Marjo S. van der Knaap,
MD, PhD
Gerre Vermeulen
Frederik Barkhof, MD, PhD
Augustinus A. M. Hart, MSc
J. Gerard Loeber, PhD
Jan F. L. Weel, MD, PhD
Index terms:
Brain, diseases, 10.8721
Brain, MR, 10.12141
Brain, white matter, 10.2066
Infants, central nervous system,
10.8721
Magnetic resonance (MR), in infants
and children, 10.12141
Viruses, 10.2066
Published online
10.1148/radiol.2302021459
Radiology 2004; 230:529 –536
Abbreviations:
CMV = cytomegalovirus
PCR = polymerase chain reaction
1
From the Departments of Child Neu-
rology (M.S.v.d.K., G.V.) and Radiol-
ogy (F.B.), Vrije Universiteit Medical
Center, De Boelelaan 1117, 1081 HV
Amsterdam, the Netherlands; Depart-
ments of Clinical Epidemiology and
Biostatistics (A.A.M.H.) and Medical
Microbiology (J.F.L.W.), Academic
Medical Center, Amsterdam, the
Netherlands; and Diagnostic Labora-
tory for Infectious Diseases and Perina-
tal Screening, National Institute for
Public Health, Bilthoven, the Nether-
lands (J.G.L.). Received November 6,
2002; revision requested January 15,
2003; final revision received June 10;
accepted August 6. Address corre-
spondence to M.S.v.d.K. (e-mail:
ms.vanderknaap@vumc.nl).
Author contributions:
Guarantor of integrity of entire study,
M.S.v.d.K.; study concepts, M.S.v.d.K.,
A.A.M.H., J.F.L.W.; study design,
M.S.v.d.K., J.F.L.W.; literature re-
search, M.S.v.d.K., J.F.L.W.; clinical
studies, M.S.v.d.K., F.B.; experimen-
tal studies, G.V., J.F.L.W., J.G.L.; data
acquisition, M.S.v.d.K., G.V., F.B.,
J.G.L.; data analysis/interpretation,
M.S.v.d.K., J.F.L.W., F.B.; statistical
analysis, A.A.M.H.; manuscript prep-
aration, M.S.v.d.K., F.B., A.A.M.H.,
J.F.L.W.; manuscript definition of in-
tellectual content, M.S.v.d.K.; manu-
script editing and final version ap-
proval, M.S.v.d.K., F.B.; manuscript
revision/review, all authors
©
RSNA, 2004
Pattern of White Matter
Abnormalities at MR Imaging:
Use of Polymerase Chain
Reaction Testing of Guthrie
Cards to Link Pattern with
Congenital Cytomegalovirus
Infection
1
PURPOSE: To define a magnetic resonance (MR) imaging pattern suggestive of
congenital cytomegalovirus (CMV) infection by using polymerase chain reaction
(PCR) testing to detect CMV DNA in neonatal blood on Guthrie cards for validation.
MATERIALS AND METHODS: On the basis of findings in eight patients with
documented congenital CMV infection, the authors developed MR imaging inclu-
sion criteria, including multifocal lesions predominantly located in the deep parietal
white matter. If gyral abnormalities were present, white matter lesions were either
multifocal or diffuse. The criteria were applied to 152 patients with static leukoen-
cephalopathy of unknown etiology. Guthrie cards for 22 of the 43 patients fulfilling
the MR imaging criteria, 20 patients not fulfilling them, and 300 control subjects
were analyzed. Fisher exact testing was used to evaluate the association between
MR imaging characteristics and CMV status, and backward elimination linear dis-
criminant analysis was used to identify MR imaging characteristics predictive of CMV
infection in addition to the initial criteria.
RESULTS: PCR test results were positive in 12 of 22 patients suspected of having
congenital CMV infection, in no patient not suspected of having infection (P
.001), and in two of 300 control subjects (negative predictive value [NPV] of MR
imaging criteria, 100% [95% CI: 83%, 100%]; positive predictive value [PPV], 55%
[95% CI: 32%, 76%]). The most important additional MR imaging finding predict-
ing a positive PCR result was abnormality of the anterior part of the temporal lobe,
including abnormal white matter, cysts, and enlargement of inferior horns. Includ-
ing this finding in the MR imaging criteria enhanced the PPV (89%; 95% CI: 52%,
99%) at the expense of the NPV (88%; 95% CI: 72%, 97%).
CONCLUSION: In patients with static encephalopathy, an MR imaging pattern of
multifocal lesions predominantly involving deep parietal white matter, with or
without gyral abnormalities, is predictive of congenital CMV infection. When gyral
abnormalities are present, leukoencephalopathy may also be diffuse. The presence
of abnormalities in the anterior part of the temporal lobe increases the likelihood
that CMV infection is present.
©
RSNA, 2004
White matter disorders of unknown etiology constitute a considerable problem in pedi-
atric neurology (1,2). Children with neurologic deficits frequently are observed to have
white matter abnormalities at magnetic resonance (MR) imaging. These abnormalities are
Pediatric Imaging
529
R adiology