Visual Outcomes After Treatment for Sporadic Optic Pathway Gliomas in Pediatric Patients: A Systematic Review.

OBJECTIVE: Optic pathway gliomas (OPGs) typically occur in the first decade of life and 40%-50% are not associated with neurofibromatosis 1 (NF1) (sporadic). Management strategies are often patient specific because of the variable and unpredictable course. No study has summarized the effect of treatment strategies on visual outcomes in the subset of pediatric patients with sporadic OPG. METHODS: We conducted a systematic review to determine the nature of visual outcomes in pediatric patients with sporadic, non-NF1-associated OPG using the PubMed, Embase, Scopus, Cochrane, and CINAHL Plus databases. Visual outcomes were categorized as improved, unchanged, or deteriorated. RESULTS: Of 1316 results, 31 articles were included. Treatment indications are unknown with full clinical detail. A total of 45.2% (14/31) reported deteriorated outcomes after treatment, 35.5% (11/31) no change, and 19.4% (6/31) improvement. Of radiotherapy studies, 50.0% (4/8) found no change, 37.5% (3/8) deterioration, and 12.5% (1/8) improvement. Of chemotherapy studies, 35.7% (5/14) each showed improvement and deterioration, whereas 28.6% (4/14) showed no change. Of surgical studies, 62.5% (5/8) indicated deterioration, and 37/5% (3/8) indicated no change. The singular study examining observation reported deterioration in visual outcomes. Factors associated with poor visual outcomes included signs and symptoms of visual decline at presentation, involvement of the intraorbital optic nerve, and intracranial hypertension requiring surgery. Causality cannot be determined from systematic review. CONCLUSIONS: Most studies showed that vision in pediatric patients with sporadic OPG is stable to poor after observation, chemotherapy, radiotherapy, or surgery. Chemotherapy may be associated with most favorable visual outcomes.

The role of blood product removal in intraventricular hemorrhage of prematurity: a meta-analysis of the clinical evidence.

INTRODUCTION: Premature neonates have a high risk of intraventricular hemorrhage (IVH) at birth, the blood products of which activate inflammatory cascades that can cause hydrocephalus and long-term neurological morbidities and sequelae. However, there is no consensus for one treatment strategy. While the mainstay of treatment involves CSF diversion to reduce intracranial pressure, a number of interventions focus on blood product removal at various stages including extraventricular drains (EVD), intra-ventricular thrombolytics, drainage-irrigation-fibrinolytic therapy (DRIFT), and neuroendoscopic lavage (NEL). METHODS: We performed a systematic review and meta-analysis to compare the risks and benefits commonly associated with active blood product removal treatment strategies. We searched MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases through Dec 2020 for articles reporting on outcomes of EVDs, thrombolytics, DRIFT, and NEL. Outcomes of interest were rate of conversion to ventriculoperitoneal shunt (VPS), infection, mortality, secondary hemorrhage, and cognitive disability. RESULTS: Of the 10,398 articles identified in the search, 23 full-text articles representing 22 cohorts and 530 patients were included for meta-analysis. These articles included retrospective, prospective, and randomized controlled studies on the use of EVDs (n = 7), thrombolytics (n = 8), DRIFT therapy (n = 3), and NEL (n = 5). Pooled rates of reported outcomes for EVD, thrombolytics, DRIFT, and NEL for ventriculoperitoneal shunt (VPS) placement were 51.1%, 43.3%, 34.3%, and 54.8%; for infection, 15.4%, 12.5%, 4.7%, and 11.0%; for mortality, 20.0%, 11.6%, 6.0%, and 4.9%; for secondary hemorrhage, 5.8%, 7.8%, 20.0%, and 6.9%; for cognitive impairment, 52.6%, 50.0%, 53.7%, and 50.9%. Meta-regression using type of treatment as a categorical covariate showed no effect of treatment modality on rate of VPS conversion or cognitive disability. CONCLUSION: There was a significant effect of treatment modality on secondary hemorrhage and mortality; however, mortality was no longer significant after adjusting for year of publication. Re-hemorrhage rate was significantly higher for DRIFT (p < 0.001) but did not differ among the other modalities. NEL also had lower mortality relative to EVD (p < 0.001) and thrombolytics (p = 0.013), which was no longer significant after adjusting for year of publication. Thus, NEL appears to be safer than DRIFT in terms of risk of hemorrhage, and not different than other blood-product removal strategies in terms of mortality. Outcomes-in terms of shunting and cognitive impairment-did not differ. Later year of publication was predictive of lower rates of mortality, but not the other outcome variables. Further prospective and randomized studies will be necessary to directly compare NEL with other temporizing procedures.

Pediatric spinal intramedullary anaplastic myxopapillary ependymoma: a case report.

A 6-year-old girl presented with a 1-week history of progressive upper and lower extremity weakness and bilateral upper extremity dysesthesia. Imaging demonstrated a 4.7 × 1.2-cm enhancing intramedullary lesion in the cervical spine from level C2 to C5 with associated cystic components and syringomyelia. The patient underwent a C2-C5 laminoplasty, with gross total resection of the intramedullary lesion. Histological analysis showed small to medium-sized epithelioid cells, with predominantly a solid architecture focally infiltrating into the adjacent spinal cord tissue. Focal papillary differentiation was present along with peri-vascular pseudorosettes, mucin microcysts, and globules of dense collagen. Focal anaplasia was noted with mitosis (5/10 HPF), focal necrosis, and elevated Ki67 10-15%. These findings were consistent with a myxopapillary ependymoma with anaplastic features. CSF cytology was negative for tumor cells. MYCN amplification was not present. She was treated with targeted proton-beam radiation therapy. This is the fourth case of an intramedullary anaplastic myxopapillary ependymoma to date, and the first case in the cervical spine reported in the literature.

Spreading Depolarization After Chronic Subdural Hematoma Evacuation: Associated Clinical Risk Factors and Influence on Clinical Outcome.

BACKGROUND: Chronic subdural hematoma (cSDH) is a common neurosurgical condition responsible for excess morbidity, particularly in the geriatric population. Recovery after evacuation is complicated by fluctuating neurological deficits in a high proportion of patients. We previously demonstrated that spreading depolarizations (SDs) may be responsible for some of these events. In this study, we aim to determine candidate risk factors for probable SD and assess the influence of probable SD on outcome. METHODS: We used two cohorts who underwent surgery for cSDH. The first cohort (n = 40) had electrocorticographic monitoring to detect SD. In the second cohort (n = 345), we retrospectively identified subjects with suspected SD based on the presence of transient neurological symptoms not explained by structural etiology or ictal activity on electroencephalography. We extracted standard demographic and outcome variables for comparisons and modeling. RESULTS: Of 345 subjects, 80 (23%) were identified in the retrospective cohort as having probable SD. Potential risk factors included history of hypertension, worse clinical presentation on the Glasgow Coma Scale, and lower Hounsfield unit density and volume of the preoperative subdural hematoma. Probable SD was associated with multiple worse-outcome measures, including length of stay and clinical outcomes, but not increased mortality. On a multivariable analysis, probable SD was independently associated with worse outcome, determined by the Glasgow Outcome Scale score at the first clinic follow-up (odds ratio 1.793, 95% confidence interval 1.022-3.146) and longer hospital length of stay (odds ratio 7.952, 95% confidence interval 4.062-15.563). CONCLUSIONS: Unexplained neurological deficits after surgery for cSDH occur in nearly a quarter of patients and may be explained by SD. We identified several potential candidate risk factors. Patients with probable SD have worse outcomes, independent of other baseline risk factors. Further data with gold standard monitoring are needed to evaluate for possible predictors of SD to target therapies to a high-risk population.

Use of Standardized History and Physical Examination for Neurosurgical Patients Improves Clinical Documentation and Reimbursement.

BACKGROUND: Documentation is the cornerstone of good patient care and vital to proper coding and billing. Consistent and standardized documentation improves communication among physicians and can lead to better reimbursement. By understanding which elements in the neurosurgery history and physical examination are omitted the most often and the effects on the coding level, institutional-specific solutions can be implemented. METHODS: We performed a retrospective study of neurosurgical patients at a single academic institution who undergone a neurosurgery history and physical examination for an initial inpatient admission from July 2015 to July 2016. The data collected included documentation type (typed, dictated, dynamic documentation without a template, neurosurgery history and physical examination template [NHPT]) and ultimate coding level (1, 2, or 3) determined by a review by a professional coder. RESULTS: A total of 609 notes were reviewed. Of the 609 notes, 88 (14.4%) were missing an element of documentation. The most common missing element was the physical examination (40 of 88; 45.5%), followed by a combination (27 of 88; 30.7%), review of systems (14 of 88; 15.9%), and medical, family, and/or social history (7 of 88; 8.0%). The dynamic documentation without template notes had the highest percentage of missing elements (49 of 96; 51.0%), followed by the typed notes (7 of 49; 14.3%) and dictated notes (30 of 268; 11.2%) compared with the NHPT notes (2 of 196; 1.0%). CONCLUSION: The most common missing elements for inpatient neurosurgery documentation were the review of systems and physical examination. The documents with the highest percentage of missing elements were those that used dynamic documentation without a template. We recommend implementing a dedicated NHPT to improve capturing these elements for improved clinical documentation. Such changes could also improve the coding level and subsequent reimbursement.

Vision Outcomes for Pediatric Patients With Optic Pathway Gliomas Associated With Neurofibromatosis Type I: A Systematic Review of the Clinical Evidence.

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding.

Laser speckle imaging to evaluate scalp flap blood flow during closure in neurosurgical procedures.

Background: To measure the degree of relative ischemia caused by skin closure, we explored the potential utility of intraoperative surface blood flow measurement with laser speckle imaging (LSI). Methods: Prospective observational study of eight subjects that underwent intraoperative LSI during elective cranial neurosurgical procedures at the time of skin closure. Results: Seven 1st time incisions, with closure techniques including sutures (n = 3), staples (n = 3), and one after galeal sutures. When compared to the control region, there was a mean 63.7% reduction in flow across all seven subjects (range 18.7-95.32%). Comparing by closure type, a higher flow reduction in the three subjects with suture closure (80.7% reduction) compared to staples (61.9% reduction, P = 0.0379). One subject had a complex wound where tightening and loosening of sutures were performed to ensure adequate perfusion. Suturing resulted in significantly more local decreased flow compared to staples (P < 0.0001). Conclusion: These findings demonstrate the relative feasibility of using LSI for preoperative vascular flow assessment in planning complex incision closure. These data also provide preliminary support for the hypothesis that skin closure itself causes relative ischemia compared to deep approximation or cautery of the skin edge and that the relative ischemia from staples closure is generally less than from suture closure.

Necessity of brain imaging in COVID-19 infected patients presenting with acute neurological deficits.

BACKGROUND: Patients undergoing cardiopulmonary stabilization in the intensive care unit for novel coronavirus (COVID-19) are often sedated, placing timely assessment of a neurological decline at risk. CASE DESCRIPTION: Here, we present two cases of COVID-19 infected young patients transferred to our facility in a cardio-pulmonary crisis, with a poor neurological exam. While there was significant delay in obtaining brain imaging in the first patient, the second patient had timely recognition of her ischemic infarct, underwent emergent surgery, and is now doing well. CONCLUSIONS: These cases highlight the importance of early head imaging in COVID-19 patients with a poor neurological exam. While lungs remain the primary target of COVID-19, these cases alert the medical community to suspect involvement of the central nervous system, since there may be life-saving surgical interventions available.

Spreading depolarization may represent a novel mechanism for delayed fluctuating neurological deficit after chronic subdural hematoma evacuation.

OBJECTIVE: Most patients with chronic subdural hematoma (cSDH) recover after surgical evacuation with a straightforward course. There is a subset of patients who develop transient and fluctuating deficits not explained by seizures, stroke, or mass effect after evacuation. The objective of this study was to investigate whether these postoperative neurological deficits may be related to temporary brain dysfunction caused by cortical spreading depolarizations (SDs). METHODS: The authors conducted a prospective observational study of 40 patients who underwent cSDH evacuation. At the time of surgery, a 1 × 6 subdural electrode strip was placed on the cortex parallel to the subdural drain. Clinical outcomes were assessed utilizing the Markwalder Grading Scale, need for clinical EEG for new deficit, and presence of new deficits. RESULTS: Definitive SD was detected in 6 (15%) of 40 patients. Baseline and cSDH characteristics did not differ between patients with and without SD. More patients experienced postoperative neurological deterioration if they had SD (50%) compared to those without SD (8.8%; p = 0.03). Only 2 patients in the entire cohort demonstrated early neurological deterioration, both of whom had SD. One of these cases demonstrated a time-locked new focal neurological deficit (aphasia) at the start of a series of multiple clusters of SD. CONCLUSIONS: This is the first observation of SD occurring after cSDH evacuation. SD occurred at a rate of 15% and was associated with neurological deterioration. This may represent a novel mechanism for otherwise unexplained fluctuating neurological deficit after cSDH evacuation. This could provide a new therapeutic target, and SD-targeted therapies should be evaluated in prospective clinical trials.

Fluoroscopic Cranial Radiation Exposure in Spine Surgery: A Prospective Single-Center Evaluation in Operating Room Personnel.

BACKGROUND: Cranial radiation exposure during instrumented spine surgery is not well documented. We set out to measure this risk to the patient, surgeon, surgical resident, and scrub technician during these procedures. METHODS: Forty-seven individuals were enrolled during a 1.5-year period between October 2014 and March 2016 at the University of New Mexico Department of Neurosurgery. Radiation doses were obtained through electronic dosimeters placed on the surgical cap over the temporal scalp (bilaterally on surgeon and resident assist, unilaterally on surgical scrub on the side facing radiation source) and on the midline of the patient's exposed cranium. RESULTS: Of the 47 procedures, 39 (83%) were open and 8 (17%) were minimally invasive or percutaneous instrumented procedures. A total of 91 motion segments were treated, with a mean of 1.9 levels per case (57% lumbosacral, 34% cervical, and 2.1% thoracic). Total fluoroscopic time was 12.9 minutes. Mean dose per case (mrem/case) was calculated for the spine surgeon (1.4), resident assist (1.4), surgical scrub (1.2), and the patient (3.6). All doses were within federal safety guidelines. A spine surgeon would need to perform more than 1400 cases per year to reach the current federal maximum permissible dose for head exposure. CONCLUSIONS: There was no difference in cranial radiation exposure between operating room staff during spine surgeries. Moreover, the doses measured at the cranium were within national safety limits. Current protective technologies have significantly reduced the amount of ionizing radiation exposure during routine spine procedures; however, changes in behavior or equipment may further reduce radiation exposure to health care workers. CLINICAL RELEVANCE: Radiation exposure to patients and hospital staff remains a major concern in the practice of modern spine surgery. Cranial exposure remains the only established environmental risk factor for brain tumors, such as gliomas and meningiomas. Our study shows that all those exposed to radiation during spine surgery had cranial doses well within the national safety limits.

Dickkopf-1 Expression in Androgenetic Alopecia and Alopecia Areata in Male Patients.

BACKGROUND: Androgenetic alopecia (AGA) results from shortening of the anagen phase of the hair cycle and, subsequently, miniaturization of hair follicles. Alopecia areata (AA) is a disease of autoimmunity where T cells attack anagen hair follicles and shows multifactorial etiology. Dickkopf-1 (DKK-1) is a gene that is responsible for transformation of anagen to catagen, which suggests that it is involved in development of both diseases. OBJECTIVES: To evaluate the tissue levels of dickkopf-1 in male patients with AGA and AA in comparison with controls, in an attempt to know its role in the pathogenesis of both disorders. METHODS: DKK-1 immunohistochemical expression was evaluated in lesional scalp biopsies taken from 20 male patients with AGA evaluated clinically by the modified Norwood-Hamilton score, 20 male patients with AA evaluated clinically by SALT score, and 20 healthy controls within the same age and sex of the studied patients. RESULTS: A highly significant difference in DKK-1 expression between patients with AGA and healthy controls was found (P2 < 0.001). There were also significant differences in DKK-1 expression between patients with AA and healthy controls (P3 = 0.013), and between both patient groups (P1 = 0.002). CONCLUSIONS: Both AGA and AA showed significant increase in DKK-1 immunohistochemical expression. This may enhance the idea of its possible role in the pathogenesis of AGA and AA, and being a new target for treatment of these hair disorders.

Resolution of giant basilar artery aneurysm compression and reversal of sensorineural hearing loss with use of a flow diverter: case report.

The authors present an unusual case of a 15-year-old boy in whom sensorineural hearing loss and disequilibrium developed in the setting of a giant basilar artery aneurysm. This patient was treated with a flow-diverting stent and had complete resolution of his clinical symptoms including hearing loss. This case demonstrates the efficacy of flow diversion in select pediatric patients with posterior circulation aneurysms. The features that are thought to result in successful treatment are discussed.

Unusual persistent primitive trigeminal artery with a superior duplicated basilar system.

A 67-year-old patient who presented with a right cerebellar hemorrhage underwent vascular workup for suspicion of underlying vascular anomalies. A diagnostic cerebral angiogram demonstrated a duplicated basilar system fed solely by a persistent primitive trigeminal artery. The findings proved to be incidental and unrelated to the patient's hemorrhage. These developmental abnormalities are consistent with embryological development.

Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development.

ERα is expressed in macrophages and other immune cells known to exert dramatic effects on glucose homeostasis. We investigated the impact of ERα expression on macrophage function to determine whether hematopoietic or myeloid-specific ERα deletion manifests obesity-induced insulin resistance in mice. Indeed, altered plasma adipokine and cytokine levels, glucose intolerance, insulin resistance, and increased adipose tissue mass were observed in animals harboring a hematopoietic or myeloid-specific deletion of ERα. A similar obese phenotype and increased atherosclerotic lesion area was displayed in LDL receptor-KO mice transplanted with ERα(-/-) bone marrow. In isolated macrophages, ERα was necessary for repression of inflammation, maintenance of oxidative metabolism, IL-4-mediated induction of alternative activation, full phagocytic capacity in response to LPS, and oxidized LDL-induced expression of ApoE and Abca1. Furthermore, we identified ERα as a direct regulator of macrophage transglutaminase 2 expression, a multifunctional atheroprotective enzyme. Our findings suggest that diminished ERα expression in hematopoietic/myeloid cells promotes aspects of the metabolic syndrome and accelerates atherosclerosis in female mice.