Matthew Protas

Evaluation of metabolic and synaptic dysfunction hypotheses of alzheimer’s disease (AD): A meta-analysis of CSF markers

Background: Alzheimer’s disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focus-ing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and met-abolic dysfunction are increasingly implicated in AD. Objective: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Methods: Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF con-centration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published Eng-lish articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard er-rors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software. Results: Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were in-cluded comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and met-abolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0.03), glutathione (1.11, 1.01-1.21, p=0.03), alanine (1.10, 0.98-1.23, p=0.09), and lower levels of significance for lactate (1.2, 1.00-1.47, p=0.05). Of note, CSF glucose and glutamate levels in AD were not significantly different than that of the controls. Conclusion: This study provides proof of concept for the use of meta-analysis validation of AD hypothe-ses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity and GABAergic resistance to neurodegeneration, given ob-served unchanged glutamate levels and decreased GABA levels. With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and anaple-rosis of the tricarboxylic acid cycle using glutamate. Future applications of meta-analysis indicate the pos-sibility of further in silico evaluation and generation of novel hypotheses in the AD field.

Cervical Spine Aneurysmal Bone Cysts in the Pediatric Population: A Systematic Review of the Literature

Cervical spine aneurysmal bone cysts (ABCs) in pediatric patients have not been thoroughly studied. Using PubMed and Google Scholar, a systematic review of the literature was conducted for publications that included patients aged ≤15 years with a confirmed diagnosis of ABC in the cervical spine. Thirty-five studies with a total of 71 patients met the inclusion criteria. Nearly 80% of patients presented with neck or shoulder pain. The axis was the level most frequently involved (34.28%), followed by C5 (24.28%). Posterior elements were most likely to be affected (88.46%) while exclusive involvement of the body was uncommon. To our knowledge, this is the first systematic review of the literature regarding ABCs of the cervical spine in a pediatric population. Spinal ABCs are rarely found in the cervical region, and their treatment remains challenging due to their location, vascularization, and a high overall recurrence rate even with surgical resection.

Review of Treatment of Gunshot Wounds to Head in Late 19th Century

INTRODUCTIONnDuring the late 19th century, the seeds of modern neurosurgery were planted to bloom into what it is now known. Wars such as the American Civil War and Crimean War drove the need to find better ways of preventing mortality from gunshot wounds to the head. However, the mortality rate from all major surgical procedures to the head, neck, and face remained staggering. Herein, we describe the surgical treatments for head and neck injuries in order to improve our understanding of neurosurgical procedures performed during the late 19th century.nnnMETHODSnA literature search was conducted using PubMed and Google Books for available articles pertaining to treatment for gunshot wounds to the head during the 19th century. Search terms included Gunshot wounds, Treatment, Civil War, Gunshot wound, Treatment 19th century, and Gunshot wounds, Treatment, 1800s. Literature was excluded if not in English or if no translation was provided. Most of the information was taken from the International Encyclopedia of Surgery Volume II.nnnRESULTSnSurgical care for gunshot wounds to the cranium were based on depth and involved finding the bullet, controlling the bleeding, and preventing further brain injury. Surgical treatment for a gunshot wound to the face or neck involved controlling the bleeding, with a focus on maintaining the airway.nnnCONCLUSIONSnBecause of improved understanding of infectious processes and technologic advances in surgical equipment, the late 19th century was a major milestone in creating modern day neurosurgery. The methodology behind todays treatments is no different from that of the late 19th century.

Treatment of Gunshot Wounds to Spine During Late 19th Century

BACKGROUNDnThe demand for neurosurgical procedures increased drastically in the late 19th century owing to advances in ballistics during the American Civil War and Crimean War.nnnMETHODS AND RESULTSnSurgical care for a gunshot wound to the spine relied on skilled identification and removal of the fractured bone. Hemorrhage control and infection prevention were also imperative for improving survival rates.nnnCONCLUSIONSnAlthough new techniques were implemented, the mortality rate from spinal injuries during this period was staggering. Nevertheless, those 19th century procedural methods provided the basis for present-day treatment for spinal injury patients.

The accessory obturator nerve: an anatomical study with literature analysis

Objectives: The accessory obturator nerve (AON) is often underrepresented in the literature and unknown to many surgeons. As this variant nerve has been mistaken for other regional nerves e.g., obturator nerve, nerve injury has occurred. Therefore, the current study was undertaken to better understand the surgical anatomy of the AON. Methods: In the supine position, 20 adult fresh frozen cadavers (40 sides) underwent an anterior approach to the retroperitoneal space. When present, the length and diameter of the AON were measured with microcalipers. The position, course and origin of each AON were documented. Results: The AON was identified on 12 sides (30%). The origin was found to be L2–L3 on four sides; L3 on two sides, L3–L4 from three sides, from the obturator nerve on two sides, and from the femoral nerve on three sides. The average length from the origin to the superior pubic ramus was 14.5 cm. The average diameter was found to be 1.2 mm. All AON were found to lie medial to the psoas major muscle. Additionally, on all sides, the AON was medial to the femoral nerve and lateral to the obturator nerve. Two left sides anastomosed with the anterior division of obturator nerve at its exit from the obturator foramen. Eight sides terminated deep (two) or superficial (six) to the origin of pectineus; two of these had demonstrable branches to the hip joint. Conclusion: The AON is a normal anatomical variant and there are many variations in its origin and terminal branches can be “strong” or “weak.” Knowing the normal anatomy and variations of the AON is important for surgeons including neurosurgeons, orthopaedic surgeons, and urologists who deal with the pathologies of this area.

USING CSF MARKERS TO VALIDATE METABOLIC AND SYNAPTIC DYSFUNCTION HYPOTHESES OF ALZHEIMER’S DISEASE (AD): META-ANALYSIS

panel of rat (APPsi) and mouse (Tg4-42) biofluids and tissues. This give further help to understand the devastating neurodegenerative disease, related complex biochemical pathways and pathophysiological processes of AD.Conclusions:UsingNMR-basedmetabolic phenotyping we defined a quantitative readout of transgenic animal models in the form of a biomarker panel. These biomarkers not only contribute to the understanding of this devastating neurodegenerative disease and the related pathophysiological processes on a systemic level, but set the base for a wide range of biomedical applications. Our approach can be easily extended to other tissues, matrices, or disease models and translated across species since metabolic pathways are conserved through evolution, and are essentially similar in rodents and humans.

KNOWLEDGE BARRIERS TO IDENTIFYING ALZHEIMER'S DISEASE INCIDENCE IN GRENADA, WEST INDIES

P2-536 THE PREVALENCE OF PRECLINICAL ALZHEIMER’S DISEASE IN A POPULATION STUDY OF 70-YEAR-OLDS Silke Kern, Henrik Zetterberg, Anna Zettergren, Jurgen Kern, Anne B€orjesson-Hanson, Kaj Blennow, Ingmar Skoog, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, M€olndal, Sweden; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; University College London, London, United Kingdom; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden. Contact e-mail: silke.kern@neuro.gu.se