Review Article Translating pathology in multiple sclerosis: the combination of postmortem imaging, histopathology and clinical findings Introduction Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, most commonly affecting young adults and leading to substantial neurological disability (1, 2). The majority (80%) of MS patients present with a relapsing-remitting disease course, which is characterized by a waxing and waning of neurological symptoms. Over time, the initial (partial) recovery from relapses gives way to a steady progression and irreversible neurological deficits, the so-called secondary progressive phase. About 15% of the cases follow a primary progressive course, which is characterized by disease progression from onset without intermit- tent remissions (3–7). Clinically, MS is charac- terized by a wide range of symptoms, dependent on the localization of the damage. The most common symptoms, include visual deterioration, sensory problems, central paresis, brainstem symptoms and neuropsychological impairment including memory deficits (8). Histopathologically, MS is characterized by multifocal lesions in the white matter (WM), with various degrees of de- and remyelination, axonal damage and ⁄ or loss, gliosis, blood-brain barrier leakage, infiltrated T lymphocytes and macrophag- es and complement deposition (9, 10). Besides the occurrence of MS lesions in the WM, lesions are also extensively present in the cerebral and cere- bellar cortex, deep grey matter (GM) and spinal cord (11–18). Due to the possibility of following lesions over time in vivo, magnetic resonance imaging (MRI) has considerably contributed to the understanding and early diagnosis of MS (19–21). MRI is also routinely used to monitor disease course and progression in MS patients and as a surrogate outcome marker in clinical trials. However, for correlations with clinical measures, it is not only important to be able to identify abnormalities on MRI, but also to reliably interpret these abnor- malities in terms of underlying pathology. Postmortem MRI and histopathology correla- tion studies have provided important insights into Acta Neurol Scand 2009: 119: 349–355 DOI: 10.1111/j.1600-0404.2008.01137.x Copyright Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Seewann A, Kooi E-J, Roosendaal SD, Barkhof F, van der Valk P, Geurts JJG. Translating pathology in multiple sclerosis: the combination of postmortem imaging, histopathology and clinical findings. Acta Neurol Scand 2009: 119: 349–355. Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard. Background – Studies combining postmortem magnetic resonance imaging (MRI) and histopathology have provided important insights into the abnormalities reflected by MRI. Materials and methods – A short overview of these studies applied to multiple sclerosis (MS) is provided in this review, and the Amsterdam postmortem imaging protocol is specifically highlighted. Conclusion – Postmortem MRI and histopathology correlation studies have enabled a direct translation of basic pathology in MS to the clinical setting, and have simultaneously served as a biological validation of new MRI techniques. A. Seewann 1 *, E-J. Kooi 2 *, S. D. Roosendaal 3 , F. Barkhof 3 , P. van der Valk 2 , J. J. G. Geurts 2,3 Departments of 1 Neurology, 2 Pathology and 3 Radiology, VU University Medical Centre, MS Centre Amsterdam, Amsterdam, The Netherlands Key words: postmortem imaging; multiple sclerosis; histopathology; magnetic resonance imaging Evert-Jan Kooi, MSc, Department of Pathology, VU University Medical Center, Room 0E18, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Tel.: +31 20 4444096 Fax: +31 20 4442964 e-mail: e.kooi@vumc.nl * Both authors contributed equally. Accepted for publication October 8, 2008 349