MISCELLANEA ON ENCEPHALOPATHIES Edited by Radu Tanasescu Miscellanea on Encephalopathies Edited by Radu Tanasescu Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Publishing Process Manager Molly Kaliman Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published April, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Miscellanea on Encephalopathies, Edited by Radu Tanasescu p. cm. ISBN 978-953-51-0499-5 Contents Chapter 1 Posttransplantation Encephalopaties 1 Daniela Anghel, Laura Dumitrescu, Catalina Coclitu, Amalia Ene, Ovidiu Bajenaru and Radu Tanasescu Chapter 2 HIV Encephalopathy – Now and Then 19 Cristina Loredana Benea, Ana-Maria Petrescu and Ruxandra Moroti-Constantinescu Chapter 3 Central Nervous System Involvement in Lyme Disease – Making the Diagnosis and Choosing the Correct Treatment 55 Ruxandra Calin, Adriana Hristea and Radu Tanasescu Chapter 4 Mechanisms of Cell Death in the Transmissible Spongiform Encephalopathies 69 Fiona Lane, James Alibhai, Jean C. Manson and Andrew C. Gill Chapter 5 Molecular Pathogenesis of Prion Diseases 95 Giuseppe Legname and Gianluigi Zanusso Chapter 6 Acute Encephalopathies and Psychiatry 113 Karim Sedky, Racha Nazir and Steven Lippmann Chapter 7 Current Advances in Cerebral Malaria Associated Encephalopathy 129 Mingli Liu, Shanchun Guo, Monica Battle and Jonathan K. Stiles Chapter 8 Encephalopathy Related to Ivermectin Treatment of Onchocerciasis in Loa loa Endemic Areas: Operational Considerations 169 Takougang Innocent and Muteba Daniel VI Contents Chapter 9 Past and Future of Diagnosis and Therapy of Transmissible Spongiform Encephalopathy 187 Chih-Yuan Tseng and Jack Tuszynski 1 Posttransplantation Encephalopaties Daniela Anghel1,2, Laura Dumitrescu3, Catalina Coclitu4, Amalia Ene4, Ovidiu Bajenaru1,4 and Radu Tanasescu1,3 1University of Medicine and Pharmacy "Carol Davila" Bucharest, 2Department of Neurology, Fundeni Clinical Institute, 3Department of Neurology, Colentina Hospital, 4Department of Neurology, University Emergency Hospital, Romania 1. Introduction Neurological complications may occur in 30 to 60% of the patients undergoing organ transplantation, especially liver and bone marrow (Padovan et al. 2000). Because of the constantly changing protocols regarding the transplantation procedure and the subsequent immunosuppression required for the prevention of graft rejection and graft versus host disease, the nature of the neurologic complications has changed over time. Recipients of solid organ or bone marrow cell transplants are at risk of life-threatening neurological complications including encephalopathies, seizures, brain infections and malignancies, stroke, central pontine myelinolysis and neuromuscular disorders. Many of these disorders are linked directly or indirectly to the immunosuppressive therapy. However, they may also result from graft versus host disease, from pretransplantation radiation or chemotherapy, and from injuries induced during surgery and intensive care unit(ICU) stay. In rare cases neuroinfectious pathogens may be transmitted with the transplanted tissue. Though most of the neurological complications occur disrespectful of the transplanted organ, transplant-specific complications also exist. Heart and pulmonary transplants are frequently associated to cerebral hypoxia, ischemia and bleeding. Bone marrow transplant is commonly associated with prolonged thrombocytopenia that may lead to catastrophic cerebral haemorrhage (Bashir 2001). In spite of the advances that have been made in the management of transplanted patients, the so-called posttransplantation encephalopathy (PTE), a complex syndrome with various etiologies characterized especially by disturbance of consciousness, is still frequently observed. The spectrum of PTE is vast and changes along in relationship with the time that has passed since transplantation (see Table1). Metabolic disturbances (secondary to the underlying or associated systemic disease or iatrogenic), drug neurotoxicity (caused by immunosuppressant, but also by antibiotics or other drugs), disimmunity and opportunistic central nervous system infections are frequent PTE etiologies. Though commonly the encephalopathies with these etiologies are well circumscribed clinical entities, highlighting the diagnostic and therapeutic particularities arising from their occurrence in the posttransplantation setting is of great utility for the current clinical practice. Moreover, 2 Miscellanea on Encephalopathies encephalopathies of different etiologies may overlap in the same transplanted patient (Mathew and Rosenfeld 2007). The etiological diagnosis of PTE is challenging because the clinical presentation and the neuroimagistic findings lack specificity and the unique circumstances related to the underlying disease, the transplant procedure and the subsequent management may give rise to less typical presentations. Most clinical signs of PTE are nonspecific and do not reliably identify a particular etiology. Humoral or tissue samples are often required for definite diagnosis. The major clinical feature is impaired attention, but the clinical findings can range from subtle cognitive difficulties to delirium or coma. A characteristic abnormality is marked fluctuation in the level of consciousness. The motor signs are variable and include tremor, asterixis and multifocal myoclonus, the latter particularly involving the face and the proximal muscles. In the severely affected subjects decorticate and decerebrate posturing may occur. Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain is mandatory when signs suggestive for diffuse or focal brain injury are present. If clinical examination shows no focal signs and brain MRI is normal, the most probable causes of the encephalopathy are systemic metabolic abnormalities or drug toxicity (commonly related to cyclosporine, tacrolimus or amphotericin-B). In postransplatation encephalopathic patients with normal MRI cytomegalovirus (CMV) infection should also be considered. In the setting of CNS signs and symptoms the electroencephalogram (EEG) is a useful investigation since it can identify diffuse non-specific slowing of the normal activity translating diffuse brain injury, and it can confirm the presence of non-convulsive seizures which may be difficult to differentiate from confusion or other mental status changes on clinical grounds only. The required laboratory investigations include complete blood count, coagulation studies, electrolyte panel, glucose, renal and liver function parameters and arterial blood gases. Assessment of the blood immunosuppressive drug levels should be performed when overdose may have occurred and blood and CSF cultures should be obtained when infection is suspected. Early Subacute Chronic posttransplantation period posttransplantation period posttransplantation period (first 30 days) (1-6 months) (>6 months) METABOLIC OPPORTUNISTIC OPPORTUNISTIC DISTURBANCES INFECTION (SOLID INFECTION (SOLID ORGAN ALLOGRAFTS) ORGAN ALLOGRAFTS) HYPOXIC-ISCHEMIC METABOLIC METABOLIC ENCEPHALOPATHY DISTURBANCES DISTURBANCES IMMUNOSUPPRESSIVE IMMUNOSUPPRESSIVE IMMUNOSUPPRESSIVE DRUG TOXICITY DRUG TOXICITY DRUG TOXICITY OPPORTUNISTIC INFECTION (BONE MARROW TRANSPLANTATION) Table 1. The time relationship with the transplant procedure of the common causes of PTE