Burkhardt BW, Simgen A, Wagenpfeil G, Reith W, Oertel JM. Adjacent Segment Degeneration After Anterior Cervical Discectomy and Fusion With an Autologous Iliac Crest Graft: A Magnetic Resonance Imaging Study of 59 Patients With a Mean Follow-up of 27 Years. Neurosurgery. 2018;82(6):799-807. doi:10.1093/neuros/nyx304.
Despite the high surgical acceptance of ACDF, it is associated with several disadvantages. One of those is the acceleration of adjacent segment degeneration (ASD). Adjacent segment degeneration might become a symptomatic condition that requires repeat surgery. The literature presents 2 different opinions on the development of adjacent segment degeneration. One supports the hypothesis that ASD is the result of a physiological process of degeneration. Other authors believe that fusion increases the stress and strain at the 2 adjacent segments and thereby accelerate segmental degeneration.
This study reports the evaluation of MRI findings of disc degeneration of 59 (36 male, 23 female) patients who underwent ACDF. The mean follow-up was 27 yr (18-45 yr). Besides measuring the disc height, a 5-step grading system (segmental degeneration index [SDI]) including disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis was used to assess the grade of adjacent and adjoining segments.
The authors state that the present study is unique and presents 2 important aspects. This is the first study that assessed the grade of degeneration of the 2 segments that are located cranial and caudal to the fused level (adjacent segments) using MRI with a follow-up of 27 yr. Secondly, this study assessed and compared the grade of degeneration of the first and second segments, which are located cranial to the cranial adjacent segment (cranial adjoining segments) and located caudal to the caudal adjacent segment (caudal adjoining segments). Depending on the location of the initial fusion, 2 adjacent segments (1 cranial and 1 caudal) and 4 adjoining segments (2 cranial and 2 caudal) were assessed.
An segmental degeneration index of 0 describes a segment without signs of degeneration, whereas an segmental degeneration index of 1.0 describes a segment that shows the most distinct signs of degeneration according to the 5-step grading system. The segmental degeneration index of cranial and caudal adjacent segments was significantly higher compared to adjoining segments. The disc height of cranial and caudal adjacent segments was significantly lower compared to adjoining segments.
The conclude that the physiological aging of the cervical spine does not overcome adjacent segment degeneration. The disc height and the SDI in adjacent segment are significantly worse compared to adjoining segments. ACDF seems to increase the stress on the cranial adjacent segment more than on the caudal adjacent segment and ACDF has a major influence on the acceleration of ASD.
3 Figures, 7 tables
This seems like something we should already know the answer to, but the data on this point is contentious. I think the bulk of the evidence points to adjacent segment degeneration as a result of altered biomechanics of the fusion, and not just progression of the underlying degenerative disc disease.
Oravec CS, Motiwala M, Reed K, et al. Big Data Research in Neurosurgery: A Critical Look at this Popular New Study Design. Neurosurgery. 2018;82(5):728-746. doi:10.1093/neuros/nyx328.
This study aimed to shed light on the approach to clinical research of using “big data”. The authors compiled a list of commonly used databases that were not specifically created to study neurosurgical procedures, conditions, or diseases. Three North American journals were manually searched for articles published since 2000 utilizing these and other non-neurosurgery-specific databases (Journal of Neurosurgery Publishing Group (n= 200), Neurosurgery (n = 71), World Neurosurgery (n = 53)). A number of data points per article were collected, tallied, and analyzed. A total of 324 articles were identified since 2000 with an exponential increase since 2011 (257/324, 79%). The Journal of Neurosurgery Publishing Group published the greatest total number (n = 200). The National Inpatient Sample was the most commonly used database (n = 136). The average study size was 114 841 subjects. The most prevalent topics were vascular (n = 77) and neuro-oncology (n = 66). Harvard Medical School was the top institution, using this research technique with 59 representations.
With the data already organized, digitized, and a researcher’s access to such data and time for analysis is more streamlined than ever at low cost. Databases that are based on real-world clinical practices are able to paint a broad portrait of a particular disease in areas such as demographics, treatments, complications, outcomes, and cost. Geographic and socioeconomic variation in disease prevalence, incidence, treatment, and health care utilization can also be assessed. Institutional review board approval is usually not required because datasets are deidentified and HIPAA compliant. The greatest strength of these data sets is likely the very large sample size, typically much larger than any one institution or even group of institutions could obtain within a reasonable time period.
Previously investigators have identified a number of major limitations to this big data approach, such as the data source, coding issues, linkages, confounders, definitions, and data validation.
One of the most serious weaknesses is data integrity. Inputting the correct information for any patient with any disease and comorbidities requires a substantial amount of medical knowledge. The more complex the patient or the process of gathering and importing the information, the greater the risk of introducing errors.
At the core of “big data” research is exploratory data analysis, the results of which should lead to more focused, hypothesis driven studies. Key steps of traditional clinical study design include the formulation of a hypothesis or question, the delineation of inclusion and exclusion criteria, followed by collection and analysis of data. The determination of which data points to collect, the actual data gathering, and concomitant quality control (ie, data integrity) is extremely important. The authors note that only 3 of the publications they reviewed included comparative data from either the primary or senior author’s own institution. In other words, virtually none of the investigators that used a ready-made database attempted to answer the same question(s) or confirm or refute their exploratory data analysis findings with data from their own institution.
Publications that utilize big databases are generally lauded and accepted as authoritative and accurate. They are favored by journals, likely stemming from their large patient populations and complex statistics with numerous P-values. The Results section of many big data articles contains univariate followed by multivariate analyses on the outcome(s) of interest, the consequence often being an inordinate number of p-values. Authors then proceed to expound on all “statistically significant” findings with little discussion on the magnitude of the effect size or clinical meaningfulness.
7 Tables
Al-Mufti F, Amuluru K, Roth W, Nuoman R, El-Ghanem M, Meyers PM. Cerebral Ischemic Reperfusion Injury Following Recanalization of Large Vessel Occlusions. Neurosurgery. 2018;82(6):781-789. doi:10.1093/neuros/nyx341.
Cerebral ischemic reperfusion injury (CIRI) is defined as deterioration of brain tissue suffered from ischemia that concomitantly reverses the benefits of re-establishing cerebral blood flow following mechanical or chemical therapies for acute ischemic stroke. The authors examine in this review article the pathophysiology of cerebral ischemic reperfusion injury, imaging modalities, and potential neuroprotective strategies. They try to lay down a potential treatment approach for patients with cerebral ischemic reperfusion injury following emergent endovascular recanalization for acute ischemic stroke.
Cerebral ischemic reperfusion injury includes a range of manifestations. On one end, there is a subgroup of patients who fail to improve despite evident recanalization. This is hypothesized to occur due to incomplete tissue reperfusion, injury of the neurovascular unit, and/or distal microthrombosis, which has been termed the “no-reflow phenomenon.” At the other end, there is unregulated reperfusion with hemorrhagic transformation (HT). This process occurs due to activation of inflammatory mediators along with an impaired autoregulatory of the brain vasculature. These factors predispose to blood extravasation when the ischemic brain tissue is ultimately reperfused.
Some imaging characteristics may help predict reperfusion injury. A continuous increase of T2 value during the first 2 hours of reperfusion, in spite of initial ADC improvement, may predict secondary deterioration. This may indicate improving cytotoxic edema, in the presence of progressing vasogenic edema during early reperfusion. HT of ischemic infarction is predicted by proportion of very low ADC voxels. MRI has been utilized to assess for degree of BBB breakdown, as T2 signal is indicative of cytotoxic cerebral edema. BBB disruption is higher in subjects who demonstrate reperfusion by perfusion-weighted imaging, and that these patients were more likely to have a poor clinical outcome and increased risk of HT. Another retrospective review of imaging in stroke patients similarly demonstrated an association between reperfusion and BBB breakdown, which, in turn, correlated with a higher incidence of HT in those managed with IV tpa.
Multiple studies have sought to find predictors for hemorrhagic complications following endovascular reperfusion therapy. Patients with evidence of radiographic large hemispheric infarct (ASPECTS < 7) before mechanical reperfusion, or TIMI ≥ 2 after reperfusion with an ASPECTS < 7 were more likely to develop HT. Additionally multimodal endovascular therapies with IV-tPA were associated with higher risk of developing parenchymal hematomas. Also, tandem occlusions, hyperglycemia on admission, and poorly controlled hypertension with a systolic BP > 220 mm Hg or diastolic BP >105 mm Hg were also risk factors for HT.
1 Table
Simonsen CZ, Yoo AJ, Sørensen LH, et al. Effect of General Anesthesia and Conscious Sedation During Endovascular Therapy on Infarct Growth and Clinical Outcomes in Acute Ischemic Stroke. JAMA Neurol. 2018;75(4):470. doi:10.1001/jamaneurol.2017.4474.
Does infarct growth depend on the type of anesthesia used during endovascular therapy for stroke?
The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Patients were randomized to either the general anesthesia (GA) group or the conscious sedation (CS) group (1:1 allocation) before EVT. The primary end point was infarct growth between MR scans performed before EVT and 48 to 72 hours after EVT. The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance. There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91. They conclude that for patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS.
A longer delay for patients in the GA group was observed from arrival at the neurointerventional suite to groin puncture. However, the median difference was only 9 minutes. This time delay for induction and intubation is acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms. Regarding to the authors choice of MRI as a stroke imaging tool, the time delay from hospital admission to vessel puncture in this study was much shorter (68 minutes) than in the SWIFTPRIME trial (90 minutes), which largely employed computed tomography imaging.
2 Figures, 3 Tables
Jeon S-B, Sohn CH, Seo D-W, et al. Acute Brain Lesions on Magnetic Resonance Imaging and Delayed Neurological Sequelae in Carbon Monoxide Poisoning. JAMA Neurol. 2018;75(4):436. doi:10.1001/jamaneurol.2017.4618.
The authors sought to answer the question as to whether DWI detected acute brain lesions effected the probability of delayed neurological sequelae after carbon monoxide poisoning.
In this observational study of 387 patients with acute carbon monoxide poisoning, brain lesions on diffusion-weighted imaging were observed in 104 patients (26.9%) and delayed neurological sequelae occurred in 101 patients (26.1%). Globus pallidus lesion was the most common pattern (19.9%); Diffuse lesions, 13 [3.4%]; and focal asymmetric lesions, 57 [14.7%]). But 37 (35.6%) had multiple types of lesions. Most lesions were supratentorial or cerebellar, with the brainstem and thalami only rarely involved. Splenial lesions were seen in 5 patients.
They conclude that the presence of acute brain lesions was independently associated with the development of delayed neurological sequelae. Diffusion-weighted imaging during the acute phase of CO poisoning may therefore help identify patients at risk of developing these debilitating sequelae.
1 Figure, 3 Tables.
Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;May 16:NEJMoa1804355. doi:10.1056/NEJMoa1804355.
In a multicenter trial, the authors randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. They excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days.
The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group. The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group.
Patients were selected on the basis of mismatch between findings on MRI diffusion-weighted imaging and FLAIR. Interobserver agreement for this combination of findings was 73 to 78% in two previous studies. The presence of intracranial-artery occlusion or penumbral pattern before thrombolysis was not a prerequisite for randomization in this trial, and they did not assess recanalization or reperfusion as a biologic marker of treatment effectiveness.
They conclude that in patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days.
3 Tables, 2 Figures (no MRI)
Wouters A, Cheng B, Christensen S, et al. Automated DWI analysis can identify patients within the thrombolysis time window of 4.5 hours. Neurology. 2018;90(18):e1570-e1577. doi:10.1212/WNL.0000000000005413.
The authors developed an automated model based on diffusion-weighted imaging (DWI) to detect patients within 4.5 hours after stroke onset and compare this method to the visual DWI-FLAIR mismatch.
The authors performed a subanalysis of the “DWI-FLAIR mismatch for the identification of patients with acute ischemic stroke within 4.5 hours of symptom onset” (PRE-FLAIR) and the “AX200 for ischemic stroke” (AXIS 2) trials. They developed a prediction model with data from the PREFLAIR study by backward logistic regression with the 4.5-hour time window as dependent variable and the following explanatory variables: age and median relative DWI (rDWI) signal intensity, interquartile range (IQR) rDWI signal intensity, and volume of the core. They obtained the accuracy of the model to predict the 4.5-hour time window and validated the findings in an independent cohort from the AXIS 2 trial. They compared the receiver operating characteristic curve to the visual DWI-FLAIR mismatch.
In the derivation cohort of 118 patients, they retained the interquartile range rDWI as explanatory variable. A threshold of 0.39 was most optimal in selecting patients within 4.5 hours after stroke onset resulting in a sensitivity of 76% and specificity of 63%. The accuracy was validated in an independent cohort of 200 patients. They conclude that an automated analysis of DWI performs at least as good as the visual DWI-FLAIR mismatch in selecting patients within the 4.5-hour time window.
The authors put forth several speculative advantages to rDWI analysis compared to a visual rating technique. First, the technique is automated, resulting in consistent and reliable predictions. Second, the analysis does not require a FLAIR sequence, thereby shortening the duration of imaging recording time. This will reduce the risk of motion artifacts, improve the comfort of patients, and shorten the door-to-needle time. Third, patients with moderate or severe white matter disease hampering the visual DWI-FLAIR mismatch, rating can be analyzed with this automated approach.
3 Tables, 3 Figures
Hacohen Y, Wong YY, Lechner C, et al. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody–Associated disease. JAMA Neurol. 2018;75(4):478-487. doi:10.1001/jamaneurol.2017.4601.
Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of acquired demyelinating syndromes (ADSs) in adults and children and in up to 50% of children at first presentation of acquired demyelinating syndromes. Although MOG-Abs were initially reported in predominantly monophasic disease, a recent report of 210 children with acquired demyelinating syndromes who were followed up for at least 2 years observed that 22 of 65 MOG-Ab–positive children (33.8%) experienced clinical relapse and were diagnosed with multiphasic disseminated encephalomyelitis (MDEM), recurrent optic neuritis (RON), acute disseminated encephalomyelitis followed by optic neuritis (ADEM-ON), or neuromyelitis optica spectrum disorder (NMOSD). Two recent reports identified MOG-Abs in 22 of 35 children (62.8%) and 26 of 48 children (54%) with non–multiple sclerosis (MS) relapsing demyelination, which is more than 3 times more common than the aquaporin 4 antibody (AQP4-Ab).
Current therapeutic strategies are largely center specific, formal consensus guidelines are yet to be formulated, and no clinical trials have been performed. They conducted this retrospective, multicenter study to describe the first attack features, paraclinical characteristics, disease course, and responses to different treatment strategies.
In this multinational European cohort study of 102 children, neuromyelitis optica spectrum disorder (43.1%) was the predominant relapsing phenotype. In this cohort, in which more frequently relapsing patients were treated, azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were effective in managing relapses but not multiple sclerosis disease-modifying drugs.
A key finding of this study is that IVIG as maintenance therapy was associated with the greatest improvements in annualized relapse rates and Expanded Disability Status Scale (EDSS) score. Intravenous immunoglobulin is the only treatment that does not induce immunosuppression. Its mechanisms of action may go beyond the known immunomodulatory effect and may also be beneficial in patients with secondary inflammation.
3 Figures, 2 Tables
