Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

Traumatic brain injury (TBI) survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP). Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ) peptides, a hallmark finding in Alzheimer’s disease (AD). At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF) using cerebral microdialysis and/or cerebrospinal fluid (CSF) following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long-term consequences of TBI

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain injury

Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short-and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI

Favorable clinical outcome following surgical evacuation of deep-seated and lobar supratentorial intracerebral hemorrhage : a retrospective single-center analysis of 123 cases

Background: In spontaneous supratentorial intracerebral hemorrhage (ICH), the role of surgical treatment remains controversial, particularly in deep-seated ICHs. We hypothesized that early mortality and long-term functional outcome differ between patients with surgically treated lobar and deep-seated ICH. Method: Patients who underwent craniotomy for ICH evacuation from 2009 to 2015 were retrospectively evaluated and categorized into two subgroups: lobar and deep-seated ICH. The modified Rankin Scale (mRS) was used to evaluate long-term functional outcome. Result: Of the 123 patients operated for ICH, 49.6% (n = 61) had lobar and 50.4% (n = 62) deep-seated ICH. At long-term follow-up (mean 4.2 years), 25 patients (20.3%) were dead, while 51.0% of survivors had a favorable outcome (mRS score ≤ 3). Overall mortality was 13.0% at 30 days and 17.9% at 6 months post-ictus, not influenced by ICH location. Mortality was higher in patients ≥ 65 years old (p = 0.020). The deep-seated group had higher incidence and extent of intraventricular extension, younger age (52.6 ± 9.0 years vs. 58.5 ± 9.8 years; p < 0.05), more frequently pupillary abnormalities, and longer neurocritical care stay (p < 0.05). The proportion of patients with good outcome was 48.0% in deep-seated vs. 54.1% in lobar ICH (p = 0.552). In lobar ICH, independent predictors of long-term outcome were age, hemorrhage volume, preoperative level of consciousness, and pupillary reaction. In deep-seated ICHs, only high age correlated significantly with poor outcome. Conclusions: At long-term follow-up, most ICH survivors had a favorable clinical outcome. Neither mortality nor long-term functional outcome differed between patients operated for lobar or deep-seated ICH. A combination of surgery and neurocritical care can result in favorable clinical outcome, regardless of ICH location

Cerebrospinal fluid biomarkers of white matter injury and astrogliosis are associated with the severity and surgical outcome of degenerative cervical spondylotic myelopathy

BACKGROUND CONTEXT: Degenerative cervical spondylotic myelopathy (DCM) is the commonest form of spinal cord injury in adults. However, a limited number of clinical reports have assessed the role of biomarkers in DCM. PURPOSE: We evaluated cerebrospinal fluid (CSF) biomarkers in patients scheduled for DCM surgery and hypothesized that CSF biomarkers levels (1) would reflect the severity of preoperative neurological status; and (2) correlate with radiological appearance; and (3) correlate with clinical outcome. STUDY DESIGN/SETTING: Prospective clinical and laboratory study. PATIENT SAMPLE: Twenty-three DCM patients, aged 66.4±12.8 years and seven controls aged 45.4±5.3 years were included. OUTCOME MEASURES: The American Spinal Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire and EuroQol 5-dimensions were assessed preoperatively and at 3 months post-surgery. METHODS: We measured preoperative biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], phosphorylated neurofilament-H [pNF-H] and Ubiquitin C-terminal hydrolase L1) in CSF samples collected from patients with progressive clinical DCM who underwent surgical treatment. Biomarker concentrations in DCM patients were compared with those of cervical radiculopathy controls. RESULTS: The median symptom duration was 10 (interquartile range 6) months. The levels of GFAP, NFL, pNF-H, Ubiquitin C-terminal hydrolase L1 were significantly higher in the DCM group compared to controls (p=.044, p=.002, p=.016, and p=.006, respectively). Higher pNF-H levels were found in patients with low signal on T1 Magnetic Resonance Imaging sequence compared to those without (p=.022, area under the receiver operating characteristic curve [AUC] 0.780, 95% Confidence Interval: 0.59–0.98). Clinical improvement following surgery correlated mainly with NFL and GFAP levels (p<.05). CONCLUSIONS: Our results suggest that CSF biomarkers of white matter injury and astrogliosis may be a useful tool to assess myelopathy severity and predict outcome after surgery, while providing valuable information on the underlying pathophysiology

Management of symptomatic sacral perineural cysts with microsurgery and a vascularized fasciocutaneous flap

Background: The optimal treatment of symptomatic perineural (Tarlov) cysts is controversial. Numerous surgical techniques have been proposed with conflicting results. A series of Tarlov cysts treated with a novel surgical approach is presented.Methods: Patients with surgically treated symptomatic perineural cysts during 2013-2016 were included. The main indications for surgery were persistent radicular symptoms, pelvic pain, urinary and/ or bowel disturbances. At surgery, the cyst was opened and fenestrated. The cyst wall was then closed with packing, fibrin glue and a pedicled vascularized fasciocutaneous flap rotated into the area for obliteration of the dead space. Patients were followed-up with clinical visits and repeat magnetic resonance imaging (MRI) scans.Results: Seven consecutive patients were included. The mean age was 50.3 years (range, 25-80 years) and the mean duration of symptoms was 49.3 months (range, 3-130 months). With one exception, all patients had urine and/or bowel problems (incontinence) preoperatively. A lumbar drain was inserted in five patients. The mean follow-up period was 15.4 months. Symptoms improved in 4/7 patients, in two cases no clinical difference was noted while one patient deteriorated. In two cases, a spinal cord stimulator was eventually implanted. In all seven cases, a significantly decreased cyst size was noted on MRI.Conclusions: Cyst fenestration and the use of a vascularized fasciocutaneous flap successfully obliterated all cysts, with satisfactory clinical efficacy. Larger and comparative studies are warranted to clarify the long-term effects of this surgical technique in patients with symptomatic Tarlov cysts

Cerebrospinal fluid biomarkers of glial and axonal injury in cervical spondylotic myelopathy

OBJECTIVE Degenerative cervical spondylotic myelopathy (CSM) is a major cause of spinal cord dysfunction with an unpredictable prognosis. Βiomarkers reflecting pathophysiological processes in CSM have been insufficiently investigated. It was hypothesized that preoperative cerebrospinal fluid (CSF) biomarker levels are altered in patients with CSM and correlate with neurological status and outcome. METHODS CSF biomarkers from patients with CSM and controls were analyzed with immunoassays. Spinal cord changes were evaluated with MRI. The American Spinal Cord Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and the EQ-5D questionnaire were applied prior to and 3 months after surgery. A p value 0.05) were included in the study. In the CSM subjects, CSF neurofilament light subunit (NF-L) and glial fibrillary acidic protein (GFAP) concentrations were higher (p 20). CONCLUSIONS CSF biomarkers of glial and axonal damage, inflammation, and synaptic changes are altered in symptomatic CSM patients, indicating that axonal injury, astroglial activation, and Aβ dysmetabolism may be present in these individuals. These findings reflect CSM pathophysiology and may aid in prognostication. However, future studies including larger patient cohorts, postoperative biomarker data and imaging, and longer follow-up times are required to validate the present findings

Neurosurgical untethering with or without syrinx drainage results in high patient satisfaction and favorable clinical outcome in post-traumatic myelopathy patients

Study design: Retrospective data collection and patient-reported outcome measures. Objectives: To investigate surgical outcome, complications, and patient satisfaction in patients with chronic SCI and symptomatic post-traumatic progressive myelopathy (PPM) who underwent neurosurgical untethering and/or spinal cord cyst drainage with the aim of preventing further neurological deterioration. Setting: Single-center study at an academic neurosurgery department. Methods: All SCI patients who underwent neurosurgery between 1996 and 2013 were retrospectively included. All medical charts and the treating surgeon’s operative reports were reviewed to identify surgical indications, surgical technique, and post-operative complications. A questionnaire and an EQ-5D-instrument were used to assess patient's self-described health status and satisfaction at long-term follow-up. Results: Fifty-two patients (43 men, 9 women) were identified, of whom five were dead and one was lost to follow-up. Main indications for surgery were pain (54%), motor (37%), or sensory (8%) impairment, and spasticity (2.0%). Overall complications were rare (8%). At follow-up, the subjectively perceived outcome was improved in 24 and remained unchanged in 21 patients. Thus, the surgical aim was met in 87% of patients. Of the 46 eligible patients, 38 responded to the questionnaire of whom 65% were satisfied with the surgical results. Patients with cervical lesions were more satisfied with the surgical treatment than patients with thoracic/thoracolumbar lesions (p = 0.05). Conclusions: Neurosurgical untethering and/or cyst drainage in chronic SCI patients and PPM resulted in a high degree of patient satisfaction, particularly in cervical SCI patients with minimal complications