18 -Acquired Metabolic, WHITE ,GRAY MATTER DEGENERATIVE DISEASES .

Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain Normal Aging Brain White Matter Sulci, Cisterns, and Ventricles Brain Iron and the Striatonigral System Cortica

Acquired Metabolic, White Matter, and Degenerative Diseases of the

Brain

Normal Aging Brain

White Matter

Sulci, Cisterns, and Ventricles

Brain Iron and the Striatonigral System

Cortical Gray Matter

White Matter Neurodegenerative Disorders

Gray Matter Neurodegenerative Disorders

Alzheimer Disease and Other C3rtical Dementias

Extrapyramidal Disorders and Subcortical Demen-

Miscellaneous Cerebellar Degenerations

Numerous inherited and acquired neurodegenerative

disorders affect the central nervous system Inherited

metabolic, white matter, and degenerative diseases were

delineated in Chapter 17 Here we briefly discuss the

normal aging brain, then turn our attention to the broad

spectrum of acquired neurodegenerative diseases

NORMAL AGING BRAIN

Just as certain imaging findings reflect the dramatic changes in brain morphology that occur with fetal and postnatal development, others mirror normal alterations in the aging brain.1 Specific age-related changes take place in the cerebral white and gray matter, the cerebrospinal fluid

spaces, and the basal ganglia (see box, p 750)

White Matter

Foci of increased signal intensity are often identified on T2-weighted MR scans in demented and healthy elderly patients The clinical significance of these findings is uncertain, and their precise etiology remains unclear These foci are found in several different locations: the subcortical, central, and periventricular white matter (Fig 18-1).2

Subcortical lesions Subcortical white hyperintensities

(WMHs) are commonly identified on T2-weighted MR scans in healthy elderly patients.3 WMHs have different etiologies, depending on location and configuration Punctate lesions are characterized histologically by dilated perivascular spates

C H A P T E R

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain

749

Fig 18-1 A and B, Axial anatomic drawings depict basal ganglia iron deposition and white

matter hyperintensities (WMHs) seen in the typical aging brain Iron deposition is most

noticeable in the globus pallidus (B, 1, black areas), less prominent in the putamen and caudate nucleus, and even less prominent in the thalamus (B, 2, 3, dotted and crosshatched

areas) Note triangular-shaped "caps" around the frontal horns (curved arrows), thin

periventricular hyperintense halo (A, arrowheads), and dilated perivascular spaces, seen as

punctate or linear hyperintensities (small arrows) in the subcortical white matter, centrum semiovale, and basal ganglia Patchy periventricular and subcortical WMHs (large arrows)

represent areas of myelin pallor and small vessel arteriosclerosis C, Coronal T2-weighted

MR scan in a normal 80-year-old woman shows WMHs in the subcortical white matter, centrum semiovale, and periventricular white matter The linear WMHs represent dilated

perivascular (Virchow-Robin) spaces (arrows), whereas more focal patchy lesions (see D, arrows) represent myelin pallor or atherosclerosis Note prominent sulci and ventricles D,

Axial T2-weighted MR scan in a 76-year-old man with hypertension, confusion, and decreasing mental status shows numerous patchy subcortical and periventricular WMHs

(arrows) The sulci and ventricles are enlarged but are not as prominent as seen in C

750 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 18-1, contd E and F, Axial proton density-weighted MR scans in a normal

72-yearold man show normal periventricular white matter hyperintensities These consist of triangular, high signal "caps" around the frontal horns and a fine, thin

hyperintense rim around the lateral ventricles (open arrows) Note WMHs (curved arrow).

and perivascular gliosis, whereas more patchy lesions are associated with myelin pallor, dilated perivascular

spaces, and arteriosclerosis (Fig 18-1, A and B) 2

Although early reports identified a history of emic stroke as predictive for the presence and severity

isch-of subcortical white matter lesions, 4 recent investigations indicate the major correlative factor is age.5 Cognitive function is not related to presence or absence of WMHs

Central lesions WMHs in the corona radiata and

centrum semiovale are typically found in a perivascular distribution.5 Dilated perivascular spaces are round or linear lesions that are oriented perpendicularly to the ventricles and cortex (Fig 18-1,

A and B) Patchy, more confluent WMHs are probably related to small-vessel atherosclerosis and myelin pallor.2,2a They are most commonly located in the watershed zones between the middle and anterior or the middle and posterior cerebral arteries; they rarely occur in the temporal or occipital subcortical areas.6

The extent and frequency of central WMHs are closely related to age Patients with hypertension (Fig 18-1, D), diabetes, hyperlipidemia, and heart disease have more WMHs compared to patients without these risk factors but this becomes statistically significant only in the eighth decade.6

Periventricular lesions Several different types of

periventricular hyperintensities (Figs 18-1 A and B) are seen on the T2-weighted MR scans in elderly pa-tients, as follows:

1 Triangle-shaped "caps" around the frontal horns

2 Thin, smooth periventricular rims

3 Patchy periventricular hyperintensities

"Caps" adjacent to the frontal horns are a o finding

in patients of all ages (Figs 18-1, A, B, and E) In this

location, myelin is more loosely compacted and there

is a relative increase in periependymal fluid

Many healthy elderly patients also exhibit ally symmetric thin rims of periventricular high signal

bilater-intensity on T2-weighted scans (Figs 18-1, A, B, E,

and F) These are characterized histologically by subependymal gliosis and focal loss of the ependymal lining with increased periependymal CSF and are not indicative of normal pressure hydrocephalus.2 This type of periventricular hyperintensity is also correlated with increasing age.7

Patchy periventricular hyperintensities represent deep white matter infarction and are more com-

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 751

mon in patients with hypertension or normal pressure

hydrocephalus (NPH) than age-matched controls,

although there is significant overlap between these

groups (Figs 18-1, A, B, and D).8,9 Some

hypertension-related white matter lesions may resolve

with blood pressure normalization

Perivascular spaces Perivascular spaces, also

known as Virchow-Robin spaces (VRSs), are piallined

extensions of the subarachnoid space that surround

penetrating arteries as they enter either the basal

ganglia or the cortical gray matter over the high

convexities10 (see Fig 12-191) VRSs may extend

deep into the basal ganglia and centrum semiovale

(Figs 18-1 to 18-3)

Small VRSsare found in patients of all ages and are a normal anatomic variant.10 VRSs increase in size and frequency with advancing age.10 Other factors such as hypertension, dementia, and incidental white-matter lesions are also associated with large VRSs but are considered part of the aging process and are not independent variables.10

High-resolution MR scans routinely demonstrate small rounded or linear perivascular foci that follow CSF on all pulse sequences (Fig 18-2, B and C) VRSs surround the lenticulostriate arteries as they course through the anterior perforated substance into the basal ganglia (Fig 18-3) VRSs are less frequently identified in the high-convexity gray matter and centrum semiovale Prominent VRSs in the basal ganglia,

Fig 18-2 A, Coronal gross pathology shows unusually prominent perivascular spaces B and

C, Axial T1-weighted MR scans in a normal 45-year-old man show numerous prominent

Virchow-Robin spaces (VRSs) in the subcortical white matter (B, arrows) and centrum semiovale (C, arrows) Compare with A Note that where the plane of the scan is parallel to the penetrating vessels, the VRSs appear linear (B, arrows), but if the scan plane is perpen- dicular to the VRSs, they appear more rounded (C, arrows) (A, Courtesy J Townsend.)

752 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 18-3 Axial T2-weighted MR scan in a

67-year-old woman shows small perivascular spaces

in the right basal ganglia (small arrows), large

Virchow-Robin spaces in the left basal ganglia (large

arrows), and a more focal, confluent hyperintense

lesion (curved arrow) that probably represents a

lacunar infarct

Fig 18-4 Axial NECT scan in an intellectually

normal 80year-old man with head trauma shows

prominent sulci and basilar cisterns (small arrows) The third ventricle (curved arrow) and both lateral ventricles (large arrows) are also

prominent

Hydrocephalus

"Overproduction" hydrocephalus (questionable; may

occur with choroid plexus tumors) Hydrocephalus secondary to obstructed CSF flow

(usually refers to intraventricular obstructive drocephalus, or IVOH; extraventricular obstructive hydrocephalus, or EVOH, is sometimes loosely

hy-termed communicating hydrocephalus)

Hydrocephalus secondary to decreased CSF

absorp-tion at the arachnoid villi

"Normal pressure" hydrocephalus,

subcortical white matter, and centrum semiovale are a

normal MR finding (see Figs 18-1, A and B, and

18-2)

Sulci, Cisterns, and Ventricles

Sulci and cisterns Sulcal and cisternal

enlarge-ment is part of the normal aging process (Figs 18-1

and 18-4) Prominent CSF spaces are also common in

children under 1 year of age; craniocortical widths up

to 4 mm and interhemispheric widths up to 6 mm are

normal (Fig 18-5).11 Large sulci in elderly patients

have also been associated with diabetes, hypertension,

chronic cerebrovascular disorders, and medications.12

These factors often accompany the aging process and

do not represent independent variables.10 The degree

and progression of additional atrophy in the senile

dementias is uncertain Overlap of all volumetric

indices shows that imaging data alone cannot

Fig 18-5 Axial NECT scan in a normal 7-month-old

baby shows prominent frontal and interhemispheric

subarachnoid spaces (arrows)

be used to predict the presence or progression of dementia in individual cases (compare Figs 18-1, C and D).13

Various inherited and acquired neurodegenerative disorders, toxic encephalopathies, trauma, and other such diseases also cause generalized atrophic changes, with concomitant enlargement of the intracranial CSF spaces (see subsequent discussion)

Ventricles and hydrocephalus Under normal

conditions the cerebral ventricular system has a ume of 20 to 25 ml.14 Both hydrocephalus (Fig 18-6,

vol-Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 753

Fig 18-6 A, Gross pathology of obstructive hydrocephalus secondary to a posterior fossa

tumor (not shown) Note markedly enlarged lateral ventricles The sulci are inapparent B to G, Different types of hydrocephalus: B, Coronal proton density-weighted MR scan in a 4-year-old

child with a fourth ventricular medulloblastoma (curved arrows) Note the enlarged lateral ventricles are surrounded by a thin hyperintense rim of transependymal CSF (open arrows), an

abnormal finding in young patients but normal in elderly individuals (compare with Fig 18-1,

E and F) Obstructive hydrocephalus of the "noncommunicating" or intraventricular type

(IVOH) C to E, Axial NECT scans in a 24-year-old man with a history of meningitis as a

child show markedly enlarged lateral and third ventricles and a moderately enlarged fourth ventricle The sulci are inapparent Obstructive hydrocephalus of the "communicating" or

extraventricular (EVOH) type (A, From archives of the Armed Forces Institute of Pathology.)

Continued

A) and atrophy (see Fig 18-29, A) are characterized

by ventricular dilatation

Hydrocephalus Three possible mechanisms

ac-count for the development of hydrocephalus (see box)

With the exception of hydrocephalus caused by

increased CSF production (choroid plexus tumors),

hydrocephalus is caused by obstructed CSF flow,

de-creased CSF absorption, or a combination of both.14

The term hydrocephalus ex vacuo is inappropriate and

should be discontinued in favor of atrophy

In so-called noncommunicating hydrocephalus also

sometimes termed intraventricular obstructive hy-

drocephalus, or IVOH), flow obstruction occurs inside

the ventricular system down to and including the fourth ventricular outlet foramina (Fig 18-6, B)

In "communicating" hydrocephalus (also sometimes

termed extraventricular obstructive hydrocephalus, or

EVOH), obstruction occurs within the subarachnoid spaces or cisterns (Fig 18-6, C to E) This pattern of hydrocephalus can also occur with diminished CSF absorption at the arachnoid villi

Imaging findings in obstructive hydrocephalus vary with the site and duration of the blockage The ventricular system enlarges proximal to the obstruc-

754 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

tion With elevated intraventricular pressure, CSF

ex-trudes across the ependyma into the adjacent white

matter (Fig 18-6, B) Periventricular high signal

in-tensity rims or fingerlike CSF projections that extend

outward from the ventricles can be delineated on proton

density-weighted MR scans (see Figs 13-38, E, and

18-6, B)

Normal pressure hydrocephalus (Fig 18-6, F to H) is

differentiated from generalized atrophy by ventricular

dilatation out of proportion to sulcal enlargement on CT

or MR scans (Fig 18-6, F to G) Some investigators

report CSF flow through the cerebral aqueduct is

hyperdynamic, producing an accentuated "CSF flow

void" on MR studies in patients with NPH.8,15 Others

disagree Still others have recently suggested that

symptoms seen in NPH (memory loss, gait disturbance,

urinary incontinence) relate not to ventricular dilatation

but rather to impingement of the corpus callosum by the

faIx cerebri.16

Atrophy Aging causes enlargement of both the

cerebral sulci and ventricles, indicating a process of

mixed central and cortical volume loss.13 Prominent sulci and ventricles are a normal finding on imaging studies,

particularly in patients over 70 years of are (see Figs 18-1,

C, and 18-4).14 Volumetric indexes in healthy aging patients remain fairly stable over time, whereas patients with Alzheimer-type senile dementias show progressive atrophy.13 However, the over lap between groups is substantial and- as is also the case with the sulci and cisterns ventricular size can not be used to predict the presence or progression of dementia in individual cases.13

Brain Iron and the Striatonigral System

Iron is a trace element involved in brain function.17 Iron

is essential for cellular respiration, neurotransmitter synthesis, and brain development and maturation.18 Iron deposition in certain parts of the brain occurs under normal and abnormal conditions and is easily detected on MR scans because magnetic susceptibility causes preferential T2 shortening.19

Nonheme iron deposition in the brain is

indepen-Fig 18-6, cont'd F and G, Axial NECT scans in a 66-year-old man with

dementia, ataxia, and incontinence show disproportionately enlarged ventricles compared to the mildly prominent sulci The patient improved after ventricular

shunting Normal pressure hydrocephalus H, Coronal gross pathology of normal

pressure hydrocephalus shows marked dilatation of the lateral ventricles with

corpus callosum thinning (H, Courtesy E Tessa Hedley-Whyte.)

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases ofthe Brain

755

Fig 18-7 A and B, Coronal T2-weighted MR scans in this 72-year-old patient show normal

hypointensity in the putamen (open arrow), globus pallidus (curved arrows), caudate nuclei (straight arrows) and red nuclei (arrowheads), caused by nonheme iron deposition Same case

as Fig 18-1, E and F

dent of hemoglobin metabolism and iron reserves in the

rest of the body.17 With aging the extrapyramidal gray

matter nuclei normally become hypointense T2-weighted

MR scans (Fig 18-7; see Fig 18-1).20 Small quantities of

iron are first identified in the globus pallidus at 6 postnatal

months, in the zona reticulata of the substantia nigra

between 9 and 12 months, in the red nucleus at 18 to 24

months, and in the dentate nucleus at 3 to 7 years.17

Hypointense areas in the red nucleus, substantia nigra,

and dentate nucleus seen on T2-weighted MR scans

remain comparatively unchanged throughout all age

groups, whereas hypointensity in the globus pallidus

increases in middle-aged and elderly patients (Fig 18-7).21

Iron content in the putamen increases more slowly,

reaching a maximum during the fifth decade.19 The

putamen normally appears hypointense only in the elderly

(Fig 18-7, A).21 Although Perls' stain demonstrates some

ferric iron deposition in the thalami and caudate nuclei of

autopsied brains from elderly patients, hypointensity on

T2WI is normally not seen in these areas.21 Abnormal iron

deposition in the caudate and other deep gray matter

nuclei occurs with many neurodegenerative diseases and

other pathological processes (see subsequent discussion).20

Cortical Gray Matter

Volume loss in the cortex with secondary enlargement

of adjacent sulci and cisterns normally occurs with aging

(see Fig 18-4) Although patients with primary

neurodegenerative disorders such as Pick disease or

Alzheimer-type dementia have more marked :sulcal

enlargement (see subsequent discussion), substantial

overlap between normal and abnormal elderly patients

occurs (see Figs 18-1, C, and 18-4)

Acquired White Matter Degenerative

Disorders Common

Multiple sclerosis Arteriosclerosis

Trauma (diffuse axonal- injury)

Uncommon

Viral/postviral demyelination Toxic demyelination

WHITE MATTER NEURODEGENERATIVE DISORDERS

Some acquired neurodegenerative diseases primarily or

exclusively involve the cerebral white matter (see box)

These myelinoclastic diseases are sometimes termed demyelinating diseases to distinguish them from inherited

or so-called dysmyelinating disorders (see Chapter 17)

The most common and best-characterized of all the acquired demyelinating diseases is multiple sclerosis (MS).22 In this section we first consider MS, then briefly review autoimmune-mediated demyelination disorders such as acute disseminated encephalomyelitis (considered

in detail in Chapter 17) We then attend to toxic encephalopathies, concluding our discussion by delineating the effects of trauma and vascular disease on the cerebral white matter

Multiple Sclerosis Etiology and inheritance The precise etiology of MS

remains unknown, although most investigators favor autoimmune-mediated demyelination in genet-

Most common demyelinating disease (after vascular

and age-related demyelination)

Female preponderance, especially in children

Peak age between 20 and 40 years

Typical location

Calloseptal interface

Imaging

Ovoid high signal foci on T2WI

Perivenular extension (perpendicular to ventricles)

Beveled or "target" (lesion within a lesion)

appear-ance common on Tl-, PD-weighted sequences Variable enhancement (solid, ring)

Most lesions seen on MR are clinically silent

Solitary lesions can min-tic neoplasm, abscess

ically susceptible individuals (see box).22-25a

In experimental allergic encephalomyelitis (EAE),

the animal model for MS, specific encephalitogenic

peptides from myelin basic protein are presented on

class II major histocompatibility complex molecules

These then induce T-cell receptor genes on CD4+

cells.23 The exact role of such self-antigens in human

MS is undetermined but epidemiologic and

demo-graphic studies suggest an exogenous infectious agent,

possibly viral, as the most likely immunogen.23

The role of inheritance in MS is unknown but an

increased incidence of subclinical demyelination has

been demonstrated in asymptomatic first order relatives

of MS patients.24

Pathology

Gross pathology Both the gross and microscopic

morphology of MS "plaques" are variable The typical

acute MS plaque is an edematous pink-gray white

matter lesion.22 Necrosis with atrophy and cystic

changes are common in chronic lesions (Fig 18-8)

Hemorrhage and calcification are rare.26

Microscopic pathology In MS, both myelin and the

myelin-producing oligodendrocytes are destroyed

Lesions are defined as histologically active if moderate

macrophage infiltration and at least mild perivascular

inflammatory changes are present Inactive lesions

demonstrate minimal or no perivascular inflammation,

mild or no macrophage infiltration, and

well-established astrogliosis.26

Incidence MS is by far the most common of all

demyelinating diseases except for age-related vascular

disease Although MS preponderantly affects young

adults of Northern European extraction and

occurs most often in temperate climates,27 it as world-wide racial and geographic distribution.28

Age and gender Symptom onset in MS is usually

between 20 and 40 years of age The female to male ratio in adults is 1.7-2: 1 MS is less common in children and adolescents; when it occurs in these age groups, the female: male ratio is much higher, between 5 and 10:

1.29,30

Location More than 85% of MS patients have ovoid

periventricular lesions that are oriented perpendicularly

to the long axis of the brain and lateral ventricles.31 This correlates well with the histologic localization of demyelination around subependymal and deep white matter medullary veins The next most common site is the corpus callosum, involved in 50% to 90% of patients with clinically definite MS.27,32 The callososeptal interface is a typical location; lesions here are optimally imaged in the sagittal plane (Fig 18-9, A).33

In adults the brainstem and cerebellum are paratively less common sites Approximately 10% of

com-MS plaques in adults are infratentorial, whereas the posterior fossa is a frequent site of MS plaques in children and adolescents (Fig 18-9, B).29 Occasionally,

MS plaques are identified in the cortex (Fig 18-9, C) Multiple lesions are typical, although large, solitary plaques do occur and can be mistaken on imaging

studies for neoplasm (see subsequent discussion)

Clinical presentation and natural history The

clinical spectrum and the natural history of MS are variable The most typical course is prolonged relapsing-remitting disease.34 Later, the disease often shifts into a chronic-progressive phase.27 A rare ful-

Fig 18-8 Coronal gross autopsy specimen of multiple

sclerosis shows confluent periventricular demyelinating

plaques (arrows) (Courtesy E Tessa Hedley-Whyte.)

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 757

Fig 18-9 A, Sagittal T2-weighted MR scan shows

multiple ovoid areas of high signal intensity along

the callososeptal interface (large arrows) Note

perivenular extension into the centrum semiovale

(open arrows), sometimes called "Dawson's

fin-gers." Typical MS B, Axial T2-weighted MR scan

in a 16-year-old girl with facial numbness and MS

shows multiple brainstem lesions (arrows) C,

Ax-ial T2-weighted MR scan in this 23-year-old woman with MS and typical periventricular

plaques (straight arrows) also shows a large right frontal plaque that involves the cortex (curved ar-

row) (B, From Osborn AG et al: AJNR

11:489-494,1990.)

minant form, acute fulminant MS of the Marburg type,

is associated with rapid clinical deterioration,

substantial morbidity, and high mortality.25

Imaging In a prospective 2-year study, the sensitivity

of MR imaging in detecting MS was nearly 85% and

exceeded all other tests, including oligoclonal bands,

evoked potentials, and CT scans.35 Imaging findings

vary with disease activity, although clinical correlation

with specific lesions is generally poor Most foci

identified on standard MR scans are clinically silent.34,36

CT Scans are often normal early in the disease

course Lesions are typically iso- or hypodense with

brain on NECT studies (Fig 18-10, A) Enhancement

following contrast administration is variable Some

lesions show no change, whereas others enhance

in-tensely Both solid (Fig 18-10, B and C) and ringlike

patterns are observed Some lesions become apparent

only after high-dose delayed scans are performed (Fig

18-10, C).28

MR Most MS plaques are iso- to hypointense on

T1-weighted scans and hyperintense compared to

brain on T2-weighted scans Because there are many causes of white matter hyperintensities on T2WI (see subsequent discussion), most authorities require the presence of three or more discrete lesions that are 5 mm or greater in size, as well as lesions that occur in a characteristic location and have a compatible clinical history, to establish the MR diagnosis of MS.37,38,38a Oblong lesions at the callososeptal interface are typical (Fig 18-11) Perivenular extension into the deep white matter,

the so-called Dawson's finger, is characteristic (see Fig

18-9, A).38

MS lesions are often seen as round or ovoid areas with a

"beveled" (lesion within a lesion) appearance on T1- and proton density-weighted studies (Fig 18-12, A) Confluent periventricular lesions are common in severe cases Abnormal basal ganglia hypointensity is seen in about 10%

of long-standing severe MS cases (Fig 18-13)

Enhancement following contrast administration represents blood-brain barrier disruption Enhancement is highly variable and typically transient, seen during the

active demyelinating stage Both solid (see Fig 18-12, C)

and ringlike (Fig 18-14)

enhance-758 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 18-10 A, Precontrast axial CT scan in a patient

with MS shows only an ill-defined low density

lesion (arrow) in the left posterior temporal lobe B,

Routine CECT scan obtained immediately following contrast administration shows an enhancing lesion in

the left frontal lobe (arrow) adjacent to the lateral

ventricle The right posterior temporal lobe lesion

does not enhance C, Double dose delayed CECT

scan shows the left frontal lobe lesion now appears

larger (curved arrow) The right temporal lobe lesion

now partially enhances (open arrow) (A, From

Osborn AG et al: AJNR 11:489-494, 1990.)

Fig 18-11 Axial T2-weighted MR scan in this

42-year-old woman with long-standing MS shows multiple ovoid or oblong lesions in the deep periventricular white matter and corpus callosurn

(solid arrows) Note extension into the centrum

semiovale along the course of the deep medullary

veins (open arrows)

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 759

Fig 18-12 Typical MS plaques are demonstrated on

the MR scans obtained in this 23-year-old woman with clinically definite MS and CSF studies positive for oligoclonal bands A, Axial precontrast T1-weighted scan shows a hypointense lesion in the corpus callosurn splenium and deep periventricular

white matter (large arrows) Note the beveled or

"lesion within a lesion" appearance (open arrow) B,

Axial T2WI shows the lesion (arrows) appears very

hyperintense compared to normal white matter C,

Postcontrast T1WI shows the lesion (arrow) enhances

strongly but somewhat inhomogeneously

Fig 18-13 Axial T2-weighted MR scans in this 42-year-old woman with

long-standing, severe MS show abnormal nonheme iron deposition in the

putamina (large arrows), thalami (small arrows), and midbrain (open arrows)

Same case as Fig 18-11

760 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 18-14 Axial postcontrast T1-weighted MR scan

in this 20-year-old woman with a temporal lobe seizure disclosed this solitary ring enhancing mass

(arrow) Because of the history, biopsy was

performed MS was found at histologic examination

Fig 18-15 This 32-year-old woman developed sudden onset of left extremity

paresthe-sias A, Sagittal T1-weighted MR scan shows a large, solitary parietotemporal mass

with concentric ringlike hypointense areas (arrows) Axial proton density- (B) and

T2-weighted (C) studies show the mass is inhomogeneously hyperintense The overlying cortical gray matter is spared D, Sagittal postcontrast T1WI shows patchy

ring enhancement (arrows) E, Axial T2-weighted MR scan obtained 8 months later

shows the right parietotemporal lesion (short arrows) has largely resolved A new left frontal mass is now present (long arrows) that has concentric ringlike hyperintense

areas The patient expired; autopsy (see Fig 18-15, F) showed multiple sclerosis (A to

E, From M Tersegno; A and C, Reprinted from AJR 160:901, 1993.)

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 761

Fig 18-15, cont'd F, Axial brain specimen shows

concentric laminae of spongiform demyelination (arrows)

in the left frontal lobe (specimen seen from below) (F,

From G.H Collins.)

ment patterns are seen.39 Enhanced T1-weighted scans

can detect additional lesions that are not apparent on

T2WI,34 although most MS plaques do not enhance

following contrast administration.37 Some solitary or

highly atypical MS lesions may be indistinguishable

from abscess (Fig 18-14) or neoplasm (Fig

18-15).40,40a

Cranial neuropathies, particularly optic neuritis, are

common in patients with MS Lesions in the brainstem

tracts and nuclei are seen on T2WI, whereas

contrast-enhanced T1-weighted studies may delineate

enhancement in the nerves themselves (Fig 18-16)

Fat-saturation and short inversion recovery scans are

useful in separating optic nerve enhancement from

high-signal orbital fat.41

Miscellaneous Early evidence indicates that 1H

spectroscopy may be more sensitive than

contrast-enhanced MR in delineating the true time course of

demyelination in MS plaques.42

Viral and Postviral Diseases

Viral and postviral white matter diseases are

dis-cussed extensively in Chapter 16 Acute disseminated

encephalomyelitis (ADEM) is characterized by

immune-mediated disseminated demyelination

Mul-tifocal high intensity lesions are seen on T2-weighted

MR scans; both the supratentorial and posterior fossa

white matter are typically affected (see Figs 16-37 to

16-39) The basal ganglia are sometimes also

in-volved.43

Toxic Demyelination

Toxic encephalopathy (TE) results from interaction f a

chemical compound with the brain A large number of

chemicals are potential neurotoxins; some of the more

common and important substances are listed in the box

Toxins cause temporary or permanent disturbance of

normal brain function in several ways,44 including

1 Depletion of oxidative energy

2 Nutritional deprivation

Toxic Demyelination Common

3 Disturbances in neurotransmission

4 Altered ion balance Toxins can be endogenous or exogenous to the CNS Endogenous CNS toxins typically result from inborn errors of metabolism such as the amino acidopathies and globoid cell leukodystrophy (Krabbe disease) These inherited neurodegenerative disorders are detailed in Chapter 17

Exogenous TE can be internal or external Internal TEs are caused by systemic disorders that produce toxins, which then cross the BBB and damage the CNS Examples are paraneoplastic syndromes (see Chapter 15) and ion balance disorders such as central pontine myelinolysis (CPM) and the hepatocerebral syndromes External TEs include lead or mercury poisoning, solvent exposure, alcohol abuse, and chemotherapy.44

In this section we consider two of the more common exogenous TEs that primarily affect the white matter: osmotic myelinolysis and chronic alcoholism Toxins that involve mostly the gray matter and basal ganglia are discussed in a later section of this chapter

762 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 18-16 Pathology and imaging findings in several patients with cranial nerve palsies

caused by MS A, Gross pathology specimen shows multiple plaques, including the root

entry zones of the trigeminal nerves (arrows) B, Coronal T2WI in this 15-year-old girl

with left trigeminal neuralgia and MS show supratentorial white matter lesions (straight arrows) and a large plaque at the root entry zone of the left trigeminal nerve (curved

arrow) Compare with A Sagittal (C) and coronal (D) postcontrast T1-weighted MR scans

in this 44-year-old woman with optic neuritis show optic chiasm enhancement (arrows) E,

Coronal postcontrast T1WI in another patient who has left facial numbness shows left

trigeminal nerve enhancement (large arrow) Compare with the normal, unenhancing right

CN V (small arrow) (F) This 40-year-old woman with multiple neurologic symptoms and

known MS developed right-sided sensorineural hearing loss Postcontrast axial T1WI shows an enhancing plaque in the right restiform body and root entry zone of CN VIII

(arrow) (A, From Okazaki H, Scheithauer B: Slide Atlas of Neuropathology, Gower

Medical Publishing.)

Chapter 18 Acquired Metabolic, White Matter, and Degenerative Diseases of the Brain 763

Osmotic myelinolysis Osmotic myelinolysis (OM)

is a toxic demyelinating disease that classically occurs

in alcoholic, malnourished, or chronically debilitated

adults.45 Over 75% of cases are associated with chronic

alcoholism or rapid correction of hyponatremia,

although other conditions such as hypematremia have

also been implicated.46,47

Pathologically, OM is characterized by myelin loss

(myelinolysis) with relative neuron sparing The central

pons is the most common site (central pontine

myelinolysis, or CPM), although OM also occurs in

other locations (Fig 18-17, A) So-called extrapontine

myelinolysis (EPM) is identified pathologically in about

half of all osmotic demyelination cases Reported

extrapontine sites include the putamina, caudate nuclei,

midbrain, thalami, and subcortical white matter.48

Imaging manifestations of OM syndromes reflect

increased water content in the affected areas NECT

scans are normal or disclose nonspecific hypodense

areas OM lesions are hypointense on T1- and

hyper-intense on T2-weighted MR scans (Fig 18-17, 13)

Transverse pontine fibers are most severely affected,

whereas the descending corticospinal tracts are often

spared.45 Enhancement following contrast

adminis-tration varies; some lesions enhance but most do not.49

Pontine signal abnormalities have a broad differential

diagnosis that includes infarct, metastasis, glioma,

multiple sclerosis, encephalitis, and radiation or

chemotherapy.46 However, pontine plus concomitant

basal ganglia involvement is fairly specific for OM

In such cases the imaging differential diagnosis is much more narrow and includes hypoxia, Leigh disease, and Wilson disease OM can usually be distinguished from these entities using a combination of imaging findings and clinical history.45

Chronic alcoholism Various specific processes

related to ethanol intoxication affect the CNS These include Wernicke encephalopathy, Marchiafava-Bignami disease, and osmotic myelinolysis.50 Ethanol adversely affects vascular, glial, and neural tissues and also causes myelin degeneration Nonspecific deep white matter and periventricular demyelinating lesions are seen on the MR scans of patients with chronic alcoholism (Fig 18-18).50 Demyelination is the main pathological finding in Marchiafava-Bignami disease and is the earliest, most constant lesion in Wernicke disease

Marchiafava-Bignami disease Marchiafava-Bignami

disease (MBD) is an uncommon disorder associated with chronic alcoholism.51 This disorder was originally described in poorly nourished Italian men addicted to crude red wine consumption MBD has now been reported in other population groups and with various alcoholic beverages.52

Pathologically, MBD is characterized by corpus losum demyelination and necrosis, although the cerebral hemispheric white matter and other commissural fibers may also be affected.52 Focal cystic necrosis occurs in the middle layers of the corpus callosum genu, body, or splenium Sagittal MR scans show callosal atrophy and focal necrosis as linear or punctate

cal-Fig 18-17 A, Axial gross pathology shows central pontine myelinolysis (arrows) B,

Axial T2-weighted MR scan in this 49-year-old man with rapid correction of severe hyponatremia shows the typical imaging findings of osmotic demyelination in the pons, also known as central pontine myelinolysis The central pons appears

hyperintense (white arrows) Note relative sparing of the descending corticospinal

tracts (black arrows) (A, Courtesy E Ross.)