopyridine, the toxin DTX-I, which targets the Kv1.1 and Kv1.2, but not DTX- K, which has higher selectivity for Kv1.1, increased the amplitude and area of CAPs of shiverer mice spinal cord axons but had insignificant effects in wild-type mice. Confocal immunohistochemistry showed that, unlike wild-type mice, which have a precise juxtaparanodal localization of the Kv1.l and Kv1.2 K + channel subunits, shiverer mouse axons displayed a dispersed distribution of these subunits along the internodes. In contrast, the Kv1.l and Kv1.2 subunits, Na + channels remained highly localized to the nodal regions. Western blotting showed an increased expression of Kv 1.1 and 1.2 in the shiverer mouse spinal cord. These results provide evidence that the neurological deficits associated with myelin deficiency reflect the altered distribution and expression of the K + channel subunits Kv1.l and Kv1.2 along the internodes of spinal cord axons associated with the biophysical consequences caused by alterations in the myelin sheaths.
Abstract OBJECTIVE: Occipital condyle fractures (OCFs) are infrequently recognized. Three recent cases of OCF in our center prompted a review of the incidence, clinical presentation, diagnosis, and treatment of this entity. METHODS: A retrospective review of medical records and radiographic results was performed for 93 of 316 consecutive patients who were victims of trauma, who presented at the Toronto Hospital during a 13-month period, and who had undergone computed tomography of the occiput. RESULTS: A review of the literature regarding OCF revealed that cranial nerve deficits occurred in 31% of the patients with OCFs; of those, the deficits were delayed in 38%. Three new cases of OCF, with neck pain but without cranial nerve deficits, have been reported. The cervical spine x-rays revealed nothing abnormal in 96% of the reported cases. In our retrospective review, asymptomatic OCF was revealed by computed tomography for 1 of the 93 patients. CONCLUSION: OCF is a diagnostic challenge. We suggest that computed tomographic scans of 0-C2 be obtained in the following circumstances: presence of lower cranial nerve deficits, associated head injury or basal cranial fracture, or persistent severe neck pain despite normal radiographic results. We propose a new classification system for the management and treatment of OCF based on the stability of the 0-C1-C2 joint complex reflected by the presence of displacement of the condyle, computed tomographic or radiographic evidence of 0-C1-C2 instability, and magnetic resonance evidence of ligamentous injury. OCFs are divided into the following types: Type 1 (stable), undisplaced fracture; Type 2A (stable), displaced fracture with no ligamentous instability; and Type 2B (unstable), displaced fracture with ligamentous instability.
Spinal cord injuries (SCIs) result in devastating lifelong disability for patients and their families. The initial mechanical trauma is followed by a damaging secondary injury cascade involving proapoptotic signaling, ischemia, and inflammatory cell infiltration. Ongoing cellular necrosis releases ATP, DNA, glutamate, and free radicals to create a cytotoxic postinjury milieu. Long-term regeneration of lost or injured networks is further impeded by cystic cavitation and the formation of an inhibitory glial-chondroitin sulfate proteoglycan scar. In this article, we discuss important neuroprotective interventions currently applied in clinical practice, including surgical decompression, blood pressure augmentation, and i.v. methylprednisolone. We then explore exciting translational therapies on the horizon, such as riluzole, minocycline, fibroblast growth factor, magnesium, and hypothermia. Finally, we summarize the key neuroregenerative strategies of the next decade, including glial scar degradation, Rho-ROCK inhibition, cell-based therapies, and novel bioengineered adjuncts. Throughout, we emphasize the need for combinatorial approaches to this multifactorial problem and discuss relevant studies at the forefront of translation. We conclude by providing our perspectives on the future direction of SCI research.Spinal cord injuries (SCIs) result in devastating, lifelong disability for patients and their families. This article discusses important neuroprotective interventions currently applied in clinical practice, including surgical decompression, blood pressure augmentation, and i.v. methylprednisolone. Translational therapies on the horizon are discussed, such as riluzole, minocycline, fibroblast growth factor, magnesium, and hypothermia. The key neuroregenerative strategies of the next decade are summarized, including glial scar degradation, Rho-ROCK inhibition, cell-based therapies, and novel bioengineered adjuncts. The need for combinatorial approaches to this multifactorial problem is emphasized, relevant studies at the forefront of translation are discussed, and perspectives on the future direction of SCI research are presented.
Furlan, Julio C. M.D., M.B.A., M.Sc., Ph.D.; Kelvin, Chan M.D.; Sandoval, Guillermo M.B.A.; Klinger, Christopher A. M.P.A.; Lam, Kenneth B.A., M.A., M.P.A.; Patchell, Roy A. M.D.; Laporte, Audrey Ph.D.; Fehlings, Michael G. M.D., Ph.D.
