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There is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness.To compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)'s systematic review of enhanced seasonal influenza vaccines from February 2020.A systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC's systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2.Eleven analyses from nine real-world evidence (RWE) studies comprising ∼53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07-2008/09 and 2011/12-2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high.Our study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines.

Background A large number of patients have epilepsy that is intractable and adversely affects a child's lifelong experience with addition societal burden that is disabling and expensive. The last two decades have seen a major explosion of new antiseizure medication options. Despite these advances, children with epilepsy continue to have intractable seizures. An option that has been long available but little used is epilepsy surgery to control intractable epilepsy. Methods This article is a review of the literature as well as published opinions. Results Epilepsy surgery in pediatrics is an underused modality to effectively treat children with epilepsy. Adverse effects of medication should be weighed against risks of surgery as well as risks of nonefficacy. Conclusions We discuss an approach to selecting the appropriate pediatric patient for consideration, a detailed evaluation including necessary evaluation, and the creation of an algorithm to approach patients with both generalized and focal epilepsy. We then discuss surgical options available including outcome data. New modalities are also addressed including high-frequency ultrasound and co-registration techniques including magnetic resonance imaging-guided laser therapy.

Background and Importance: Diffuse leptomeningeal glioneuronal tumor (DLGNT) represents a provisional entity in the 2016 World Health Organization classification of tumors; it is characterized by a widespread leptomeningeal growth and oligodendroglial-like cytology. To this day, 4 pediatric patients have been reported to present with an isolated spinal cord tumor in the absence of leptomeningeal dissemination. Gross total resection (GTR) was achieved in only 1 patient. We present the clinical and technical nuances of this unique type of tumor, as well as the second reported case of GTR in a patient with DLGNT. Clinical Presentation: A 4-year-old boy presented to the emergency department after an episode of flaccid paralysis of bilateral lower extremities. MRI showed an intramedullary spinal cord tumor centered at T8. The patient was taken to the operative room, where a laminectomy and tumor resection were performed; cystic and solid tumor components were identified. Pathology report was consistent with DLGNT. After achieving GTR, patient is free of recurrence after a 15-month follow-up. Conclusion: No standard treatment for DLGNT has been identified. Current literature report surgery and chemotherapy with variable success rates. DLGNT presenting as an isolated intramedullary tumor is an uncommon condition which progression appears to be halted when treated promptly. Identifying solid and cystic components of this tumor is crucial for achieving GTR.

Background Myelomeningocele (MM) is a condition that is responsible for considerable morbidity in the pediatric population. A significant proportion of the morbidity related to MM is attributable to hydrocephalus and the surgical management thereof. Postnatal repair remains the most common form of treatment; however, increased rates of prenatal diagnosis, advances in fetal surgery, and a hypothesis that neural injury continues in utero until the MM defect is repaired have led to the development and evaluation of prenatal surgery as a means to improve outcomes in afflicted infants. Objective The objective of this guideline is to systematically evaluate the literature to determine whether there is a difference in the proportion of patients who develop shunt-dependent hydrocephalus in infants who underwent prenatal MM repair compared to infants who had postnatal repair. Methods The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full-text articles were then reviewed, and when appropriate, included as evidence. Results A total of 87 abstracts were identified and reviewed by 3 independent reviewers. Thirty-nine full-text articles were selected for analysis. Three studies met selection criteria and were included in the evidence table. Conclusion Class I evidence from 1 study and class III evidence from 2 studies suggest that, in comparison to postnatal repair, prenatal surgery for MM reduces the risk of developing shunt-dependent hydrocephalus. Therefore, prenatal repair of MM is recommended for those fetuses who meet specific criteria for prenatal surgery to reduce the risk of developing shunt-dependent hydrocephalus (level I). Differences between prenatal and postnatal repair with respect to the requirement for permanent cerebrospinal fluid diversion should be considered alongside other relevant maternal and fetal factors when deciding upon a preferred method of MM closure. The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-2.

PURPOSE Dosimetric studies show that proton therapy can reduce the low/intermediate radiation dose to uninvolved tissue in children with low-grade glioma (LGG). For this reason, LGG is the fourth most common pediatric tumor treated with proton therapy, yet clinical outcome data on efficacy and toxicity are limited. METHODS AND MATERIALS We reviewed the medical records of 174 children (≤21 years old) with nonmetastatic LGG enrolled on a prospective protocol and treated with proton therapy between 2007 and 2017. We assessed clinical outcomes and toxicity and analyzed patient, tumor, and treatment-related variables. RESULTS The median age was 10.2 years (range, 2-21). Fifty-eight percent of tumors were World Health Organization grade 1 and 30% were grade 2; 12% were diagnosed on imaging characteristics alone. The most common histology was pilocytic astrocytoma (47%). The most common tumor subsites were diencephalon/optic pathway (52%), caudal brainstem (16%), and cerebellum (13%). Forty-two percent received chemotherapy before radiation therapy. The median follow-up was 4.4 years. The 5-year actuarial rates of local control, progression-free survival, and overall survival were 85% (95% confidence interval [CI], 78%-90%), 84% (95% CI, 77%-89%), and 92% (95% CI, 85%-95%), respectively. On univariate analysis, brainstem/spinal cord tumor location (62% vs 90% elsewhere) and dose

The neurologic examination of an infant or child can be daunting, as they are unable to verbally communicate or follow directions. It starts with tailoring the pediatric neurologic history and examination to the child's specific age group. A good neurologic history obtained from the patient and parents is key to evaluating a pediatric patient. This article offers pearls on what information to ask the caregivers and patients, and salient aspects of a brief neurologic examination.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Daiichi Sankyo Europe GmbH Background Based on results of multiple randomised controlled trials, direct oral anticoagulants (DOACs) are frequently used to reduce stroke risk in patients with atrial fibrillation (AF). The hypothesis is that in the real-world setting DOACs are effective in reducing the risk of stroke but ensuring continuous use is essential because of the rapid decline in anticoagulation activity when doses are omitted. Purpose The aim of this study was to assess the relationship between non-adherence, discontinuation of DOAC treatment and incidence of ischaemic stroke. Methods A nested case-control study was conducted in the InGef database, an anonymised healthcare claims database in Germany. AF patients starting DOACs between drug approval date and 31/12/2018 were included. We restricted to patients aged ≥45, ≥1 year database history, ≥1 year follow-up and at least two DOAC dispensings after cohort entry date (CED) (date of first dispensing). Patients with an ischaemic stroke during follow-up were selected as cases and compared with matched controls (matched on age +/- 5 years, sex, year of CED and CHA₂DS₂-VASc-score at CED). Controls were assigned the index date (date of first stroke diagnosis) of the corresponding case. Adherence to treatment was assessed among current users (DOAC use at or within 30 days before index date) and defined as proportion of days covered (PDC) ≥80% during CED and index date. Persistent users were defined as those with continuous DOAC use from CED to index date. We also assessed the effect of current, recent (DOAC use within 30-365 days before index date) and past use (DOAC use more than 1 year before index date). Odds ratios (ORs) with 95% confidence intervals (CIs) for ischaemic stroke were determined in logistic regression models. Results 900 cases and 3,570 controls were included. Among cases and controls, mean ± sd age was 80 ± 8 years and 49% were male. Current users who were non-adherent had a significant 1.21 higher odds (95% CI 1.01-1.45) of ischaemic stroke compared to adherent users. Similar results were observed in twice-daily (BID) users (OR 1.42 (1.15-1.75)). However, among once-daily (QD) users, the odds was not different between the adherent and non-adherent users (OR 0.99 (95% CI 0.58-1.69)). The risk of ischaemic stroke was significantly higher among non-persistent users compared to persistent users (OR 1.91 (95% CI 1.64-2.22)). Similar findings were observed among QD and BID users. The comparison of past and recent users to current users showed that the OR became higher the longer a patient had stopped DOAC use. Conclusion Both non-adherence and non-persistence were found to increase the risk of ischaemic stroke, showing that continuous use is essential for both BID and QD users. In BID users, there seems to be a stronger association between non-adherence and risk of stroke than in QD users. An explanation might be the higher degree of difficulty in adhering to a BID than QD regimen.

Introduction. We surveyed nonretired American Academy of Pediatrics–member US pediatricians regarding common neurosurgical conditions, identifying specific areas of focus in education. Methods. Data were acquired via self-administered electronic questionnaire. Results. Of 505 total respondents, 56% reported neurology was not a required residency rotation, and 86% had diagnosed craniosynostosis, plagiocephaly, or macrocephaly. Craniosynostosis can mostly be diagnosed by physical examination alone, but almost 50% reported relying on skull X-rays. Fifty-four percent reported diagnosing ocular surface disease (OSD; with 15% to 40% not screening an infant despite well-established cutaneous markers). Seventy-four screened OSD in a patient with sacral dimple. Ninety-seven percent reported treating concussion, but nearly 25% did not manage these patients alone. Two out of 3 patients indicated head injury as most important for continuing education. Conclusion. Improved education for craniosynostosis, OSD, head injury, and concussion management are important for earlier diagnosis, management, and referral of some disorders, while decreasing resource utilization in others. These results should be used when considering pediatrician educational programs.

OBJECTIVE The authors sought to evaluate the contemporary management of pediatric open skull fractures and assess the impact of variations in antibiotic and operative management on the incidence of infectious complications. METHODS The records of children who presented from 2009 to 2017 to 6 pediatric trauma centers with an open calvarial skull fracture were reviewed. Data collected included mechanism and anatomical site of injury; presence and depth of fracture depression; antibiotic choice, route, and duration; operative management; and infectious complications. RESULTS Of the fractures among the 138 patients included in the study, 48.6% were frontal and 80.4% were depressed; 58.7% of patients underwent fragment elevation. The average duration of intravenous antibiotics was 4.6 (range 0–21) days. Only 53 patients (38.4%) received a single intravenous antibiotic for fewer than 4 days. and 56 (40.6%) received oral antibiotics for an average of 7.3 (range 1–20) days. Wounds were managed exclusively in the emergency department in 28.3% of patients. Two children had infectious complications, including a late-presenting hardware infection and a superficial wound infection. There were no cases of meningitis or intracranial abscess. Neither antibiotic spectrum or duration nor bedside irrigation was associated with the development of infection. CONCLUSIONS The incidence of infectious complications in this population of children with open skull fractures was low and was not associated with the antibiotic strategy or site of wound care. Most minimally contaminated open skull fractures are probably best managed with a short duration of a single antibiotic, and emergency department closure is appropriate unless there is significant contamination or fragment elevation is necessary.

The use of simulators has been described in a variety of fields as a training tool to gain technical skills through repeating and rehearsing procedures in a safe environment. In cerebrovascular surgery, simulation of skull base approaches has been used for decades. The use of simulation in neurointervention to acquire and enhance skills before treating a patient is a newer concept, but its utilization has been limited due to the lack of good models and deficient haptics. The advent of 3D printing technology and the development of new training models has changed this landscape. The prevalence of aneurysms in the pediatric population is much lower than in adults, and concepts and tools sometimes have to be adapted from one population to another. Neuroendovascular rehearsal is a valid strategy for the treatment of complex aneurysms, especially for the pediatric population. The authors present the case of an 8-year-old boy with a fusiform intracranial aneurysm and documented progressive growth, who was successfully treated after the authors rehearsed the placement of a flow diverter using a patient-specific 3D-printed replicator system model.

Our specific, measurable, attainable, relevant, and time-limited (SMART) aim was to reduce the incidence of severe intracranial hemorrhage (ICH) among preterm infants born

Background The incidence of spina bifida (SB) in the developing world is higher than in the United States because of malnutrition and folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible. Objective The objective of the guidelines are, (1) To create clinical recommendations for best practices, based on a systematic review and analysis of available literature, (2) to obtain multi-disciplinary endorsement of these guidelines from relevant organizations, and (3) to disseminate the educational content to physicians to improve the care of infants with MM. Methods The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Results Guidelines authors aimed to systematically review the literature and make evidence based recommendations about the timing of closure after birth, hydrocephalus, the impact of prenatal closure, and the effect of prenatal closure on ambulation ability and tethered spinal cord. Evidence concerning persistent ventriculomegaly and cognitive impairment was also evaluated. Hundreds of abstracts were identified and reviewed for each of the 5 topics. A total of 14 studies met stringent inclusion criteria. Conclusion Based on a comprehensive systematic review, a total of 5 clinical practice recommendations were developed, with 1 Level I, 2 Level II and 2 Level III recommendations.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-1.

Background The incidence of spina bifida (SB) is higher in the developing world as compared to the United States because of folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible. Objective The objective of this guideline was to determine if there is a difference in the rate of development of tethered cord syndrome (TCS) in infants who had prenatal closure compared to infants who had MM repair after birth. Methods The Guidelines Task Force developed search terms and strategies to search PubMed and Embase for the relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used. Full text articles were reviewed and, when appropriate, included as evidence. Results A total of 261 abstracts were reviewed. Fifty-four full-text articles were selected for further analysis. Three studies met inclusion criteria. Conclusion There was Class II evidence from 1 study and Class III evidence from another 2 studies demonstrating that TCS develops in infants with prenatal MM closure at an equal or higher rate than with postnatal closure. There was an increased risk of development of inclusion cysts in infants who underwent in utero closure. Continued surveillance for TCS and/or the development of inclusion cysts in children with prenatal and postnatal closure of MM is indicated (Level II). Differences between prenatal and postnatal repair with respect to the development of TCS and/or inclusion cysts should be considered alongside other relevant maternal and fetal outcomes when deciding upon a preferred method for MM closure.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-6.

Background Myelomeningocele (MM) is an open neural tube defect treated by pediatric neurosurgeons with prenatal or postnatal closure. Objective The objective of this systematic review was to answer the question: What is the evidence for the effectiveness of prenatal vs postnatal closure of MM regarding short and long-term ambulatory status? Treatment recommendations were provided based on the available evidence. Methods The National Library of Medicine PubMed database and Embase were queried using MeSH headings and keywords relevant to ambulatory status after prenatal or postnatal closure of MM. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidence table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). Results One randomized controlled trial (Class II) and 3 retrospective cohort studies (Class III) were included as evidence. Initial ambulatory status depended on anatomic level of the neural tube defect. In the short term, prenatal closure may improve ambulatory status compared to postnatal closure. Spinal cord tethering or dermoid inclusion cyst has been associated with neurologic deterioration in infants closed in utero and after birth. Ambulation may cease in both groups over time. No long-term studies evaluated whether there is a difference in the ability to ambulate upon reaching adulthood. Conclusion Prenatal closure of MM may improve ambulatory status in the short term (Level II). Spinal cord tethering in both groups caused deterioration in the ability to walk. Evaluation and treatment of spinal cord tethering may help maintain ambulatory status (Level III). No studies evaluate whether prenatal or postnatal repair provides improved ability to ambulate upon reaching adulthood.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-3.

Tumors involving the sella are commonly craniopharyngiomas, optic pathway gliomas, or pituitary adenomas. Functioning adenomas are expected, with prolactinomas topping the differential. The authors present the case of a silent corticotroph adenoma, which has not been described in the pediatric population, and they detail the use of proton therapy, which is also novel.

Background Appropriate timing for closure of myelomeningocele (MM) varies in the literature. Older studies present 48 h as the timeframe after which infection complication rates rise. Objective The objective of this guideline is to determine if closing the MM within 48 h decreases the risk of wound infection or ventriculitis. Methods The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full text articles were then reviewed and when appropriate, included in the evidentiary table. The class of evidence was evaluated, discussed, and assigned to each study that met inclusion criteria. Results A total of 148 abstracts were identified and reviewed. A total of 31 articles were selected for full text analysis. Only 4 of these studies met inclusion criteria. Conclusion There is insufficient evidence that operating within 48 h decreases risk of wound infection or ventriculitis in 1 Class III study. There is 1 Class III study that provides evidence of global increase in postoperative infection after 48 h, but is not specific to wound infection or ventriculitis. There is 1 Class III study that provides evidence if surgery is going to be delayed greater than 48 h, antibiotics should be given.The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-4.

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Background An arteriovenous malformation (AVM) consists of a pathologic arteriovenous shunt formed from a tangle of vessels lacking a capillary bed. AVMs were previously accepted as congenital in nature; however, an increase in the number of reported de novo cerebral AVMs challenges the assertion that all AVMs develop in utero hence, the possibility of these lesions presenting postnatally cannot be excluded. A review of literature revealed 31 published cases of de novo AVM formation between 1996 and 2017. Case Description We present the case of a 7-year-old boy with a history of an intracranial aneurysm that was found to have an asymptomatic de novo AVM formation on a routine follow-up angiography. He was being followed since the age of 8 months when the aneurysm was incidentally found during work-up for mild hemiparesis. At that time, magnetic resonance imaging revealed a 4-mm right posterior communicating artery aneurysm along with a right hemispheric stroke and cortical dysplasia. No arteriovenous malformation was noted. Conclusions The exact pathophysiology of de novo AVMs is not completely understood, but a combination of genetic, molecular, and environmental factors may play a role. Our case report only adds to the growing body of clinical evidence supporting the notion that these lesions may be acquired. It would be appropriate to consider an AVM as an abnormal vascular response to an injury rather than a static congenital lesion.

Traumatic brain injuries afflict a large number of pediatric patients. The most severe injuries lead to increased intracranial pressure and herniation, with resultant changes in the brainstem. Traumatic brainstem hemorrhages have previously been associated with poor neurological outcome and fatality. However, this report discusses 2 pediatric patients who sustained severe head trauma with subsequent brainstem hemorrhages, and yet experienced good neurological outcome; the possible mechanism is described.

Background No evidence-based guidelines exist on the role of cranial-molding orthosis (helmet) therapy for patients with positional plagiocephaly. Objective To address the clinical question: "Does helmet therapy provide effective treatment for positional plagiocephaly?" and to make treatment recommendations based on the available evidence. Methods The US National Library of Medicine Medline database and the Cochrane Library were queried by using MeSH headings and key words relevant to the objective of this systematic review. Abstracts were reviewed, after which studies meeting the inclusion criteria were selected and graded according to their quality of evidence (Classes I-III). Evidentiary tables were constructed that summarized pertinent study results, and, based on the quality of the literature, recommendations were made (Levels I-III). Results Fifteen articles met criteria for inclusion into the evidence tables. There was 1 prospective randomized controlled trial (Class II), 5 prospective comparative studies (Class II), and 9 retrospective comparative studies (Class II). Conclusion There is a fairly substantive body of nonrandomized evidence that demonstrates more significant and faster improvement of cranial shape in infants with positional plagiocephaly treated with a helmet in comparison with conservative therapy, especially if the deformity is severe, provided that helmet therapy is applied during the appropriate period of infancy. Specific criteria regarding the measurement and quantification of deformity and the most appropriate time window in infancy for treatment of positional plagiocephaly with a helmet remains elusive. In general, infants with a more severe presenting deformity and infants who are helmeted early in infancy tend to have more significant correction (and even normalization) of head shape. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_5.

Background Plagiocephaly, involving positional deformity of the calvarium in infants, is one of the most common reasons for pediatric neurosurgical consultation. Objective To answer the question: "what is the evidence for the effectiveness of repositioning for positional plagiocephaly?" Treatment recommendations are provided based on the available evidence. Methods The National Library of Medicine MEDLINE database and the Cochrane Library were queried using MeSH headings and key words relevant to repositioning as a means to treat plagiocephaly and brachycephaly. Abstracts were reviewed to identify which studies met the inclusion criteria. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). Results There were 3 randomized trials (Class I), 1 prospective cohort study (Class II), and 6 retrospective cohort studies (Class III). Repositioning education was found to be equal to a repositioning device and inferior to a physical therapy program. Five of the 7 cohort studies comparing repositioning with a helmet reported helmets to be better and take less time. Conclusion Within the limits of this systematic review, repositioning education is effective in affording some degree of correction in virtually all infants with positional plagiocephaly or brachycephaly. Most studies suggest that a molding helmet corrects asymmetry more rapidly and to a greater degree than repositioning education. In a Class I study, repositioning education was as effective as repositioning education in conjunction with a repositioning wrap/device. Another Class I study demonstrated that a bedding pillow was superior to physical therapy for some infants. However, in keeping with the American Academy of Pediatrics' warning against the use of soft positioning pillows in the sleeping environment, the Task Force recommends physical therapy over any positioning device. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_3.

BACKGROUND Positional plagiocephaly is a common problem seen by pediatricians, pediatric neurologists, and pediatric neurosurgeons. OBJECTIVE To create evidence-based guidelines for the treatment of pediatric positional plagiocephaly. METHODS This guideline was prepared by the Plagiocephaly Guideline Task Force, a multidisciplinary team made up of physician volunteers (clinical experts), medical librarians, and clinical guidelines specialists. The task force conducted a series of systematic literature searches of PubMed and the Cochrane Library, according to standard protocols for each topic addressed in subsequent chapters of this guideline. RESULTS The systematic literature searches returned 396 abstracts relative to the 4 main topics addressed in this guideline. The results were analyzed and are described in detail in each subsequent chapter included in this guideline. CONCLUSION Evidence-based guidelines for the management of infants with positional plagiocephaly will help practitioners manage this common disorder. The full guidelines documents can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly.

Hemiconvulsion-hemiplegia-epilepsy (HHE) is an uncommon epileptic syndrome that affects young children. Typical management includes early initiation of benzodiazepines to abate the initial seizure activity quickly. Patients in whom epilepsy develops require prolonged use of antiepileptic agents. Herniation due to diffuse cerebral edema from HHE is rare; however, decompressive craniectomy has been described as a lifesaving measure. The authors present the case of a patient in whom a decompressive craniectomy was performed. They advocate a proactive approach in the detection and management of cerebral edema in HHE causing intracranial hypertension. In HHE cases that exhibit radiographic evidence of malignant cerebral edema (although not previously described in this disease, but similar to the setting of stroke and trauma), the authors advocate early neurosurgical consultation and evaluation for insertion of an intracranial pressure monitor for those patients who do not have a reliable neurological examination (i.e., Glasgow Coma Scale score ≤ 8).

Object Diagnosis and management of atlantoaxial rotatory subluxation (AARS) is challenging because of its variability in clinical presentation. Although several treatment modalities have been employed, there remains no consensus on the most appropriate therapy. The authors explore this issue in their 9-year series on AARS. Methods Records of patients diagnosed radiologically and clinically with AARS between May 2001 and March 2010 were retrospectively reviewed. Of 40 patients identified, 24 were male and were on average 8.5 years of age (range 15 months–16 years). Causes of AARS included trauma, congenital abnormalities, juvenile rheumatoid arthritis, infection, postsurgical event, and cryptogenic disease. Four patients had dual etiologies. Symptom duration varied: 29 patients had symptoms for less than 4 weeks, 5 patients had symptoms between 1 and 3 months, and 6 patients had symptoms for 3 months or more. Results Treatment with a cervical collar was sufficient in 21 patients. In 1 patient collar management failed and halter traction was used to reduce the subluxation. Seven patients underwent initial halter traction, but in 4 the subluxation progressed and the patients required halo traction. A halo vest was placed in 2 patients on presentation because the rotatory subluxation was severe; both patients required subsequent operative fusion. One patient required decompression and fusion due to severe canal compromise and myelopathy. All patients requiring fusion presented with subacute symptoms. Conclusions Management of AARS varies due to the spectrum of clinical presentations. Patients presenting acutely without neurological deficits can likely undergo collar therapy; those in whom the subluxation cannot be reduced or who present with a neurological deficit may require traction and/or surgical fixation. Patients presenting subacutely may be more prone to requiring operative intervention.

Summary In Helicobacter pylori gastritis gastric epithelium plays a central role in the innate immunity to H. pylori. However, epithelial receptors interacting with H. pylori have been poorly characterized so far. Recently a new triggering receptor expressed on myeloid cells-1 (TREM-1) has been identified on human neutrophils and monocytes. On these cells TREM-1 triggers innate immunity by stimulating the secretion of interleukin (IL)-8 and tumour necrosis factor (TNF)-α and thus amplifies bacterial-induced inflammation. In this study expression and function of TREM-1 in gastric epithelium exposed to H. pylori has been investigated. TREM-1 mRNA and protein were expressed on gastric epithelial cell lines as demonstrated by reverse transcription–polymerase chain reaction (RT–PCR) and fluorescence activated cell sorter analysis. Gastric epithelial TREM-1 expression was up-regulated directly by H. pylori and was independent of epithelial IL-8 induced by H. pylori. Immunohistochemistry and tissue RT–PCR demonstrated significantly stronger TREM-1 expression in H. pylori gastritis compared with the non-inflamed gastric mucosa supporting in vivo that epithelial TREM-1 is up-regulated during H. pylori infection. Stimulation of gastric epithelial TREM-1 receptor resulted in IL-8 up-regulation on mRNA and protein level, as shown by real-time PCR and immunoassay. This is the first study localizing TREM-1 on gastric epithelium. Functional data suggest that TREM-1 expressed on gastric epithelium amplifies inflammation of the underlying gastric mucosa by up-regulation of IL-8.

Background Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a chronic inflammatory disease of unknown origin that is morphologically characterized by a local fibrotic thickening of the dura mater with a sterile lymphocytic infiltrate. Patients usually present with chronic headache, ataxia and cranial nerve palsies. Because of the great diversity of symptoms and the fact that IHCP can be associated with many other disorders, there is often a long time between the occurrence of clinical features and making the diagnosis. During this time symptoms can further increase. In addition, this is the third case report describing bone involvement in this disorder. Case report In May 2000, a 51-year-old woman presented with reduced visual acuity on both eyes, complete palsies of the fourth and sixth cranial nerve, a partial palsy of the third cranial nerve and numbness and pain concerning the area of the fifth cranial nerve on the left side, painful eye movement on the left side, headache, and numbness and palsies on the left side of her body. Magnetic resonance imaging of the brain showed a focal gadolinium-enhanced small thickening of the dura mater close to the left hemisphere and a homogeneous bone thickening in the same area close to the thickened dura mater. Cerebrospinal fluid analysis revealed an elevated cell count (lymphocytic pleocytosis), routine blood counts and serum chemistry showed an elevated white blood count, an elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Therapy with corticosteroids resulted in a complete remission in November 2000 except for a persistent numbness of the left side of her face and body and reduced visual acuity on both sides. The following three years were characterized by repeated clinical deteriorations followed by a temporary increase of the daily steroid dose. Altogether, daily oral steroid therapy could slow down the progression of disease and improve the visual acuity when compared with the first examination. Conclusions Chronic headache, ataxia and cranial nerve palsies in combination with inflammation and dural thickening should call to mind idiopathic hypertrophic cranial pachymeningitis. In principle, every ophthalmological or neurological symptom can be associated with IHCP.

Background No evidence-based guidelines exist for the imaging of patients with positional plagiocephaly. Objective The objective of this systematic review and evidence-based guideline is to answer the question, Is imaging necessary for infants with positional plagiocephaly to make a diagnosis? Methods The National Library of Medicine Medline database and the Cochrane Library were queried with the use of MeSH headings and key words relevant to imaging as a means to diagnose plagiocephaly. Abstracts were reviewed, and an evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). Based on the quality of the literature, a recommendation was rendered (Level I, II, or III). Results A total of 42 full-text articles were selected for review. Of these, 10 were eliminated; thus, 32 full-text were manuscripts selected. There was no Class I evidence, but 2 Class II and 30 Class III studies were included. Three-dimensional cranial topographical imaging, ultrasound, skull x-rays, computed tomography, and magnetic resonance imaging were investigated. Conclusion Clinical examination is most often sufficient to diagnose plagiocephaly (quality, Class III; strength, Level III). Within the limits of this systematic review, the evidence suggests that imaging is rarely necessary and should be reserved for cases in which the clinical examination is equivocal. Many of the imaging studies were not designed to address the diagnostic utility of the imaging modality, and authors were actually assessing the utility of the imaging in longitudinal follow-up, not initial diagnosis. For this reason, some of the studies reviewed were downgraded in Level of Evidence. When needed, 3-dimensional cranial topographical photo, skull x-rays, or ultrasound imaging is almost always sufficient for definitive diagnosis. Computed tomography scanning should not be used to diagnose plagiocephaly, but it may be necessary to rule out craniosynostosis. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-positional-plagiocephaly/Chapter_2.

Pediatric intracranial aneurysms are exceedingly rare and account for less than 5% of all intracranial aneurysms. Open surgery to treat such aneurysms has been shown to be more durable than endovascular techniques, and durability of treatment is particularly important in the pediatric population. Over the past 2 decades, however, a marked shift in aneurysm treatment from open surgery toward endovascular procedures has occurred for adults. The authors describe their early experience in treating 3 unruptured pediatric brain aneurysms using the Pipeline embolization device (PED). The first patient, a girl with Majewski osteodysplastic primordial dwarfism Type II who was harboring multiple intracranial aneurysms, underwent two flow diversion procedures for a vertebrobasilar aneurysm and a supraclinoid internal carotid artery aneurysm. The second patient underwent PED placement on a previously coiled but enlarging posterior communicating artery aneurysm. All procedures were uneventful, with no postsurgical complications, and led to complete angiographic obliteration of the aneurysms. To the authors' knowledge, this is the first series of flow diversion procedures in children reported in the medical literature. While flow diversion is a new and relatively untested technology in children, outcomes in adults have been promising. For challenging lesions in the pediatric population, flow diversion may have a valuable role as a well-tolerated, safe treatment with durable results. Many issues remain to be addressed, such as the durability of flow diverters over a very long follow-up and vessel response to growth in the presence of an endoluminal device.

Proton therapy can reduce the low and intermediate radiation dose to uninvolved brain tissue in children with intracranial ependymomas, which may improve functional outcomes and reduce second malignancies in survivors. Accordingly, ependymoma has become the most common pediatric tumor treated with proton therapy, yet data on efficacy and toxicity are limited.Between June 2007 and February 2017, 179 children (≤21 years old) with nonmetastatic grade II/III intracranial ependymoma received proton therapy at our institution. Median age, 3.5 years (range, 0.7-21); 58% were male. Most (66%) tumors were in the posterior fossa and classified as WHO grade III (67%). 27% underwent multiple operations to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection before radiotherapy. 33% received preradiation chemotherapy. Median radiation dose in children ≤3 years old, 54 Gy(RBE). Most (90%) children over 3 years old received 59.4 Gy(RBE). Patient and treatment variables were assessed for correlation with disease control.Median follow-up, 3.2 years. 3-year local control, progression-free survival, and overall survival rates were 85%, 76%, and 90%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17 and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (67% vs. 88%; p ≤ .01) and progression-free survival (59% vs. 79%; p .05). Male sex was associated with inferior progression-free (67% vs. 87%; p .05) and overall survival (84% vs. 99%; p .01). The 3-year CTCAE grade 2 + brainstem toxicity rate was 5.5% (95% CI: 2.9-10.2), including 1 grade 5 toxicity.This series of proton therapy for pediatric intracranial ependymoma demonstrates disease control comparable to photon series without unexpected toxicity. Subtotal resection and male sex were associated with inferior disease control. Additional follow-up to quantify the expected reductions in late toxicity with proton therapy is ongoing.

With the reports of the DNA sequence of the human and mouse genomes, research attention is now on questions of protein function and interactions, developmental and physiological pathways, and systems biology. The International Mouse Mutagenesis Consortium proposes goals and outlines plans for the next 10 years for annotating the mouse genome and compiling data on mouse mutations. In addition to the challenges of identifying new assays to probe biological functions, more efficient and reliable methods are needed for archiving, managing, analyzing, displaying, and disseminating the complex phenotype data sets resulting from mutagenesis programs. Achieving these goals will require the biomedical research community to improve efficiencies, to reduce costs, and to coordinate international expertise and resources.

The surgical options available for intractable hemispheric epilepsy have evolved since their initial description in the early 20th century. Surgical techniques have advanced, as has the ability to predict good surgical outcomes with noninvasive diagnostics. The authors review the history of hemispherectomy and detail the novel imaging and surgical strategies used to confer seizure freedom.

Abstract A new method of mapping multiple species of oral bacteria in intact biofilms has been developed, using the optical technique of confocal Raman microscopy. A species classification algorithm, developed on dried biofilms, was used to analyze spectra of hydrated biofilms containing two microbial species central to dental health: Streptococcus sanguinis and Streptococcus mutans. The algorithm transferred successfully to the hydrated environment, correctly identifying the species of origin of single-species biofilms. We then used the algorithm successfully both to detect the presence of two species in mixed biofilms and to create spatial maps within these biofilms.

Diagnosis and management of atlantoaxial rotatory subluxation (AARS) is challenging because of its variability in clinical presentation. Although several treatment modalities have been employed, there remains no consensus on the most appropriate therapy. The authors explore this issue in their 9-year series on AARS.Records of patients diagnosed radiologically and clinically with AARS between May 2001 and March 2010 were retrospectively reviewed. Of 40 patients identified, 24 were male and were on average 8.5 years of age (range 15 months-16 years). Causes of AARS included trauma, congenital abnormalities, juvenile rheumatoid arthritis, infection, postsurgical event, and cryptogenic disease. Four patients had dual etiologies. Symptom duration varied: 29 patients had symptoms for less than 4 weeks, 5 patients had symptoms between 1 and 3 months, and 6 patients had symptoms for 3 months or more.Treatment with a cervical collar was sufficient in 21 patients. In 1 patient collar management failed and halter traction was used to reduce the subluxation. Seven patients underwent initial halter traction, but in 4 the subluxation progressed and the patients required halo traction. A halo vest was placed in 2 patients on presentation because the rotatory subluxation was severe; both patients required subsequent operative fusion. One patient required decompression and fusion due to severe canal compromise and myelopathy. All patients requiring fusion presented with subacute symptoms.Management of AARS varies due to the spectrum of clinical presentations. Patients presenting acutely without neurological deficits can likely undergo collar therapy; those in whom the subluxation cannot be reduced or who present with a neurological deficit may require traction and/or surgical fixation. Patients presenting subacutely may be more prone to requiring operative intervention.

Background: Gliomas that aggregate in families with history of malignancy may have an inheritable genetic basis. Gliomas can occur in several well known tumor syndromes. However, their occurrence in the absence of these syndromes is quite rare. High-grade gliomas, such as glioblastoma multiforme (GBM), are the most common and most lethal primary cancers of the central nervous system (CNS). Case Description: We present a case of two brothers both diagnosed with GBM. Both siblings underwent biopsy with debulking of the tumors by different surgeons. Only one sibling elected to undergo chemotherapy and radiation. Cytogenetic studies were possible only on one sibling and the tumor specimen revealed multiple chromosomal abnormalities, including triploidies 4, 8, 12, 22 and loss of heterozygosity of 1p, 9p, and 10. Histological samples for both tumors were similar, both revealing increased cellularity consisting of gemistocytic astrocytes, central necrosis, and microvascularization. Conclusion: We present two brothers who display a rare familial relationship in the development of their GBMs. Supplementary and improved genetic studies may allow for specific treatment modalities as certain genetic abnormalities have better response to tailored treatments and carry better prognoses.

Implemented through a confocal microscope, Raman spectroscopy has been used to distinguish between biofilm samples of two common oral bacteria species, Streptococcus sanguinis and mutans, which are associated with healthy and cariogenic plaque, respectively. Biofilms of these species are studied as a model of dental plaque. A prediction model has been calibrated and validated using pure biofilms. This model has been used to identify the species of transferred and dehydrated samples (much like a plaque scraping) as well as hydrated biofilms in situ. Preliminary results of confocal Raman mapping of species in an intact two-species biofilm will be shown.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is occasionally seen after hypothalamic injury or dysfunction, although it typically occurs in association with other endocrine disturbances. It is has never been described as a presenting feature of a suprasellar arachnoid cyst (SAC) in the pediatric population. The authors describe the case of an enlarging SAC resulting in SIADH as the only presenting feature, with an otherwise normal hypothalamic-pituitary axis. An SAC was diagnosed in utero in this 5-month-old girl who had a normal functioning hypothalamic-pituitary axis on presentation. Because of cyst enlargement and hydrocephalus, the patient was scheduled for surgery; however, preoperative labs revealed SIADH. After stabilizing the serum sodium concentration with fluid restriction and the administration of 3% sodium chloride, the patient underwent endoscopic cyst fenestration. Postoperatively, she had complete resolution of the SIADH. Syndrome of inappropriate antidiuretic hormone secretion as the presenting symptom of an SAC has not been previously described. In the aforementioned patient, the proposed mechanism for SIADH was enlargement of the suprasellar arachnoid cyst causing compression of the supraoptic and paraventricular nuclei and thus overstimulating the secretion of arginine vasopressin, which resulted in SIADH. The association of SIADH with an SAC is reportable, as is the resolution of the SIADH via cyst fenestration. The authors suggest that SIADH is an uncommon presenting feature of SACs and that syndrome resolution is possible with cyst decompression.

Confocal Raman microscopy has been used to distinguish between biofilms of oral bacteria species Streptococcus sanguis and mutans. This capability has been applied to the study of mixed biofilms as a model for dental plaque.

Background context Subdural hematomas (SDHs) have been described as a rare complication from durotomy after lumbar spine surgery. In half of the reported cases, the durotomy was unnoticed intraoperatively. The most common presenting symptom was persistent headache. Purpose To report a case of SDH after routine microdiscectomy and to review the literature. Study design Case report and review of the literature. Methods Retrospective review of patient's history and imaging studies. Results A 39-year-old female underwent routine microdiscectomy for L5–S1 herniated disc. There were no complications, and no dural tear was noted. Approximately 1 week postoperatively, the patient complained of severe headaches. Imaging revealed a right intracranial chronic SDH and a lumbar pseudomeningocele. Operative exploration of her lumbar wound revealed a dural tear, which was closed primarily. The patient had subsequent resolution of her SDH. Conclusions The authors present a case of a routine microdiscectomy complicated by delayed cerebrospinal leak causing a chronic SDH. This report illustrates the need for a comprehensive evaluation of headaches after spine surgery.

Introduction The authors present a 31-year-old man with a Chiari type I malformation (CM-1) occurring in conjunction with LEOPARD syndrome. He presented with severe dysphagia requiring placement of a percutaneous endoscopic gastrostomy (PEG) tube. Evaluation included magnetic resonance imaging (MRI) of the brain and cervical spine that revealed CM-1 with an extensive cervical syrinx. The patient underwent a suboccipital craniectomy with C1 laminectomy and duraplasty. His symptoms quickly resolved and his PEG tube was removed. Discussion The occurrence of a CM-1 with LEOPARD syndrome has only been reported once, whereas CM-1 and Noonan syndrome have been linked in several cases. The similarity between LEOPARD and Noonan syndromes has been reported and many propose they represent 2 entities along a spectrum. Conclusion In light of this spectrum, we propose that CM-1 should be considered in all patients presenting with LEOPARD-Noonan syndrome.

Confocal Raman microscopy has been used to differentiate the spectra from biofilms of oral bacterial species Streptococcus sanguis and mutans. Improvements in processing algorithms allow this study to be performed using glass as a substrate.