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ABSTRACT BACKGROUND The Congress of Neurological Surgeons reviews its guidelines according to the Institute of Medicine's recommended best practice of reviewing guidelines every 5 yrs. The authors performed a planned 5-yr review of the medical literature used to develop the “Pediatric hydrocephalus: systematic literature review and evidence-based guidelines” and determined the need for an update to the original guideline based on new available evidence. OBJECTIVE To perform an update to include the current medical literature for the “Pediatric hydrocephalus: systematic literature review and evidence-based guidelines”, originally published in 2014. METHODS The Guidelines Task Force used the search terms and strategies consistent with the original guidelines to search PubMed and Cochrane Central for relevant literature published between March 2012 and November 2019. The same inclusion/exclusion criteria were also used to screen abstracts and to perform the full-text review. Full text articles were then reviewed and when appropriate, included as evidence and recommendations were added or changed accordingly. RESULTS A total of 41 studies yielded by the updated search met inclusion criteria and were included in this update. CONCLUSION New literature resulting from the update yielded a new recommendation in Part 2, which states that neuro-endoscopic lavage is a feasible and safe option for the removal of intraventricular clots and may lower the rate of shunt placement (Level III). Additionally a recommendation in part 7 of the guideline now states that antibiotic-impregnated shunt tubing reduces the risk of shunt infection compared with conventional silicone hardware and should be used for children who require placement of a shunt (Level I).

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.

Oncolytic herpes simplex virus (oHSV) type I constructs are investigational anti-neoplastic agents for a variety of malignancies, including malignant glioma. Clinical trials to date have supported the safety of these agents even when directly administered in the CNS. Traditional pre-clinical US Food and Drug Administration (FDA) toxicity studies for these agents have included the use of two species, generally including murine and primate studies. Recently, the FDA has decreased its requirement of non-human primates as an animal model for ethical reasons, especially for established viral systems where there are good alternative model systems. Here we present data demonstrating the safety of C134, a chimeric oHSV construct, in CBA mice as well as in a limited number of the HSV-sensitive non-human primate Aotus nancymaae as a proposed agent for clinical trials. These data, along with the previously conducted clinical trials of oHSV constructs, support the use of the CBA mouse model as sufficient for the pre-clinical toxicity studies of this agent. We summarize our experience with different HSV recombinants and differences between them using multiple assays to assess neurovirulence, as well as our experience with C134 in a limited number of A. nancymaae.

Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of phase I and phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied and the history of their development are summarized here. In addition, the results of clinical trials in patients and their implication for future trials are also discussed.

Chari 1 malformation, a radiologic finding of caudal cerebellar tonsillar displacement, has a clinical course that can range from benign to complications involving life-threatening hydrocephalus. While the pathophysiologic processes underlying this variation in outcome remain a matter of scientific debate, the clinical realities and decision-making conundrums that these patients pose require a coherent approach to this entity. In this review, we seek to highlight the various processes underlying the development of hydrocephalus in patients with Chiari 1 malformations. Hydrocephalus may occur as a cause, consequence, or in parallel with the development of Chiari 1 malformation, and understanding the etiology of such hydrocephalus is critical to the treatment of Chiari 1 malformations with associated hydrocephalus. We further discuss the literature pertaining to the management of these patients and unify the current scientific thinking on Chiari 1 malformations with the extant data on operative management of Chiari 1 to develop a structured and pragmatic approach to the diagnosis and management of patients with Chiari 1-associated hydrocephalus.

We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor. The syngeneic but unrelated H6 hepatocellular tumor cell line grew unrestricted in vaccinated mice, indicative of vaccine-mediated specific immunity to Neuro 2a tumors. Longitudinal analyses of tumor-infiltrating lymphocytes revealed a primary adaptive T cell response involving both CD4+ and CD8+ T cell subsets. Spleen cell mononuclear preparations from vaccinated mice were significantly more cytotoxic to Neuro 2a tumor cells than spleen cells from control mice as demonstrated in a four-hour in vitro cytotoxicity assay. These results strongly suggest that an irradiated whole cell tumor vaccine incorporating IL-12-expressing M002 HSV can produce a durable, specific immunization in a murine model of intracranial tumor.

No evidence-based guidelines exist on the role of cranial-molding orthosis (helmet) therapy for patients with positional plagiocephaly. To address the clinical question: \"Does helmet therapy provide effective treatment for positional plagiocephaly?\" and to make treatment recommendations based on the available evidence. 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). 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). 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.

Abstract BACKGROUND: Ventriculostomy placement is an important diagnostic and therapeutic tool for neurosurgeons. Multiple authors have presented retrospective series of patients evaluating periprocedure hemorrhage. OBJECTIVE: We performed a meta-analysis of existing studies to determine a more accurate rate of hemorrhage. METHODS: A MEDLINE and PubMed search was performed to find all studies of 25 or more patients conducted since 1970 that found a hemorrhagic complication rate from placement of a ventriculostomy. Studies in which a non-neurosurgeon placed the ventriculostomy and studies involving premature infants were excluded. RESULTS: Sixteen studies were used to obtain data from 2428 ventriculostomy procedures. Hemorrhage was found after 203 procedures, and 52 of these hemorrhages were deemed significant by the authors. The cumulative rate of hemorrhage was 7.0% (95% confidence interval: 4.5%-9.4%), with P < .05. The cumulative rate of significant hemorrhage was 0.8% (95% confidence interval: 0.2%-1.4%) with P < .05. CONCLUSION: Based on our meta-analysis, the overall hemorrhagic complication rate from ventriculostomy placement by neurosurgeons is approximately 7%. The rate of significant hemorrhage from ventriculostomy placement is approximately 0.8%. Further prospective studies are warranted to better address this question.

Purpose Hirayama disease, a rare cervical myelopathy in children and young adults, leads to progressive upper limb weakness and muscle loss. Non-invasive external cervical orthosis has been shown to prevent further neurologic decline; however, this treatment modality has not been successful at restoring neurologic and motor function, especially in long standing cases with significant weakness. The pathophysiology remains not entirely understood, complicating standardized operative guidelines; however, some studies report favorable outcomes with internal fixation. We report a successful surgically treated case of pediatric Hirayama disease, supplemented by a systematic review and collation of reported cases in the literature. Methods A review of the literature was performed by searching PubMed, Embase, and Web of Science. Full-length articles were included if they reported clinical data regarding the treatment of at least one patient with Hirayama disease and the neurologic outcome of that treatment. Articles were excluded if they did not provide information on treatment outcomes, were abstract-only publications, or were published in languages other than English. Results Of the fifteen articles reviewed, 63 patients were described, with 59 undergoing surgery. This encompassed both anterior and posterior spinal procedures and 1 hand tendon transfer. Fifty-five patients, including one from our institution, showed improvement post-treatment. Eleven of these patients were under 18 years old. Conclusion Hirayama disease is an infrequent yet impactful cervical myelopathy with limited high-quality evidence available for optimal treatment. The current literature supports surgical decompression and stabilization as promising interventions. However, comprehensive research is crucial for evolving diagnosis and treatment paradigms.

Abstract 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.