Dr. Ortiz is the Chairman of the Department of Radiology and Dr. Baadh is a Resident, in the Department of Radiology, Winthrop-University Hospital, Mineola, NY; and Dr. Lustrin is a Diagnostic Radiologist at NRAD Medical Associates, Lake Success, NY.
matter (WM) consists of myelinated axons that arise from either the
neuronal cell bodies in the cerebral cortex or the nuclei of deep gray
matter structures. In the brain, most of these axons are located
centrally, whereas in the spinal cord, they are positioned
peripherally.Any WM injury regardless of mechanism is associated with
inflammation and/or edema. The damaged axons lose their myelin and
subsequent gliosis results in volume loss. The term “white matter
disease” is an imaging reference to magnetic resonance imaging (MRI) or
computed tomography (CT) findings. These imaging findings reflect a
variety of pathologic processes that can be acute, subacute, or chronic
in nature and have concomitantly affected the WM of the brain and/or
Significance of white matter disease
appearance of white matter disease (WMD) on imaging studies is often
nonspecific. However, the imaging appearance of WMDon cross-sectional
imaging may aid in classification and diagnosis. Furthermore, the
presence of WMD on an imaging study may initiate additional imaging and
clinical investigation so that a working diagnosis can be established
and appropriate medical treatment initiated.The clinical presentation in
patients with WMD, in turn, is quite variable. Patients can be affected
at any age from childhood to adulthood.Patients can present with
significant acute neurologic deficits, gradual neurologic deterioration,
or no symptoms at all. Disease entities may result in monophasic
illness or may manifest in progressive or relapsing fashion.
Nevertheless, it is some sort of neurologic symptom or sign that prompts
imaging of the central nervous system with subsequent identification of
a WM abnormality within the brain and/or spinal cord.These
abnormalities are most elegantly depicted on MRI studies of these
structures. Occasionally, however, in situations where the patient’s
medical condition precludes MRI, WM lesions may indeed be seen, though
with less sensitivity, on CT studies of the brain (Figure 1). OnCT,
multiple sclerosis (MS) lesions present as small foci of decreased
attenuation, which may demonstrate enhancement following contrast
Classification of white matter disease
differential diagnosis of WMD is extensive (Table 1). WMD traditionally
has been divided into demyelinating and dysmyelinating processes. In
the former category, normally formed myelinated axons are adversely
affected with resultant destruction and loss of myelin. Dysmyelinating
processes reflect the sequelae of enzymatic deficiencies that lead to
abnormally myelinated axons and subsequent breakdown of the abnormal
myelin. An example of a few entities in this latter category include
adrenoleukodystrophy, metachromatic leukodystrophy, Canavan’s disease,
Alexander’s disease, Krabbe’s disease, and sudanophilic leukodystrophy.
In general, many of these metabolic disorders are most frequently
encountered in children and young adults. This article will focus on
demyelinating conditions that manifest as WMD on neuroimaging studies of
the craniospinal axis, as these entities overall are more common and
likely to be encountered in both inpatient and outpatient radiology
practice settings. An emphasis will be placed on clinical and imaging
findings that distinguish these entities, especially as they compare to
sclerosis (MS) is an inflammatory demyelinating disease, in which there
is autoimmune mediated injury to myelin sheaths surrounding axons in the
brain and spinal cord.1 Recent studies have proposed chronic
cerebrospinal venous insufficiency as a potential etiologic factor.
These studies have used color Doppler ultrasound to demonstrate
obstructive anomalies of extracranial veins, such as the internal
jugular and azygous along with venographic evidence of significant
stenoses in venous structures adjacent to the central nervous system.2 Additional
studies from other centers are forthcoming to further assess this
venous insufficiency model. MS is included as part of the working
diagnosis in a large and diverse set of neurologic presentations,
particularly in young adults in their 2nd through 4th decades of life.
Twenty percent of patients are > 40-years-old and 10% of patients are
< 20-years-old. An age of onset > 55-years-old is rare and in
this situation the possibility of an alternative diagnosis should be
considered.3 The estimated prevalence of MS is between 2 and
150 cases per 100,000 people, depending on racial/ethnic background and
geography.4 MS is defined as an idiopathic inflammatory
demyelinating disease of the central nervous system characterized by the
presence of focal plaques of demyelination with reactive scarring in
the cerebral and spinal cord WM (Figure 2).5 Cerebrospinal
fluid abnormalities, such as the presence of oligoclonal bands, are not
always present and are not necessarily specific to the diagnosis. The
clinical presentation and course in patients with MS is variable. To
better characterize a clinical course that includes clinical
exacerbations or relapses, periods of quiescence, and/or neurologic
progression, a consensus statement groups the disease course into 4
- Relapsing/remitting MS,
- Progressive relapsing MS,
- Secondary progressive MS, and
- Primary progressive MS.6
This classification is significant in that, in the United States,
medical treatments are presently approved by the Food and Drug
Administration only for relapsing/remitting MS.
conventional and advanced imaging techniques is the gold standard for
diagnosing and monitoring patients with suspected or clinically proven
MS. MRI is used to identify other WMD processes that may clinically
mimic MS. MRI findings are also used to provide prognostic information.
MRI is used not only to monitor a patient’s response to medical therapy
but also to assess for any complications that might be caused by a
treatment. All major clinical research trials that are attempting to
assess possible treatments for MS utilize MRI as a fundamental part of
the research design to report, quantify, and monitor treatment outcomes.
MS lesions are often located in a perivenular distribution.7 They
tend to have a predilection for areas of high perivenular density, such
as the periventricular and subcortical WM, the optic nerves and chiasm,
the cerebral and cerebellar peduncles, and the lateral columns of the
spinal cord.5 MRI is sensitive for detecting WM lesions in
the brain and spinal cord (Figure 3). Proton-density, T2-weighted and
fluid-attenuated inversion recovery (FLAIR) sequences are ideal for
detecting and characterizing MS plaques.8 On MRI, the typical
MS lesion presents as an ovoid or flame-shaped, hyperintense lesion on
the aforementioned sequences. Periventricular WM lesions often have a
perpendicular orientation relative to the margins of the lateral
ventricles (Figure 4). The lesions are of variable size and often > 3
mm in diameter. These lesions can manifest a dynamic imaging appearance
with respect to signal intensity and morphology over time, regardless
of treatment status (Figure 5).9 The MRI signal changes reflect the presence of inflammatory cells and foci of demyelination as well as foci of remyelination.5 Lesions
may also show a thin,less-T2-hyperintense rim along their periphery
(Figure 6). Rarely, as seen in patients with Balo’s concentric
sclerosis, prominent alternating bands of hyperintensity and
hypointensity may be observed in larger lesions. Small lesions do not
have mass effect, whereas large lesions can exert focal mass effect,
such as in young patients with Schilder’s type MS (Figure 7).10,11 On
T1-weighted images, MS lesions are either hypointense or isointense to
WM. WM lesions that show significant hypointensity are referred to as T1
“black holes;” their neuropathologic substrate consists of foci of
demyelination and axonal loss (Figure 3).12
can and do occur within gray matter structures, such as the cerebral
cortex, reflecting cortical demyelination, but these are not readily
identified with conventional imaging techniques. Contrast-enhanced MRI
is useful in the evaluation of patients with MS. Supposedly“active” MS
lesions that are newly formed and have a prominent inflammatory and
demyelinating component may undergo sufficient blood-brain barrier
disruption as to show enhancement with gadolinium contrast agents
(Figures 8-11). This contrast enhancement, however, like the underlying
lesion, is dynamic in that it is transient. Re-activated MS lesions may
also show contrast enhancement. The absence of contrast enhancement
should not mistakenly be equated with lesion quiescence or absence of
disease activity. In this case, the extent of inflammation,
demyelination, and underlying tissue injury might be below a threshold
that can be detected with current imaging approaches.13 Contrast
enhancement occurs less frequently in the progressive forms of MS. A
radiologically isolated syndrome has been described in patients who
present with incidental imaging findings that are suggestive of possible
MS. This condition is referred to as “pre-MS” because up to 33% of
these patients convert to a clinically isolated syndrome, or so called
first attack, within 5 years. These patients may have abnormal visual
evoked responses, spinal cord involvement, and contrast-enhancing
cerebral white matter plaques.14 The McDonald diagnostic
criteria for MS were recently revised in 2010 to allow for a more prompt
diagnosis of MS in patients who have experienced a clinically isolated
syndrome.15 For example, a clinical presentation of 2 or more
episodes of an inflammatory neurologic insult or attack, combined with
MRI evidence of 2 or more brain lesions, would suffice to make a
clinical diagnosis of MS based on the modified McDonald criteria. In
instances of either one prior attack or one brain lesion detected by
MRI, then additional data, such as evidence of dissemination of lesions
in space or time within the brain and/or spinal cord, are required to
confirm a diagnosis of MS.15
The application of
advanced MRI techniques in evaluating MS is still under investigation.
These techniques include magnetization transfer(MT), diffusion weighted
and diffusion tensor imaging (DWI and DTI), susceptibility-weighted
imaging, functional MRI (fMRI), and MR spectroscopy (MRS) (Figure 3).
For example, some studies have shown the MT changes precede the
subsequent development of enhancing MS lesions in what are initially
areas of normal-appearing white matter.5 Cerebral atrophy is a
significant imaging finding that occurs over time inpatients with MS.
Patients with MS show an average annual cerebral volume loss of 0.6% to
0.8% per year compared to healthy controls (0.3%per year) as shown on
volumetric MR studies.13 Initial reports have shown increased
levels of iron accumulation within the deep gray matter nuclei, such as
the basal ganglia, of patients with MS compared to normal control
subjects (Figure 12).16
The other key structures that
can be affected by demyelination include the optic nerves and spinal
cord. Indeed, optic neuritis can be the initial presentation as a
clinically isolated syndrome in patients who subsequently are diagnosed
with MS (Figure 13). Patients present with monocular visual loss and
focal areas of T2 signal change and optic nerve enlargement. Focal
enhancement of the lesion after contrast agentadministration is best
demonstrated with fat-suppressed, T1-weighted imaging and, when combined
with the clinical presentation, often distinguishes optic neuritis from
optic nerve-sheath neoplasms. Spinal cord involvement in MS often
occurs with brain involvement, but it can occur as an isolated finding.17 The
MS spinal cord lesion is located within the periphery of the spinal
cord and occupies less than half of the cross-sectional area of the
spinal cord (Figure 14). The lesions are focal and usually do not extend
for more than 1 or 2 vertebral body segments. MS spinal cord lesions
are isointense to hypointense on T1-weighted images, hyperintense on T2,
and show varying amounts and types of enhancement after contrast
administration. Spinal cord atrophy may also be observed, especially in
patients with chronic disease.
Acute disseminated encephalomyelitis (ADEM)
disseminated encephalomyelitis (ADEM) is an autoimmune disorder that
affects the white matter in the brain and spinal cord.18 This
is often a monophasic WMD process that occurs within a few weeks of a
prior viral or bacterial infection or vaccination. ADEM has an estimated
incidence of 0.8/100,000 population per year. Cerebrospinal fluid
analysis shows increased albumin and proteins with absent oligoclonal
bands. Oligoclonal bands are rarely present in the cerebrospinal fluid
and when observed, are transient. Gray matter structures,such as the
basal ganglia or cortex, may also be affected.19 Children are
most frequently affected, but ADEM may also be observed in adults.MRI
shows either multiple small or large flocculent T2 or FLAIR hyperintense
lesions within the subcortical WM (Figure 15). These lesions may show
patchy or partial peripheral enhancement. Unlike MS, gray matter
involvement is commonly seen with ADEM. ADEM, however, tends to spare
the corpus callosum and does not show the perivenular distribution seen
with MS. Spinal cord involvement in ADEM is often patchy, but it can be
quite extensive. ADEM is a self-limited process in the majority of cases
and follow-up imaging will show lesion stability or resolution in those
patients who go on to recover. ADEM, however, may cause permanent
neurologic deficits. Current treatments for ADEM include
anti-inflammatory or immunosuppressive medications. ADEM should be
suspected in a child that develops neurologic symptoms and WMD shortly
after an infection or vaccination.
Subacute sclerosing panencephalitis (SSPE)
sclerosing panencephalitis (SSPE) is a rare, measles-mediated
encephalitis associated with progressive neurologic deterioration and
death. This disease has a subacute course and is often seen in children
with prior measles infection. SSPE is rare in adults. Cerebrospinal
fluid analysis will show elevated antibody titers against measles and
elevated gamma globulin. The MR imaging appearance is one of asymmetric,
T2-hyperintense, nonenhancing lesions within the periventricular and
subcortical WM of the cerebral hemispheres (Figure 16).Corpus callosum
and deep gray matter involvement may be observed. Cerebral swelling may
be seen. Cerebral volume loss with reduced gray matter volume may be
observed in the frontal and temporal cortex.20 MRS may show normal to increased choline and myoinositol and decreased n-acetyl aspartase.21
optica, or Devic’s disease, is a unique idiopathic WM inflammatory
process in which there is an auto-antibody response against astrocytic
aquaporin 4. A highly specific serum marker, NMO-IgG, is identified in
60% of patients. Both optic nerve and spinal cord involvement are
observed in patients with Devic’s disease (Figure 17). The spinal cord
lesions have a prominent longitudinal extent and may also involve the
central-cord gray matter. T2-weighted images show expansile hyperintense
signal within at least 3 vertebral segments of the spinal cord and
increased T2 signal within the affected optic nerve. Both optic nerve
and spinal cord lesions tend to enhance in the acute phase of the
illness. The cerebral WM is spared or may show the presence of
nonspecific WM lesions, a key differentiating feature from multiple
sclerosis. The clinical presentation is monophasic and rapidly
disabling, with a subsequent relapsing disease process that is
associated with a poor prognosis. Rituximabtherapy, a treatment
employing a monoclonal antibody against CD20 B lymphocytes, has been
shown to potentially decrease the frequency of relapses as well as the
associated disability.22 Acute transverse myelitis (ATM) is
an idiopathic inflammatory disorder that affects the spinal cord in
adolescents and young adults.23 Patients may have experienced
a prior infectious event prior to presenting with ATM. Furthermore, MS
is eventually diagnosed in a small percentage of patients with ATM.
Patients typically present with motor deficits, autonomic dysfunction,
and a sensory disturbances. MR imaging shows involvement of > 2/3 of
the cross-sectional area of the spinal cord that extends for a least 3
or more vertebral segments. An extensive T2-hyperintense lesion, which
may be associated with a cord expansion that shows peripheral contrast
enhancement, is the most common imaging finding (Figure 18). Advanced
imaging techniques with DTI show decreased fractional anisotropy values
in both the affected spinal cord segment and in the adjacent distal
normal-appearing spinal cord in patients with ATM.24 With respect to spinal-cord imaging findings, there is overlap between ATM and NMO, and MS isolated to the spinal cord.
neuroborreliosis is a multisystem infectious disease that affects the
cerebral WM, cranial nerves, the cauda equina, eye,joints, heart, and
skin. The causative agent is a spirochete, Borrelia burgdorferi in the United States and Borrelia garinnii and afzelii in
Europe that is transmitted by a tick bite. There is usually a seasonal
pattern to exposure to these tick bites during the spring and summer in
endemic areas. An erythema migrans rash with a target-like appearance,
arthritis, and carditis are common clinical presentations. MRI
abnormalities in patients with Lyme disease are rare.25 When
present, MRI shows small nonspecific, T2-hyperintense periventricular WM
lesions that variably enhance (Figure 19). Unlike MS, cranial nerve,
cauda equine, or meningeal enhancement may be observed in Lyme disease.25,26 Early diagnosis is important as prompt treatment may reduce or prevent disease progression.
Progressive multifocal leukoencephalopathy (PML)
multifocal leukoencephalopathy (PML) is a demyelinating process that
results from infection with the John Cunningham (JC) virus of the
myelin-producing oligodendrocytes in patients that are immunosuppressed.
Immunocompromised patients that are affected include patients with
acquired immunodeficiency syndrome, organ transplant patients on
immunosuppression therapy, patients receiving chemotherapy, steroid
therapy, or treatment for multiple sclerosis. Patients with PML present
with progressive neurologic deterioration. The MRI findings include one
or more variable sized confluent, yet asymmetric, WM T2-signal
abnormalities that involve the subcortical WM, including the U-fibers,
and extend to the periventricular WM (Figure 20). Corpus callosum
involvement may be observed. PML usually shows no contrast enhancement
(Figure 21). When large confluent areas of WM involvement are seen, the
absence of mass effect is notable. In patients who are infected with the
human immunodeficiency virus (HIV), the clinical and imaging appearance
of PML may simulate that of HIV encephalitis. In HIV encephalopathy,
the white matter T2-signal abnormality may show a less discrete or a
fuzzy appearance with a diffuse periventricular predisposition and
relative sparing of the subcortical U fibers. Cerebral atrophy is common
in both PMLand HIV encephalitis. Advanced imaging techniques, such as
MT, show a decreased MT relaxation in PML compared to HIV
encephalitis.As with PML, mass effect and contrast enhancement are often
lacking. Contrast enhancement in HIV-positive patients receiving
antiretroviral therapy may be due to the immune reconstitution
inflammatory syndrome, which is attributed to an aberrant immune
response and is associated with worsening of a pre-existing disease.27
Central nervous system vasculitis
Central nervous system vasculitis may present with subcortical WM ischemic lesions in children and adults (Figure 22).28 The
additional involvement of deep gray matter structures such as the basal
ganglia or cortical gray matter may help to distinguish vasculitis from
otherWMD processes. Furthermore, acute lesions will show restricted
diffusion on DWI sequences. Central nervous system vasculitis may
require catheter angiography to show areas of vascular contour
irregularities or biopsy to confirm the diagnosis. Vasculitis may also
be associated with other systemic vasculitides such as systemic lupus
erythematosis and polyarteritis nodosa (Figure 23).
autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) is a progressive, hereditary, small vessel
angiopathy that affects young adults. The autosomal dominant NOTCH3
gene is located on chromosome 19.29 Patients present with
recurrent symptoms due to transient ischemic attacks or subcortical
stroke. As with vasculitis, the WMD involvement is that of T2
hyperintensity with restricted diffusion in acute ischemic lesions. Foci
of microscopic hemorrhage manifest as areas of hypointensity on
gradient echo and susceptibility-weighted images.29 The WMD
in CADASIL may be present prior to symptom onset. The anterior temporal
lobe WM and corpus callosum may also be affected, a finding that
distinguishes CADASIL from subcortical arteriosclerotic encephalopathy
(Figure 24). The latter condition is associated with hypertension.
Unlike other vasculitides, gray matter involvement is rare and catheter
angiography does not show vascular contour abnormalities. Perfusion
imaging will show decreased cerebral blood flow and volume in the areas
of signal abnormality. In elderly patients with extensive chronic
ischemic WMD and lacunes, it may be difficult to distinguish from
inflammatory conditions that affect the WM. Clinical parameters, such as
patient age and a history of hypertension, help to identify these
patients. Additionally, the absence of corpus callosum involvement,
perivenular inflammatory change and contrast enhancement, and the
presence of deep gray matter lacunar infarcts are more consistent with a
diagnosis of chronic white matter ischemic change in the elderly.
Susac’s syndrome is another microangiopathy that can present with WMD in adults in their 3rd to 5th decades of life.30 In
this condition, T2 hyperintense WM lesions are characteristically
present within the body of the corpus callosum in addition to the
subcortical WM, brainstem,and deep gray matter structures. Patients with
Susac’s syndrome present with a clinical triad of encephalopathy,
bilateral hearing loss and retinal artery branch occlusions. Other
vascular etiologies that may also involve the cerebral WM include
hypoxic encephalopathy and posterior reversible encephalopathy syndrome
(PRES). The clinical presentations in these patients and the imaging
findings, which may involve the gray matter structures in hypoxic
encephalopathy and the parieto-occipital lobes in PRES, readily
distinguishing these entities from more typicalWMD pathologic conditions
(Figures 25, 26). Hemorrhagic foci ranging from petechial hemorrhages
to sulcal hemorrhages to hematoma maybe seen in up to 15% of patients
with PRES, particularly those who have received bone marrow transplants
or are on undergoing systemic anticoagulation.31
therapy may be associated with WMD, as oligodendrocytes are very
sensitive to radiation. WM injury may be seen at any point in time
following radiation treatment to the brain for primary or metastatic
tumors.32 The extent of WM damage may vary from edema to
necrosis. Radiation necrosis may be focal or diffuse (Figure 27). The
subcortical U fibers are spared while the periventricular WM is
diffusely affected. In diffuse necrotizing leukoencephalopathy extensive
areas of WM injury are present (Figure 28). This may also be seen in
patients receiving chemotherapy. Increased T2-signal abnormality is
present in areas of WM edema and/or necrosis. T1-hypointense signal is
seen in areas of radiation necrosis. Peripheral, irregular or ring like
contrast enhancement may be indistinguishable from underlying
neoplasm.Advanced imaging techniques such as MRS show decreased NAA and
increased lactate and lipid peaks or decreased cerebral blood volume
with perfusion imaging. Radiation necrosis is hypometabolic on positron
emission tomography. Radiation necrosis should be considered in the
differential diagnosis of a new enhancing WM lesion remote to the
original treated lesion or if there is interval development of lesion
enhancement in what was initially a non-enhancing tumor, or if there is
corpus callosum or periventricular WM enhancement that caps the
Osmotic demyelination syndrome
Osmotic demyelination syndrome is a metabolic disorder that results from abrupt correction of serum sodium osmolality.33 This
rare condition is observed in chronic alcoholic patients, but may also
be seen in patients with liver failure, liver transplant patients being
treated with cyclosporine, burn victims and patients with prolonged
heavy use of diuretics. Rapid correction of hyponatremia in increments
> 12 mmol/L/d results in destruction of the myelin sheath. Affected
patients present with encephalopathy, spastic quadriplegia and/or
pseudobulbar palsy. WMD in this condition is characterized by
nonenhancing T2-signal hyperintensity within the central pons (Figure
29). Extrapontine sites of potential involvement within the brain
include the basal ganglia, capsular region, hippocampi, lateral
geniculate bodies and peripheral cortex. Lesions may be either
isointense or hypointense on T1-weighted sequences. Anecdotal reports
have shown restricted diffusion on DWI images in areas of acute
demyelination. Patients are treated with supportive care with a variable
prognosis, but few patients avoid permanent neurologic damage.
is another rare toxic metabolic disorder also seen in chronic
alcoholics and which primarily results in demyelination of the corpus
callosum (Figure 30). A vitamin B complex deficiency is thought to be
the cause of progressive laminar necrosis in the corpus callosum.34 WMD
may also occur in the anterior and posterior commissures, the
periventricular WM and the cerebellar peduncles. There is relative
sparing of the subcortical U fibers. Patients present with alteration of
mental status, seizures or cognitive deficits. T1-weighted images show
foci of decreased signal intensity within the affected WM. These areas
are hyperintense on T2-weighted and FLAIR images. The treatment for this
disease is limited and includes supportive therapy with vitamin B
complex replacement therapy.
Subacute combined degeneration (SCD)
condition that is associated with a vitamin B deficiency, in this case
B12, is subacute combined degeneration (SCD). Numerous etiologies may
result in B12 deficiency including malnutrition, prior surgeries of the
gastrointestinal tract such as ileal resection, deficiency of intrinsic
factor, malabsorption syndromes, Crohn’s disease, nitrous oxide abuse,
and HIV infection. In contradistinction to Marchiafava-Bignami
disease,SCD affects the posterior columns of the spinal cord.35 The
imaging findings consist of an inverted “V” shaped focus of T2
hyperintensity on axial images within the dorsal aspect of the spinal
cord with lateral greater than medial dorsal column involvement (Figure
31). A long continuous band of T2 signal abnormality is seen within the
cervical and thoracic portions of the spinal cord on sagittal images.
The lesion may be associated with spinal cord enlargement and mild
enhancement may be observed. Patients with SCD present with the
insidious onset of sensory disturbances, including paresthesias and
abnormal proprioception with ataxia. The clinical presentation and the
lack of cerebral WMD distinguish this entity fromMS, NMO, ATM and ADEM.
Diffuse axonal injury
axonal injury is another condition that may manifest with focal WM
lesions on imaging. These lesions reflect the sequelae of shearing
injury and are often found within the subcortical WM, the corpus
callosum and the brainstem. A clinical history of significant head
trauma along with the identification of hemorrhagic foci on
gradient-echo or susceptibility-weighted images helps to confirm this
WMD comprises a variety of
disorders that demonstrate overlap in MRI findings. MS is a common WMD
process that affects young adults.MS is a dynamic disease process with
respect to both clinical and imaging features. A better understanding of
demyelinating WMD entities with respect to their more common clinical
and imaging manifestations can assist in narrowing the differential
diagnosis and potentially suggesting the diagnosis in certain clinical
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