Ebook Neuroradiology - Key differential diagnoses and clinical questions: Part 1

(BQ) Part 1 book Neuroradiology - Key differential diagnoses and clinical questions presents the following contents: Computed tomography hyperdense lesions, T1 hyperintense lesions, multiple susceptibility artifact lesions, ring enhancing lesions, leptomeningeal enhancement, dural enhancement,...

NEURORADIOLOGY Key Differential Diagnoses and Clinical Questions JUAN E SMALL, MD, M.Sc Section Chief, Neuroradiology Division Director, Neuroimaging Education Assistant Professor of Radiology Lahey Hospital and Medical Center Tufts University School of Medicine Burlington, Massachusetts PAMELA W SCHAEFER, MD Associate Director of Neuroradiology Clinical Director of MRI Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Boston, Massachusetts 1600 John F Kennedy Blvd Ste 1800 Philadelphia, PA 19103-2899 NEURORADIOLOGY: KEY DIFFERENTIAL DIAGNOSES AND CLINICAL QUESTIONS Copyright © 2013 by Saunders, an imprint of Elsevier Inc ISBN: 978-1-4377-1721-1 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the Publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein Library of Congress Cataloging-in-Publication Data Small, Juan E Neuroradiology : key differential diagnoses and clinical questions / Juan E Small, Pamela W Schaefer p ; cm Includes bibliographical references and index ISBN 978-1-4377-1721-1 (hardcover : alk paper) I Schaefer, Pamela W II Title [DNLM: Diagnostic Techniques, Neurological–Case Reports Nervous System Diseases–­ radiography–Case Reports Diagnosis, Differential–Case Reports Neuroradiography–­ methods–Case Reports WL 141] 617’.075 dc23 2012016008 Executive Content Strategist: Pamela Hetherington Content Development Specialist: Margaret Nelson Publishing Services Manager: Patricia Tannian Project Manager: Carrie Stetz Design Direction: Steven Stave Printed in China Last digit is the print number:  9  8  7  6  5  4  3  This book is dedicated to my beautiful wife and best friend Kirstin Thank you for helping me to understand the things that really matter in life, in ways I never could before we met Without you, my life would be incomplete I love you and cherish our life together And to my parents, Aurora and Richard Without your support and unconditional love, none of my achievements would have been possible Thank you for encouraging me to follow my heart Juan E Small This book is dedicated to my wonderful husband, Douglas Raines, and my beautiful daughter, Sarah Raines, who always give me unconditional love, support, and wisdom Pamela W Schaefer SECTION EDITORS HUGH D CURTIN, MD Chief of Radiology Massachusetts Eye and Ear Infirmary Professor of Radiology Harvard Medical School Boston, Massachusetts R GILBERTO GONZALEZ, MD, PhD Director of Neuroradiology Massachusetts General Hospital Professor of Radiology Harvard Medical School Boston, Massachusetts HILLARY R KELLY, MD Neuroradiologist Massachusetts General Hospital Instructor in Radiology Harvard Medical School Boston, Massachusetts STUART R POMERANTZ, MD Associate Director of Neuro-CT Neuroradiologist Massachusetts General Hospital Harvard Medical School Boston, Massachusetts vi PAMELA W SCHAEFER, MD Associate Director of Neuroradiology Clinical Director of MRI Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Boston, Massachusetts JUAN E SMALL, MD, M.Sc Section Chief, Neuroradiology Division Director, Neuroimaging Education Assistant Professor of Radiology Lahey Hospital and Medical Center Tufts University School of Medicine Burlington, Massachusetts TINA YOUNG-POUSSAINT, MD Neuroradiologist Boston Children’s Hospital Professor of Radiology Harvard Medical School Boston, Massachusetts CONTRIBUTORS JALIL AFNAN, MD Clinical Associate Lahey Clinic Tufts University School of Medicine Burlington, Massachusetts KENNETH S ALLISON, MD Instructor Harvard Medical School Clinical Assistant Massachusetts General Hospital Boston, Massachusetts NINO BOALS, MD Neuroradiology Fellow and Research Assistant Massachusetts General Hospital Boston, Massachusetts FARGOL BOOYA, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts HUI J JENNY CHEN, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts ROBERT CHEN, MD Department of Radiology Massachusetts General Hospital Boston, Massachusetts SAMI ERBAY, MD Assistant Professor Lahey Clinic Tufts University School of Medicine Burlington, Massachusetts JOHN FAGNOU, MD Assistant Clinical Professor Diagnostic Imaging University of Calgary Calgary, Alberta, Canada REZA FORGHANI, MD, PhD Associate Chief Jewish General Hospital Assistant Professor of Radiology McGill University Montreal, Quebec, Canada DANIEL THOMAS GINAT, MD Neuroradiology Fellow Harvard Medical School Boston, Massachusetts MAI-LAN HO, MD Resident, Scholar’s Track Department of Radiology Beth Israel Deaconess Medical Center Boston, Massachusetts LIANGGE HSU, MD Assistant Professor Harvard Medical School Staff Neuroradiologist Brigham and Women’s Hospital Boston, Massachusetts SCOTT EDWARD HUNTER, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts JASON MICHAEL JOHNSON, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts HILLARY R KELLY, MD Neuroradiologist Massachusetts General Hospital Instructor in Radiology Harvard Medical School Boston, Massachusetts GIRISH KORI, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts MYKOL LARVIE, MD, PhD Instructor Harvard Medical School Radiologist Massachusetts General Hospital Boston, Massachusetts GUL MOONIS, MD Assistant Professor Beth Israel Deaconess Medical Center; Staff Radiologist Massachusetts Eye and Ear Infirmary Boston, Massachusetts vii viii Contributors MICHAEL T PREECE, MD Department of Radiology Massachusetts General Hospital Boston, Massachusetts AMMAR SARWAR, MD Radiology Fellow Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts PAMELA W SCHAEFER, MD Associate Director of Neuroradiology Clinical Director of MRI Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Boston, Massachusetts SANTOSH KUMAR SELVARAJAN, MD Neuroradiology Fellow Brigham and Women’s Hospital Children’s Hospital Boston Boston, Massachusetts JUAN E SMALL, MD, M.Sc Section Chief, Neuroradiology Division Director, Neuroimaging Education Assistant Professor of Radiology Lahey Hospital and Medical Center Tufts University School of Medicine Burlington, Massachusetts HENRY S SU, MD, PhD Neuroradiology Fellow Massachusetts General Hospital Clinical Fellow Harvard Medical School Boston, Massachusetts KATHARINE TANSAVATDI, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts NICHOLAS A TELISCHAK, MD Radiology Resident Beth Israel Deaconess Medical Center Department of Radiology Harvard Medical School Boston, Massachusetts BRIAN ZIPSER, MD Neuroradiology Fellow Massachusetts General Hospital Boston, Massachusetts PREFACE This book is based on the premise that one of the most powerful learning techniques for imaging interpretation is the presentation of unknown cases Although primarily a case book of unknowns, the style is intentionally out of the ordinary, with several unknown cases presented together The choice of this format presented several challenges, but we believe that the added value is well worth the investment We are convinced that ­side-by-side comparison and contrast of similar-appearing lesions is essential for building an invaluable visual database for imaging interpretation It is with the hope of increasing our diagnostic specificity that the format of the book was chosen Juan E Small, MD Pamela W Schaefer, MD ix ACKNOWLEDGMENTS We would like to gratefully acknowledge Lora Sickora, Pamela Hetherington, Sabina Borza, Rebecca Gaertner, Colleen McGonigal, Carrie Stetz, and all the support staff and illustrators at Elsevier for their help throughout this endeavor We would also like to acknowledge our mentors, fellows, and residents at Massachusetts General Hospital, Brigham and Women’s Hospital, and Lahey Clinic Medical Center for their persistent hard work and dedication to neuroradiology xi HOW TO USE THIS BOOK Although this book does not have to be read in sequence from cover to cover, it is essential that the cases be approached as unknowns Attempting to interpret several unknown cases at once can be overwhelming To gain the most from this text, the cases within a series should be first interpreted individually The main challenge is to formulate a specific differential diagnosis for each individual unknown case We encourage readers to then compare and contrast cases within that series The goal is to find the often subtle imaging characteristics that are specific xii or highly suggestive of individual diagnostic considerations The text should be read only after this process has occurred Each series of cases is supported by individual diagnoses, a description of findings, and a brief discussion of the various diagnostic considerations Additional cases illustrate other manifestations and considerations important for the imaging interpretation of these entities We have tried to highlight major teaching points and hope that you benefit as much from reading this book as we have benefited from writing and ­editing it Cerebral Cortical Neurodegeneration deficits when neurodegenerative disease is under consideration At the least it is helpful to know the type of deficits being displayed, such as cognitive, motor, or sensory, and the major cognitive domains that are affected, such as memory, language, attention, executive function, behavior, and visuospatial orientation The duration and course of progression of symptoms are important determinants of the differential diagnosis With structural imaging, both CT and MRI, the principal abnormality to be discerned is a pattern of brain atrophy or focal brain parenchyma volume loss Structural imaging evaluated by eye therefore is a relatively insensitive and nonspecific examination, although larger abnormalities may be identified with good confidence In comparison, FDG-PET identifies essentially the same abnormality, namely decreased cortical neurons, but is far more sensitive with visual interpretation Methods of MRI-based quantitative structural volumetric analysis, including voxel-based morphometry and brain segmentation methods, can provide marked improvements in both sensitivity and specificity that may rival those of FDG-PET examination Nevertheless, atrophy as discerned by CT or MRI structural imaging is the correlate of hypometabolism on FDG-PET, as indicated by diminished radiotracer uptake Perhaps the single most important diagnosis to be made from an imaging examination performed to evaluate cognitive deficits is the distinction of abnormal and normal This distinction can be challenging and the degree of confidence may not be high, depending on the abnormality and the imaging modality A normal examination has relatively high negative predictive value and can be significantly reassuring In contrast, an abnormal result, even in the absence of a distinct disease pattern, is not reassuring and is a significant risk factor for progression of cognitive decline and subsequent diagnosis of a specific disease process The signature feature of specific neurodegenerative disease is asymmetry Many processes cause diffuse brain parenchymal volume loss, including chronic systemic disease (e.g., congestive heart failure, cancer, and chronic kidney disease), chemotherapy, whole brain radiation, alcohol abuse, and human immunodeficiency virus In these cases, diffuse, symmetric brain atrophy involving the cerebrum, cerebellum, and brainstem usually is present When atrophy is present, including 151 both lateral asymmetry and asymmetric intrahemispheric lobar and sublobar abnormalities, suspicion of a neurodegenerative process should increase SPECTRUM OF DISEASE Although patients usually come to medical attention when they have mild to moderate stages of disease, in some circumstances diagnosis is delayed, and thus the range of imaging findings in practice may extend from the earliest to the latest stages of disease Unfortunately, the advanced stages of many cerebral cortical neurodegenerative processes are similar, with diffuse abnormality involving heteromodal association cortices in the frontal, parietal, and temporal lobes and relative, although not absolute, preservation of primary somatic motor and sensory cortices A relatively common scenario is seen with elderly patients who not receive regular medical attention, and in whom advanced cognitive deficits may be neglected In some cases, these patients may come to acute medical care and cognitive deficits are identified but cannot be definitively established as chronic or progressive Consequently, the patient is evaluated for possible delirium, with neurodegenerative disease included among the diagnostic considerations In more advanced cases of neurodegenerative disease, and especially when a reliable history is not available to identify the pattern and pace of cognitive decline, identification of an advanced neurodegenerative disease may be made with good confidence, although it may not be possible to identify a specific disease entity Consequently, it may happen that a patient is identified with an advanced neurodegenerative disease but a specific diagnosis cannot be determined because of the lack of an appropriate history Alzheimer Disease In persons with Alzheimer disease (AD), temporal and parietal heteromodal association cortices are the most prominently affected brain regions, although as the disease progresses, other brain areas become involved, including frontal and occipital cortices The degree of abnormality in the hippocampi may be underestimated on FDG-PET compared with the degree of atrophy seen on 152 Brain and Coverings structural imaging, which likely is related to differences in glucose metabolism in the allocortex of the hippocampus The precuneus is affected early in the course of the disease, although identifying this feature on FDG-PET may be difficult because of the normal robust, relative hypermetabolism in this region Atrophy and corresponding hypometabolism in the inferior parietal lobe that extends contiguously into the adjacent temporal lobe is a typical appearance (Figure 24-1) Most patients (on the order of 70%) have greater involvement of the left hemisphere, although this finding is not diagnostically significant Visual variant AD, also known as posterior cortical atrophy, is an uncommon entity that presents with visual deficits and marked abnormality that ­initially may be relatively confined to the occipital lobes An invariant molecular feature of AD is abnormal accumulation of amyloid-β protein in the brain Parkinson Disease with Dementia As previously described, PDD is in the spectrum of synucleinopathies and typically arises from progression of PD The clinical history typically is diagnostic Usually no findings of early PD are noted on either conventional MRI or FDG-PET As the disease progresses to PDD, a pattern of atrophy and corresponding cortical hypometabolism similar to that of DLB typically is seen A reliable history is essential to the diagnosis of PDD Frontotemporal Dementia Dementia with Lewy Bodies The principal molecular pathology of Lewy bodies is α-synuclein, which aggregates to form abnormal intraneuronal inclusions known as Lewy bodies The aggregation of α-synuclein is the principal abnormality of dementia with Lewy bodies (DLB), as well as PD, PDD, and multiple system atrophy, A which are collectively regarded as synucleinopathies The cerebral cortical manifestations of DLB are similar to those of AD, with the exception of disproportionate involvement of occipital cortices Clinically, DLB is typically distinguished by rapid fluctuation in cognitive function, visual hallucinations, and Parkinsonian motor deficits B A number of subtypes of FTD exist, including behavioral variant, semantic dementia, and primary progressive aphasia The appearance of these conditions is especially variable with respect to both the imaging findings and the clinical presentation Asymmetry is typical, and abnormality typically is manifest principally within the frontal and/or ­temporal C Figure 24-1  Marked cerebral cortical hypometabolism, most pronounced in the frontal and parietal heteromodal association cortices, and slight preservation of primary motor and sensory cortices, as seen in the perirolandic regions and occipital regions A diagnosis of Alzheimer disease was established based on the patient’s clinical history Otherwise, this appearance is relatively nonspecific and could represent a late stage of Alzheimer disease, frontotemporal dementia, or Parkinson disease with dementia Advanced dementia with Lewy bodies could have this appearance, although less residual occipital lobe metabolic activity may be present in that setting Cerebral Cortical Neurodegeneration lobes Temporal lobe involvement usually begins anteriorly Initial frontal lobe abnormality often is principally medial or lateral and advances to become more confluent As the disease progresses, increasing involvement of other heteromodal association cortices occurs, including the parietal lobes, with relative sparing of the primary somatic motor and sensory cortices As previously described, in severe disease a nonspecific pattern similar to that shown in Figure 24-1 is observed Although specific patterns of brain abnormality may suggest a subtype of FTD, the clinical presentation is more relevant in identifying the specific diagnosis, and in most circumstances an imaging diagnosis of FTD is adequate Creutzfeldt-Jakob Disease Few specific symptoms suggest the diagnosis of Creutzfeldt-Jakob disease, and it is the rapid progression of multidomain cognitive, motor, and sensory decline that best signifies this disease On imaging, Creutzfeldt-Jakob disease is distinguished by abnormality involving cortical and deep gray matter nuclei, typically in a patchy and asymmetric pattern that may be unusual for other cerebral cortical neurodegenerative processes MRI typically reveals a pattern of restricted diffusion in cerebral cortex and deep gray matter nuclei, whereas FDG-PET shows a corresponding pattern of hypometabolism, although occasionally hypermetabolism is seen Vascular Dementia/Multiinfarct Dementia Although small infarctions frequently are seen in patients with other neurodegenerative diseases, vascular dementia (VD) as a primary diagnosis is unusual in American and European populations; it is more prevalent in Asia The rarity of this condition is related in part to the challenge of sustaining a sufficient number of small infarctions adequate to substantially impair cognitive function without suffering a life-ending event The clinical symptoms of VD and the severity of disease relate to the distribution and overall burden of cortical abnormality and may mimic other neurodegenerative syndromes Mixed neurodegenerative processes, such as small strokes in a patient with AD, are far more common than pure VD Encephalomalacia is the hallmark of chronic infarction on structural imaging 153 and corresponds to hypometabolism on FDG-PET DIFFERENTIAL DIAGNOSIS Alzheimer dementia DLB FTD PDD Corticobasal degeneration Progressive supranuclear palsy Creutzfeldt-Jakob disease Multiinfarct dementia Seizure Limbic encephalitis Hashimoto encephalopathy PEARLS • History: An appropriate history is essential to an accurate diagnosis of neurodegenerative disease The time course, earliest symptoms, amnestic versus nonamnestic quality, age, family history, motor deficits, and rate of progression all play an important role in formulating a differential diagnosis that guides evaluation of imaging findings • Normal or abnormal: The distinction between normal and abnormal findings is the most important diagnosis to be made from imaging that is performed for the evaluation of cognitive deficits A normal examination has good negative predictive value relative to the development of dementia, whereas an abnormal examination, even if the pattern is nonspecific, markedly increases the likelihood of an eventual diagnosis of a neurodegenerative disease • Pattern: Although end stages of the most common neurodegenerative diseases have a similar appearance that renders diagnosis inaccurate, early-stage disease often reveals a pattern of regional cortical involvement that may permit a more specific diagnosis • Progression: Progression is the rule for all neurodegenerative diseases, although the rate of progression is highly variable and may represent a significant diagnostic feature if longitudinal examinations are available for comparison 154 Brain and Coverings • Concordant findings with multimodality imaging: MRI and PET are the most useful imaging modalities for the evaluation of dementia and reveal correlative findings that may establish concordance and thus increase the accuracy of diagnosis Atrophy as seen on structural examinations correlates with hypometabolism as seen on FDG-PET • Clinical context: AD affects approximately 50% of persons older than 95 years Consequently, its manifestations are frequently seen on examinations of elderly patients that are done for indications other than cognitive decline, such as head trauma The degree to which these findings are relevant, and the confidence with which a diagnosis of AD may be made, depend on the context In many circumstances, a discussion between the radiologist and the referring physician may be helpful in relaying findings that are a cause for concern and in discerning their relevance to the care of the patient FUTURE DEVELOPMENTS Several amyloid imaging agents have been extensively tested and have been found to reveal abnormal accumulation of amyloid in the brain The prototype of these agents, Pittsburgh Compound B, is an 11C-labeled agent and thus is not practical for clinical development 18F-labeled compounds have been developed that soon will be available for clinical use Although any amount of amyloid in the brain is abnormal, the specific diagnostic criteria for amyloidopathy, principally AD, remain a matter of investigation Additionally, Tau-specific imaging agents that are under development as well also may have widespread utility in the diagnosis of neurodegenerative conditions, including frontotemporal lobar degeneration, chronic traumatic encephalopathy, and AD Advanced MRI methods that will have broad application in persons with neurodegenerative disease are being developed In particular, quantitative volumetric analyses based on brain segmentation are able to reveal patterns of atrophy with a sensitivity and specificity similar to that of FDG-PET Other methods, including diffusion tensor imaging, functional connectivity MRI, and magnetic resonance spectroscopy also offer insight into brain function and integrity and are likely to be more widely used for the diagnosis of neurodegenerative diseases SUGGESTED READINGS Henkel K, Zerr I, Hertel A, et al: Positron emission tomography with [(18)F]FDG in the diagnosis of CreutzfeldtJakob disease (CJD), J Neurol 249:699–705, 2002 Herholz K, Herscovitch P, Heiss WD: NeuroPET, Berlin, 2004, Springer-Verlag Ishii K, Soma T, Kono AK, et al: Comparison of regional brain volume and glucose metabolism between patients with mild dementia with Lewy bodies and those with mild Alzheimer’s disease, J Nucl Med 48:704–711, 2007 Karow DS, McEvoy LK, Fennema-Notestine C, et  al: Relative capability of MR imaging and FDG PET to depict changes associated with prodromal and early Alzheimer disease, Radiology 256:932–942, 2010 Mosconi L: Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease FDG-PET studies in MCI and AD, Eur J Nucl Med Mol Imaging 32:486–510, 2005 Rabinovici GD, Rosen HJ, Alkalay A, et  al: Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD, Neurology 77(23):2034–2042, 2011 Silverman DHS, Mosconi L, Ercoli L, et al: Positron emission tomography scans obtained for the evaluation of cognitive dysfunction, Semin Nucl Med 38:251–261, 2008 25 Cerebral Subcortical Neurodegeneration MYKOL LARVIE, MD, PHD A C B PET CASE A:  A 66-year-old woman presenting with left-sided motor deficits, including increased tone and loss of dexterity PET, positron emission tomography A B T2 MRI PET CASE B:  A 59-year-old woman presenting with asymmetrically increased tone and bradykinesia on the left side MRI, magnetic resonance imaging; PET, positron emission tomography 155 156 Brain and Coverings C B A T2 MRI PET PET CASE C:  A 62-year-old woman presenting with ataxia, dysarthria, saccadic breakdown of smooth visual pursuit, appendicular ataxia, and orthostasis MRI, magnetic resonance imaging; PET, positron emission tomography B A T1 MRI T2 MRI CASE D:  A 48-year-old woman presenting with ataxia, dysarthria, and labile emotions, including crying disproportionate to perception of sadness MRI, magnetic resonance imaging Cerebral Subcortical Neurodegeneration DESCRIPTION OF FINDINGS • Case A: A brain FDG-PET examination shows cortical hypometabolism in the right frontal lobe that is most pronounced in the perirolandic region (arrow) Additionally, hypometabolism is present in the right thalamus and, to a lesser extent, in the right striatum The relative hypometabolism in the left cerebellum represents crossed cerebellar diaschisis related to the right frontal lobe abnormality • Case B: A brain FDG-PET examination shows marked hypometabolism involving the right striatum (arrow), corresponding to atrophy in these nuclei seen on the axial T2 MRI (arrow) Note that the right and left thalami are approximately normal and symmetric in size and activity • Case C: A sagittal T2 MRI shows marked atrophy involving the midbrain, pons, and cerebellum Brain FDG-PET shows corresponding marked and diffuse hypometabolism in the cerebellum • Case D: Sagittal T1 and axial T2 MRI shows marked cerebellar atrophy and a normal appearance of the brainstem and cervical spinal cord DIAGNOSIS Case A:  Corticobasal degeneration Case B:  Multiple systems atrophy—Parkin- son type (MSA-P, striatonigral degeneration) Case C:  Multiple systems atrophy—cerebellar type (MSA-C, olivopontocerebellar degeneration) Case D:  Spinocerebellar ataxia (SCA) SUMMARY Subcortical neurodegenerative syndromes may have a particularly insidious onset, and diagnoses frequently are delayed or unrecognized Common features of subcortical neurodegenerative disorders include movement disorders, dysautonomia, oculomotor nerve dysfunction, behavioral disorders, and cognitive deficits The combination of these symptoms may suggest a specific diagnosis, 157 implicate one of a small number of disorders, or be entirely nonspecific and defy simple classification As with cortical neurodegenerative diseases, the history is an essential element in the interpretation of imaging examinations performed for the evaluation of possible subcortical neurodegenerative disease, and it is important to derive a broad differential diagnosis from the clinical history to ensure that all relevant structures have been evaluated Some syndromes such as Huntington disease (HD) and certain forms of SCA have a dominant inheritance pattern In these cases, family history and physical examination together may be adequate for a confident diagnosis, and thus imaging frequently has little role in the diagnosis of these disorders In other situations, such as when a patient presents with an atypical movement disorder with extrapyramidal features, no family history may be pertinent and imaging may play a vital role in diagnosis In many cases, movement disorders may be difficult to characterize because the features may be unusual, difficult to reproduce, and asymmetric with respect to laterality and upper and lower extremity involvement Considerable overlap exists between subcortical and cortical neurodegenerative diseases, particularly in their advanced stages, when symptoms of both types may be present As with the cortical neurodegenerative diseases, history is an essential element of diagnosis, and early symptoms and imaging findings may provide the most specific diagnosis Some findings may be highly suggestive of a specific disorder; for example, particular gaze palsies may strongly suggest a progressive supranuclear palsy (PSP) However, confounding features may exist that prevent definitive diagnosis on the basis of a clinical examination In these cases, imaging may be useful to exclude other diagnoses, with the recognition that good positive findings may not be available to support a specific diagnosis, as typically is the case with PSP As with cortical neurodegenerative syndromes, a strong correlation exists between hypometabolism as identified by FDG-PET and atrophy depicted on structural imaging, including both MRI and computed tomography Similarly, the PET findings frequently are much more sensitive and may reveal abnormality earlier than may be apparent on structural imaging scans However, unlike with cortical neurodegenerative diseases, normal 158 Brain and Coverings findings of an FDG-PET examination not strongly exclude a neurodegenerative process The structures that are affected in some subcortical syndromes—such as the substantia nigra in persons with Parkinson disease (PD) and the midbrain nuclei involved with oculomotor function that are affected in persons with PSP—are not sensitively evaluated with FDG-PET or MRI and may appear normal on these examinations in the presence of significant disease Subcortical neurodegenerative diseases may have predominantly symmetric manifestations (e.g., spinocerebellar atrophy and MSA) or markedly asymmetric manifestations (e.g., corticobasal degeneration) Although asymmetric abnormalities may be relatively conspicuous, it may be challenging to discern a symmetric abnormality As previously noted, the history is essential and should be used to formulate a list of structures that require scrutiny, and this scrutiny should be applied while recognizing the wide range of normal appearance of subcortical structures SPECTRUM OF DISEASE The most important point to recognize on the spectrum of subcortical neurodegenerative disease is “normal.” This finding may be relevant to argue against certain diseases but does not exclude the presence of certain disorders that are less sensitive to imaging diagnosis, such as PSP and certain spinocerebellar atrophy syndromes If sufficient clinical concern exists and a diagnosis is not otherwise established, repeat imaging at an appropriate interval, such as 6, 12, or 24 months, may be useful Corticobasal Ganglionic Degeneration Both motor and cognitive deficits are seen frequently in corticobasal ganglionic degeneration (CBD), and a striking asymmetry to the motor deficits is usually noted The cortical signature of CBD includes asymmetric hypometabolism and atrophy involving the brain contralateral to the more profoundly affected side of the body, most pronounced in the frontal and perirolandic regions Subcortical involvement is most evident in the thalamus and to a lesser extent in the striatum, and as the disease progresses, more pronounced involvement of deep gray matter and brainstem structures occurs The principal differential considerations are PSP and PD A relatively sudden onset of symptoms occasionally is seen with CBD, which is uncommon in other disorders Multiple Systems Atrophy MSA is a heterogeneous family of disorders and may involve mixed patterns of abnormality Disease principally involving dysautonomia is classified as autonomic type MSA (MSA-A), also known as Shy-Drager syndrome Disorders principally involving coordination are classified as cerebellar type, MSA-C, also known as olivopontocerebellar degeneration Motor deficits characterized by abnormal tone are classified as Parkinson type, MSA-P, also known as striatonigral degeneration A given patient may present with a unique combination of symptoms that represent a combination of the known MSA phenotypes and therefore may present a substantial diagnostic challenge As MSA progresses, greater involvement of all systems tends to occur; in particular, dysautonomia becomes more prevalent and more severe with disease progression The pattern of imaging abnormality may correlate with the dominant clinical presentation, such as the cerebellar hypometabolism in the patient with MSA-C, depicted in Case C The “hot cross bun” sign is an MRI finding on axial T2-weighted images that represents a specific pattern of atrophy and gliosis in the pons and is seen in more advanced cases of MSA (Figure 25-1) Progressive Supranuclear Palsy The more common initial symptoms of PSP include balance and gait disturbance, often resulting in frequent falls and bumping into people and objects As the disease progresses, gaze palsies, cognitive deficits, speech disturbance, and swallowing disorders become more pronounced The gaze palsy tends to be more pronounced vertically, with downward palsy typically preceding upward gaze palsy Imaging in early stages of the disease may show no apparent abnormality, either by structural or FDG-PET examination As disease progresses, anterior midbrain atrophy, as evidenced by the so-called hummingbird sign, often is apparent (Figure 25-2) Additionally, in more advanced disease, medial frontal lobe hypometabolism may be seen on FDG-PET, although this finding is relatively nonspecific Cerebral Subcortical Neurodegeneration Figure 25-1  Axial T2 image through the mid pons demonstrating the “hot cross bun” sign in a patient with multiple system atrophy Also note the atrophy involving the middle cerebellar peduncles and cerebellum, with associated enlargement of the fourth ventricle This patient has multiple-system atrophy, cerebellar type Figure 25-2  Midbrain atrophy as seen on a sagittal T1-weighted magnetic resonance image representing the hummingbird sign (arrow) in a patient with progressive supranuclear palsy Note that the pons is relatively preserved, forming the wings on the hummingbird and distinguishing this appearance from the more diffuse brainstem atrophy that may be seen in other processes, such as multiplesystem atrophy (see Case C, for example) Spinocerebellar Ataxia SCA is a heterogeneous family of disease syndromes, many of which are related to a 159 Figure 25-3  Caudate head atrophy in a 51-yearold woman with Huntington disease (arrow) Also note the diffuse brain atrophy s­ pecific genetic abnormality, that predominantly involve degeneration within the cerebellum and spinal cord Depending on the genotype, degeneration may occur relatively selectively within the cerebellum or spinal cord, and symptoms may include gait disorder, ataxia, dysarthria, and dysphagia Although behavioral and cognitive deficits may be seen, many patients progress to endstage, terminal disease without marked cognitive deficits Imaging findings typically reflect the region of involvement and may show abnormalities in the brainstem and cerebellum FDG-PET may show hypometabolism in these areas, corresponding to atrophy on structural imaging Especially in the early stages of the disease, FDG-PET and routine MRI results may not reveal any ­findings Huntington Disease The choreiform movement disorder typical of HD, together with the family history and onset in mid adulthood (during the 30s and 40s), often is adequate to establish the diagnosis of HD Additionally, genetic testing for expansion of a CAG trinucleotide repeat in the HTT gene is quite reliable Imaging is seldom used to establish the diagnosis of HD, although the stereotypic finding of caudate head atrophy (Figure 25-3) usually is apparent on imaging that is obtained for other purposes for these patients 160 Brain and Coverings Parkinson Disease A pattern of motor deficits including bradykinesia, cogwheel rigidity, tremor, and gait abnormality typifies PD, although patients often may present with asymmetric or atypical features that raise questions about the specific diagnosis Routine MRI and FDGPET may show no definite abnormality, even in cases with striking clinical findings Proton density MRI may reveal subtle changes in the substantia nigra in persons with PD, although these findings are not sensitive or specific, and MRI is not required for diagnosis of PD FDG-PET may show subtle findings, including hypermetabolism in the dorsolateral putamen and thalami, although these findings typically are not reliable for definitive diagnosis of PD In more advanced cases of PD—in particular, as cognitive and behavior changes become more prominent— cerebral cortical defects may become more pronounced and may be seen as parietal cortical hypometabolism, similar to Alzheimer disease Motor Neuron Disease A pattern of motor neuron disease (MND) is seen in approximately 15% of patients with frontotemporal dementia (FTD), a syndrome known as FTD-MND This syndrome is most commonly found in persons with behavioral variant FTD, and in some cases the MND may cause the presenting symptoms The most common type of MND is amyotrophic lateral sclerosis (ALS), and symptoms may include dysarthria, dysphagia, and asymmetric extremity weakness Moreover, FTD develops in most patients with ALS as the disease progresses Because MND/ALS predominantly involves the spinal cord and peripheral nerves, typically no findings are noted in the brain, and the diagnosis is determined by clinical diagnosis and the exclusion of other causes If present, the brain findings typically are those of FTD DIFFERENTIAL DIAGNOSIS MSA-A (Shy-Drager syndrome) MSA-C (olivopontocerebellar degeneration) MSA-P (striatonigral degeneration) Neurodegeneration with brain iron accumulation SCA CBD HD PSP Creutzfeldt-Jakob disease PD/PD with dementia MND, seen in association with FTD PEARLS • History: An appropriate history is essential to an accurate diagnosis of neurodegenerative disease, whether it is cortical or subcortical in etiology Factors such as the time course, earliest symptoms, age, family history, and rate of progression all play an important role in formulating a differential diagnosis that guides the evaluation of imaging findings • Normal findings not exclude disease: No abnormality may be identified on routine MRI or FDG-PET in many subcortical neurodegenerative diseases, in particular PD and PSP The absence of a positive finding does not exclude disease and does not have the same strong negative predictive value as is the case for cortical neurodegenerative diseases • A specific diagnosis may not be available from imaging findings alone: A given imaging appearance, including normal or subtle brainstem hypometabolism, may be seen in multiple syndromes, and thus a unique or single best diagnosis may not be apparent Often the addition of ­clinical history may focus the considerations, although in some cases a differential diagnosis may be the best possible interpretation • Distribution: Some subcortical neurodegenerative processes progress to more diffuse involvement of the cerebrum, and the pattern of cerebral involvement may be revealing, such as an AD pattern in persons with PD/PDD and an FTD pattern in persons with FTD-MND In contrast, some processes remain relatively focal, such as SCA variants that principally may involve the brainstem or cerebellum even in their advanced stages • Progression: Progression is the rule for all neurodegenerative diseases, although the rate of progression is highly variable and Cerebral Subcortical Neurodegeneration may represent a significant diagnostic feature if longitudinal examinations are available for comparison • Concordant findings with multimodality imaging: MRI and PET are the most useful imaging modalities for the evaluation of dementia and reveal correlative findings to establish concordance and to increase the accuracy of diagnosis However, given the small size and wide range of normal metabolic activity in brainstem nuclei, FDGPET may be less accurate in the diagnosis of subcortical neurodegenerative diseases compared with cortical neurodegenerative diseases FUTURE DEVELOPMENTS A number of different radiotracers have been developed for the diagnosis of subcortical neurodegenerative syndromes The majority of these radiotracers are dopamine receptor ligands, including raclopride, which has 161 been used extensively as an investigational agent, and ioflupane, which is clinically available in Europe and the United States The use of dopamine receptor imaging is most relevant in persons with atypical movement disorders that are not clearly Parkinsonian FDG findings generally are correlative with dopamine receptor imaging, reflecting striatal hypometabolism corresponding to regions of decreased dopamine receptors SUGGESTED READINGS Ahmed Z, Asi YT, Sailer A, et  al: The neuropathology, pathophysiology and genetics of multiple system atrophy, Neuropathol Appl Neurobiol 38:4–24, 2012 Eckert T, Barnes A, Dhawan V, et al: FDG PET in the differential diagnosis of parkinsonian disorders, Neuroimage 26:912–921, 2005 Herholz K, Herscovitch P, Heiss WD: NeuroPET, Berlin, 2004, Springer Verlag Otsuka M, Ichiya Y, Kuwabara Y, et al: Glucose metabolism in the cortical and subcortical brain structures in multiple system atrophy and Parkinson’s disease: a positron emission tomographic study, J Neurol Sci 144:77–83, 1996 26 Epidermoid Versus Arachnoid Cyst JUAN E SMALL, MD A B T1 C T2 D FLAIR DWI CASE A:  A 33-year-old woman with a history of chronic headaches DWI, diffusion-weighted imaging; FLAIR, fluid attenuated inversion recovery A B T1 C T2 D FLAIR DWI CASE B:  A 74-year-old woman with a history of unsteady gait DWI, diffusion-weighted imaging; FLAIR, fluid attenuated inversion recovery 163 164 Brain and Coverings DESCRIPTION OF FINDINGS DIAGNOSIS On CT, epidermoids appear as ­lobulated extraaxial masses that generally approximate the density of CSF However, slight hyperdensity compared with CSF can be seen Rarely, an epidermoid may present as a hyperdense lesion By contrast, arachnoid cysts are always isodense to CSF on CT. Enhancement is not seen with either lesion Magnetic resonance imaging can readily distinguish epidermoid cysts from arachnoid cysts The key to differentiating them is DWI: an epidermoid is markedly hyperintense on DWI because of the relatively restricted diffusion of its proteinaceous components compared with CSF and its marked T2 hyperintensity Epidermoid cysts also are hyperintense compared with CSF on FLAIR images On the other hand, the fluid within arachnoid cysts is similar to CSF and therefore is markedly hypointense on DWI and FLAIR images In addition, arachnoid cysts displace vessels and nerves, whereas these structures can travel through epidermoid cysts Case A:  Epidermoid cyst (bright on DWI) Case B:  Arachnoid cyst (dark on DWI) SPECTRUM OF DISEASE SUMMARY These lesions may occur in various intracranial compartments (Figure 26-1) • Scans demonstrate two different pineal region extraaxial masses roughly following CSF intensity: hypointense on T1-weighted images and hyperintense on T2-weighted images • Closer inspection demonstrates that the lesion in Case A has crenulated, irregular margins compared with the smoothly marginated contours of the lesion in Case B • In addition, in Case A, the lesion is hyperintense compared with CSF on FLAIR and DWI In contrast, the internal signal characteristics of the lesion in Case B are isointense compared with CSF on all sequences, including the FLAIR and DWI sequences A diagnostic dilemma often arises when an extraaxial cystic lesion exhibits signal characteristics that approximate CSF As their name implies, arachnoid cysts are space-occupying cystic lesions within the arachnoid space Their imaging characteristics reflect their internal CSF content On imaging, they generally appear as unilocular, smoothly contoured cystic lesions that follow CSF on all sequences Their complications generally relate to mass effect and their location Scalloping of the adjacent calvarium reflects their long-standing presence Epidermoids are benign congenital lesions of ectodermal origin They are slowly growing lesions that tend to insinuate themselves into the subarachnoid cisterns and sulci and therefore have lobulated, crenulated, and irregular margins Epidermoid cysts may appear anywhere in the neural axis; however, the most common intracranial sites include the cerebellopontine angle and the sellar region DIFFERENTIAL DIAGNOSIS Epidermoid cyst Arachnoid cyst Neurocysticercosis Dermoid cyst PEARLS • Diffusion: Both can look like CSF on T1and T2-weighted sequences, but an epidermoid is markedly hyperintense on DWI, whereas an arachnoid cyst, like CSF, is markedly hypointense • FLAIR: An epidermoid cyst is hyperintense compared with CSF, whereas an arachnoid cyst is isointense compared with CSF • Morphology: Epidermoid cysts tend to have irregular, crenulated walls, whereas arachnoid cysts tend to have smooth walls Epidermoid Versus Arachnoid Cyst • Vessels and nerves: Arachnoid cysts displace these structures whereas vessels can travel through epidermoid cysts FLAIR 165 SIGNS AND COMPLICATIONS For signs and complications, see Figures 26-2 and 26-3 T2 DWI Figure 26-1  Posterior fossa arachnoid cyst DWI, diffusion-weighted imaging; FLAIR, fluid attenuated ­inversion recovery Ax CT Cor CT MRI T1 Post FLAIR T2 DWI Figure 26-2  Complications are generally due to mass effect This case demonstrates a smoothly marginated, posterior fossa arachnoid cyst The arachnoid cyst compresses the fourth ventricle, resulting in severe hydrocephalus and necessitating ventriculoperitoneal shunts Ax, axial; Cor, coronal; CT, computed tomography; DWI, diffusion-weighted imaging; FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging 166 Brain and Coverings T2 T1 DWI CISS CISS Figure 26-3  Epidermoid cysts often surround and encase vessels and nerves as opposed to arachnoid cysts, which displace them Encased vessels and nerves often make surgical dissection difficult or impossible This case demonstrates an irregularly marginated left cerebellopontine angle epidermoid cyst exhibiting restricted diffusion Heavily T2-weighted constructive interference in steady state (CISS) images demonstrate that the epidermoid cyst encases the left trigeminal nerve as it exits the effaced brainstem and throughout its course toward Meckel’s cave DWI, diffusion-weighted imaging SUGGESTED READINGS Chen S, Ikawa F, Kurisu K, et al: Quantitative MR evaluation of intracranial epidermoid tumors by fast fluid attenuated inversion recovery imaging and echo-­planar DWI, AJNR Am J Neuroradiol 22:1089–1096, 2001 Dutt SN, Mirza S, Chavda SV, et  al: Radiologic differentiation of intracranial epidermoids from arachnoid cysts, Otol Neurotol 23(1):84–92, 2002 Gosalakkal JA: Intracranial arachnoid cysts in children: a review of pathogenesis, clinical features, and management, Pediatr Neurol 26(2):93–98, 2002 Kallmes DF, Provenzale JM, Cloft HJ, et  al: Typical and atypical MR imaging features of intracranial epidermoid tumors, AJR Am J Roentgenol 169:883–887, 1997 MacKay CI, Baeesa SS, Ventureyra EC: Epidermoid cysts of the pineal region, Childs Nerv Syst 15(4):170–178, 1999 Osborn AG, Preece MT: Intracranial cysts: radiologicpathologic correlation and imaging approach, Radiology 239(3):651–664, 2006 Park SH, Chang KH, Song IC, et al: Diffusion-weighted MRI in cystic or necrotic intracranial lesions, Neuroradiology 42(10):716–721, 2000 ... School Boston, Massachusetts 16 00 John F Kennedy Blvd Ste 18 00 Philadelphia, PA 19 10 3-2 899 NEURORADIOLOGY: KEY DIFFERENTIAL DIAGNOSES AND CLINICAL QUESTIONS Copyright © 2 013 by Saunders, an imprint... T1 C– Ax T1 C+ Ax T2 CASE B:  A 64-year-old man with a history of renal cell carcinoma, difficulty walking, and diplopia 10 Brain and Coverings Sag T1 C– Ax T1 C– Ax T1 C+ Ax T1 C– Ax T2 Ax T1... C:  A 25-year-old man presenting after sustaining trauma Sag T1 C– Ax T1 C– Ax T1 C+ Ax T2 CASE D:  A 50-year-ol man presenting with a history of headaches Ax T1 C– Ax T1 C+ Ax T1 C– Ax T1 C+ CASE