ORIGINAL ARTICLE

Magnetic Resonance Imaging Abnormalities in the Corpus
Callosum of a Patient With Neuropsychiatric Lupus
Brent Fogel, MD, PhD, Doris Cardenas, MD, and Bruce Ovbiagele, MD

Background: Systemic lupus erythematosus (SLE) is a multisystem
autoimmune disorder which can present with a variety of neurologic
and psychiatric complications. Currently, there are no consensus
neuroimaging findings associated with neuropsychiatric SLE.
Case Summary: We describe the unusual neuroimaging findings in
a patient with SLE and a history of epilepsy who presented to a
tertiary care emergency department with features of neuropsychiatric lupus, as well as recent seizures. Magnetic resonance imaging of
the brain revealed an isolated lesion with T2 signal hyperintensity
and restricted diffusion in the midline splenium of the corpus
callosum.
Conclusions: While establishing the precise etiology underlying the
clinical and radiographic observations in this case is difficult, several
possibilities are discussed, including acute ischemia and epileptic
sequelae. The location of the patient’s lesion in a region potentially
associated with pure psychotic disorders raises the possibility that
such a lesion may be sufficient to produce acute behavior changes
and psychotic features in certain patients.
Key Words: lupus, magnetic resonance imaging, corpus
callosum, splenium, psychosis
(The Neurologist 2006;12: 271–273)

S

ystemic lupus erythematosus (SLE) is a multisystem autoimmune disorder which can cause diverse neurologic
symptoms, including behavioral changes, psychosis, and encephalopathy.1,2 While the precise mechanisms behind these
complications are unclear, both direct and indirect immunemediated effects on the cerebral vasculature and the brain
itself have been implicated.2 Currently there are no consensus
neuroimaging findings associated with the neuropsychiatric
manifestations of SLE.1 Here, we describe a patient with SLE
and a history of epilepsy who presented with neuropsychiatric
lupus, characterized by behavioral changes and psychosis,
and was found to have an isolated lesion with increased T2
signal intensity and restricted diffusion in the midline sple-

From the Department of Neurology, UCLA Medical Center, Los Angeles,
California.
Reprints: Brent Fogel, MD, PhD, Department of Neurology, University of
California at Los Angeles, 710 Westwood Plaza, Los Angeles, CA
90095. E-mail: bfogel@ucla.edu.
Copyright © 2006 by Lippincott Williams & Wilkins
ISSN: 1074-7931/06/1205-0271
DOI: 10.1097/01.nrl.0000237119.00864.d7

The Neurologist • Volume 12, Number 5, September 2006

nium of the corpus callosum on magnetic resonance imaging
(MRI), a region potentially associated with pure psychotic
disorders.3

CASE REPORT
A 44-year-old Hispanic female with a history of SLE,
as well as a known seizure disorder, was brought to the
emergency room by her family following 2 days of behavioral changes and 1 generalized seizure. She had recently
discontinued all regular medications, including prednisone,
azathioprine, and phenytoin. On examination, the patient was
fully alert but had difficulties with all aspects of orientation,
including self, and was unable to follow complex commands.
Her behavior included agitation, combativeness, and overt
psychosis with disorganized thinking, visual hallucinations,
and paranoid delusions. The remainder of her neurologic
examination was nonfocal. She was afebrile. Computed tomography imaging of the brain showed an old left lacunar
infarct but no masses or hemorrhage. Lumbar puncture revealed a CSF opening pressure of 180 mm H2O, glucose 64
mg/dL, protein 36 mg/dL, 0 white blood cells, and a negative
gram stain. Her basic chemistries, liver enzymes, and complete blood count were normal. Partial thromboplastin time
and erythrocyte sedimentation rate were elevated at 116
seconds and 94 mm/h respectively. Phenytoin was undetectable but approximately 1 week prior had been mildly elevated
at 25 ␮g/mL. MRI of the brain performed approximately 24
hours following presentation revealed a focal hyperintensity
in the midline splenium of the corpus callosum on T2 and
fluid-attenuated inversion recovery (FLAIR) images (Fig. 1).
This lesion showed restricted diffusion on diffusion weighted
imaging (DWI) and was hypointense on apparent diffusion
coefficient (ADC) sequences (Fig. 1). There were no other
acute findings noted on MRI. Magnetic resonance angiography of the brain and neck was unremarkable. Transthoracic
echocardiogram showed no thrombus and a normal ejection
fraction. Electroencephalogram demonstrated diffuse slowing
but no epileptiform activity. Based on the overall clinical
presentation, the patient was diagnosed with neuropsychiatric
lupus using established criteria.1 Treatment was initiated with
intravenous corticosteroids, cyclophosphamide, and anticoagulation. Five days post-treatment, the patient was much improved, with full orientation, following 2-step commands,
and stable behavior without overt psychotic features. Subsequent neurologic examination showed no clear evidence of
hemispheric disconnection.

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Fogel et al

FIGURE 1. Acute focal lesion in the
midline splenium of the corpus callosum in a patient with neuropsychiatric
lupus. Restricted diffusion is noted on
(A) diffusion-weighted imaging with
hyperintensity on (B) fluid-attenuated
inversion recovery and (C) T2-weighted
imaging, but hypointensity on (D) apparent diffusion coefficient imaging.
The lesion is indicated by arrows.

DISCUSSION
Here we report an unusual focal lesion in the splenium
of the corpus callosum found on diffusion-weighted MRI in
a patient with neuropsychiatric lupus and a history of epilepsy. Establishing a unifying hypothesis for the precise
etiology underlying the clinical and radiographic observations in this case is difficult, given the unclear pathogenesis of
neuropsychiatric lupus, her comorbid epilepsy, and the variety of differential diagnoses for hyperintense lesions on T2
and DWI. For instance, although such imaging findings are
often consistent with acute ischemia, the location of the
lesion within the brain in our patient is atypical for infarction.
In general, the corpus callosum is quite resistant to ischemia
due to its high degree of vascularity and collateral flow from
the opposing circulation.4,5 Indeed, ischemic lesions in the
corpus callosum involving the splenium are most often associated with large posterior cerebral artery infarcts.4
Another pathophysiological consideration could be that
of an acute demyelinating process. Demyelinating disease
can produce similar hyperintense lesions, but these are not
typically seen this early after symptom onset and frequently
are not in isolation.5 Additionally, hyperintense T2-weighted
MRI involvement of the splenium can be seen unilaterally
with traumatic injury due to sheer forces or bilaterally in
Marchiafava-Bignami disease due to acute demyelination

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secondary to alcohol abuse5; however, this patient denied
recent trauma or excessive alcohol intake.
Hyperintense T2-weighted MRI splenial lesions have
been described in epileptic patients3,6–10 and have been speculated
to result from antiepileptic drug toxicity,7 rapid antiepileptic drug
withdrawal,8 or from the seizures themselves.3,6,9,10 DWI hyperintensity has also been described in 2 such patients following
seizures.10 The precise mechanism underlying these changes
remains unclear but perhaps may reflect an inherent sensitivity
of the splenium for either transient demyelination or focal edema
due to changes in ion transport or other metabolic processes.3,6 –10 Given the mildly elevated phenytoin level in our
patient followed by an abrupt discontinuation of this medication
and a history of recent seizures, we believe this may be the most
likely basis for the abnormal MRI findings observed. This
notwithstanding, it is interesting to note that in animal models,
immunofluorescence has demonstrated binding of anticardiolipin antibodies purified from SLE patient sera to brain tissue,
notably the corpus callosum.11 One intriguing possibility is that
SLE patients may have an inherently increased predisposition to
corpus callosal injury.
On a broader note, a recent study summarized the current
literature, examining 69 patients with splenial changes noted on
MRI and reporting that 60% of the patients showed altered
mental status, while 7% reported hallucinations, reflecting psy© 2006 Lippincott Williams & Wilkins

The Neurologist • Volume 12, Number 5, September 2006

chosis.3 The precise degree of association between the lesions
and psychosis is unclear, however, as psychiatric findings may
have been underreported in previously published cases.3 Furthermore, the specificity of the lesions for psychosis is also
unclear because, although all patients had splenial MRI changes,
many had additional acute MRI findings,3 which were not fully
detailed. Still, involvement of the corpus callosum has been implicated previously in pure psychotic disorders, most notably schizophrenia.3,12–14 Studies of schizophrenic patients have found
changes within the corpus callosum relative to normal controls
both pathologically and on MRI neuroimaging, including size
differences, decreased white matter density, and microstructural
changes, suggesting a component of interhemispheric disconnectivity may be involved in the pathogenesis of schizophrenia.3,12–14 A recent review by Shenton et al14 reports that of 27
MRI imaging studies specifically examining the corpus callosum, 63% detected abnormalities in schizophrenics. Many of
these studies did not fully examine the entire corpus callosum,
so the true incidence may be even greater.14 Complete agenesis
of the corpus callosum has also been noted in patients with
psychiatric disorders, including 2 children with behavioral problems and psychosis,15 as well as in a set of adult twins with
schizophrenia.16 Our patient was found to have a single isolated
midline splenial lesion on MRI, suggesting that such a lesion
may be sufficient to produce acute behavior changes and psychotic features in certain patients. Future studies should attempt
to further examine the relationship between isolated splenial
lesions and acute psychosis, particularly in patients with SLE
who may have a predisposition to corpus callosal injury.

ACKNOWLEDGMENT
The authors thank Drs Ron Cummings and Jeremy
Rudnick for helpful comments concerning this manuscript.
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