Chapter 2 Embryology
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 154 Author(s): Parthiv Haldipur, Derek Dang, Kathleen J. Millen With the growing recognition of the extent and prevalence of human cerebellar disorders, an understanding of developmental programs that build the mature cerebellum is necessary. In this chapter we present an overview of the basic epochs and key molecular regulators of the developmental programs of cerebellar development. These include early patterning of the cerebellar territory, the genesis of cerebellar cells from multiple spatially distinct germinal zones, and the extensive migration...
Source: Handbook of Clinical Neurology - June 12, 2018 Category: Neurology Source Type: research
Chapter 1 Historic notes on anatomic, physiologic, and clinical research on the cerebellum
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 154 Author(s): Jan Voogd, Peter J. Koehler This chapter is concerned with ideas on the function, structure, and pathology that shaped our present knowledge of the cerebellum. One of the main themes in its early history is its localization subtentorially, leading to misattributions due to clinical observations in trauma and lesion experiments that caused collateral damage to the brainstem. Improvement of techniques led to the insight that it plays a role in movement control (Rolando) or coordination (Flourens). Purkinje initiated the histology of the c...
Source: Handbook of Clinical Neurology - June 12, 2018 Category: Neurology Source Type: research
Chapter 28 Concluding remarks
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Maurizio Pocchiari, Jean Manson This is the first volume of the Handbook of Clinical Neurology totally devoted to prion diseases. The reason for this choice is to inform neurologists and neuroscientists about the remarkable advances that this field has made in the diagnosis of human and animal prion diseases, understanding the pathogenesis of disease, and in the development of novel in vivo and in vitro models. In recent years, the knowledge of prion replication and mechanisms of prion spreading within the brain and peripheral organs of...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 27 Public health: surveillance, infection prevention, and control
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Hester Ward, Anna Molesworth, Sulisti Holmes, Katy Sinka Human prion diseases, though relatively rare, remain an ongoing public health problem. They are fatal diseases, with unconventional host responses and no early diagnostic tests or robust treatments. Public health measures were put in place to protect the food chain in the United Kingdom from the late 1980s, with similar measures following elsewhere. However, human prion diseases are transmissible through other routes, including through blood transfusion and surgery. As a result,...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 26 Safety of blood, blood derivatives, and plasma-derived products
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Marc L. Turner There has been concern for several decades around the possibility that prion diseases may be transmissible by blood components and / or plasma products. Whilst the evidence in respect of transmission of sporadic Creutzfeldt–Jakob disease (CJD) is largely circumstantial, the identification of variant CJD gave rise to increased concern due to the evidence of prion accumulation in peripheral lymphoid tissue at the time of clinical disease. A series of studies of appendix tissues in the United Kingdom revealed prion accumula...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 25 The zoonotic potential of animal prion diseases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Fiona Houston, Olivier Andréoletti Bovine spongiform encephalopathy (BSE) is the only animal prion disease that has been demonstrated to be zoonotic, causing variant Creutzfeldt–Jakob disease (vCJD) in humans. The link between BSE and vCJD was established by careful surveillance, epidemiologic investigations, and experimental studies using in vivo and in vitro models of cross-species transmission. Similar approaches have been used to assess the zoonotic potential of other animal prion diseases, including atypical forms identified thr...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 24 Clinical trials
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Simon Mead, Fabrizio Tagliavini Arguably the most important goal of prion research is the discovery of a safe and effective treatment for the human diseases. The final stages of the pathway to develop a treatment require clinical trials. Choices about how a trial is designed and conducted have a large impact on the chances of success. The gold-standard large randomized double-blind placebo-controlled study, which minimizes sources of bias and has been incredibly successful in other diseases, has been hard to achieve in Creutzfeldt–Jak...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 23 Vaccination strategies
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Thomas Wisniewski, Fernando Goñi Currently all prion diseases are without effective treatment and are universally fatal. It is increasingly being recognized that the pathogenesis of many neurodegenerative diseases, such as Alzheimer disease (AD), includes “prion-like” properties. Hence, any effective therapeutic intervention for prion disease could have significant implications for other neurodegenerative diseases. Conversely, therapies that are effective in AD might also be therapeutically beneficial for prion disease. AD-like pri...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 22 Identifying therapeutic targets and treatments in model systems
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Corinne Lasmézas, Ruth Gabizon In this chapter, we describe current therapeutic targets for prion diseases. We focus on targets that have been validated in vitro and in vivo, leaving out a plethora of theoretic targets that still require validation. We also show how the development of improved model systems for the study of prion infection and neurotoxic mechanisms has enabled target identification. Some therapeutic targets are prion-specific, such as PrPTSE, while others are shared by other neurodegenerative diseases, for example, aut...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 21 Symptomatic treatment, care, and support of CJD patients
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Brian S. Appleby, Deborah R. Yobs Prion diseases (e.g., Creutzfeldt–Jakob disease) are rapidly progressive neurodegenerative diseases that are invariably fatal. Diagnosing prion disease can be difficult and can lead to frustration. There is no currently available disease-altering treatment for prion diseases and the care and management of affected patients are directed towards symptomatic relief and quality of life. In this chapter, we highlight the many unique challenges of prion disease and how they affect care and management strate...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 20 Differential diagnosis with other rapid progressive dementias in human prion diseases
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Michael D. Geschwind, Katy Murray Prion diseases are unique in medicine as in humans they occur in sporadic, genetic, and acquired forms. The most common human prion disease is sporadic Creutzfeldt–Jakob disease (CJD), which commonly presents as a rapidly progressive dementia (RPD) with behavioral, cerebellar, extrapyramidal, and some pyramidal features, with the median survival from symptom onset to death of just a few months. Because human prion diseases, as well as other RPDs, are relatively rare, they can be difficult to diagnose,...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 19 Prion protein amplification techniques
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Alison J.E. Green, Gianluigi Zanusso Protein amplification techniques exploit the ability of PrPTSE to induce a conformational change in prion protein (PrP) in a continuous fashion, so that the small amount of PrPTSE found in tissues and biologic fluids in prion diseases can be amplified to a point where they are detectable by conventional laboratory techniques. The most widely used protein aggregation assays are protein misfolding cyclic amplification assay (PMCA) and real-time quaking-induced conversion (RT-QuIC). These assays have be...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 18 Prion-like mechanisms in amyotrophic lateral sclerosis
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Jacob I. Ayers, Neil R. Cashman The prion hypothesis – a protein conformation capable of replicating without a nucleic acid genome – was heretical at the time of its discovery. However, the characteristics of the disease-misfolded prion protein and its ability to transmit disease, replicate, and spread are now widely accepted throughout the scientific community. In fact, in the last decade a wealth of evidence has emerged supporting similar properties observed for many of the misfolded proteins implicated in other neurodegenerative ...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 17 Prion-like propagation of pathology in Parkinson disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Laura Volpicelli-Daley, Patrik Brundin Over 100 years ago, Lewy bodies and Lewy neurites were defined as a pathologic hallmark of Parkinson disease. Eighty years later, α-synuclein was found to be the primary component of these inclusions. Emerging evidence suggests that α-synuclein pathology propagates across interconnected networks throughout the nervous system in a prion-like manner. Pathologic α-synuclein seeds aggregation of native α-synuclein, resulting in the formation of insoluble inclusions. These seeds can propagate within...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 16 Prion-like mechanisms in Alzheimer disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Lary C. Walker Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins: Aβ protein in plaques and tau protein in tangles. At the molecular level, both proteins in a pathogenic state share key properties with classic prions, i.e., they consist of alternatively folded, β-sheet-rich forms of the proteins that autopropagate by the seeded corruption and self-assembly of like prote...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
