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▸ Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
jnnp-2013-307072).
Department of Neurology, CHU
Nîmes, Hôpital Caremeau,
Nîmes, France
Correspondence to
Dr Dimitri Renard, Department
of Neurology, CHU Nîmes,
Hôpital Caremeau, Place du
Pr Debré, 30029 Nîmes
Cedex 4, France;
dimitrirenard@hotmail.com
Received 22 October 2013
Revised 30 January 2014
Accepted 30 January 2014
Published Online First
21 February 2014
To cite: Renard D,
Castelnovo G, Campello C,
et al. J Neurol Neurosurg
Psychiatry 2014;85:
1041–1048.
Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072
REVIEW
An MRI review of acquired corpus callosum lesions
Dimitri Renard, Giovanni Castelnovo, Chantal Campello, Stephane Bouly,
Anne Le Floch, Eric Thouvenot, Anne Waconge, Guillaume Taieb
ABSTRACT
Lesions of the corpus callosum (CC) are seen in a
multitude of disorders including vascular diseases,
metabolic disorders, tumours, demyelinating diseases,
trauma and infections. In some diseases, CC involvement
is typical and sometimes isolated, while in other diseases
CC lesions are seen only occasionally in the presence of
other typical extra-callosal abnormalities. In this review,
we will mainly discuss the MRI characteristics of acquired
lesions involving the CC. Identification of the origin of the
CC lesion depends on the exact localisation of the lesion
(s) inside the CC, presence of other lesions seen outside
the CC, signal changes on different MRI sequences,
evolution over time of the radiological abnormalities,
history and clinical state of the patient, and other
radiological and non-radiological examinations.
INTRODUCTION
The corpus callosum (CC) is a large, densely
packed, white matter tract that connects both cere-
bral hemispheres, explaining the multitude of pos-
sible clinical signs and symptoms seen in CC
involvement. Absence of a clear neurological deficit
can be seen when the CC lesion is solitary and
small, in contrast to large, diffuse or multifocal CC
lesions often leading to severe neurological deficit.
Alien limb syndrome is typically seen with anterior
CC lesions, left agraphia, right constructional
apraxia and left tactile anomia in case of injury to
the body of the CC, and left hemialexia when the
splenium is involved.1–5 Briefly, the aetiology of
CC lesions can be divided into disorders typically
affecting the CC (often in an isolated manner; eg,
Marchiafava–Bignami disease (MBD), mild enceph-
alitis/encephalopathy with a reversible splenial
lesion (MERS)), disorders where the coexistence of
callosal and extra-callosal lesions is often present (eg,
multiple sclerosis (MS), trauma, leucodystrophy), and
disorders where CC involvement is only seen occa-
sionally together with typical extra-callosal abnormal-
ities (eg, Wernicke encephalopathy (WE)). MRI is a
powerful tool to analyse CC lesions. Because of the
anterior–posterior orientation of the CC, sagittal
MRI imaging is of special interest in patients with
CC abnormalities. T1-, T2-, T2*-weighted imaging,
fluid-attenuated inversion recovery (FLAIR) and dif-
fusion-weighted imaging (DWI)/apparent diffusion
coefficient (ADC) sequences together with
gadolinium-enhanced T1-weighted images are essen-
tial to analyse CC lesions. Axial, sagittal and coronal
images give information of the precise localisation of
the CC lesion.
Additional imaging techniques including mag-
netic resonance spectroscopy, perfusion-weighted
Cerebrovascular disease
MRI, positron emission tomography and single-
photon emission CT can sometimes be useful in the
diagnosis of these CC lesions.
VASCULAR LESIONS
Infarction
The large anterior part of the CC is supplied by
the pericallosal artery, a branch of the anterior cere-
bral artery, while the splenium is supplied by the
posterior pericallosal artery, a branch of the poster-
ior cerebral artery. The most common location of
CC infarction is the splenium (see online supple-
mentary figure S1). Infarctions are most often
central (ie, respecting the upper and lower margins)
in the CC and accompanied by infarction in other
brain areas supplied by the same artery. Because of
the bilateral arterial supply, most ischaemic CC
lesions are confined to one side although they may
cross the midline. Rare midline CC lesions are seen
in case of watershed infarction between both anter-
ior (eg, in case of occlusion of a common anterior
cerebral artery) or both posterior (eg, in case of
top-of-the-basilar infarction) cerebral arteries, or in
case of occlusion of a third small artery originating
from the anterior communicating artery as seen in
the majority of postmortem angiograms (see online
supplementary figure S2). Signal intensities and
radiological evolution are like those seen in classical
brain infarction. Gadolinium enhancement, often
peripheral, can be seen in the subacute phase of
ischaemic lesions. Lesions may become necrotic,
seen as a central FLAIR hypointensity surrounded
by FLAIR hyperintensity.
Ischaemic CC involvement can also be seen in
small vessel disease including cerebral autosomal
dominant arteriopathy with subcortical infarcts and
leucoencephalopathy (CADASIL), small vessel vas-
culitis, Susac syndrome, and autosomal dominant
hereditary cerebrovascular disease due to COL4A1
point mutations (figure 1, and see online supple-
mentary figures S3 and S4). In CADASIL, diffuse
bilateral (T2 and FLAIR hyperintense) leucoence-
phalopathy is usually observed, sometimes asso-
ciated with cerebral microbleeds.6 7 When
CADASIL-related leucoencephalopathy is less
severe, the external capsula and anterior part of the
temporal lobes are the most frequently involved
structures. Susac syndrome is a rare disorder affect-
ing the precapillary arterioles of the brain, retina
and cochlea leading to cerebral symptoms, branch
retinal artery occlusions, and visual and hearing
loss.8 The CC is almost always involved in Susac
syndrome, typically affecting the central CC
portion (with microinfarctions that are typically
small), together with ischaemic involvement of the
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Cerebrovascular disease
Figure 1 DWI sequences (A–C) showing multifocal lateralised corpus callosum (CC) involvement in a Susac patient. On sagittal FLAIR imaging (D),
a typical wedge-shaped lesion in the splenium extending from the roof of the CC (the so-called ‘icicle’) can be observed.
periventricular areas and often also the posterior fossa struc-
tures. When CC infarctions are larger, the so-called ‘snowball’
appearance can be seen. Sometimes, linear defects (‘spokes’) are
observed from the callosal–septal surface extending to the
superior margin of the CC or wedge-shaped lesions extending
from the roof of the CC (the so-called ‘icicles’). In the chronic
phase, lesions appear as holes (ie, as hypointensity on T1 and
FLAIR sequences), together with CC atrophy. COL4A1 point
mutations have been recently identified as a rare cause of an
autosomal dominant hereditary cerebrovascular disease, often
associated with systemic injury affecting eyes, kidney and
muscles.9 Other COL4A1-related cerebral manifestations
include asymptomatic porencephaly, diffuse white matter
lesions, intracerebral haemorrhage, transient ischaemic attack,
brain infarction, dilated perivascular spaces, silent microbleeds,
mental retardation, epilepsy, migraine with aura, dolichoid
carotid siphons and intracranial aneurysms.
Delayed posthypoxic leucoencephalopathy
Delayed posthypoxic leucoencephalopathy (DPL) has been
reported in patients with carbon monoxide poisoning, narcotic
overdose, myocardial infarction and other global cerebral
hypoxic events. DPL is often associated with other manifesta-
tions of posthypoxic brain injury including acute haemorrhagic
necrosis of the pallidum, arterial borderzone infarction or late
laminar necrosis.10 The proposed pathophysiological mechanism
postulates that prolonged moderate hypo-oxygenation in white
matter disrupts adenosine triphosphate-dependent enzymatic
pathways involved in myelin turnover which would result in
delayed demyelination. Another possible explanation is that oli-
gaemia restricted to white matter may result in delayed apop-
tosis of the oligodendrocytes.
The most frequent involved areas are the frontal and the par-
ietal white matter and the CC. Lesions in these areas are seen as
hyperintensity on T2 and FLAIR sequences, together with tran-
sient (lasting for up to several weeks) reduced diffusion on DWI
and ADC map, and usually without contrast enhancement (see
online supplementary figure S5). DPL lesions are transitory in a
portion of patients.
Haemorrhage
Rare cases of bleeding in the CC have been reported due to
anterior communicating artery or distal anterior cerebral artery
aneurysm, arteriovenous malformation or cavernoma (see online
supplementary figure S6). These, usually large, haemorrhagic
lesions are often associated with intraventricular haemorrhage.
Cavernous malformations often show calcification.
Susceptibility-weighted imaging (SWI) is more sensitive than
1042 Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072
T2*-weighted imaging in detecting cavernous malformations,
especially in multifocal/familial cases.11 Cavernous malforma-
tions are typically not enhanced on gadolinium-injected
T1-imaging, although minimal enhancement may be present.
Haemorrhagic CC lesions, most often small, can also be seen
secondary to trauma, haemorrhagic small vessel disease, infarc-
tion and brain tumour.
A rare cause of CC (and extra-CC) haemorrhages, most often
small and multiple, is extracorporeal membrane oxygenation
(ECMO), which occurs usually in association with infarction
and involvement of other brain areas (see online supplementary
figure S7).12 ECMO is used for severe respiratory or cardiac
failure unresponsive to conventional therapy and is associated
with a high mortality and morbidity. Neurological complications
occur more frequently when venoarterial ECMO is used com-
pared with venovenous ECMO. ECMO therapy may cause
hypoxia during cannulation, solid or air emboli during perfu-
sion, haemodynamic instability and bleeding. ECMO-related
cerebral haemorrhages may result from continuous heparin infu-
sion during ECMO and/or from haemorrhagic diathesis (an
adverse effect of ECMO).
DEMYELINATING LESIONS
Multiple sclerosis
The CC is frequently affected in MS, most characteristically
involving asymmetrically the inferior part of the CC, radiating
from the ventricular surface into the overlying CC, appearing as
T2 and FLAIR hyperintensity (figure 2). These so-called callosal–
septal interface lesions are highly specific for MS. Therefore, T2/
FLAIR-weighted sagittal MRI imaging is essential in the work-up
when MS is suspected. Acute lesions are isointense or mildly
hypointense on T1 sequences, often with ‘open-ring’ enhance-
ment after gadolinium injection. Rare cases of acute MS lesions
with transient reduced diffusion on diffusion-weighted imaging
have been described. When T1 hypointensity persists in the
chronic stage, these MS lesions are called ‘black hole’ on imaging.
Beside the CC, MS lesions commonly affect the periventricular
white matter (often presenting as ovoid or linear lesions) and the
posterior fossa (especially the cerebellar peduncles) and sometimes
also the cerebral cortex. Diffuse brain atrophy, which also affects
the CC, is typical in chronic MS, making the T2 hyperintense CC
lesions sometimes difficult to interpret, especially since these T2
lesions often become diffuse and confluent in long-standing MS
(see online supplementary figure S8).13
Acute disseminated encephalomyelitis
In acute disseminated encephalomyelitis (ADEM), radiological
features overlapping with MS are often observed although CC
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Figure 2 Sagittal T2 (A) and FLAIR
(B) imaging of two different multiple
sclerosis patients showing in the first
patient a callosal–septal interface
lesion in the anterior part of the
corpus callosum (CC) (A) and in the
second patient multifocal callosal–
septal interface lesions along the
entire CC (B).
and periventricular lesions are less frequent. CC lesions at the
callososeptal interface are usually not seen. In contrast, basal
ganglia lesions are more frequent in ADEM than in MS.
Gadolinium-enhanced T1 imaging typically shows enhancement
of all (or near all) lesions in ADEM, whereas in MS enhance-
ment is completely absent or seen in only some of the lesions.
Distinction between both entities is important since MS patients
seem to benefit from long-term treatment, while ADEM is most
often a monophasic postinfectious or postvaccination disorder
not requiring long-term treatment.
Neuromyelitis optica
Classically, neuromyeltis optica (NMO) was thought to show
any or only discrete brain MRI signal changes. However, recent
studies analysing systematically brain lesions in NMO showed
that these lesions are extremely frequent, although they present
different radiological characteristics (ie, more often diffuse, het-
erogeneous, cystic and with blurred margins) as compared with
MS.14 15 When present, the periventricular white matter is the
most frequently area involved followed by the CC (see online
supplementary figure S9). NMO-related CC lesions are typically
diffuse and heterogeneous; they principally involve the splenium
(more frequently than in MS), spreading from the lower to the
upper edges of the CC.14 15 The predominant inferior involve-
ment of the NMO-related CC lesions is probably explained by
the high expression of aquaporin-4 protein along the callosal
lower surface.
NON-DEMYELINATING INFLAMMATORY DISEASES
In non-demyelinating inflammatory diseases (eg, Sjögren syn-
drome, lupus erythematosis, sarcoidosis), CC lesions can be
often observed together with more frequent periventricular
white matter lesions. Both enhancing and non-enhancing lesions
have been described in these disorders, sometimes associated
with leptomeningeal involvement.
Chronic lymphocytic inflammation with pontine perivascular
enhancement responsive to steroids (CLIPPERS) is a recently
described CNS inflammatory syndrome. The most characteristic
lesions in CLIPPERS are multiple small, punctuate and curvilin-
ear gadolinium-enhancing lesions peppering the brainstem.
Associated lesions in the cerebellum, the spinal cord and the
cerebral hemispheres (including the CC) are relatively frequent
(see online supplementary figure S10).16 After corticoid treat-
ment, contrast-enhancing lesions typically improve dramatically,
at least transitory.
TRAUMA
Diffuse axonal injury
Diffuse axonal injury (DAI) typically involves the CC (with the
posterior CC part as most frequently involved CC area), mid-
brain (especially the dorsolateral portion) and the lobar white
Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072
Cerebrovascular disease
matter (most often at the grey–white matter junction). When
small, CC lesions are often unilateral and slightly eccentric to
the midline, whereas large, bilateral and symmetric lesions
sometimes involving the entire CC can also be seen (see online
supplementary figure S11). DIA is best seen on DWI and FLAIR
sequences as hyperintense signal, frequently associated with
haemorrhagic hypointense lesions on T2*-weighted images (and
even better seen on SWI sequences).17 When present, DAI
lesions tend to be multiple. On ADC map, lesions may be
hypointense indicating cytotoxic oedema. Traumatic CC lesions
are usually focal although diffuse CC lesions are sometimes
encountered. Small traumatic CC lesions are often eccentric
whereas large lesions most frequently involve the complete
extent of the CC in coronal sections. DAI is often associated
with other radiological manifestations of head trauma (including
epidural, subdural, subarachnoid or intraventricular haemor-
rhage, contusion). DAI lesions tend to reduce in number and
volume over time.18
NEOPLASTIC
Glioblastoma multiforme
Glioblastoma multiforme (GBM) commonly affects the CC as
the tumour progresses from one cerebral hemisphere to another
along the CC, giving sometimes the aspect of an asymmetrical
or symmetrical ‘butterfly glioblastoma’ (figure 3). GBM MRI
signal is typically heterogeneous, isointense to hypointense
(especially when necrosis is present) on T1 sequences, and
hyperintense on T2 and FLAIR imaging. Central necrosis, peri-
lesional vasogenic (T2/FLAIR/ADC hyperintense) oedema and
strong (solid, nodular, patchy or ‘closed-ring’) enhancement are
typical, and sometimes haemorrhage occurs inside the tumour.
Gliomatosis cerebri
In gliomatosis cerebri, diffuse white matter infiltration (best seen
as homogenous T2 and FLAIR hyperintensity, and hypointense
on T1) involving two or more lobes is seen with enlargement of
the involved structure. Absent (or minimal) enhancement on
gadolinium-injected T1-weighted imaging is typically seen.
Associated CC, basal ganglia and/or thalamic involvement are
often observed (see online supplementary figure S12).
Lymphoma
Lymphoma often involves the CC, periventricular white matter
and basal ganglia, with homogenous contrast enhancement in
absence of central necrosis. They appear isointense or hypoin-
tense on unenhanced T1 sequences while hyperintense on T2/
FLAIR imaging (see online supplementary figures S13 and S14).
In immunocompromised patients and rarely in non-
immunocompromised patients, contrast enhancement is rather
peripheral than homogeneous, or may be less evident or even
absent. Surrounding oedema as well as central necrosis may be
1043
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Cerebrovascular disease
Figure 3 Diffuse infiltration of the genu and the anterior part of the body of the corpus callosum is observed on sagittal FLAIR sequences (A) in a
patient with a gliobastoma multiforme. On gadolinium-enhanced T1-weighted imaging (sagittal view (B); coronal view (C); and axial view (D)),
central hypointense necrosis is seen with strong peripheral contrast enhancement in the callosal and frontal white matter giving an aspect of the
so-called ‘butterfly lesion’.
seen in HIV-related lymphoma. In contrast to glioblastoma,
there is less (or absent) peritumoural oedema, and necrosis and
haemorrhage are less common in lymphoma. Reduced diffusion
has been reported occasionally. Lymphoma often responds dra-
matically (and frequently disappear on MRI), but temporarily,
to steroid treatment and radiation therapy.
Other primary brain tumours
CC involvement can rarely be seen in other primary brain
tumours including pilocytic astrocytoma and germinoma.
Metastasis
Metastatic CC lesions are rare and most often seen in the pres-
ence of other metastatic brain lesions. Imaging characteristics
depends on the primary malignancy but usually present with
mass effect, surrounding oedema and contrast enhancement.
INFECTION
Progressive multifocal leucoencephalopathy
The JC virus-related progressive multifocal leucoencephalopathy
(PML) typically occurs in immunocompromised patients and
has a high mortality. These T2/FLAIR hyperintense and T1
hypointense lesions can be unifocal (especially in the early
stage) or multifocal, and typically involve the subcortical white
matter (involving also the CC in 10%–15% of cases) respecting
basal ganglia and the cortex.19 20 There is usually no mass
effect. Although usually absent faint contrast enhancement can
be observed at the periphery of the lesions. Patients surviving
PML typically show profound atrophy of the involved brain
structures (see online supplementary figure S15).
Encephalitis
Although not typical, CC involvement can be seen in some
cases of infectious (mainly viral) encephalitis. However, in
CMV encephalitis (frequently HIV/AIDS-related), periventricu-
lar lesions often also involving the CC are seen as T2/FLAIR
hyperintensities, frequently with reduced diffusion on diffusion-
weighted imaging and enhancement on gadolinium-enhanced
T1-weighted imaging.
Haemorrhagic changes can be observed in rare cases of infec-
tious (eg, due to influenza virus, EBV, VZV, HSV-6 or tickborne
infection) or postinfectious haemorrhagic encephalitis, some-
times referred to as Hurst leucoencephalitis.21 In the rare cases
of autopsy-proven acute haemorrhagic leucoencephalitis, exten-
sive asymmetrical demyelinating lesions are seen together with
foci of microhaemorrhages.
1044 Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072
Brain abscess
Brain abscesses commonly occur supratentorially at the grey–
white matter junction, with radiological characteristics varying
with the stage of abscess development. Reduced diffusion
(because of a high content of protein) on diffusion-weighted
imaging and (most often ring) enhancement on gadolinium-
enhanced T1-weighted imaging are typically observed. In some
rare cases of brain abscess, the CC is also involved.22
METABOLIC DISEASES
Marchiafava–Bignami disease
MBD is mainly reported in patients with chronic and severe
alcoholism and multiple vitamin deficiencies. MBD preferen-
tially affects the central and medial part of the CC, with the
splenium as the most frequently CC part involved. Often, the
entire CC or a large part of it is involved with a low signal on
T1 and high signal on T2/FLAIR, leading to necrosis and cavi-
tary lesions profoundly hypointense on T1 and FLAIR imaging
giving a ‘sandwich-like’ appearance (figure 4). In the acute
phase, reduced diffusion is often seen on diffusion-weighted
imaging. Contrast enhancement can be occasionally seen in the
acute phase, and sometimes slight haemorrhage can also occur
inside the lesion.23 Less frequently, other brain structures includ-
ing white matter tracts, cerebral cortex and middle cerebellar
peduncles may be involved in MBD.
Wernicke encephalopathy
WE typically affects periaqueductal grey matter, mamillary
bodies, hypothalamus, medial thalamus, perirolandic regions,
and less frequently cranial nerve nuclei, frontal and parietal
lobes and rarely the CC. It is best seen as hyperintensity on T2/
FLAIR sequences. Involved structures sometimes show enhance-
ment (especially in alcoholic WE patients) and/or reduced diffu-
sion in the acute phase. Haemorrhagic lesions can be seen in
catastrophic WE cases.
Osmotic demyelinating syndrome
The osmotic demyelinating syndrome is associated with any
kind of osmotic gradient changes (most commonly in rapid iat-
rogenic correction of hyponatriemia in patients with alcoholism,
chronic liver disease or malnutrition). It was formerly called
central pontine myelinolysis because of the frequent pontine
involvement, or extrapontine myelinolysis when other than
pontine lesions are present. Frequent sites of extrapontine loca-
lisations are the cerebellum, basal ganglia, thalamus, cerebral
white matter, hippocampus and the CC (especially the sple-
nium).24 The lesions are T2/FLAIR hyperintense and T1
hypointense in the acute phase, often resolving after the acute
phase. Haemorrhage and contrast enhancement are uncommon.
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Cerebrovascular disease

Figure 4 In a patient with Marchiafava–Bignami disease in the subacute phase, a diffuse symmetrical splenial lesion is present, seen as
hypodensity on CT (A), hypointensity on T1 (B) and hyperintensity on FLAIR (axial view (C); sagittal view (D)) sequences, with reduced diffusion
(hyperintensity on DWI (E) and hypointensity on ADC map (F)) on diffusion-weighted imaging. In the chronic phase, a central splenial midline corpus
callosum (CC) lesion is seen (and to a lesser degree also in the body of the CC) as hypointensity on both axial FLAIR (G) and sagittal T1-weighted
(H) imaging.

Lesions may occur with a certain delay after the onset of clinical
symptoms or may even be seen in absence of clinical
abnormalities.
TRANSIENT LESION OF THE SPLENIUM
A transient (most often splenial) CC lesion can be seen in the
so-called MERS. Frequently, an isolated lesion in the splenium is
seen (figure 5). Associated involvement of the entire CC, sym-
metrical white matter, caudal nucleus, putamen and/or thalami is
rarely encountered (see online supplementary figure S16).
Possible mechanisms in MERS include intramyelinic oedema,
dysfunction of cerebral blood flow autoregulation, and influx of
inflammatory cells and macromolecules and related cytotoxic
oedema. Risk factors for MERS are antiepileptic drugs, corticoid
treatment, immunoglobulin therapy, mild hyponatremia and
encephalitis. The transient round or ovoid lesion of the central
splenium is typically T2 and FLAIR hyperintense, T1 hypoin-
tense, with reduced diffusion on diffusion-weighted imaging, in

Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072 1045

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Cerebrovascular disease
Figure 5 MRI showing an ovoid symmetrical midline lesion in the central part of the splenium, hyperintense on T2 (B), FLAIR (C) and DWI image (D),
and hypointense on T1-weighted images (A) and ADC map (E). Control MRI 6 weeks later shows complete disappearance of the splenial lesion (F–J).
the absence of contrast enhancement. These reversible splenial
lesions, with similar signal abnormalities as seen in MERS, are
sometimes also encountered in cases with altitude sickness and
hypoglycaemia (see online supplementary figure S17).25 26
REVERSIBLE POSTERIOR LEUCOENCEPHALOPATHY
SYNDROME
Risk factors for reversible posterior leucoencephalopathy syn-
drome (RPLS) include immunosuppressive and cytotoxic agents,
hypertension, eclampsia and metabolic abnormalities. The
common clinical features of RPLS are headache, decreased alert-
ness, vomiting, seizures and visuoperceptual disturbances. Brain
imaging typically shows bilateral white matter lesions in the
occipital and posterior parietal lobes. Watershed areas between
middle and posterior cerebral arteries are frequently involved.
However, associated involvement of grey matter and other
regions of the brain including frontal and temporal lobes, brain-
stem, cerebellum, basal ganglia, thalamus, and CC is frequently
seen (see online supplementary figure S18).
Characteristics on diffusion-weighted images are indicative
for vasogenic oedema. Lesions are isointense or slightly hyperin-
tense on DWI, hyperintense on T2, FLAIR, and ADC
sequences, and isointense to hypointense areas on T1-weighted
images. Because of the suppression of the subarachnoid CSF
signal, FLAIR sequences are of special interest to detect cortical
abnormalities. ADC values seem to be more sensitive to show
brain abnormalities than conventional T2 and FLAIR images.27
Associated infarction (in areas of massive oedema, elevated
tissue perfusion pressure leads to decreased cerebral blood flow
and ischaemia), haemorrhage (especially when RPLS is related
to hypertension) and/or gadolinium enhancement are sometimes
seen and associated with poorer outcome. In case of infarction,
affected regions show highly increased signal on DWI, and pseu-
donormalised or decreased signal on ADC sequences. In uncom-
plicated patients, regression (at least partially) of radiological
abnormalities is typically seen after discontinuation of offending
drug and treatment of elevated blood pressure.
LEUCODYSTROPHY
Diffuse white matter abnormalities (including associated CC
involvement) is often seen in hereditary leucodystrophies. The
part of the CC affected most frequently corresponds to the part
1046 Renard D, et al. J Neurol Neurosurg Psychiatry 2014;85:1041–1048. doi:10.1136/jnnp-2013-307072
of the cerebral white matter involved. Since leucoencephalopa-
thy is usually diffuse, signal abnormalities are often observed
along the entire CC. Lesions are typically hypointense on T1
and hyperintense on T2/FLAIR imaging, in the absence of con-
trast enhancement. Rare cases with contrast enhancement have
been described.28
RADIATION-INDUCED LEUCOENCEPHALOPATHY
Radiation-induced leucoencephalopathy (RIL) is most often a
late and delayed effect of radiation therapy, occurring months
or years after radiation and frequently leading to irreversible
neurological deficit. Neurological and radiological abnormalities
depend on different factors including the volume of irradiated
brain, cumulative dose of radiation administered, (fractionated)
protocol followed and age of the patient. In whole brain radi-
ation in particular, diffuse white matter involvement, which
often includes the CC, can be observed with frequently asso-
ciated cognitive deficit. These white matter lesions are best
detected on T2 and FLAIR sequences as hyperintense signal
sparing the U-fibres, involving the brain bilaterally and symmet-
rically in case of whole brain radiation (see online supplemen-
tary figure S19). RIL lesions most typically do not show mass
effect nor enhance after gadolinium administration (in contrast
to what is most often seen in tumour relapse or radiation necro-
sis), and are permanent.
TOXIC LEUCOENCEPHALOPATHY
A multitude of agents, including immunosuppressive drugs, anti-
neoplastic agents, antimicrobial medication, drugs of abuse and
environmental toxins, may lead to toxic leucoencephalopathy.
Since toxic leucoencephalopathy principally involves the white
matter of both hemispheres diffusely, the CC is also frequently
affected. Lesions are often bilateral and relatively symmetrical,
seen as T2 and FLAIR hyperintensity and T1 hypointensity, typ-
ically without contrast enhancement or haemorrhage (see online
supplementary figure S20).
WALLERIAN DEGENERATION
Chronic unilateral or bilateral cerebral hemispherical lesion
often lead to atrophy or the related part of the CC. MRI typic-
ally shows diffuse hyperintensity on T2 and FLAIR sequences,
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Cerebrovascular disease

Table 1 List of the most typical localisations of CC lesions in Table 3 List of the most typical signal changes of corpus
different diseases with frequent CC involvement callosum lesions on different MRI sequences
Midline Paramedian/assymetrical Diffuse symmetrical Diffuse reduced Hypointensity on GRE Gadolinium
lesion lesion lesion diffusion on ADC map sequences enhancement

MBD Haemorrhage Leucodystrophy DPL Haemorrhage Lymphoma

MERS GBM RIL MERS DAI Abscess
MS Lymphoma DPL DAI Infarction Acute MS lesion
Infarction GC Toxic leucoencephalopathy Infarction GBM Infarction
PML DAI Abscess (MBD)
DAI Wallerian degeneration Acute MS lesion (MBD)
Wallerian degeneration MERS (MBD)
MS DAI, diffuse axonal injury; DPL, delayed posthypoxic leucoencephalopathy; GBM,
Infarction glioblastoma multiforme; GRE, gradient-echo-weighted imaging; MBD, Marchiafava–
Bignami disease; MERS, mild encephalitis/encephalopathy with a reversible splenial
CC, corpus callosum; DAI, diffuse axonal injury; DPL, delayed posthypoxic lesion; MS, multiple sclerosis.
leucoencephalopathy; GBM, glioblastoma multiforme; GC, gliomatosis cerebri; MBD,
Marchiafava–Bignami disease; MERS, mild encephalitis/encephalopathy with a
reversible splenial lesion; MS, multiple sclerosis; PML, progressive multifocal
leucoencephalopathy; RIL, radiation-induced leucoencephalopathy.
INBORN ERRORS
Although inborn errors (like embryological callosal malforma-
tions, dilated perivascular Virchow–Robin spaces and lipoma)
especially of the inferior part of the CC (see online supplemen- are not discussed in this review, we want to mention only
tary figures S21 and S22). lipomas since these lesions are often incidentally encountered.
Lipomas are considered as developmental lesions of the CNS,
HYDROCEPHALUS typically asymptomatic, occurring most often in the region of
In chronic hydrocephalus, CC lesions generated by the disease the CC and the pericallosal cistern. Lesions are well circum-
itself or by its treatment (drainage or overdrainage) can be scribed and homogenous, hyperintense on both T1- and
observed and they usually involve the midline of the superior T2-weighted sequences, and disappearing on fat-suppressed
CC part. sequences (see online supplementary figure S23).

BRAIN SAGGING CONCLUSIONS

Brain sagging can be seen in patients with intracranial hypoten- Identification of the origin of the CC lesion depends on their
sion, mainly associated with orthostatic headache and pachyme- exact localisation within the lesion(s) inside the CC (eg, midline
ningeal gadolinium enhancement, and sometimes in patients lesion, paramedian–assymetrical lesion, diffuse symmetrical
without headache and without pachymeningeal gadolinium lesion), volume (eg, focal delineated vs diffuse lesions) of the
enhancement presenting with progressive behaviour and cogni- lesions and signal changes they produce on different MRI
tive changes mimicking behavioural variant frontotemporal sequences.
dementia: the so-called frontotemporal brain sagging syn- Tables 1–3 and online supplementary figures S24–S26 show
drome.29 In brain sagging, transtentoral herniation of medial lesion characteristics in different diseases with frequent CC
temporal lobe structures and CC (especially the posterior part) involvement depending on the localisation of the CC lesion,
are seen together with brainstem swelling and low-lying cerebel- lesion volume and MRI characteristics.
lar tonsils. Signal changes of the CC are usually absent in brain
sagging. Acknowledgements We would like to thank Dr Mariella Lomma (BESPIM, Nîmes
University Hospital) for proofreading the paper.
Contributors All the authors contributed to the following: (1) conception and
design, acquisition of data, or analysis and interpretation of data; (2) drafting the
Table 2 List of the most typical volumetric characteristics of article or revising it critically for important intellectual content; (3) final approval of
different corpus callosum lesions the version to be published.
Focal delineated lesion Diffuse lesion Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
Infarction GC
Haemorrhage Leucodystrophy
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An MRI review of acquired corpus callosum

lesions
Dimitri Renard, Giovanni Castelnovo, Chantal Campello, Stephane Bouly,
Anne Le Floch, Eric Thouvenot, Anne Waconge and Guillaume Taieb

J Neurol Neurosurg Psychiatry 2014 85: 1041-1048 originally published

online February 21, 2014
doi: 10.1136/jnnp-2013-307072

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