1. Lakomkin N, Stannard B, Fogelson JL, et al. Comparison of surgical invasiveness and morbidity of adult spinal deformity surgery to other major operations. Spine J 2021;21:1784–92. Available from: https://doi.org/10.1016/j.spinee.2021.07.013
Adult spinal deformity (ASD) surgery treats a variety of debilitating spinal conditions including degenerative scoliosis, idiopathic scoliosis, kyphoscoliosis, and flat-back syndrome, among others. Although ASD surgery leads to excellent postoperative outcomes, numerous studies have identified rates of perioperative complications at approximately 50% to 70%, along with large incidence of intraoperative transfusions, prolonged hospital length of stay (LOS), and mortality.
A prospective surgical registry was used to identify all patients undergoing ASD surgery involving ≥ 7 segments. Seventeen additional procedures were included: coronary artery bypass grafting (CABG), pancreatectomy, and esophagectomy, among others. Perioperative factors (operative time, transfusions, ventilation) and complications were collected and combined with a previously validated Postoperative Morbidity Survey to create a Surgical Invasiveness and Morbidity Score (SIMS).
A total of 1,245,282 surgical patients were included, 4,656 of which underwent ASD surgery. After multiple regression modeling controlling for patient demographics and comorbidities, ASD surgery ranked fourth in Surgical Invasiveness and Morbidity Score. ASD surgery had a significantly greater SIMS than 13 other major procedures including 6th esophagectomy, 8th pancreatectomy, 11th craniotomy for tumor, and 12th sacral chordoma resection.
Among the 18 surgical procedures, ASD surgery ranked third in operative duration (351 min), surpassed only by microsurgical free flap (486 min) and esophagectomy (354 min). ASD ranked fourth in the proportion of patients requiring transfusion (50.9%), with only CABG (64.1%), open AAA repair (61.6%), and MVR (57.1%) with a greater incidence.
These data suggest that the surgical invasiveness and morbidity of ASD correction may exceed some of the largest and traditionally highest-risk surgical operations. These relationships held true despite the fact that ASD patients presented with a significantly decreased comorbidity burden when compared to their counterparts. Indeed, among the procedures with SIMS that exceeded ASD (CABG, AAA repair, cystectomy), all three are known to be associated with inherently sicker patients.
1 figure, 5 tables, no imaging
2. Maiese A, Manetti AC, Bosetti C, et al. SARS-CoV-2 and the brain: a review of the current knowledge on neuropathology in COVID-19. Brain Pathol 2021;31:1–17
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease, is able to affect the central nervous system. Compared with its well-known pulmonary tropism and respiratory complications, little has been studied about SARS-CoV-2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID-19 (coronavirus disease 2019). The authors present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID-19. They found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS-CoV- 2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID-19.
Tables 2 in the paper tabulates the most common features from the literature. The most common features were microgliosis and microglia activation, both with or without microglia nodules (37.6%), followed by hypoxic changes (29.4%) and astrogliosis (26.4%). Inflammatory infiltrates were present in 15.7% of cases, considering the parenchymal and perivascular localization, while leptomeningeal inflammation and infiltrates were observed in 5.6% of cases. Inflammation was mainly maintained by macrophages and T-lymphocytes. CNS samples showed microthrombi in 21 cases up to 197 (10.6%) and large ischemic lesions in 30 (15.2%). On the other hand, micro-and perivascular hemorrhages were described in 12.2% of cases, while focal hemorrhagic lesions in 6.6% of cases. Concerning olfactory bulb involvement, the presence of SARS-CoV-2 or inflammatory features of this part of the CNS was observed in 57 cases (28.9%).
2 large tables, and 2 figures, all pathology
3. Reid LB, Martínez-Heras E, Manjón JV, et al. Fully automated delineation of the optic radiation for surgical planning using clinically feasible sequences. Hum Brain Mapp 2021;42:5911–26
Quadrantanopia caused by inadvertent severing of Meyer’s Loop of the optic radiation is a well-recognized complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer’s Loop varies considerably between individuals. Quantifying this for individual patients is thus an important step to improve the safety profile of temporal lobectomies. Previous attempts to delineate Meyer’s Loop using diffusion MRI tractography have had difficulty estimating its full anterior extent, required manual ROI placement, and/or relied on advanced diffusion sequences that cannot be acquired routinely in most clinics. In this article the authors present CONSULT: a pipeline that can delineate the optic radiation from raw DICOM data in a completely automated way via a combination of robust preprocessing, segmentation, and alignment stages, plus simple improvements that bolster the efficiency and reliability of standard tractography. They tested CONSULT on 696 scans of predominantly healthy participants (539 unique brains), including both advanced acquisitions and simpler acquisitions that could be acquired in clinically acceptable timeframes. Delineations completed without error in 99.4% of the scans. The distance between Meyer’s Loop and the temporal pole closely matched both averages and ranges reported in dissection studies for all tested sequences. Median scan-rescan error of this distance was 1 mm. When tested on two participants with considerable pathology, delineations were successful and realistic. Through this, they demonstrate not only how to identify Meyer’s Loop with clinically feasible sequences, but also that this can be achieved without fundamental changes to tractography algorithms or complex post-processing methods.
2 tables, 8 figures with MR images
4. Nagahama Y, Zervos TM, Murata KK, et al. Real-world preliminary experience with responsive neurostimulation in pediatric epilepsy: a multicenter retrospective observational study. Neurosurgery 2021;89:997–1004
Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients.
Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in this cohort or between this cohort and the adult literature.
Considering this procedure invariably involves a craniectomy for device implantation, the benefits and potential harm based on the variable skull development in individual patients should be considered. Children experience rapid skull growth within the first 2 yr and reach ∼90% of the adult skull volume by 7 yr. There were 2 patients under 7 yr at the time of RNS implantation included in this study. The youngest was 3 yr of age at the time of RNS implantation, which is the youngest reported patient to undergo RNS implantation.
Open sutures in infants would be a contraindication due to the small head size and the difficulty in securing the device. Although skull immaturity may be considered a relative contraindication in very young patients, this must be determined on a case-by-case basis, given the variability in skull growth and skull thickness in individual patients (eg, 4-mm thickness of the skull at the site of RNS implant in the author’s case of a 3-yr-old patient). Variable skull thickness can be assessed with use of CT scans routinely obtained as part of presurgical workups (eg, scans used to localize intracranial electrodes; positron emission tomography). Given the smaller head size and potentially thinner scalp, it is more critical to optimize the positioning of the device to best fit the contour of the skull thus minimizing the risk of skin breakdown in young children (usually parietal area).
They conclude that these preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age.
2 figures, 4 tables
5. Ryvlin P, Rheims S, Hirsch LJ, et al. Neuromodulation in epilepsy: state-of-the-art approved therapies. Lancet Neurol 2021;20:1038–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/34710360
Neuromodulation is an alternative therapy to antiseizure drugs and surgery for individuals with drug-resistant epilepsy. By interfering with the nervous system through various approaches, neuromodulation might prevent or abort ictal events. Methods of neuromodulation include invasive therapies requiring an implantable device and electrodes—such as vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and responsive neurostimulation (RNS) of the epileptogenic zone or zones—and non-invasive methods, such as transcutaneous VNS and transcranial stimulation. Only VNS, ANT-DBS, and RNS are currently approved for the treatment of refractory focal epilepsy.
The primary objective of neuromodulation is to lessen seizure frequency. The 50% responder rate is the main measure used to quantify the reduction in frequency of seizures by neuromodulation. It is defined as the proportion of individuals achieving a reduction of at least 50% of their baseline seizure frequency. Neuromodulation should be considered palliative, in that only a few individuals might achieve freedom from seizures for longer than 12 months. By contrast, epilepsy surgery is viewed as a curative treatment option for drug-resistant epilepsy in that it can offer sustained seizure freedom in most people who undergo this procedure. However, some individuals with refractory focal epilepsy might be reluctant to undergo surgery or might not be eligible for surgery because of poor clinical predictors. In these cases, neuromodulation might be an option.
VNS has been used in more than 100 000 people with drug-resistant epilepsy over the past 20 years. ANT-DBS was approved in Europe in 2010 and in the USA by the Food and Drug Administration (FDA) in 2018, with RNS approved by the FDA in 2014. Accordingly, most data about the long-term safety and efficacy of these therapies have been published in the past 5 years.
Long-term extension studies of the original randomized controlled trials of VNS, ANT-DBS, and RNS might better reflect the real-life effects of neuromodulation. Findings of these studies suggest a comparable and progressively increased efficacy over time with ANT-DBS and RNS, for which the 50% responder rate reaches 73–74% at 7–9 years of follow-up. However, such observational studies also have less objective reporting and an uncontrolled placebo, are affected by the Hawthorne effect (tendency in some individuals to alter their behavior in response to their awareness of being observed) and regression to the mean, have substantial loss to follow-up, and change the antiseizure drug regimen over time. Furthermore, 34–37% of participants had discontinued ANT-DBS and RNS at the longest follow-up.
The idea of neuromodulation for epilepsy has led to many proposed therapies and thousands of reports during the past 50 years, but only four appropriately powered, double-blind, randomized controlled trials of three approved therapies have been published. This low number of trials is in stark contrast to those in the field of movement disorders, for which much more high-level evidence has been gathered for DBS to delineate the optimal anatomical targets and stimulation parameters based on individual characteristics.
2 tables and 2 figures including an illustration. No images.
6. Santoro JD, Pagarkar D, Chu DT, et al. Neurologic complications of Down syndrome: a systematic review. J Neurol 2021;268:4495–509. Available from: https://doi.org/10.1007/s00415-020-10179-w
Down syndrome (DS) is one of the most well-recognized genetic disorders. Persons with DS are known to have a variety of co-morbid medical problems, affecting nearly all organ systems. Improved healthcare interventions and research have allowed for increased life span of persons with DS, although disorders of the neurologic system remain underexplored. The purpose of this systematic review is to provide clinically pertinent information on the neurological phenotypes of frequently occurring or clinically relevant conditions. A retrospective review of MEDLINE, Scopus, and Pubmed were used to identify sources among seventeen, clinically relevant, search categories. MeSH terms all contained the phrase “Down Syndrome” in conjunction with the topic of interest. ‘Frequently-occurring’ was defined as prevalent in more than 10% of persons with DS across their lifespan, whereas ‘clinically-relevant’ was defined as a disease condition where early diagnosis or intervention can augment the disease course. In total, 4896 sources were identified with 159 sources meeting criteria for inclusion. Seventeen clinical conditions were grouped under the following subjects: hypotonia, intellectual and learning disability, cervical instability, autism spectrum disorder, epilepsy, cerebrovascular disease, Alzheimer’s disease and neuropsychiatric disease.
Cervical or atlantoaxial instability is defined as excessive movement/ligamentous laxity between the C1 and C2 vertebrae. Its prevalence in persons with DS ranges between 9.5 and 14.6%, with 1.5–3.8% of these cases becoming symptomatic, typically in the pre-teen and teen years. Symptoms are usually caused by compressive myelopathy, which can present as a decrease in muscle strength and tone, hyperreflexia, and gait instability. Bowel and bladder symptoms are only present in severe cases of cervical myelopathy secondary to atlantoaxial instability. In terms of screening guidelines for persons with DS, the American Academy of Pediatrics (AAP) no longer recommends routine X-rays in children with DS and persons with DS who participate in high-risk contact sports. Their rationale is related to the low prevalence of symptomatic cases, a low reliability of X-rays, and an inability to predict the risk of spinal myelopathy on radiographs.
3 figures including MR
7. Shepard MJ, Snyder MH, Soldozy S, et al. Radiological and clinical outcomes of pituitary apoplexy: comparison of conservative management versus early surgical intervention. J Neurosurg 2021;135:1310–18. Available from: https://thejns.org/view/journals/j-neurosurg/135/5/article-p1310.xml
64 patients with symptomatic PA were identified. Radiological, endocrinological, and ophthalmological data were reviewed. Patients with progressive visual deterioration or ophthalmoplegia were candidates for early surgery (within 7 days). Patients without visual symptoms or whose symptoms improved on high-dose steroids were treated conservatively. Log-rank and univariate analysis compared clinical and radiological outcomes between those receiving early surgery and those who underwent intended conservative management.
47 (73.4%) underwent intended conservative management, while 17 (26.6%) had early surgery. Patients receiving early surgery had increased rates of impaired visual acuity (VA; 64.7% vs 27.7%); visual field (VF) deficits (64.7% vs 19.2%); and cranial neuropathies (58.8% vs 29.8%) at presentation. Tumor volumes were greater in the early surgical cohort (15.1 cm3 vs 4.5 cm3). The median clinical and radiological follow-up visits were longer in the early surgical cohort (70.0 and 64.4 months vs 26.0 and 24.7 months, respectively). Among those with VA/VF deficits, visual outcomes were similar between both groups (p > 0.9).
PA volumes spontaneously regressed in 95.0% of patients (38/40) with successful conservative management, with a 6-month regression rate of 66.2%. Younger age, female sex, and patients with VF deficits or chiasmal compression were more likely to experience unsuccessful conservative management. Surgical outcomes were similar for patients receiving early versus delayed surgery.
This study suggests that conservative management is a viable strategy in the majority of patients with PA, particularly those who present with no visual deficits or less severe deficits (i.e., incomplete bitemporal hemianopsia or partial cranial neuropathy) that improve with steroids, as long as close neurosurgical and endocrine follow-up is available.
5 tables, 1 figure and amazingly no imaging
8. Han HJ, Lee W, Kim J, et al. Formation, growth, or rupture of de novo intracranial aneurysms: long-term follow-up study of subarachnoid hemorrhage survivors. Neurosurgery 2021;89:1104–11. Available from: https://academic.oup.com/neurosurgery/article/89/6/1104/6389807
The authors included 1601 patients with aSAH treated by clipping from January 1993 to May 2010. According to the inclusion and exclusion criteria, 233 patients had no de novo intracranial aneurysms, and 63 patients had 77 de novo intracranial aneurysms. They assessed the incidence rate of DNIAs and risk factors for de novo intracranial aneurysm formation. After dichotomizing the de novo intracranial aneurysms group into the heed group (patients with DNIA rupture or growth) and stable groups (patients without DNIA growth), they assessed the risk factors for de novo intracranial aneurysm growth or rupture.
The total follow-up period was 4427.9 patient-years. The incidence rate per patient-year was 1.42%. Age ≤50 yr, family history of aneurysm, and multiplicity at initial aSAH were significant risk factors for DNIA formation. Multivariate regression analysis revealed that female sex, duration from initial aSAH to DNIA detection <120 mo, multiplicity at initial aSAH, and maximum DNIA diameter ≥4 mm were significant risk factors for DNIA growth or rupture.
DNIAs had a higher incidence rate than expected. Taking into account the presented incidence rate and risk factors, long-term surveillance in aSAH survivors for more than a decade may be worth considering, at least on a case-by-case basis.
2 figures, 3 tables
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