CHAPTER 7 White Matter Diseases White matter diseases are heterogeneous conditions linked lesions with either (1) two or more episodes of worsening, each together because they involve the same real estate. Magnetic lasting at least 24 hours and each at least a month apart, or (2) slow resonance (MR) imaging is quite sensitive and, when combined stepwise progression of signs or symptoms for at least 6 months. with age and other pertinent clinical information, provides a rea- The criteria accepted by the International Panel in 2005 has sonable amount of specificity with regard to white matter dis- been adopted by the mainstream neurology community and is ease. We are going to start by dividing white matter diseases into outlined in Table 7-1 and Box 7-3. It advances a greater role for demyelinating and dysmyelinating diseases (Box 7-1). MR imaging in supporting the diagnosis of MS and now requires Demyelinating disorders have a common inflammatory compo- radiologists to count lesions and to determine if they are infraten- nent that injures and, in some cases, destroys white matter. Keep torial, supratentorial, or spinal; if they are juxtacortical; and if they in mind, the white matter starts out normal and is then injured enhance. MR is also used to demonstrate when lesions are dis- by the particular pathologic process. The oligodendrocyte is the tributed over time to differentiate MS from acute disseminated cell responsible for wrapping the axon concentrically to form the encephalomyelitis (ADEM) and other monophasic diseases that myelin sheath, and although we speak of white matter diseases as have a different course and prognosis. those that affect myelin, in actual fact, there is now a great deal of evidence that myelin is not the only brain tissue damaged in “demyelinating diseases”; axons and neurons are also commonly BOX 7-1. Classification of White Matter Diseases affected. Our appreciation of the nature of these disorders has improved dramatically with more precise histopathology and new PRIMARY DEMYELINATING DISEASE MR methodologies. We can further divide these diseases based MULTIPLE SCLEROSIS on their presumed etiology (Box 7-2). Balo disease Dysmyelinating disorders involve intrinsic abnormalities of Devic disease myelin formation or myelin maintenance because of a genetic Schilder disease defect, an enzymatic disturbance, or both. These diseases are Marburg disease rare, usually seen in the pediatric or adolescent population, and SECONDARY DEMYELINATING DISEASE often are associated with a bizarre appearance on MR. Some ALLERGIC (IMMUNOLOGIC) diseases, such as adrenoleukodystrophy, have characteristics of Acute disseminated encephalomyelitis (ADEM) both demyelinating and dysmyelinating processes (although in Box 7-1 it is operationally listed in the dysmyelinating category). VIRAL The term leukodystrophy is used interchangeably with dysmyelinat- HIV-associated encephalitis ing diseases and represents primary involvement of myelin. For Progressive multifocal leukoencephalopathy concerned clinicians-in-training, 99.9% of what you will see in an Subacute sclerosing panencephalitis (SSPE) adult private practice of radiology, however, will be demyelinat- VASCULAR (HYPOXIC/ISCHEMIC) ing disease. Binswanger disease CADASIL PRIMARY DEMYELINATING DISEASE Postanoxic encephalopathy Multiple Sclerosis Reversible posterior leukoencephalopathy Multiple sclerosis (MS), first described by Charcot in 1868, is METABOLIC the most common demyelinating disease encountered in clini- Osmotic demyelination or central pontine myelinolysis cal practice (as well as in imaging). Affecting nearly 350,000 TOXIC Americans, 100,000 Britons, and more than 2 million persons Alcohol worldwide, it is the leading cause of nontraumatic neurologic Radiation disability in young and middle-aged adults. MS has a peak age Marchiafava-Bignami disease range of 30 years, with a female predominance; however, it can Disseminated necrotizing leukoencephalopathy present in children and adolescents (3% to 5%) and in those over Drugs, including chemotherapeutic agents and intravenously age 50 (9%). abused drugs (metamphetamine, cocaine, heroin) Toxins (triethyl tin, lead, mercury) Clinical Presentation Symptoms range from isolated cranial nerve palsy, optic neuri- TRAUMATIC tis, and vague sensory complaints, to paresis and paraplegia of Diffuse axonal injury limbs, and myelopathy. Subtle and obvious changes in intellec- DYSMYELINATING DISEASE tual capacity are also identified in patients with MS. Alexander disease Krabbe disease Clinical Criteria Sudanophilic leukodystrophy The diagnosis of MS is presently still based on clinical and para- Pelizaeus-Merzbacher disease clinical criteria alone. These parameters were initially proposed Canavan disease to select patients for treatment trials. The clinical diagnosis of Metachromatic leukodystrophy MS (according to the Schumacher criteria) is made by history or Adrenoleukodystrophy neurologic examination resulting from two or more white matter 227 228 Neuroradiology: The Requisites BOX 7-2. Demyelinating Diseases Categorized BOX 7-3. MRI Criteria for Brain Abnormality: by Presumed Etiology Space and Time Dissemination AUTOIMMUNE (IDIOPATHIC) MRI LESIONS DISSEMINATED IN SPACE Multiple sclerosis At least three of the following criteria must be met: Monophasic demyelination 1. One gadolinium-enhancing lesion or nine T2 hyperintense ADEM lesions in the brain or spine Acute hemorrhagic leukoencephalitis 2. At least one infratentorial or spine lesion Optic neuritis (may be the first presentation of MS) 3. At least one juxtacortical lesion Acute transverse myelitis (may be the first presentation of MS) 4. At least three periventricular lesions VIRAL MRI LESIONS DISSEMINATED IN TIME Progressive multifocal leukoencephalopathy At least one criterion must be met: SSPE 1. Gadolinium-enhancing lesion r3 mo after initial HIV-associated encephalitis presentation, but in a different location from the initial event VASCULAR (HYPOXIC/ISCHEMIC) 2. New T2 lesion, compared with a reference MRI done r30 CADASIL days after onset of initial event Postanoxic encephalopathy Reversible posterior leukoencephalopathy Binswanger disease METABOLIC/NUTRITIONAL Laboratory Tests Osmotic demyelination Laboratory tests, including visual, auditory, and somatosensory Marchiafava-Bignami disease evoked responses, can confirm the presence of lesions, but they Combined systems disease (vitamin B12 deficiency) are nonspecific and provide no clue to the cause of the abnormal TOXIC finding. Approximately 70% of patients with MS have elevated Radiation cerebrospinal fluid (CSF) levels of IgG index and approximately Toxins 90% have elevated oligoclonal bands. Drugs Disseminated necrotizing leukoencephalopathy Clinical Course MS is a disease characterized by a variety of clinical courses. TRAUMA Terminology about clinical classification can be confusing and Diffuse axonal injury even contradictory. Relapsing remitting MS is the most com- mon course of the disease, initially occurring in up to 85% of cases. At the beginning, exacerbations are followed by remis- sions. However, over years, additional exacerbations result in incomplete recovery. Within 10 years 50% (and within 25 years, TABLE 7-1. International Panel Criteria (McDonald Criteria) 90%) of these cases enter a progressive phase, termed second- for the Diagnosis of Multiple Sclerosis ary progressive (or relapsing progressive) MS. During this phase deficits are progressive without much remission in the disease. Additional Data Needed Clinical Presentation for MS Diagnosis Less commonly, the disease is progressive from the start. This entity, first distinguished in 1952, has been termed primary pro- Two or more attacks; None gressive (or chronic progressive) MS. These patients (5% to 10% objective clinical of the MS population) may present at a later age with progres- evidence of two or more sive neurologic findings, including paraparesis, hemiparesis, lesions brain stem syndromes, or visual loss, and typically have a more Two or more attacks; Dissemination in space, demonstrated by: severe disability. They may have occasional plateaus and tem- objective clinical s -2) OR porary improvements but do not have distinct relapses. Primary evidence of one lesion s 4WOORMORE-2)LESIONSCONSISTENT progressive patients tend to have a smaller lesion load, fewer with MS plus positive CSF, or new lesions on monthly T2-weighted images (T2WI), and s !WAITFURTHERCLINICALATTACK implicating a different site. fewer enhancing lesions when compared to patients with sec- ondary progressive disease, despite progressive declining neu- One attack; objective Dissemination in time, demonstrated rologic status. Progressive relapsing MS, a rare clinical course, is clinical evidence of two or by MRI, or second clinical attack. defined as progressive disease with clear acute relapses, with more lesions or without full recovery, and with the periods between relapses One attack; objective Dissemination in space, demonstrated by: characterized by continuing progression. All of these groups also clinical evidence of one s -2) OR have been lumped together and identified as chronic progres- lesion (clinically isolated s 4WOORMORE-2)LESIONSCONSISTENT sive MS; however, some experts believe the term should be syndrome) with MS plus positive CSF‡, AND Dissemination in time, demonstrated abandoned because of its vague nature and the variable clinical by: MRI or second clinical attack. courses and corresponding MR patterns. Benign MS describes those