Understanding and Treating Cerebral Small Vessel Disease

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Alina Gonzalez-Quevedo, MD, PhD (Editor) – Institute of Neurology and Neurosurgery, Havana, Cuba
Svetlana Dambinova, PhD, DSc (Editor) – Emory Decatur Hospital, Emory Healthcare, Decatur, GA, USA
Kerstin Bettermann, MD, PhD (Editor) – Department of Neurology, Penn State College of Medicine, Hershey, PA, USA

Series: Neurology – Laboratory and Clinical Research Developments
BISAC: MED056000

Cerebral small vessel disease (CSVD) silently affects a large part of the population, increasing in prevalence with age and with the presence of vascular risk factors. Its harmful effects on brain parenchyma increase the risk of stroke, cognitive decline and dementia, and it is responsible for a spectrum of symptoms that are much less obvious, such as unrecognized mild signs or symptoms of neurocognitive dysfunction, mild mood or behavioral disturbances, gait dysfunction, and a general decline in function generally attributed to normal aging. These consequences pose a heavy burden on patients, families and countries that need to be addressed.
Understanding and Treating Cerebral Small Vessel Disease provides an insight into a broad area of research in this field, focusing on topics that deal with the underlying pathophysiological mechanisms of CSVD, recent clinical and neuroimaging findings, biomarker developments, comorbidities, prevention strategies and emerging therapeutic options. The contents are distributed in five sections that span these topics.
Section I, “Pathophysiology and Subtypes of Cerebral Small Vessels Disease”, includes three chapters that deal with the prevalence of different forms of small-vessels disease in vascular cognitive impairment, and the pathophysiological mechanisms of CSVD.
Section II, “New Approaches for Diagnosis and Treatment of CSVD”, includes six chapters which deal with the microvascular assessment of CSVD through the study of retinal blood (chapter four), a global vision of brain MRI findings in CSVD (chapter five), and digital electroencephalographic changes and computerized analysis methods in CSVD (chapter six). Chapters seven, eight and nine approach the treatment of CSVD, from the assessment of advanced immunoactive therapy for CSVD to the use of non-pharmacological therapies such as transcranial magnetic stimulation and extracorporeal shock wave therapy. The targeting of key pathogenic mechanisms is also discussed in light of experimental data and clinical trials, as well as the introduction of neuroprotection in the treatment of symptomatic and asymptomatic CSVD.
Section III, “Potential Biomarkers for CSVD”, includes chapters 10—13 dedicated to the early detection of CSVD through brain MRI imaging and the development of alternative circulating biomarkers (brain specific proteins, inflammatory and oxidative stress biomarkers, autoantibodies). The application of these biomarkers in other conditions closely associated with small vessel neurovascular networks, such as migraine, is also discussed.
Section IV, “Cerebral Small Vessels Disease and Comorbid Conditions” is comprised of five chapters (14—18) which approach the relationship of CSVD with infectious diseases (viral, bacterial and parasitic infections), highlighting findings in COVID-19. Conditions related with the nervous system, such as cognitive impairment, schizophrenia and chronic alcohol consumption in association with the development of small vessel pathology in the brain are also discussed.
Section V includes chapter 19, which briefly summarizes the main topics presented in this book and offers a quick vision from the editors of future trends in microangiopathy diagnosis and treatment.

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Table of Contents

Preface

Part I: Pathophysiology, and Subtypes of Cerebral Small Vessel Disease

Chapter 1. Prevalence of Different Forms of Small-Vessel Disease in Vascular Cognitive Impairment
(Raquel Manso Calderón, MD, PhD, Department of Neurology, University Hospital of Salamanca, Salamanca, Spain)

Chapter 2. The Pathophysiological Mechanism of Cerebral Small Vessel Disease and Brain-Derived Proteins as Biochemical Markers
(Sergio González-García, PhD, Alina González-Quevedo, MD, PhD, Marisol Peña-Sánchez, Zenaida Hernández-Diaz, MD, Anay Cordero-Eiriz, Melany Betancourt-Loza, Caridad Menéndez-Saínz, PhD, and Rebeca Fernández-Carriera,“Dr. Miguel Enriquez” Faculty, Medical University of Havana, Havana, Cuba, and others)

Chapter 3. The Role of Nitric Oxide and Superoxide Anion Radical Cycles in Cerebral Small Vessels Pathology
(Valentin P. Reutov, PhD, DSc, Elena G. Sorokina, PhD, Lyudmila A. Davydova, PhD, Victor M. Chertok, MD, PhD, Oleg I. Sukmansky, MD, PhD, and Vsevolod G. Pinelis, MD, PhD, Institute of Higher Nervous Activity and Neurophysiology. Russian Academy of Sciences. Moscow, Russia, and others)

Part II: New Approaches for Diagnosis and Treatment of CSVD

Chapter 4. Microvascular Assessment in Cerebral Small Vessel Disease
(Kusum Sinha, PhD, and Kerstin Bettermann, MD, PhD, Department of Neurology, Penn State College of Medicine, Hershey, PA, US)

Chapter 5. Global Vision of Brain MRI Findings in Cerebral Small Vessel Disease
(Zenaida Milagros Hernández-Díaz, MD, Joshua P. Klein, MD, PhD, Sergio González-García, PhD, Alina González-Quevedo, MD, PhD, Marisol Peña-Sánchez and Armando Abreu Duque, Neuroradiology Department, International Center for Neurological Restoration, Havana, Cuba, and others)

Chapter 6. EEG in Cerebral Small Vessel Disease
(Marta Brown Martínez, MD, Department of Clinical Neurophysiology, Sport Medicine Institute, Havana, Cuba)

Chapter 7. Advanced Treatment Options for Cerebral Small Vessel Disease Assessed by Ultra-High-Field MRI Findings, and Autoimmune Biomarkers of Neurotoxicity
(Thomas A. Gennarelli, MD, Svetlana A. Dambinova, PhD, DSc, Mario Estevez Baez, MD, PhD, and John D. Mullins, MD, Medical College of Wisconsin. West Chester, PA, USA, George Washington University, Washington DC, USA, and others)

Chapter 8. Key Pathogenetic Mechanisms and Therapeutic Approaches to Modify the Course of Cerebral Small Vessel Disease
(Ella Yu. Solovyeva, MD, PhD, and Аndrey V. Сhekanov, PhD, Laboratory of Biomedical Studies in Neurology, Department of Neurology, Pirogov Russian National Research Medical University, Moscow, Russia)

Chapter 9. Neuroprotection in Cerebral Small Vessel Disease
(Julio César García Rodríguez, PhD, Yamila Rodríguez Cruz, MD, PhD, and Alina González-Quevedo, MD, PhD, CENPALAB, National Center for Animal Breeding, BioCubaFarma, Havana, Cuba, and others)

Part III: Potential Biomarkers for CSVD

Chapter 10. Detecting Asymptomatic Cerebral Small Vessel Disease. Brain Specific Proteins as Surrogate Biomarkers
(Alina González-Quevedo, MD, PhD, Sergio González García, PhD, Marisol Peña Sánchez, Zenaida Hernández Díaz, MD, María Caridad Menéndez Saínz, PhD, Rebeca Fernández Carriera, Anay Cordero Eiriz and Melany Betancourt Loza, Institute of Neurology and Neurosurgery, Havana, Cuba, and others)

Chapter 11. Circulating Inflammatory and Oxidative Stress Biomarkers in Subclinical Cerebral Small Vessel Disease
(Marisol Peña Sánchez, Alina González-Quevedo, MD, PhD, Zenaida Hernández Díaz, MD, and Sergio González García, PhD, Neurobiology Department, Institute of Neurology and Neurosurgery, Havana, Cuba, and others)

Chapter 12. Potential Biochemical Markers for Migraine and CSVD
(Svetlana А. Dambinova, PhD, DSc, Vladimir L. Beloborodov, PhD, DSc, Ivan I. Кrasnyuk, PhD, DSc, Мario Estevez Baez, MD, PhD, Gyuzyal R. Tabeeva, MD, PhD, DSc, Vladimir А. Parfenov, MD, PhD, DSc, Emory Decatur Hospital, Emory Healthcare, Decatur, GA, USA, and others)

Chapter 13. Assessment of Cognitive Impairment Due to CSVD Using Neuroimaging and Liquid Neurovascular Biomarkers
(Larisa A. Dobrynina, MD, PhD, DSc, Evgenia V. Alexandrova, MD, PhD, Maryam R. Zabitova, MD, Ludmila A. Kalashnikova, MD, PhD, DSc, Marina V. Krotenkova, MD, PhD, Elena V. Gnedovskaya, MD, PhD, DSc, Elena I. Kremneva, MD, PhD, and Bulat M. Akhmetzyanov, MD, N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia, and others)

Part IV: Cerebral Small Vessels Disease and Comorbid Conditions

Chapter 14. Endothelial Dysfunction Induced by Infectious Agents in Cerebral Small Vessel Disease
(Claudia O. Rodrigues, PhD, Cristiane M. De Leis, PhD and Andrew V. Oleinikov, PhD. University of Miami Miller School of Medicine, Department of Molecular and Cellular Pharmacology, Miami, FL, USA, and others)

Chapter 15. Cerebral Vascular Disorders in COVID-19
(Anatoly I. Fedin, MD, PhD, DSc, and Svetlana A. Dambinova, PhD, DSc, Neurology Department of Russian National Research Pirogov Medical University, Moscow, Russia, and others)

Chapter 16. Interactive Effects of Vascular Disease, Cognitive Impairment, and Dementia
(Jorge J. Llibre-Guerra, MD, Neurology Department, Havana School of Medicine, Havana, Cuba)

Chapter 17. Particularities of Cerebral Small Vessel Disease in Schizophrenia
(Ileana Marinescu, PhD, Dragoş Marinescu, PhD, Liana Pauna-Cristian, MD, and Puiu Olivian Stovicek, PhD, Department of Psychiatry, University of Medicine and Pharmacy of Craiova, Romania, and others)

Chapter 18. The Risk of Cerebral Small Vessel Disease Due to Uncontrolled Alcohol Consumption
(Galina A. Izykenova, PhD, Svetlana A. Dambinova, PhD, DSc, Institute Pharmacy, I.M. Sechenov First Moscow State Medical University. Moscow, Russia, and others)

Part V: Conclusion

Chapter 19. Future Trends in Microangiopathy Diagnosis and Treatment
(Alina Gonzalez-Quevedo, MD, PhD, Svetlana A. Dambinova, PhD, DSc, Kerstin Bettermann, MD, PhD, Institute of Neurology and Neurosurgery, Havana, Cuba, and others)

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