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White Matter Disease

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Stroke Genetics

Abstract

Cerebral white matter (WM) plays a fundamental role in transmitting electrical signals between the neurons; thus, any disorder affecting structural or functional integrity of the WM is bound to present with diverse neurological manifestations. The range of neurological dysfunction varies greatly from relentless failure to thrive in a spectrum of pediatric leukodystrophies to subtle cognitive decline in the elderly with leukoaraiosis. Pathophysiology of these disorders is heterogeneous, but invariably there is a known genetic contribution ranging from monogenetic disorders such as metachromatic and globoid cell leukodystrophies, adrenoleukodystrophy, leukoencephalopathy with vanishing WM disease in the pediatric population to common genetic risk factors in the elderly. In this chapter, we will explore the neurogenetics of sporadic WM disease caused by cerebrovascular pathology, which has been linked to risk of ischemic and hemorrhagic strokes. This subtype of WM disease, also known as WM lesions (WMLs), WM hyperintensity (WMH), or leukoaraiosis, has been described in the context of epidemiological studies of aging adults with subtle, but progressive, signs of neurological dysfunction and manifest clinical cerebrovascular disease. This chapter will discuss how genetic analysis applies to a spectrum of cerebrovascular WM diseases, outline the current state of knowledge, and delineate the potential implications for future research and neurological practice in the new era of genetic discovery.

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Acknowledgments and Funding

Dr. Natalia S. Rost is in part supported by the National Institute of Neurological Disorders and Stroke (NINDS) (K23NS064052, R01NS082285 & R01NS086905) and the Massachusetts General Hospital Dean Institute for Integrative Study of Atrial Fibrillation and Stroke.

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Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, 175 Cambridge St, Suite 300, Boston, MA, 02114, USA

    Anne-Katrin Giese M.D.

  2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 175 Cambridge St, Suite 300, Boston, MA, 02114, USA

    Anne-Katrin Giese M.D.

  3. Stroke Service, Department of Neurology, Massachusetts General Hospital, 175 Cambridge St, Suite 300, Boston, MA, 02114, USA

    Natalia S. Rost M.D., M.P.H.

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  1. Anne-Katrin Giese M.D.
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Correspondence to Natalia S. Rost M.D., M.P.H. .

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  1. Department of Neurology, Institute of Cardiovascular Research Royal Holloway College, University of London Imperial College London Healthcare NHS Trust, London, United Kingdom

    Pankaj Sharma

  2. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA

    James F. Meschia

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Giese, AK., Rost, N.S. (2017). White Matter Disease. In: Sharma, P., Meschia, J. (eds) Stroke Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-56210-0_11

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