The Prion-like Properties of Amyloid-beta Peptide and Tau: Is there Any Risk of Transmitting Alzheimer's Disease During Neurosurgical Interventions?

Recent studies have recognized similarities between the peptides involved in the neuropathology of Alzheimer's disease and prions. The Tau protein and the Amyloid ß peptide represent the theoretical pillars of Alzheimer's disease development. It is probable that there is a shared mechanism for the transmission of these substances and the prion diseases development; this presumption is based on the presentation of several cases of individuals without risk factors who developed dementia decades after a neurosurgical procedure. This article aims to present the role of Aß and Tau, which underlie the pathophysiologic mechanisms involved in the AD and their similarities with the prion diseases infective mechanisms by means of the presentation of the available evidence at molecular (in-vitro), animal, and human levels that support the controversy on whether these diseases might be transmitted in neurosurgical interventions, which may constitute a wide public health issue.

Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer's Disease.

Although immunotherapies against the amyloid-ß (Aß) peptide tried so date failed to prove sufficient clinical benefit, Aß still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aß from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aß clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aß-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aß-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aß including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aß oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aß will probably produce a steady clearance of Aß in the ISF and therefore it may represent a new therapeutic strategy in AD.

Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson's Disease.

This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson's disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain.

Sacroiliac Pain: A Clinical Approach for the Neurosurgeon.

Pain originating from sacroiliac joint may also cause pain in the lumbar and gluteal region in 15% of the population. The clinical manifestation represents a public health problem due to the great implications on the quality of life and health-related costs. However, this is a diagnosis that is usually ignored in the general clinical practice; probably because of the unknown etiology, making harder to rule out the potential etiologies of this pathology, or maybe because the clinical criteria that support this pathology are unknown. By describing several diagnostic techniques, many authors have studied the prevalence of this pathology, finding more positive data than expected; coming to the conclusion that even though there is no diagnostic gold standard yet, an important amount of cases might be detected by properly applying several tests at the physical examination. Thus, it is necessary to have knowledge of the physiopathology and clinical presentation so that diagnosis can be made to those patients that manifest this problem. We present a clinical approach for the neurosurgeon.

Síndrome de Locked-In: Reporte de Caso y Revisión de Literatura / Locked-In Syndrome: Case Report And Review Of Literature

RESUMEN El Síndrome de Locked-In también conocido como Síndrome de Enclaustramiento, de Deseferentización o de Encerramiento, se definió por primera vez en 1966 por Plum y Posner. Las causas pueden agruparse en vasculares y no vasculares, siendo las primeras las más frecuentes. Clínicamente este síndrome se caracteriza porque la conciencia y el estado de vigila están conservados, pero existe cuadriplejía, anartria, disfagia y dificultad para coordinar la mecánica ventilatoria, representando las complicaciones pulmonares la principal causa de muerte. En la mayoría de los casos, el paciente conserva la movilidad ocular vertical, por tanto, el único método de comunicación es por medio de parpadeo ocular y movimientos verticales oculares. A continuación, se hace la presentación de un caso y revisión de la literatura con los aspectos fisiopatológicos, clínicos, diagnósticos y terapéuticos más relevantes.

ABSTRACT Locked-In Syndrome, also known as Enclaustration, Deseferentization, or Enclosure Syndrome, was first defined in 1966 by Plum and Posner. Causes can be grouped into vascular and non-vascular, the former being the most frequent. Clinically this syndrome is characterized by consciousness and the state of watch conserved, but there is quadriplegia, anartria, dysphagia and difficulty to coordinate the ventilatory mechanics, representing pulmonary complications the main cause of death. In most cases, the patient retains vertical eye mobility, so the only method of communication is through eye blinking and vertical eye movements. Next, a case presentation and review of the literature with the most relevant pathophysiological, clinical, diagnostic and therapeutic aspects is done.

Hidrocefalia De Presión Normal / Normal Pressure Hydrocephalus

Resumen La hidrocefalia de presión normal es una patología reversible que forma parte de las demencias. A pesar del tiempo que ha transcurrido desde su descubrimiento, su fisiopatología no ha sido claramente establecida y se han planteado dos teorías que buscan explicar el proceso. Una está basada en cambios en el flujo de líquido cefalorraquideo y la otra en el flujo sanguíneo cerebral. Además, el proceso de evaluación y diagnóstico no está determinado, puesto que no existe un método estándar y los síntomas son similares a otras patologías de sistema nervioso central, haciendo que el diagnóstico se realice gracias a la suma de los síntomas clínicos y ciertos hallazgos imagenológicos que no son siempre constantes.

Abstract Normal pressure hydrocephalus is a pathology causing dementia that is reversible. Despite the time elapsed since its discovery, its pathophysiology has not been clearly established and two theories have been proposed that try to explain the process, one based on changes in cerebrospinal fluid flow and the other on cerebral blood flow. In addition, the evaluation and diagnosis process is not determined, since there is no standard method and the symptoms are similar to other pathologies of the central nervous system, leading to the diagnosis as the summation of clinical symptoms and some findings in imaging which are not always constant.