Work-up and Management of Asymptomatic Extracranial Traumatic Vertebral Artery Injury.

BACKGROUND: Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1-2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains. METHODS: A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics. RESULTS: One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3-6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1-3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3-6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1-3 months. CONCLUSION: This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

Case costing in spine surgery: Can surgeons assist with accurate capture of operating room costs?

Surgical case costing is critical for health leaders to make decisions about resource utilization. Synoptic reporting offers the potential for surgeons to capture these costs and work with other leaders to make evidence-based decisions. The purpose of this study was to determine whether surgeons documented intra-operative cost drivers as part of their operative report. This article outlines a synoptic reporting system at a quaternary spine care centre. Data were captured from 2015 to 2020. Surgeon rates of documentation for specific devices, bone graft, and surgical adjuncts were evaluated. It is hoped that the results of this survey will help to guide programs to capture costs in other settings.

Behavioural and anatomical analysis of selective tibial nerve branch transfer to the deep peroneal nerve in the rat.

Nerve transfer procedures involving the repair of a distal denervated nerve element with that of a foreign proximal nerve have become increasingly popular for clinical nerve repair as a surgical alternative to autologous nerve grafting. However, the functional outcomes and the central plasticity for these procedures remain poorly defined, particularly for a clinically relevant rodent model of hindlimb nerve transfer. We therefore evaluated the effect of selective tibial branch nerve transfer on behavioural recovery in animals following acute transection of the deep peroneal nerve. The results indicate that not only can hindlimb nerve transfers be successfully accomplished in a rat model but that these animals display a return of skilled locomotor function on a par with animals that underwent direct deep peroneal nerve repair (the current gold standard). At 2 months, ground reaction force analysis demonstrated that partial restoration of braking forces occurred in the nerve transfer group, whereas the direct repair group had fully restored these forces to similar to baseline levels. Ankle kinematic analysis revealed that only animals in the direct repair group significantly recovered flexion during the step cycle, indicating a recovery of surgically induced foot drop. Terminal electrophysiological and myological assessments demonstrated similar levels of reinnervation, whereas retrograde labelling studies confirmed that the peroneal nerve-innervated muscles were innervated by neurons from the tibial nerve pool in the nerve transfer group. Our results demonstrate a task-dependent recovery process, where skilled locomotor recovery is similar between nerve transfer and direct repair animals, whereas flat surface locomotion is significantly better in direct repair animals.

Will cost transparency in the operating theatre cause surgeons to change their practice?

Surgeons may not have a thorough knowledge about the costs of devices or surgical equipment. The main reason for this in many systems is price insensitivity. The purpose of this study was to determine whether spine surgical procedural expenses change once physicians are aware of the costs for surgical implants and the total associated costs with the procedure. A thorough bottom up case costing methodology was used to capture the costs of admission for three comparable spine surgical procedures at a large tertiary care center. Costs were collected for an initial 5-month period where surgeons were not aware of costs, followed by another 5-month period with detailed cost information. Instrumental costs, procedural costs and costs of admission were captured as well as health related quality of life (HRQOL) measures at 3 months. Statistical analysis was undertaken with STATA software. Costs decreased by $478 for instrumentation once actual prices were known (p = 0.069). Only ACDF procedures demonstrated statistically significant instrumental cost savings of $754 (p = 0.009). Total procedural costs were also less ($297, p = 0.194) but the total overall costs of admission increased ($401, p = 0.228). There were no differences in VAS, EQ-5D, or SF-12 scores. Although costs decrease for implants in surgery when prices are known, this appears to have little or no effect on overall costs of care. Length of stay and operating room time have greater effects on global costs. Future efforts to encourage efficient cost savings should focus on practice patterns/pathways for similar conditions rather than limiting the use of certain implants.

Brief Electrical Stimulation Promotes Nerve Regeneration Following Experimental In-Continuity Nerve Injury.

BACKGROUND: Brief electrical stimulation (ES) therapy to the nerve may improve outcome in lacerated, repaired nerves. However, most human nerve injuries leave the nerve in continuity with variable and often poor functional recovery from incomplete axon regeneration and reinnervation. OBJECTIVE: To evaluate the effect of brief ES in an experimental model for neuroma-in-continuity (NIC) injuries in rodents. METHODS: Lewis rats were randomly assigned to 1 of 4 groups: NIC injury immediately followed by brief (1 h) ES; NIC injury without ES; sham-operated controls; sciatic nerve transection without repair. Outcome measures included serial behavioral evaluation and electrophysiology together with terminal retrograde spinal cord motor neuron labeling and histomorphological analysis for axonal regeneration. RESULTS: Applying brief ES immediately after in-continuity nerve injury resulted in earlier recovery and significantly improved locomotion function at 4 and 6 wk. At 8 wk, brief ES resulted in higher compound action potential amplitude. By 12 wk there was no significant difference between the 2 groups in behavior or electrophysiology. Histomorphological analysis demonstrated a significantly higher percentage of neural tissue in the brief ES group. Spinal cord motor neuron pool cell counts revealed a preference for regeneration into a motor over a sensory nerve, for the group receiving ES. CONCLUSION: The application of brief ES for in-continuity nerve injury promotes faster recovery, although in a rat model where regeneration distances are short the control group ultimately recovers to a similar degree. Brief EF requires further evaluation as a promising therapy for in-continuity nerve injuries in humans.

The impact of motor axon misdirection and attrition on behavioral deficit following experimental nerve injuries.

Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomical substrates that underlie the poor functional recovery associated with these devastating injuries. Yet, functional deficits associated with axonal misdirection in experimental neuroma-in-continuity injuries have not yet been studied. We hypothesized that experimental neuroma-in-continuity injuries would result in motor axon misdirection and attrition with proportional persistent functional deficits. The femoral nerve misdirection model was exploited to assess major motor pathway misdirection and axonal attrition over a spectrum of experimental nerve injuries, with neuroma-in-continuity injuries simulated by the combination of compression and traction forces in 42 male rats. Sciatic nerve injuries were employed in an additional 42 rats, to evaluate the contribution of axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks. Retrograde motor neuron labeling techniques were utilized to determine the degree of axonal misdirection and attrition. Characteristic histological neuroma-in-continuity features were demonstrated in the neuroma-in-continuity groups and poor functional recovery was seen despite successful nerve regeneration and muscle reinnervation. Good positive and negative correlations were observed respectively between axonal misdirection (p<.0001, r(2)=.67), motor neuron counts (attrition) (p<.0001, r(2)=.69) and final functional deficits. We demonstrate prominent motor axon misdirection and attrition in neuroma-in-continuity and transection injuries of mixed motor nerves that contribute to the long-term functional deficits. Although widely accepted in theory, to our knowledge, this is the first experimental evidence to convincingly demonstrate these correlations with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes the need to focus on strategies that promote both robust and accurate nerve regeneration to optimize functional recovery. It also demonstrates that clinically relevant neuroma-in-continuity injuries can now also be subjected to experimental investigation.

Doxycycline-regulated GDNF expression promotes axonal regeneration and functional recovery in transected peripheral nerve.

Increased production of neurotrophic factors (NTFs) is one of the key responses seen following peripheral nerve injury, making them an attractive choice for pro-regenerative gene therapies. However, the downside of over-expression of certain NTFs, including glial cell line-derived neurotrophic factor (GDNF), was earlier found to be the trapping and misdirection of regenerating axons, the so-called 'candy-store' effect. We report a proof-of-principle study on the application of conditional GDNF expression system in injured peripheral nerve. We engineered Schwann cells (SCs) using dendrimers or lentiviral transduction with the vector providing doxycycline-regulated GDNF expression. Injection of GDNF-modified cells into the injured peripheral nerve followed by time-restricted administration of doxycycline demonstrated that GDNF expression in SCs can also be controlled locally in the peripheral nerves of the experimental animals. Cell-based GDNF therapy was shown to increase the extent of axonal regeneration, while controlled deactivation of GDNF effectively prevented trapping of regenerating axons in GDNF-enriched areas, and was associated with improved functional recovery.

Traumatic neuroma in continuity injury model in rodents.

Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. Optimal experimental injuries that consistently resulted in NIC combined both intense focal compression and traction forces. Nerves were harvested at 0, 5, 13, 21, and 65 days for histological examination. Skilled locomotion and ground reaction force (GRF) analysis were performed up to 9 weeks on the experimental (n=6) and crush-control injuries (n=5). Focal widening, disruption of endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated in 14 of 14 nerves with refined experimental injuries. At 8 weeks, experimental animals displayed a significantly greater slip ratio in both skilled locomotor assessments, compared to nerve crush animals (p<0.01). GRFs of the crush- injured animals showed earlier improvement compared to the experimental animals, whose overall GRF patterns failed to recover as well as the crush group. We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes.

Traumatic neuroma in continuity injury model in rodents: a preliminary report.

Consistent with EBSJ's commitment to fostering quality research, we are pleased to feature some of the most highly rated abstracts from the 8th Annual AOSpine North America Fellows Forum in Banff Canada. Enhancing the quality of evidence in spine care means acknowledging and supporting the efforts of young researchers within our AOSpine North America network. We look forward to seeing more from these promising researchers in the future. STUDY TYPE: Basic science research report Introduction: Spinal nerve-injury management and prevention constitute a substantial proportion of a spinal surgeon's practice. Functional recovery after peripheral nerve injuries is often unsatisfactory and to optimize the outcomes, an intimate understanding of these injuries is required. Sunderland classified peripheral nerve injuries into five grades.1 Grade 1 (neurapraxia) and grade 2 (axonal disruption) injuries usually recover with no or insignificant functional deficits within weeks to a few months, respectively. Injuries that are most difficult to manage clinically are the often mixed grade 3 (endoneurial disruption) and grade 4 (perineurial disruption) lesions where spontaneous functional recovery is limited or absent, resulting in neuroma in continuity (NIC). Traumatic NIC is characterized by aberrant intra- and extra- fascicular axonal regeneration and scar formation within an unsevered injured nerve, resulting in impaired and erroneous end-organ reinnervation.2,3 Animal models reproducing grade 1, 2, 3, and 5 lesions have been developed, but to our knowledge a clinically relevant rodent model of NIC has not been developed.4,5,6,7,8 The effective peripheral nerve regeneration and resilience of rodents make it challenging to recreate the NIC scenario. OBJECTIVE: Our goal was to develop a practical rodent model for focal traumatic NIC, demonstrating the characteristic histological features, supported by concordant functional deficits. Such a model may help us to identify this injury pattern earlier and allow development of intervention strategies to reduce neuronal misdirection, scar formation, and enhance regeneration for improved functional recovery. METHODS: Various injury techniques were tested on freshly harvested Lewis rat sciatic nerves ex vivo, and examined histologically before inflicting more refined injuries in vivo. The optimal experimental injuries combined a 50 g traction force applied with a spring scale hooked around the sciatic nerve, and focal three second maximal compression using a malleus nipper (Figure 1). Nerves were harvested at 0, 5, 13, 21, and 65 days, and processed for longitudinal 8 micron cryostat sectioning, H&E, laminin, neurofilament, and Masson's trichrome staining. Skilled locomotion (tapered beam, ladder rung) and flat plane locomotion for ground reaction force (GRF) analysis were performed serially up to 9 weeks with the experimental (n = 4) and simple (control) crush (n = 1) injuries by blinded animal behavior experts, using methods as recently described.9 Figure 1 Photograph illustrating the experimental injury. Fifty grams of traction is applied in a direction orthogonal to the native nerve course after external neurolysis, simultaneously, three second maximal compression is applied at the sciatic trifurcation, just distal to a mesoneurial suture. Malleus nipper with tip detail and 100 g spring scale in bottom left. In situ sciatic nerve immediately after injury (top right). RESULTS: Disruption of the endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated histologically in ten out of ten nerves with experimental injuries. In contrast, crush injuries showed only signs of Wallerian degeneration (Figure 2). At 8 weeks, experimental animals made more errors during skilled locomotion as compared to nerve crush animals. GRFs revealed impaired vertical and fore-aft force generation by the injured limbs at week 9 in the experimental group, whereas GRFs from the simple crush animal revealed recovery at the same time point (Figure 3). Figure 2 Injury zones at five days (a-d, bar = 200 µm) and 65 days (e-h, bar = 50 µm), comparing crush (top) to experimental (bottom) injuries; Masson's trichrome and neurofilament. Note the aberrant axonal sprouting and regeneration in the experimental injury group, associated with increased intrafascicular collagen, in contrast to orderly regeneration and lack of scar in the simple crush group.Figure 3 Mean vertical and fore-aft ground reaction forces at both baseline and 9 weeks from representative animals. Compared to baseline and crush-injured animal at 9 weeks, animals in the experimental group bear less weight on both their right (surgical) hind limb (solid line), and fore limb (dotted line) at 9 weeks. Comparable with historical data, the crush animal have improved braking ((*)) and propulsive (#) forces in fore and hind limbs (injured side) compared to the experimental group, though these have not returned to baseline values. CONCLUSIONS: We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rodent model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. Additional validating experiments are in progress.