CT of Subacute Sclerosing Panencephalitis

35
CT of Subacute Sclerosing
Panencephalitis
Eugene E. Duda 1
Peter R. Huttenlocher 2
Nicholas J. Patronas 1
Subacute sclerosing panencephalitis is a progressive, frequently fatal slow virus
infection of the brain attacking children and young adults and caused by measles virus .
Computed tomography (CT) of the brain in 15 patients with this disease was normal in
seven and abnormal in eight. CT demonstrated varying degrees of cortical atrophy
associated with focal and multifocallow density lesions of the white matter. Two cases
demonstrated low density lesions of the caudate nuclei. The CT lesions were seen in
chronic cases and reflect the gliosis and atrophy that occur in this disease. Differential
diagnoses include other viral infections and demyelinating and dysmyelinating diseases. Diagnostic laboratory evaluation includes serum and cerebrospinal f luid titers
for measles antibodies, cerebrospinal fluid protein electrophoresis, electroencephalography , and cranial CT.
Subacute sclerosing panencephalitis (SSP E) is a progressive, frequently fatal
disease of the brain attacking children and young adults . It has been known by
other names including Dawson's inclusion body enc ephaliti s [1 ,2], van Bogaert' s
subacute sclerosing leukoencephalitis [3], and the panencephalitis of Pette and
Doring [4]. Subsequent research clearly established that SSPE is a slow viru s
infection of the brain caused by measles virus [5].
We discuss computed tomographic (eT) c haracteristic s in 15 pati ents proven
to have this disease.
Materials and Methods
Received April 26 . 1979; accepted after revision September 6 . 1979.
This wo rk was supported by U.S. Public Health
Se rvice. National Institutes of Hea lth . Children 's
Clini cal Researc h Center granl M01 RR 00305.
, Departm ent of Radiology , University of Chicago, 9 50 E. 59th St. , Chicago , IL 60637. Address reprint requ ests to E. E. Duda.
2 Departm ents of Pedialrics and Neurolog y,
University o f Chicag o, Chicago , IL 6063 7 .
AJNR 1 :35-38, January / February 1980
95-61 08 / 80 / 0011-0035 $00 .00
© Ameri can Roentgen Ray Society
O~
Th e seven male and eight female pati ents we re 11- 2 1 years old . All pati ents we re
proven to have subacute scl erosing panencephalitis by th e accepted c riteri a [6 , 7] of
elevated titers of measl es antibody in both the serum and cerebral spinal fluid and an
el ectroenceph alogram c haracterized by syn c hronous, periodic, high voltage co mpl exes.
We reviewed the patients ' c harts and assigned a c linic al stage of disease acc ording to th e
method of Jabbour et al. [8], classifying th e pati ent into one of four c linica l stages. Ch anges
in mental abiliti es and behavior c haracterize stage 1 pati ent s. Myoc lonic seizures, whi c h
often occ ur at regul ar intervals of 5-10 sec, and motor signs herald stage 2, wh en th e
patient usuall y com es to th e attenti on of a p hysic ian. Ataxia and c horeiform movements are
see n. On e-h alf of th e pati ents have oc ular sigr. s includin g co rti cal blindn ess, opti c atroph y,
and c horioretiniti s [9 ]. Com a, opi sth otonous, d ecerebrate ri gid ity , imp aired autonomi c
nervou s fun ction , and deranged temperature homeostasis are among th e alarmin g sign s o f
stage 3 . Stage 4 pati ents di spl ay loss of co rti ca l fun cti on. Death soon occurs and is usually
caused by vaso motor coll apse or infec ti on.
W e reviewed c rani al CT scans o f all 15 pati ent s with proven SSPE . All but two (cases 9
and 1 2 ) had repeat c rani al CT with intrave nous iod ine infu sion of a solution of meglumin e
di atrizoate (5 2%) an d sodium di atrizoate (8% ) ad mini stered ove r 4 min at a dose o f 2 mi l
kg bod y weight. Th e ve ntricular di ameter was measured at th e level o f the ca ud ate nuc leus
36
DUDA ET AL.
AJNR : 1, January / February 1980
TABLE 1 : Clinical Data and Cranial CT Findings in Subacute Sclerosing Panencephalitis
Clinica l
Stage
[81
Di sease
Durati on
(M onths)
1
2
3
4
5
6
7
8
9
10
11
2
3
2
2
2
2
2
2
2
2
12
Case
No .
CT Data
VCR
Sulc i
Vi sible
Subarachnoid
Spac e
5
3
6
6
6
60
15
8
24
36
86
0.08
0.09
0.10
0.11
0.11
0.12
0 .13
0 .13
0 .13
0 .13
0 .19
No
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Enlarged
Normal
Enlarged
Enlarged
3
84
0.20
Yes
Enlarged
13
14
2
4
48
68
0 .26
0 .30
Yes
Yes
Enlarged
Enlarg ed
15
2
82
0 .3 1
Yes
Enlarged
Lesion Description
No lesions
No lesions
No lesions
No lesions
No lesions
No lesions
No lesions
Diminish ed density of left basal ganglia
Diminished density of ca ud ate nuclei
Focal atrophy of frontal lobes
Diffuse cerebral cortical atrophy with multifocal bifrontal
and right parietal , low density white matter lesions
Diffuse cerebral atrophy with multifocal parietal , low density white matter lesions
Diffuse cerebral atrophy; no white matter lesions
Profound , diffuse cerebral cortical atrophy; atrophic pons ;
focal diminished density of white matter of tempora l and
parietal lobes
Moderate ce rebral atrophy; multifocal diminished density
of centrum semiovale
No le.-VCR = ventric ul ocep halic ra tio of B anna. No rm al = 0 .08- 0 . 15 .
Fig . 1.-Case 11 , 17-year- old g irl wi th symptoms fo r 86 mo nth s. Focal
areas o f dimin ished densit y in para ventri cular frontal white matter and in
wh ite and gray matter o f right parieta l lobe . Diffu se co rti ca l atrophy .
Fig . 2. -Case 12 , 17-year-o ld g irl. Mild diffuse cortical atrophy and focal
areas of dimin ished density in central white matter.
and expressed as a rati o of th e inn er table diameter measured at
th e sa me level, th e ventric ulocep halic rati o of Bann a [10]. Th e
measurement s were mad e with a millim eter ru le on 4 :1 minificati on
transparenc ies . We also recorded th e vi sibility of cort ica l su lc i and
mad e subjec tive es tim ates of th e size of the subarac hn oid space
inc lu d in g th e c istern s, fi ssures , and sulci.
Results
Tab le 1 co mpares th e clinical data with the CT findings .
Th e CT findings were abnorma l in those cases following a
chro ni c co urse. Cases 1 -5 and 7 had rapidly progressive
disease and reached late stage 2 or stage 3 within a few
month s after onset. No les ion s were found in this group.
Cases 9. 10. and 12- 15 were ch roni cally progressive and
in so me th e disease had been quiescent for several months .
Th ese patients had diffuse cerebral atrophy and multifocal
low density lesions of white matter.
Varying degrees of morpho logic abnorma liti es typically
Fig . 3. - Case 15 , 1 2-year-o ld boy . Moderate diffuse corti ca l at rophy and
d im in ished paraventric ul ar densit y involving fronta l and pari eta l lo bes.
seen in the chroni c cases of subacute sclerosing panence phalitis were demonstrated. Figures 1- 3 show varying
degrees of cortical atrophy and multifocal low density lesions of the subcortical and periventricu lar white matter. A"
AJNR:1 , Jan uary / Febru ary 1980
Fig . 4 .atrophy .
SUBACUTE SCLEROSING PAN ENCEPHALITIS
37
Case 14 , 14-year-old boy . Extensive atrophy affecting both wh ite and gray matt er of cerebral hemispheres, especially of temporal lobes . Po ntine
lobes were randomly affected . Figure 4 shows th e most
extensive changes of atrophy in our series. Both cerebral
hemispheres were severe ly affected . Th e iemporal lobes in
parti c ular showed striking atrophy . The pons showed mild
atrophy.
Case 8 expe ri enced a rapidly progressive clinical course
but th e CT was abnormal, showing diminished density in th e
left basa l ganglia. Cases 6 and 11 were atypical in that they
experienced a rapidly progressive early c lini cal course followed by prolonged remission with remarkable recovery of
both intell ectual and motor functions . Both of these cases
were treated with an experimental antiviral agent, isoprinosine [11], before CT.
There was no correlation between clinical stage and the
location or severity of the brain lesions. No abnormal areas
of iodine contrast enhancement could be discerned.
Discussion
Subacute sclerosing panencephalitis (SSPE) is an uncommon disease with an incidence of 1: 1,000,000 in the United
States [12] and a possible male preponderance [8]. Onehalf of the patients have clinical measles before age 2 [12]
and c lin ical signs are usually manifest after a latent period
of 6 years [1 3]. Alth ough earlier reports indi cated th at most
patients died within 9 months [14], subsequent reports have
shown many cases with a chronic course of several years
[15, 16]. Although uncommon , spontaneous remissions do
occur; they most often begin during clini cal stage 2 [15] and
may last for years [17].
It is still unclear what circumstances cause the rare patient
with measles to experience this progressive, insidiou s slow
virus infection . Although the host lymphocytes are probably
immunologically competent [18], a measles-specifi c inhibitory substance that blocks expression of cellul ar immunity
has been suggested [19]. Although three patients in our
series (cases 2, 4, and 5) were immunized with live measles
vaccine, no increase of SSPE has been noted after mass
immunization in the United States [20].
The best proof of the SSPE diag nosis is recovery of
measles virus from brain tissue . However, diagnosis is usually firmly established by clin ical criteria incl uding a high
cerebrospinal fluid gamma globulin level, elevated serum
and cerebrosp inal fluid measles titers, and an abnormal
encephalograp hi c pattern of " suppression, burst " [8].
Care was taken in revi ewing our data to record all med ications, toxins, physical agents, or associated illnesses that
may cause CT findings to rese mbl e cerebral atrophy. Except
for case 1 5 (neurofibromatosis), no other chroni c diseases
or ste roid therapy was reco rded. The most common drug s
used were anticonvul sants, which are not known to produ ce
CT findings resembling atrop hy . Isoprinos in e [11] was admini stered to thi s patient group afte r c rani al CT sca ns in
cases 2 , 4, 5, 10, and 12-15 . Thi s age nt is not known to
produce atrophi c c hang es. A searc h for other co nc urrent
infections, particularly viral, fai led to impli cate oth er possibl e
agents for the CT find ings. M alnutrition and dehydration
were not present in our patients .
Th e pathology of SS PE is variable and depends to a larg e
extent on the rate of progression of the illness. Cases with
a rapidly fatal course may have primarily corti cal changes
with perivascular inflammatory infiltrates and with intranuc lear inclusion bodies in cortical neurons and oligodendrogli a. Thi s is the pathologic c hange initi ally described by
Dawso n [1] in 1933, and referred to as "subac ute inc lu sion
body ence ph aliti s." More c hron ic cases may show prominent subcorti cal white matte r lesio ns with periv asc ul ar infiltration by lymphocytes and plasma cell s, gliosis, and demye lin ation. Th ese pathologic c hanges, described by van
Bogaert [3] as " subacu te sclerosing leukoencephalitis, " are
often associated with neuronal loss and with astrocytic and
microgli al hyperpl asia in cerebral cortex, thalamu s , basal
gangli a, and brain stem. Cases with such wid espread
cha ng es gave rise to the term " subacute sc lerosing panencephaliti s " that is now commonly applied to all cases of
subac ute enceph aliti s related to rubeola viru s.
Known pathologic c hanges correlate quite well with CT
finding s. Cases with sho rt c lini cal hi storie s and a rap id ly
progressive course, in which pathologic c hang es might be
expected to be prim arily intracortical and subtl e (viral inclusions in neurons) , had normal o r minim ally abnormal CT
pattern s. With one exception, the eight cases with abnormal
CT findings had a c hroni c clinical course and would be
expected to show the patho logic changes of sclerosing
panencephalitis , in c luding cerebral cortical and subcortical
nuc lea r atrophy and gliosis and demye lination of the subco rtical white matter. The CT patterns of cerebral atrophy,
low density lesion s in white matter, and basal ganglia lesions
38
DUDA ET AL.
found in these cases reflect the ~xpected pathologic
changes. The presence of di screte lesions in the caudate
nuclei in two of th e patients [8, 9] is interesting in view of
the freq uent occurrence of clinical manifestations of basal
gang li a involvement in SSPE , including choreiform movements, dystonia, and parkinsonian tumor and rigidity [21].
The abnormal ventriculocephali c ratios noted in our patients indi cate ventric ul ar dilatation and are direct signs of
gene ralized atrophy. The co rti cal sulci and subarachnoid
space w ere appropri ately enlarged in those patients demonstratin g cerebral atrophy. The third ventricle was dilated
in all cases that demonstrated lateral ventricle dilatation .
The fourth ventricle was normal in all cases. The cerebellar
hem ispheres were normal in all cases exce pt 14 which
showed mild cerebell ar atrophy but profound cerebral atrophy . Case 14 is th e only case showing brainstem atrophy.
None of the CT scans of the SSPE patients exh ibited
abnorm al areas of contrast enhancement. The lack of enhanceme nt may be attributed to a lack of significant, acute
infl ammatory response.
The CT finding s of SSPE may resemble other diseases.
Multiple sc lerosis may show focal low density lesions in the
periventricular and subcortical white matter with or without
cerebral atrophy . Progressive multifocal leukoencephalopathy may di splay prominent focal or multifocal areas of
decreased attenuation of white matter, often with contrast
enh ancement [22]. Similarly the gender-linked adrenoleukod ystrophies associated with adrenal insufficiency commonly show exte nsive white matter low density lesions,
often accompanied by enhancement of the margins [23].
The dysmyelinating disorders tend to show a pattern of
diffu se low density of th e centrum semiovale without contrast enh ancement. These c hanges reflect the pathologic
findings of abnormal formation of myelin and lack,of inflammatory change. They are sufficiently distinct from SSPE to
avoid general confusion .
Other viral infections may be considered in the differential
diagnosis. However, only herpe s simplex encephalitis has
been well c haracterized by CT and it tends to produce
unilateral low density lesions of the temporal lobe, sometimes hemorrhag ic, and sometimes demonstrating streaked
contrast [24].
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