Primary anterior lumbar interbody fusion, with and without posterior instrumentation: a 1,377-patient cohort from a multicenter spine registry.

BACKGROUND CONTEXT: Lumbar interbody instrumentation techniques are common and effective surgical options for a variety of lumbar degenerative pathologies. Anterior lumbar interbody fusion (ALIF) has become a versatile and powerful means of decompression, stabilization, and reconstruction. As an anterior only technique, the integrity of the posterior muscle and ligaments remain intact. Adding posterior instrumentation to ALIF is common and may confer benefits in terms of higher fusion rate but could contribute to adjacent segment degeneration due to additional rigidity. Large clinical studies comparing stand-alone ALIF with and without posterior supplementary fixation (ALIF+PSF) are lacking. PURPOSE: To compare rates of operative nonunion and adjacent segment disease (ASD) in ALIF with or without posterior instrumentation. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients (≥18 years old) who underwent primary ALIF for lumbar degenerative pathology between levels L4 to S1 over a 12-year period. Exclusion criteria included trauma, cancer, infection, supplemental decompression, noncontiguous fusions, prior lumbar fusions, and other interbody devices. OUTCOME MEASURES: Reoperation for nonunion and ASD compared between ALIF only and ALIF+PSF. METHODS: Reoperations were modeled as time-to-events where the follow-up time was defined as the difference between the primary ALIF procedure and the date of the outcome of interest. Crude cumulative reoperation probabilities were reported at 5-years follow-up. Multivariable Cox proportional hazard regression was used to evaluate risk of operative nonunion and for ASD adjusting for patient characteristics. RESULTS: The study consisted of 1,377 cases; 307 ALIF only and 1070 ALIF+PSF. Mean follow-up time was 5.6 years. The 5-year crude nonunion incidence was 2.4% for ALIF only and 0.5% for ALIF+PSF; after adjustment for covariates, a lower operative nonunion risk was observed for ALIF+PSF (HR=0.22, 95% CI=0.06-0.76). Of the patients who are deemed potentially suitable for ALIF alone, one would need to add posterior instrumentation in 53 patients to prevent one case of operative nonunion at a 5-year follow-up (number needed to treat). Five-year operative ASD incidence was 4.3% for ALIF only and 6.2% for ALIF+PSF; with adjustments, no difference was observed between the cohorts (HR=0.96, 95% CI=0.54-1.71). CONCLUSIONS: While the addition of posterior instrumentation in ALIFs is associated with lower risk of operative nonunion compared with ALIF alone, operative nonunion is rare in both techniques (<5%). Accordingly, surgeons should evaluate the added risks associated with the addition of posterior instrumentation and reserve the supplemental posterior fixation for patients that might be at higher risk for operative nonunion. Rates of operative ASD were not statistically higher with the addition of posterior instrumentation suggesting concern regarding future risk of ASD perhaps should not play a role in considering supplemental posterior instrumentation in ALIF.

Lumbar Spinal Canal Segmentation in Cases with Lumbar Stenosis Using Deep-U-Net Ensembles.

BACKGROUND: Narrowing of the lumbar spinal canal, or lumbar stenosis (LS), may cause debilitating radicular pain or muscle weakness. It is the most frequent indication for spinal surgery in the elderly population. Modern diagnosis relies on magnetic resonance imaging and its inherently subjective interpretation. Diagnostic rigor, accuracy, and speed may be improved by automation. In this work, we aimed to determine whether a deep-U-Net ensemble trained to segment spinal canals on a heterogeneous mix of clinical data is comparable to radiologists' segmentation of these canals in patients with LS. METHODS: The deep U-nets were trained on spinal canals segmented by physicians on 100 axial T2 lumbar magnetic resonance imaging selected randomly from our institutional database. Test data included a total of 279 elderly patients with LS that were separate from the training set. RESULTS: Machine-generated segmentations (MA) were qualitatively similar to expert-generated segmentations (ME1, ME2). Machine- and expert-generated segmentations were quantitatively similar, as evidenced by Dice scores (MA vs. ME1: 0.88 ± 0.04, MA vs. ME2: 0.89 ± 0.04), the Hausdorff distance (MA vs. ME1: 11.7 mm ± 13.8, MA vs. ME2: 13.1 mm ± 16.3), and average surface distance (MAvs. ME1: 0.18 mm ± 0.13, MA vs. ME2 0.18 mm ± 0.16) metrics. These metrics are comparable to inter-rater variation (ME1 vs. ME2 Dice scores: 0.94 ± 0.02, the Hausdorff distances: 9.3 mm ± 15.6, average surface distances: 0.08 mm ± 0.09). CONCLUSION: We conclude that machine learning algorithms can segment lumbar spinal canals in LS patients, and automatic delineations are both qualitatively and quantitatively comparable to expert-generated segmentations.

Brain and lung metastasis of uterine leiomyosarcoma: illustrative case.

BACKGROUND: Uterine leiomyosarcoma is a rare, extremely aggressive tumor with a high rate of metastasis. Five-year survival for individuals with metastatic disease is only 10%-15%. Metastases to the brain are exceptionally rare and are associated with poor survival. OBSERVATIONS: The authors report a case of uterine leiomyosarcoma that metastasized to the brain in a 51-year-old woman. A single lesion on magnetic resonance imaging was discovered in the right posterior temporo-occipital region 44 months after resection of the primary uterine tumor. The patient underwent a right occipital craniotomy with gross-total resection of the tumor and is receiving adjuvant stereotactic radiosurgery and chemotherapy with gemcitabine and docetaxel. At 8 months postresection, the patient remains alive and asymptomatic with no sign of recurrence. A literature review of prior reported cases was conducted to analyze patterns of approach to patient treatment and survival. LESSONS: The authors found an apparent survival benefit in patients receiving adjuvant radiation therapy.

Structural Changes in the Cervicomedullary Junction in Adult Chiari Patients.

OBJECTIVE: To assess volumetric changes in the spinal cord at the cervicomedullary junction, diameter of the cervicomedullary cord, and width of the brainstem following posterior fossa decompression (PFD). METHODS: A retrospective analysis of adult patients with Chiari malformation who underwent PFD was performed. Segmentations were done on clinical quality T2-weighted cervical magnetic resonance images obtained before and after decompression using ITK-SNAP. Volumes of neural tissue within the cervicomedullary junction were evaluated from 10 mm cranial to the medullary beak to the cervical spinal cord at the level of the caudal endplate of the second cervical vertebra. The diameter of the cervicomedullary cord was calculated perpendicular to the spinal cord. The width of the brainstem was measured perpendicular to the clivus at the level of the basion. RESULTS: Twenty adult patients, a mean age of 49.55 years, were included. The cervical cord increased in volume by 13 mm3 to 338 mm3, with an average increase of 155 mm3 (P-value of 0.00002). The diameter of the cervicomedullary cord increased 10.30% 7 mm superior to the beak (P-value of 0.00074), 11.49% at the apex of the beak (P-value of 0.00082), 8.29% 7 mm inferior to the beak (P-value of 0.00075), and the brainstem increased 14.46% perpendicular to the clivus (P-value of 0.00109). The spinal cord at the inferior aspect of the C3 vertebra changed insignificantly (P-value of 0.10580). CONCLUSION: The volume of the cervical cord at the cervical-medullary junction, width of the cervicomedullary cord, and diameter of the brainstem increase following PFD.

Neurosurgical Management of Interspinous Device Complications: A Case Series.

Background: Best practice guidelines for treating lumbar stenosis include a multidisciplinary approach, ranging from conservative management with physical therapy, medication, and epidural steroid injections to surgical decompression with or without instrumentation. Marketed as an outpatient alternative to a traditional lumbar decompression, interspinous process devices (IPDs) have gained popularity as a minimally invasive stabilization procedure. IPDs have been embraced by non-surgical providers, including physiatrists and anesthesia interventional pain specialists. In the interest of patient safety, it is imperative to formally profile its safety and identify its role in the treatment paradigm for lumbar stenosis. Case Description: We carried out a retrospective review at our institution of neurosurgical consultations for patients with hardware complications following the interspinous device placement procedure. Eight cases within a 3-year period were identified, and patient characteristics and management are illustrated. The series describes the migration of hardware, spinous process fracture, and worsening post-procedural back pain. Conclusions: IPD placement carries procedural risk and requires a careful pre-operative evaluation of patient imaging and surgical candidacy. We recommend neurosurgical consultation and supervision for higher-risk IPD cases.

Supraspinal functional and structural plasticity in patients undergoing surgery for degenerative cervical myelopathy.

OBJECTIVE: The aim of this study was to investigate cerebral reorganization, both structurally and functionally, occurring in patients with degenerative cervical myelopathy (DCM) after surgical decompression. METHODS: In the current observational study of 19 patients, high-resolution T1-weighted structural MRI and resting-state functional MRI scans were obtained pre- and postoperatively in patients with DCM and healthy controls (HCs). The resting-state functional MRI data were utilized to perform region-of-interest (ROI)-to-ROI and ROI-to-voxel functional connectivity (FC) analysis and were similarly compared between and within cohorts. Macroscopic structural plasticity was evaluated by assessing for changes in cortical thickness within the DCM cohort after decompression surgery. RESULTS: Prior to surgery, FC patterns were significantly different between DCM patients and HCs in cerebral areas responsible for postural control, motor regulation, and perception and integration of sensory information. Significantly stronger FC between the cerebellum and frontal lobes was identified in DCM patients postoperatively compared with DCM patients preoperatively. Additionally, increased FC between the cerebellum and primary sensorimotor areas was found to be positively associated with neurological improvement in patients with DCM. No macroscopic structural changes were observed in the DCM patients after surgery. CONCLUSIONS: These results support the authors' hypothesis that functional changes within the brain are associated with effective postoperative recovery, particularly in regions associated with motor regulation and with perception and integration of sensory information. In particular, increased FC between the cerebellum and the primary sensorimotor after surgery appears to be associated with neurological improvement. Macroscopic morphological changes may be too subtle to be detected within 3 months after surgery.

Predicting Spinal Surgery Candidacy From Imaging Data Using Machine Learning.

BACKGROUND: The referral process for consultation with a spine surgeon remains inefficient, given a substantial proportion of referrals to spine surgeons are nonoperative. OBJECTIVE: To develop a machine-learning-based algorithm which accurately identifies patients as candidates for consultation with a spine surgeon, using only magnetic resonance imaging (MRI). METHODS: We trained a deep U-Net machine learning model to delineate spinal canals on axial slices of 100 normal lumbar MRI scans which were previously delineated by expert radiologists and neurosurgeons. We then tested the model against lumbar MRI scans for 140 patients who had undergone lumbar spine MRI at our institution (60 of whom ultimately underwent surgery, and 80 of whom did not). The model generated automated segmentations of the lumbar spinal canals and calculated a maximum degree of spinal stenosis for each patient, which served as our biomarker for surgical pathology warranting expert consultation. RESULTS: The machine learning model correctly predicted surgical candidacy (ie, whether patients ultimately underwent lumbar spinal decompression) with high accuracy (area under the curve = 0.88), using only imaging data from lumbar MRI scans. CONCLUSION: Automated interpretation of lumbar MRI scans was sufficient to correctly determine surgical candidacy in nearly 90% of cases. Given that a significant proportion of referrals placed for spine surgery evaluation fail to meet criteria for surgical intervention, our model could serve as a valuable tool for patient triage and thereby address some of the inefficiencies within the outpatient surgical referral process.

Eigenrank by committee: Von-Neumann entropy based data subset selection and failure prediction for deep learning based medical image segmentation.

Manual delineation of anatomy on existing images is the basis of developing deep learning algorithms for medical image segmentation. However, manual segmentation is tedious. It is also expensive because clinician effort is necessary to ensure correctness of delineation. Consequently most algorithm development is based on a tiny fraction of the vast amount of imaging data collected at a medical center. Thus, selection of a subset of images from hospital databases for manual delineation - so that algorithms trained on such data are accurate and tolerant to variation, becomes an important challenge. We address this challenge using a novel algorithm. The proposed algorithm named 'Eigenrank by Committee' (EBC) first computes the degree of disagreement between segmentations generated by each DL model in a committee. Then, it iteratively adds to the committee, a DL model trained on cases where the disagreement is maximal. The disagreement between segmentations is quantified by the maximum eigenvalue of a Dice coefficient disagreement matrix a measure closely related to the Von Neumann entropy. We use EBC for selecting data subsets for manual labeling from a larger database of spinal canal segmentations as well as intervertebral disk segmentations. U-Nets trained on these subsets are used to generate segmentations on the remaining data. Similar sized data subsets are also randomly sampled from the respective databases, and U-Nets are trained on these random subsets as well. We found that U-Nets trained using data subsets selected by EBC, generate segmentations with higher average Dice coefficients on the rest of the database than U-Nets trained using random sampling (p < 0.05 using t-tests comparing averages). Furthermore, U-Nets trained using data subsets selected by EBC generate segmentations with a distribution of Dice coefficients that demonstrate significantly (p < 0.05 using Bartlett's test) lower variance in comparison to U-Nets trained using random sampling for all datasets. We believe that this lower variance indicates that U-Nets trained with EBC are more robust than U-Nets trained with random sampling.

Compensatory brainstem functional and structural connectivity in patients with degenerative cervical myelopathy by probabilistic tractography and functional MRI.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord impairment in adults. Previous supraspinal investigations have primarily focused on cortical changes in this patient population. As the nexus between the brain and the spinal cord, the brainstem has been understudied in patients with DCM. The current study examined the structural and functional connectivity between the brainstem and cortex in DCM patients using probabilistic tractography and resting-state functional MRI. A total of 26 study patients and 32 neurologically intact, healthy volunteers (HCs) participated in this prospective analysis. The study cohort included DCM patients (n = 18), as well as neurologically asymptomatic patients with evidence of cervical spine degenerative changes and spinal cord compression (n = 8). Results of the study demonstrated significant differences in fiber density (FD), fiber cross-section (FDC), and the functional connectivity (FC) between the study cohort and HCs. Through seeding the brainstem, the study cohort showed reductions in FD and FDC along the corticospinal tract, including regions extending through the corona radiata and internal capsule. By correlating FD and FDC with the Neck Disability Index (NDI), and the modified Japanese Orthopaedic Association (mJOA), we identified increasing total volume of projections to the thalamus, basal ganglia, and internal capsule, and increased functional connectivity to visual network and the posterior parietal cortices. These results support our hypothesis that DCM patients tend to have long-term FC reorganization not only localized to sensorimotor regions, but also to regulatory and visual processing regions, designed to ultimately preserve neurological function.

Subcutaneous sumatriptan: association with decreases in postoperative pain and opioid use after elective cranial surgery.

OBJECTIVE: Sumatriptan, a serotonin receptor agonist, has been used in the management of primary headache disorders and has been shown to affect trigeminal dural afferents. There is limited literature on the safety and efficacy of sumatriptan for postcraniotomy pain management. This study aimed to identify whether subcutaneous sumatriptan is a safe and efficacious pain management strategy after elective craniotomy. METHODS: The authors retrospectively reviewed patients who underwent supratentorial or suboccipital craniotomy between 2016 and 2019 that was performed by a single provider at a single institution to identify patients given subcutaneous sumatriptan in the postoperative period. Pain scores and intravenous and oral opioid use were compared in patients with (n = 15) and without (n = 45) sumatriptan administration. RESULTS: Patients with and without sumatriptan administration had no significant differences in baseline characteristics or surgery type. There were no sumatriptan-related complications. The average pain score decreased from 3.9 to 1.3 within 1 hour after sumatriptan administration (p = 0.014). In both adult and pediatric patients there was decreased postoperative pain (adults: pain score of 1.1 vs 7.1, p < 0.001; pediatric: 1.1 vs 3.9, p = 0.007) within the first 48 hours. There were decreases in intravenous opioid use, length of intravenous opioid use, maximum dose of intravenous opioid used, oral opioid use, length of oral opioid use, and maximum dose of oral opioid used in both adult and pediatric patients. CONCLUSIONS: The authors identified subcutaneous sumatriptan as a safe and efficacious tool for postoperative pain management after craniotomy. Large multicenter randomized controlled studies are needed to further evaluate the specific role of sumatriptan in postoperative pain management after craniotomy.

pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI).

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTRasym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam (R2 = 0.4777, P = 0.0021), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury (R2 = 0.5334, P = 0.0107), and a non-linear correlation with the time from injury to MRI exam (R2 = 0.6317, P = 0.0004). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.

Rigorous anaesthesia management protocol for patients with intracranial arterial stenosis: a prospective controlled-cohort study.

OBJECTIVES: Reducing variability is integral in quality management. As part of the ongoing Encephaloduroarteriosynangiosis Revascularisation for Symptomatic Intracranial Arterial Stenosis (ERSIAS) trial, we developed a strict anaesthesia protocol to minimise fluctuations in patient parameters affecting cerebral perfusion. We hypothesise that this protocol reduces the intraoperative variability of targeted monitored parameters compared to standard management. DESIGN: Prospective cohort study of patients undergoing encephaloduroarteriosynangiosis surgery versus standard neurovascular interventions. Patients with ERSIAS had strict perioperative management that included normocapnia and intentional hypertension. Control patients received regular anaesthetic standard of care. Minute-by-minute intraoperative vitals were electronically collected. Heterogeneity of variance tests were used to compare variance across groups. Mixed-model regression analysis was performed to establish the effects of treatment group on the monitored parameters. SETTING: Tertiary care centre. PARTICIPANTS: 24 participants: 12 cases (53.8 years ± 16.7 years; 10 females) and 12 controls (51.3 years ± 15.2 years; 10 females). Adults aged 30-80 years, with transient ischaemic attack or non-disabling stroke (modified Rankin Scale <3) attributed to 70-99% intracranial stenosis of the carotid or middle cerebral artery, were considered for enrolment. Controls were matched according to age, gender and history of neurovascular intervention. MAIN OUTCOME MEASURES: Variability of heart rate, mean arterial blood pressure (MAP), systolic blood pressure and end tidal CO2 (ETCO2) throughout surgical duration. RESULTS: There were significant reductions in the intraoperative MAP SD (4.26 vs 10.23 mm Hg; p=0.007) and ETCO2 SD (0.94 vs 1.26 mm Hg; p=0.05) between the ERSIAS and control groups. Median MAP and ETCO2 in the ERSIAS group were higher (98 mm Hg, IQR 23 vs 75 mm Hg, IQR 15; p<0.001, and 38 mm Hg, IQR 4 vs 32 mm Hg, IQR 3; p<0.001, respectively). CONCLUSIONS: The ERSIAS anaesthesia protocol successfully reduced intraoperative fluctuations of MAP and ETCO2. The protocol also achieved normocarbia and the intended hypertension. TRIAL REGISTRATION NUMBER: NCT01819597; Pre-results.

Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage.

Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping vs coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR 5.17; 95% confidence interval (CI) 1.21-25.02). RIC also showed a trend toward lower incidence of stroke (28.6 vs. 47.5%) and death (4.8 vs. 19.7%). Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.

Remote Ischemic Conditioning Alters Methylation and Expression of Cell Cycle Genes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC. METHODS: Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein-protein interactions. RESULTS: We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10(-4)) and inflammatory responses (P<1.4×10(-4)). The cell cycle pathway genes form a significant protein-protein interaction network of tightly coexpressed genes (P<0.00001). CONCLUSIONS: Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.

A minimally-invasive rat model of subarachnoid hemorrhage and delayed ischemic injury.

BACKGROUND: Double-injection models of subarachnoid hemorrhage (SAH) in rats are the most effective in producing vasospasm, delayed neurological deficits and infarctions. However, they require two large surgeries to expose the femoral artery and the atlanto-occipital membrane. We have developed a minimally-invasive modification that prevents confounding effects of surgical procedures, leakage of blood from the subarachnoid space and minimizes risk of infection. METHODS: Rats are anesthetized and the ventral tail artery is exposed through a small (5 mm), midline incision, 0.2 mL of blood is taken from the artery and gentle pressure is applied for hemostasis. The rat is flipped prone, and with the head flexed to 90 degrees in a stereotactic frame, a 27G angiocath is advanced in a vertical trajectory, level with the external auditory canals. Upon puncturing the atlanto-occipital membrane, the needle is slowly advanced and observed for cerebrospinal fluid (CSF). A syringe withdraws 0.1 mL of CSF and the blood is injected into the subarachnoid space. The procedure is repeated 24 hours later by re-opening the tail incision. At 8 days, the rats are euthanized and their brains harvested, sectioned, and incubated with triphenyltetrazolium chloride (TTC). RESULTS: Rats develop neurological deficits consistent with vasospasm and infarction as previously described in double-injection models. Cortical and deep infarctions were demonstrated by TTC staining and on histopathology. CONCLUSIONS: A minimally invasive, double-injection rat model of SAH and vasospasm is feasible and produces neurological deficits and infarction. This model can be used to study neuroprotective treatments for vasospasm and delayed neurological deficits following SAH, reducing the confounding effects of surgical interventions.