Tsutomu Junichi

Araki, Hachiya,

MD MD

#{149} Hiroshi #{149} Tsuneaki

Membranous MR Imaging

Ohba, MD Seki, MD

Index

terms:

Brain, atrophy, 13.1214, 14.1214 #{149} Dementia

Bones,

osteochondrodysplasias,

#{149}

Radiology

1991;

13.839 #{149} Brain,

#{149} Yoichi

Lipodystrophy: Appearance

Five patients with membranous lipodystrophy (lipomembranous polycystic osteodysplasia with progressive dementia) underwent magnetic resonance (MR) imaging of the brain. T2weighted MR images showed afrophied cerebral white matter with dilated ventricles; increased signal intensity of the white matter; and decreased signal intensity of the thalamus, putamen, caudate nucleus, and cerebral cortex. Although each single finding is not specific, the combinalion of the above MR findings when coupled with skeletal lesions strongly suggests this rare disease.

40.159 studies, 13.87

#{149} Shuichi

Brain, white

#{149}

MR matter,

180:793-797

Monzawa, Takahashi,

MD MD

ofthe

#{149} Keiko #{149} Motoshi

Brain’

lipodystrophy (ML) disease affecting the adipose tissue and the brain. This entity has been more commonly described as “lipomembranous polycystic osteodysplasia with progressive dementia” in the English literature (3-8). Approximately 70 patients with this disease have been described in Finland (3-5,9), Sweden (7), Japan (10-16), and the United States (17,i8). Clinical, pathologic, and radiologic findings, including computed tomographic (CT) findings, were described in these reports. Magnetic resonance (MR) images of the brain in patients with ML have not been described in English literature to our knowledge. We have recently examined five patients with this disease with MR imaging. MR findings in the brain and the role of these findings in the diagnosis of this disease are described. 4EMBRANOUS

(1,2)

Sakuyama, MD Yamaguchi, MD

is a rare

3. The effect on mental state was classifled into two categories: mild, without signs indicating personality disintegration,

or marked,

AND

The five patients three women and 31-37

years.

related.

None

METHODS

in this study two men; age of the patients

included range was were

In each case, the diagnosis

of ML

was made on the basis of histopathologic findings from a biopsy specimen obtained from a bone lesion. No brain tissue was available for pathologic examination.

MR imaging a 1.5-T (cases superconducting

weighted

was performed

with

1, 2) or a 0.5-T (cases system. Spin-echo

images

(repetition

times

either 3-5) Ti-

[TRsI of

400, 460, or 500 msec; echo times [TEs] of i5, 20, or 30 msec) and T2-weighted images (TR/FE = 1,900 or 2,000/80 or 100)

were I From the sity Hospital

Department of Yamanashi,

of Radiology, Tamaho,

UniverNaka-

koma, Yamanashi, Japan (TA., HO., SM., MY.); the Department of Radiology and the Third Department of Internal Medicine, Yokohama Seibu Hospital, Kanagawa,

ment

St Marianna University, Japan (KS., Y.T.); and

of Radiology,

Tokyo OH., T.S.). revision requested April 10; accepted

quests C

to TA.

RSNA,

1991

Kyorin

Yokohama, the Depart-

University,

Mitaka,

Received February 11, 1991; March 12; revision received May 1. Address reprint re-

obtained

in each case. The following

findings were noted: 1. Family history was

obtained

to deter-

the presence or absence of consanguinity or family members affected with ML or showing similar symptoms. mine

2. All

lesions.

patients had one or more bone The degree of bone involvement

5. Four

types

MR images cerebral

mild

incontinence,

decrease

was compared cortex (gray nal intensity that

of the

signal

of the determined.

on

studied.

T2-weighted

(a) Atrophy

matter

was

in the

volume

ter, with mildly dilated marked decrease in the matter, with markedly (b) The signal intensity

of

quantified

as a

of white

mat-

ventricles, or a volume of white dilated ventricles. of the white matter

with that of the cerebral matter). In normal adults, sigof white matter is less than cortex.

intensity

In patients

of white

with

ML,

the

matter

is equal to of the cortex. (c) Loss

or greater than that of signal intensity in the basal ganglia was noted relative to that of the globus pallidus.

The

range

loss

of findings

included

no

for signal

identifiable

inten-

loss,

defi-

nite loss but less prominent than that in the globus pallidus, or loss as prominent as that in the globus pallidus. (d) The number of patchy or confluent hyperintense regions in the white matter, which are often present in multi-infarct demen-

tia, was also noted. RESULTS The results of this study are summarized in the Table. Consanguinity was

confirmed

in two

patients

(cases

i, 4), and a sister of another patient (case 2) was hospitalized with similar clinical history, signs, and symptoms. Detailed family history for the remaining two patients (cases 3 and 5) was not available. Ti-weighted MR images revealed dilatation of the ventricles and cerebral cortical sulci and decreased volume of the cerebral white matter; these findings were also seen on CT

Abbreviations: phy,

bones.

personal-

as inappropriate

of findings

were

white

tures

deformed

indicating

such

4. The presence of calcification basal ganglia on CT scans was

was classified into three groups: (a) subclinical with few lesions, (b) clinically overt with one or two pathologic fractures, or (c) overt with repeated pathologic fracand

signs

behavior, lack of inhibition, and dementia.

sity

PATIENTS

with

ity disintegration

TE

=

ML echo

time,

=

TR

membranous =

repetition

lipodystrotime.

793

of Clinical,

Summary

CT, and

MR Findings

in Five

FIndIng

Patients

ML

with

Case 1

Age (y)/sex Family history

31fF

Consanguinity Affected family Bone lesions* Mental disorder

Case 2

Case 3

Case 4

Case 5

35/F

33/F

31/M

371M

Yes

No

No

Yes

No No

Yes No

No No

+

+

Marked

+

+

+

+

+

+

+

Marked

Mild

Mild

Mild

Yes

Yes

No

No

Mild W > C

Mild W = C

Marked W > C

CT

deposit

Calcium 12-weighted Atrophy

in basal ganglia

No

MR imaging

of white matter

Marked

Signal

W

intensity Signal Intensity losst Dentate nucleus

Red nucleus

and

nigra

=

+

nucleus

cortex,

For bone lesions, ttires

and

lidus,

++

tSi_

scans

deformed

+

sity

F +

= =

matter

female, M = male, W = white subdinical with few lesions,

and in the

images.

MR images, cerebral

white

+

-

-

-

+

+

+

+

++

++

+

+

+

++

-

+

+

+

1-2

0

+

+

0

1-2

matter. + +

bones.

T2-weighted

+

0 dinically

=

intensityloss was noted relative to that of the globus loss as prominent as that in the globus pallidus.

T2-weighted

+

++

No. of patchy lesions in white

C

>

+

-

Putamen

Note.-C

W

-

substantia

Thalamus

Caudate

Mild

C

>

overt

pallidus.

with =

-

one or two pathologic

Noloss

identified,

+

=

fractures, definite

+ .1- +

=

overt

with

repeated

prominent

lossbutless

pathologic

frac-

than that in the globus

pal-

On

signal

inten-

matter

was

higher than that in the cortex in four patients and was nearly equal in one patient. None showed higher signal intensity in the cortex. In all patients, symmetric loss of signal intensity was noted in the thalamus, caudate nucleus, and the globus pallidus. Two patients had one or two small white matter lesions but none had many or confluent lesions, which are frequently seen in patients with multiinfarct dementia. Calcification was noted in the globus pallidus and putamen in two patients at CT. The degree of calcification, however, was within physiologic limits.

CASE

REPORTS

3i-year-old woman had been well until age 22 years when she became restless and irritable, and experienced urinary incontinence. Although she married at the age of 24 years, she did not have a job or do housework. She ran away from home many times. Over the last several years, her behavior was inappropriate, and she was frequently incontinent. She became euphoric, and confabulation and a lack of inhibition were apparent. She was noncooperative during medical examinations. No episode of seizure was documented. An electroencephalogram showed slow wave pattern in the central parietal region. No sensory or motor disturbance was present. Hyperreflexia, abnormal Babinski reflex, and myocloCase

794

1.-A

#{149} Radiology

a.

b.

Figure 1. Case nous structures. sity

ume

in the

(a) Biopsy specimen from the sternal marrow (b) T2-weighted (2,000/80) image demonstrates

thalamus,

of the cerebral

nus were functions, deteriorated. ins.

1.

putamen,

white

and

matter

noted. Memory, and calculation Her parents

Radiographic

bone

caudate

is considerably

cognitive abilities were coussurvey

re-

vealed an old fracture of the right first toe. A biopsy specimen from the sternum disclosed membranous convolutions characteristic of ML (Fig ia). CT scans of the brain showed dilated ventricles and cerebral cortical sulci

but no calcification of basal ganglia. No other abnormality was identified. T2-weighted MR images revealed marked atrophy and higher signal

nucleus.

Lateral

shows characteristic membrasymmetric loss of signal inten-

ventricles

are

dilated,

and

the

vol-

decreased.

intensity

of the

symmetric

loss

white

matter,

of signal

with

intensity

in

the thalamus, globus pallidus, and caudate nucleus (Fig ib). Mild signal intensity loss was seen in the putamen, and no signal intensity loss was seen in the dentate nucleus, substantia nigra, and red nucleus. No localized patchy lesions were identified in the white matter. Case 2.-T2-weighted MR images of the brain and radiographs and a CT scan

woman

of both

feet

are shown

in this

35-year-old

in Figure

2.

September

1991

should also be included in this entity (1,2). Independent of these Japanese discussions, J#{228}rviet al also reported several cases with unusual bone lesions in the 1960s (9), and named this newly established bone lesion “lipomembranous polycystic osteodysplasia” (3). Their cases were associated with neuropsychiatric symptoms. Now ML and lipomembranous polycystic osteodysplasia with progressive dementia are accepted as the same entity. Although the exact cause of ML is not clear, it was suggested that the disease was inherited as an autosomal recessive trait based on the high frequency of consanguinity and affected family

members

consistent b.

Nasu

d. Figure

seen

2. Case 2. (a) On T2-weighted in the thalamus, putamen, caudate

graphs symmetric

of the right lesions

foot (b) and in both

(2,000/100) nucleus,

left foot (c) reveal

3.

Case 4.-T2-weighted MR image from a 3i-year-old man is shown in Figure 4. Case 5.-This 37-year-old man had his

lower

extremities

many

times since the age of 20 years, resulting in deformity and contracture. He could not stand unassisted for a long time. Recently he complained of difficulty in swallowing and speaking, although there was no definite psychiatric evidence of dementia. CT scans revealed dilated ventricles and calcification in the globus pallidus and putamen. T2-weighted MR images showed mild but definite loss of signal intensity in the thalamus, putamen, caudate nucleus (Fig 5a), red nucleus, and substantia nigra. More Volume

180

#{149} Number

multiple

lucent

of signal intensity is (b, c) Lateral radio-

lesions.

(d) CT scan

discloses

tall.

Case 3.-T2-weighted MR images and a CT scan of the brain in this 33year-old woman are shown in Figure

fractured

image, symmetric loss and the globus pallidus.

3

prominent signal intensity loss was seen in the globus pallidus. The signal intensity of the cerebral cortex was lower than that of the white matter. The loss of signal intensity in the cortex was most prominent along the central sulci (Fig Sb). Two small highsignal-intensity lesions were disclosed in the cerebral white matter.

reported

In the early i960s, pathologic findings in several cases with peculiar bone lesions were discussed in the Japanese literature. Nasu et al reported autopsy findings of cases with the characteristic membranous convolution in the adipose tissue and generalized cerebral leukodystrophy and named the new entity “membranous lipodystrophy.” They concluded that some previously discussed cases

(18).

this that

Our

findings

inheritance

are

mode.

consanguinity

of

parents was present in i7 of 27 patients with this disease (2). M#{228}kel#{228} et al described a representative clinical course of this disease (i9). Patients usually have no symptoms until they reach about 20 years of age (first phase), when patients begin to complain of pains in the extremities. The bone lesions grow slowly thereafter and cause pathologic fractures (second phase). Around 30 years of age, neuropsychiatric symptoms are noticed (third phase) and progress rapidly to total dementia (fourth phase). The patients usually die around the age of 40 years. There appear to be two extreme clinical types-a bonedominant type and a brain-dominant type-and an intermediate one. Cases 1 and 2 of this series were the braindominant type, and case 5 was the bone-dominant type. Cases 3 and 4 showed intermediate clinical findings. Radiographic findings of the bone lesions in this disease have been well documented (i9). The lesions first show reduction of bone trabeculae in the epiphysis and metaphysis and then progress to the formation of cystic lesions, which have poorly defined margins and lack sclerotic rims. The lesions are most conspicuous in the carpal and tarsal bones and tend to be symmetric.

DISCUSSION

with

Pathologic

fractures

are

often seen late in the second clinical phase. At macroscopic examination the bone lesions contain a yellow gelatinous substance, which is characterized by innumerable convolutional membranes at microscopic examination. Because of its strong T2 shortening effect, iron accumulation is sensitively displayed as an area of signal intensity loss on T2-weighted MR images. Hallgren and Sourander determined the presence of nonhemin iron (ferRadiology

#{149} 795

b. Figure

3. Case

slightly

weaker

3.

(a, b) T2-weighted signal

intensity

(c) CT scan shows

mild

Figure

4. Case

4.

T2-weighted

image

reveals

similar

the thalamus and prominent signal men and caudate

loss

calcification

signal

globus intensity nucleus.

(2,000/120) in the

occurred

with

pallidus and loss in the

loss in less puta-

advancing

age,

and the increase was most rapid in the first 2 decades of life. The cerebral cortex of healthy individuals younger than 65 years old did not show histologically typical

796

detectable T2-weighted

#{149} Radiology

demonstrate

and

lenticular

caudate

strong nucleus

signal

(a).

Low

intensity signal

loss in the thalamus

intensity

and

is demonstrated

globus

in the

pallidus

cerebral

and

cortex

(b).

nuclei.

(2,000/100)

intensity

ritin) in the brain with chemical and histopathologic analyses (20). It was found most abundantly in the globus pallidus, followed by the red nucleus and substantia nigra. In decreasing order, less iron was present in the putamen, dentate nucleus, caudate nucleus, motor cortex, thalamus, occipital cortex, sensory cortex, and frontal white matter. An increase of nonhemic iron in the above anatomic sites

putamen

in both

C.

images

levels of iron. On spin-echo im-

a. Figure lenticular

ages,

readily healthy of life,

b. 5. Case

nuclei

signal

tients,

T2-weighted

(a), and

intensity

(1,900/100)

cerebral

loss

cortex

cannot

nigra,

nucleus who

red

(2i).

were

nucleus,

in the

4th

bus pallidus was amus, putamen,

This is abnormal, of the patients intensity substantia

considering the less

intensity

in the

thalamus,

in

prominent

the

signal

thalamus

and

intensity

putamen

was

first documented by Seki et al After review of the five cases described herein it seems justifiable to say that loss of signal intensity in the thalamus, putamen, and caudate nu(22).

pa-

decade

the

loss

of

cleus

gb-

observed in the thaland caudate nucleus.

and

decreased

port,

and

In all of our

show

(1,).

be

life, signal intensity loss comparable to or slightly less than that in the

signal cleus,

images

appreciated in the brain of individuals in the 4th decade except in the globus pallidus,

substantia

dentate

5.

the age prominent

loss in the red nunigra, and the den-

tate nucleus of the cerebellum. Case 4 in our series was described previously in the Japanese literature. In that re-

on

T2-weighted

common

finding

however,

does

cific

drome

not

appear

to ML, because the loss in the thalamus,

sity caudate kinson

images

is a

in ML. The

finding, to be spe-

signal intenputamen, or

nucleus was observed disease, Parkinson plus (multisystem atrophy),

ple sclerosis, (21,23,24), tients with

Huntington and even or without

in Parsynmulti-

disease in very old widespread

September

pa-

1991

ischemic lesions in the white matter. The loss of signal intensity, which is mainly caused by iron accumulation, seems spread

closely breakup

related to the wideof the cerebral white

matter, regardless of its cause, although the exact mechanism of the iron accumulation has not been clarifled yet (21). Drayer et al reported that the prominence of the decreased signal intensity in the thalamus and putamen directly correlated with the extent and number of white matter lesions in patients with multiple sclerosis

(21).

The pathologic changes in the brain have been reported to be either sclerosing leukodystrophy or sudanophilic leukodystrophy with generalized brain atrophy (especially prominent in the white matter), demyelinization,

fibrous

gliosis

of the

white matter, breakup of axons, and no infiltration of inflammatory cells (i,2,i4). The reversed pattern of signal intensity of the cerebral white matter and cortex on T2-weighted images from patients with ML can be explained as follows: The pathologic change in the white matter (leukodystrophy) increases the signal intensity of the cerebral white matter, while the breakup of the white matter is closely related to the decrease in intensity of the cerebral cortex and the basal ganglia. The loss of signal intensity in the cerebral cortex, presumally due to iron accumulation, was first reported by

Drayer

in patients

with

prominent

patchy

loss

or

confluent

of hyperintensity were present in the cerebral white matter of the five patients with ML described herein. Such lesions are often prominent in patients with multi-infarct dementia or in asymptomatic older individuals (25) and result from cerebral arteriolar disease and hypoperfusion (26). The most severe manifestation of such lesions is Binswanger microangiographic leukoencephalopathy. The lack of prominent patchy or confluent hyperintense areas in the white matter in patients with ML is

180

#{149} Number

3

intensity

of the

1.

2.

3.

4.

5.

6.

7.

8.

9.

analysis

of seven

12.

13.

14.

15.

16.

1981; 5:580-582. OH, Hakola HPA, Lauttamus

Jarvi LL, Solonen KA, Vilppula MI. Cystic capillary-necrotic osteodysplasia: a systemic bone disease probably caused by arteriolar and capillary necroses: relation to brain

affections. Seventh International Congress of International Academy Pathology, Milan, Italy, 1968; 291-292. Harada K. Em fall von “membranoser lipodystrophie (Nasu),” unter besonderer berucksichtigung des psychiatrischen und neuropathologischen befundes. Fol Psych NeurolJpn 1975; 29:169-177. Laasonen EM. Das syndrom der polyzystischen osteodysplasie mit progressiver demenz. ROFO 1975; 49:223-230. Akai M, Tateishi A, Cheng CH. Membranous lipodystrophy. J Bone Joint Surg [Am] 1977; 59:802-809. Tanaka J. Leukoencephalopathic alteration in membranous lipodystrophy. Acta Neuropathol (Berl) 1980; 50:193-197. Fujiwara M. Histopathologic and histochemical studies of membranocystic lesion (Nasu). Shinshu Med J 1979; 27:78100. Sourander P. A new entity of phacomatosis. B. Brain lesions (sclerosing leukoencephalopathy). APMIS 1970; 215(suppl):44. Tanahashi N, Gotoh F, Koto A, Ishihara N,

Gomi S.

Membranous

lipodystraphy

(Nasu): report of three siblings with particular emphasis on the CT findings. Clin Neurol 1983; 23:956-962. Uapanese] 17.

Wood C. Membranous lipodystrophy of bone. Arch Pathol Lab Med 1978; 102:2227. Brid TD, Koerker RM, Leaird BJ, Vlcek BW, Thorning DR. Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): a genetic cause of presenile demen-

tia. Neurology 19.

20.

1983; 33:81-86.

M#{228}kel#{228} P,Jarvi

Radiologic

0, Hakola

P. Virtama

bone changes

P.

of polycystic

li-

with Skeletal

scleRa-

pomembranous osteodysplasia rosing leukoencephalopathy. diol 1982; 8:51-54. Hallgren B, Sourander P.

The

effect

of

age on the non-haemin iron in the human brain. J Neurochem 1958; 3:41-51. 21.

Drayer

BP, Burger

D, Cain J.

P. Hurwitz

Reduced

signal

AJR

22.

23.

1987; 149:357-363.

Seki T, Hachiya J, Korenaga T, Furuya Y, Mochiziki K. Membranous lipodystrophy (Nasu) demonstrated by MRI and other images. J Med Imagings 1989; 9:604-608. Uapanesel Drayer BP, Olanow

GA, Herfkens plus

syndrome:

MR imaging 24.

25.

26.

B, Dawson on putamen in iron content?

intensity

MR images of thalamus and multiple sclerosis: increased

cases. Neuroradi-

ology 1973; 6:162-168. Hakola HPA, Karjalaine P. Bone mineral content in hereditary polycystic osteodysplasia associated with progressive dementia. Acta Radiol 1975; 16:385-392. Yagishita 5, Ito Y, Lkezaaki R. Lipomembranous polycystic osteodysplasia. Virchows Arch [A] 1976; 372:245-251. Adolfsson R, Forsell A,Johansson C. Hereditary polycystic osteodysplasia with progressive dementia in Sweden. Lancet 1978; 1:1209-1210. Laasonen EM, Lahdenranta U. Lipomembranous polycystic osteodysplasia with progressive dementia. J Comput Assist To-

mogr

1 1.

18.

Nasu T, Tsukahara Y, Terayama K. A lipid metabolic disease: “membranous lipodystrophy”-an autopsy case demonstrating numerous peculiar membrane structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta PatholJpn 1973; 23:539559. Nasu T. Pathology of membranous lipodystrophy. Trans Soc PatholJpn 1978; 67: 57-98. [Japanesel Hakola HPA. Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia. Acta Psychiatr Scand Suppl 1972; 1:171. Hakola HPA, Livanainen M. A new hereditary disease with progressive dementia and polycystic osteodysplasia: neuroradio-

logical

10.

thala-

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regions

Volume

of signal

mus, putamen, caudate nucleus, and cerebral cortex is probably pathognomonic of ML when coupled with skeletal lesions. T2-weighted MR imaging is much more diagnostic than CT, which only shows nonspecific dilated ventricles and calcification of the basal ganglia. In the majority of cases of ML, the first diagnostic clue is bone lesions, the biopsy of which provides a definite diagnosis. In cases without symptomatic bone lesions or in cases of brain-dominant type, MR imaging can be a reliable diagnostic clue to ML, which must be differentiated from a large population of presenile dementias. #{149}

Alzheimer

disease (25). The phenomenon is also observed in patients with widespread white matter lesions such as amyotrophic lateral sclerosis and multiinfarct cerebrovascular dementia. No

useful in differentiating this rare disease from multi-infarct dementia. Taken singly, the MR imaging findings are not specific to ML, but the combination of atrophied white matter with dilated ventricles; increased signal intensity of white matter; and

W, Burger

R, Riederer diagnosis

of brain

S. using

P, Johnson

Parkinson high

iron. Radiology

field 1986;

159:493-498. Drayer BP. Brain imaging and spectroscopy. In: Wehrli FW, Shaw D, Kneeland JD. Biomedical magnetic resonance imaging. New York: VCH Publishers, 1988; 225-278. Drayer BP. Imaging of the aging brain. II. Pathologic conditions. Radiology 1988; 166: 797-806. Drayer BP. Imaging of the aging brain. I. Normal findings. Radiology 1988; 166:785796.

Radiology

#{149} 797