Elias Rizk

Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation

The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury. Here, we have shown in rodents that such repair occurs at least in part through DNA methylation. In animals with combined spinal cord and sciatic nerve injury, folate-mediated CNS axon regeneration was found to depend on injury-related induction of the high-affinity folate receptor 1 (Folr1). The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons was biphasic and dose dependent and correlated closely over its dose range with global and gene-specific DNA methylation and with expression of both the folate receptor Folr1 and the de novo DNA methyltransferases. These data implicate an epigenetic mechanism in CNS repair. Folic acid and possibly other nontoxic dietary methyl donors may therefore be useful in clinical interventions to promote brain and spinal cord healing. If indeed the benefit of folate is mediated by epigenetic mechanisms that promote endogenous axonal regeneration, this provides possible avenues for new pharmacologic approaches to treating CNS injuries.

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis

Importance Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. Objective To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. Data Sources Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. Study Selection Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. Data Extraction and Synthesis Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each others results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. Main Outcome and Measures Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. Results The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. Conclusion and Relevance This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Brachial plexus anesthesia: A review of the relevant anatomy, complications, and anatomical variations

The trend towards regional anesthesia began in the late 1800s when William Halsted and Richard Hall experimented with cocaine as a local anesthetic for upper and lower limb procedures. Regional anesthesia of the upper limb can be achieved by blocking the brachial plexus at varying stages along the course of the trunks, divisions, cords and terminal branches. The four most common techniques used in the clinical setting are the interscalene block, the supraclavicular block, the infraclavicular block, and the axillary block. Each approach has its own unique set of advantages and indications for use. The supraclavicular block is most effective for anesthesia of the mid‐humerus and below. Infraclavicular blocks are useful for procedures requiring continuous anesthesia. Axillary blocks provide effective anesthesia distal to the elbow, and interscalene blocks are best suited for the shoulder and proximal upper limb. The two most common methods for localizing the appropriate nerves for brachial plexus blocks are nerve stimulation and ultrasound guidance. Recent literature on brachial plexus blocks has largely focused on these two techniques to determine which method has greater efficacy. Ultrasound guidance has allowed the operator to visualize the needle position within the musculature and has proven especially useful in patients with anatomical variations. The aim of this study is to provide a review of the literature on the different approaches to brachial plexus blocks, including the indications, techniques, and relevant anatomical variations associated with the nerves involved. Clin. Anat. 27:210–221, 2014.

A comprehensive review with potential significance during skull base and neck operations, Part II: Glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1–4

Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra‐axial communications can be collectively considered a plexus. Clin. Anat. 27:131–144, 2014.

Arterial supply of the lower cranial nerves: A comprehensive review

The lower cranial nerves receive their arterial supply from an intricate network of tributaries derived from the external carotid, internal carotid, and vertebrobasilar territories. A contemporary, comprehensive literature review of the vascular supply of the lower cranial nerves was performed. The vascular supply to the trigeminal, facial, vestibulocochlear, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves are illustrated with a special emphasis on clinical issues. Frequently the external carotid, internal carotid, and vertebrobasilar territories all contribute to the vascular supply of an individual cranial nerve along its course. Understanding of the vasculature of the lower cranial nerves is of great relevance for skull base surgery. Clin. Anat. 27:108–117, 2014.

The muscular axillary arch: an anatomic study and clinical considerations.

OBJECTIVE The muscular axillary arch is a musculotendinous structure that arises from the latissimus dorsi muscle and crosses the axilla before inserting to the humerus, brachial fascia, or coracoid process. Case reports have described the neurovascular compression symptoms caused by this anatomic variant and have reported that the symptoms can be relieved by division of the muscle. However, there has been little information published regarding this topic in the neurosurgical literature. METHODS We evaluated 70 axillary dissections in 35 cadavers to assess for the presence of this anomaly. RESULTS The muscular axillary arch was identified unilaterally in 3 (8.6%) of the 35 cadavers. All 3 arches arose from the anterior border of the latissimus dorsi muscle and inserted at a point along a line extending from the coracoid process to the intertubercular groove deep to the insertion of the pectoralis major muscle. All 3 arches crossed over the neurovascular bundle in the axilla. CONCLUSION Compression by the muscular axillary arch should be considered in the differential diagnosis of patients with thoracic outlet and hyperabduction syndromes.

Intracardiac migration of a distal shunt catheter: an unusual complication of ventricular shunts: Report of 2 cases

Unusual complications of peritoneal shunts are a well-known occurrence. The authors present 2 cases of intracardiac migration of a distal shunt catheter, summarizing the diagnosis and management of each case. This complication seems to be a rare occurrence; the transgression of the jugular vein leading to intracardiac migration of a shunt catheter has been reported only 6 times previously. The authors highlight the importance of careful and proper placement of the distal peritoneal catheter during the tunneling process, in particular avoiding too deep a penetration of the shunt passer into the neck tissues and too medial a shunt passage near the sternal notch to avoid vascular structures.

Programmed cell death in the lithium pilocarpine model: Evidence for NMDA receptor and ceramide-mediated mechanisms

Ceramide is known to induce programmed cell death (PCD) in neural and non-neural tissues and to increase after kainic acid (KA) status epilepticus (SE). Ceramide increases have been shown to depend on NMDA receptor activation in the KA model, but these changes have not been studied in the lithium pilocarpine (LiPC) model. Thus, the purpose of this study was to determine if hippocampal ceramide levels increase after LiPC induced SE and if NMDA receptor blockade prevents PCD and any such ceramide increases. We found that LiPC induced SE resulted in ceramide increases and DNA fragmentation in the hippocampus of adult, P21, and P7 rats. The administration of MK-801, the NMDA receptor antagonist, in adults, 15min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.

Idiopathic hypertrophic spinal pachymeningitis.

Spinal idiopathic hypertrophic pachymeningitis (IHP) is a rare, chronic, nonspecific, granulomatous inflammatory disorder of the dura with unknown etiology. It can cause a localized or diffuse thickening of the dura mater with compression of the spinal canal and possible myelopathic symptoms. The authors report 3 consecutive cases of spinal IHP with a review of the literature. The diagnosis of spinal IHP was based on biopsy and pathological confirmation. Typical MR imaging findings suggestive of spinal IHP were noted in all cases. The clinical course may be marked by deterioration despite conservative therapy and may require surgical intervention to prevent irreversible neurological damage. Therefore, prompt diagnosis and institution of proper treatment is critical.

Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives

&NA; Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.