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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2745_Библиотеки_им_академика_М_И_Перельмана
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In a longitudinal study of patients with MS who presented
with an inflammatory myelitis, a high number of cord lesions
at baseline predicted worse clinical outcome and a higher
number of relapses. 41 Although the relationship between
spinal cord pathology and disease progression in MS is not
completely understood, overall, extensive spinal cord
abnormalities at presentation seem to confer an unfavorable
prognosis.
41
Cortical Lesions
Traditionally, MS has been considered a demyelinating white
matter disease, but a number of pathologic studies have
documented significant involvement of the gray matter in the
deep nuclei and the cortex.
2,8
Although cortical lesions begin
in the earliest stages of MS, they can be missed up to 95% of
the time on conventional MRI. 46 DIR allows for better
detection of cortical lesions by nulling the signal from the CSF
and white matter.
46,47
PSIR is a T1-weighted sequence with
higher signal to noise ratio, improved intensity, and gray-white
matter contrast that has been shown to improve cortical lesion
detection and classification.
33,34,48
With the use of advanced
MRI techniques, such as DIR and PSIR, cortical lesions have
been detected in up to 36% of patients with CIS and 97% of
patients with MS.
33,34,38
In addition, in accordance to the newly
revised 2017 McDonald criteria, 12 cortical lesions can now be
used in fulfilling MRI criteria for DIS.
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FIGURE 4.6 (A) Axial FLAIR (fluid attenuated inversion
recovery) sequence showing “typical” multiple sclerosis (MS)
lesions adjacent to the ventricles and involving the deep white
matter compared with (B) axial FLAIR sequence showing
punctate hyperintensities scattered throughout the subcortical
and deep white matter.
Histopathological and MRI studies show that gray matter
damage becomes increasingly prominent with disease
progression due to the accumulation of focal demyelinating
cortical lesions, meningeal inflammation, neuronal injury, and
Wallerian degeneration. 12 Over time, these degenerative
changes will result in appreciable atrophy of gray matter.
49
Because cortical lesions can represent a substantial component
of an individual’s total disease burden, it has been
hypothesized that cortical lesions contribute to disability not
accounted for by T2-weighted lesion volume.
38,50
Moreover, in
patients with CIS, the presence of cortical lesions correlates
with a higher risk of conversion to clinically definite MS.
51
Cross-sectional and longitudinal studies have shown
correlations between the number and/or volume of cortical
lesions and cognitive or physical impairment in MS. 51 A
recent study of 42 patients with MS reported that patients with
DIR-hyperintense cortical lesions showed significant global
cortical thinning and episodic memory deficits. 51 Similarly,
correlations were found between PSIR lesions and cortical
volume and PSIR and symbol digit modalities test score (a
cognitive component of the MS functional composite).
34
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Although DIR and PSIR offers high sensitivity, specificity, and
accuracy for the detection of gray matter lesions, these
techniques have not been adopted as part of everyday clinical
practice.
CNS Atrophy
Brain atrophy is evident on visual inspection of MRI scans of
patients through all stages of MS, from CIS to relapsingremitting, secondary progressive, and primary progressive
(PP) disease, and is more pronounced in the latter groups.
52
Postmortem histopathological studies have shown that CNS
atrophy predominantly results from axonal loss and neuronal
shrinkage and is largely independent of demyelination.
53
Brain atrophy is the most accepted imaging biomarker of
neurodegeneration and progression of disability in MS. When
present early in the disease, brain atrophy can predict rapid
disability progression. 54 Whole brain atrophy has been shown
to correlate with cognitive dysfunction and mood disturbances,
and measuring atrophy progression can provide clinically
relevant information.
1,52,54,55
Patients with worsening disability
have been shown to develop greater brain atrophy compared
with those who are clinically stable. 56 In clinically stable and
untreated patients with MS, brain volume loss occurs at a rate
of about 0.5% to 1% per year, compared with 0.1% to 0.3%
per year for healthy controls.
5,43,57
Patients with CIS who
convert to clinically definite MS compared with those who do
not typically have more pronounced brain atrophy.
21
Gray matter atrophy is more pronounced in the deep gray
matter nuclei than in the neocortical areas but can also occur in
the thalamus, hippocampus, and cerebellum. 52 Within the
brain, thalamic volume seems to be decreased even in patients
with radiologically isolated syndrome (RIS). Thalamic atrophy
has been shown to predict progression to clinically definite
MS in patients who have had a single attack. 44 Corpus callosal
atrophy is a key factor in cognitive impairment, 58 and
hippocampal atrophy has been associated with impairment in
memory encoding and retrieval. 57 The relationship between
spinal cord atrophy and clinical disability is also strong. 41 In a
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prospective study of patients with PPMS, increased spinal cord
atrophy over the first 2 years predicted worse outcome at 5year follow-up.
41
Quantification of brain volume on early scans provides
prognostic measures of clinical status not only for long-term
follow-up but also for short-term decline. 1 However, atrophy
rates can be confounded by a number of influences, such as
response to treatment, pseudoatrophy effects, genetics, and
vascular risk factors. 38 There are currently several
postprocessing and at-scanner methods to quantify wholebrain atrophy, although each may provide slightly different
results. 59 Intertechnique variability is high, 53 and, thus far,
large-scale trials have not been conducted to determine
validity for a given measure. 45 At present, MRI atrophy
metrics are not routinely used for diagnostic or prognostic
purposes. 59 Efforts are currently underway to create a
standardized protocol for image acquisition to allow for
incorporation of brain atrophy quantification into clinical
practice.
Central Vein Sign
Pathological studies have reported the presence of central
vessels in MS lesions for many years. 44 CNS infiltration of
mononuclear cells from peripheral blood develop around
venules and cause white matter lesions in MS. 41 With the
development of susceptibility-weighted imaging, which takes
advantage of the T2-shortening effect of deoxyhemoglobin in
venous blood (resulting in T2 hypointensity), the physical
relationship between white mater lesions and venules can now
be visualized. 45 The venocentric distribution of lesions, also
termed the “central vein sign,” has been observed across all
MS clinical phenotypes. 60 Data from studies conducted with
3.0 and 7.0 T MRI scanners suggest that the high frequency of
perivenular lesions is pathologically specific to MS, and
therefore, the central vein sign is an important candidate for
improving MRI diagnostic criteria and for reducing the rate of
misdiagnosis. 60 One small prospective study of 22 patients
with CIS who underwent a T2-weighted MRI scan found that
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all patients who eventually received a diagnosis of MS within
a median follow-up period of 26 months had a central vein
sign in >40% of brain lesions at baseline. 61 Those whose
condition was not diagnosed as MS had a central vein sign in
<40% of brain lesions at baseline. In this patient group, the
central vein sign had a 100% positive and negative predictive
value for a diagnosis of MS, However, given the small sample
size, additional large prospective multicenter trials are needed
to evaluate the clinical predictive value of the central vein sign
in the diagnosis of MS.
MRI as a Measure of Cognitive Function
Cognitive impairment in MS has an estimated prevalence of
43% to 70% and can become evident in the earliest stages of
the disease. 58 The most affected cognitive domains are
information-processing speed, working memory, complex
attention, executive functions, verbal fluency, and verbal and
visuospatial learning and memory. 62 The accumulation of
cognitive impairment is widely used as a predictor of
conversion to clinically definite MS, disability progression,
treatment compliance, depression, and low quality of life.
57
Cognitive dysfunction can, however, be subtle and require
dedicated neuropsychological testing to be detected. 52 Recent
efforts have highlighted the importance of evaluating the
dynamics of cognition throughout the disease course.
8
The most commonly used global MRI metrics for cognitive
dysfunction in MS are volumes of the whole brain, gray
matter, white matter, and white matter lesion burden. 52 Of
these tissue fractions, cognitive impairment is most often
associated with gray matter atrophy and lesion accumulation,
51
although correlations are weak. Two-dimensional MRI
markers, such as third ventricle width, bicaudate ratio, and
corpus callosal surface and index, have also been related to
cognitive impairment in MS. 62 Other regions of interest
include subcortical structures, such as the corpus callosum,
thalamus, hippocampus, putamen, caudate nucleus,
cerebellum, and cingulate gyrus, which have all been
associated with cognitive function in MS.
52,53,63
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Available data suggest that focal white matter lesions play a
role in cognition, but the overall effect of T2 lesions on MSrelated cognitive impairment is limited. 45 The impact of white
matter damage on cognition may be mediated by a disruption
of crucial tracts or interference with specific functional nodes.
62
Therefore, the location of lesions in critical brain areas
appears to be important and, in this context, the improved
capability to detect cortical lesions is likely to provide
additional pieces of information. 23 Correlations between
various brain areas and cognition currently remain weak, and
additional studies, possibly evaluating tract-specific changes,
might be needed. Currently, normalized brain volume and
lesion burden are mainly investigated in clinical trials as an
important indirect predictor of cognitive outcome.
57
Diagnostic Utility of Conventional MRI
in Multiple Sclerosis
Despite the sensitivity of conventional MRI for the
identification of focal white matter lesions in MS, there is a
discrepancy between the white matter disease burden and
clinical measures of physical disability and cognitive
impairment.
23,45
This discrepancy is largely secondary to the
intrinsic failure of conventional MRI to detect cortical lesions,
as well other diffuse structural, metabolic, and functional
abnormalities known to be present in the normal-appearing
gray and white matter.
5,45
These limitations further decrease
the specificity of MRI to the heterogeneous pathological
substrates of the disease.
MRI scanners with high-field strengths (3.0 T and greater)
may improve the early diagnosis of MS by increasing the
sensitivity and specificity for the detection of enhancing and
nonenhancing white matter lesions compared with 1.5-T
scanners.
6,20,42,64
Total lesion counts can be up to 45% higher
on high-field scanners compared with a 1.5 T scanner. 1 More
recently, ultrahigh-field MRI strengths (7.0 T) have begun to
help further elucidate our understanding of the underlying
pathophysiologic mechanisms in MS. 65 However, because
ultrahigh-field MRI is currently limited in widespread
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adoption owing to a lack of standardized protocols and large,
well-controlled trials, 3.0-T MRI systems continue to be the
most important paraclinical tool available in diagnosing and
monitoring MS.
MRI in Clinically Isolated Syndrome
CIS is defined as the first clinical episode suggestive of
demyelination or MS, which persists for at least 24 hours and
occurs in the absence of fever, infection, or encephalopathy.
16,19,38
Symptoms usually develop over the course of hours to
days and gradually remit over the ensuing weeks to months,
although remission may not be complete in all cases.
13
For patients presenting with CIS, the risk of conversion to MS
is greater in those with abnormal T2-weighted imaging (>1 T2
lesion). 1 Patients with CIS will have abnormal T2 scans
approximately 50% to 70% of the time. 63 Of those with an
abnormal baseline MRI, 82% to 88% will convert to MS,
compared with 19% to 21% of those with a normal baseline
scan. 63 In various studies, the 10- to 20-year likelihood of
developing MS for patients with CIS and MRI lesions
characteristic of MS ranges from 60% to 80%. 66 In addition,
recent studies have shown that asymptomatic spinal cord
lesions in patients with CIS confer increased risk of
conversion to clinically definite MS.
2,43
All patients with CIS should have neuroimaging of the brain
and spinal cord with a contrast-enhanced MRI to determine the
risk of progression to clinically definite MS and potentially
expedite treatment initiation with the goal of reducing future
morbidity.
MRI in Radiologically Isolated Syndrome
The term radiologically isolated syndrome (RIS) refers to the
incidental detection of radiological findings highly suggestive
of MS in the absence of clinical signs and symptoms of CNS
demyelination. 50 The MAGNIMS collaborative research
network published new recommendations in 2016 to upgrade
the imaging diagnostic criteria for MS in an effort to improve
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the previous 2010 McDonald criteria for MS. 67 These
recommendations were partially incorporated into the revised
2017 McDonald criteria (Table 4.3), which should be applied
for the establishment of DIT and DIS in patients with RIS.
Approximately one-third of individuals with RIS will be
diagnosed with MS, and the remaining two-thirds will develop
new lesions within 5 years of presentation. 12 According to a
recent large, multicenter, retrospective study performed by the
RIS Consortium, age (<37 y), sex (male), and the presence of
demyelinating lesions in the spinal cord are the significant
predictors for a first clinical event. 68 Specifically, around 58%
of patients <37 years with spinal cord lesions are predicted to
become symptomatic within 5 years and up to 90% if the male
gender is added as an additional risk factor. 69 Other risk
factors include high cerebral lesion load, gadoliniumenhancing lesions, CSF-specific oligoclonal bands, and
abnormal visual evoked potentials. 12 Active monitoring of
patients with clinical and radiological follow-up every 6 to
12 months is recommended.
70
MRI Mimics in Multiple Sclerosis:
Differential Diagnosis
More than 90% of patients with clinically definite MS have
typical white matter lesions on MRI. 4 However, a key element
in the diagnosis of MS is the exclusion of other possible
disease entities. CNS lesions resulting from other disorders
(e.g., ischemia, systemic lupus erythematosus, Behçet disease,
other vasculitides, sarcoidosis) may appear similar to MS
lesions on MRI
28,38
(Table 4.7). White matter changes related
to normal aging can further complicate the diagnostic process.
2,59
In these cases, ancillary testing (blood work, CSF analysis,
and evoked potentials) can help facilitate the diagnosis.
52
Careful assessment of MRI “red flags” can be helpful in
suggesting a diagnosis other than MS. 8 These so-called red
flags were described over a decade ago by the European
Magnetic Resonance Network in MS (MAGNIMS) to help
guide clinicians in the diagnosis of MS. 4 In addition,
MAGNIMS also published a standardized MRI protocol for
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the diagnosis of MS to help increase diagnostic yield against
possible MS mimics (Table 4.8).
Table 4.7
Differential Diagnosis of White Matter Lesions
Hypoxic/ischemic
Atherosclerosis, stroke, hypertension, migraine, amyloid
angiopathy, vasculopathy (CADASIL, Susac syndrome)
Inflammatory
Multiple sclerosis, vasculitis (SLE, Sjögren syndrome, Behçet
syndrome, primary CNS vasculitis), neurosarcoidosis
Infectious
HIV, syphilis, Lyme disease, TB, PML
Toxic/metabolic
Traumatic
Posttraumatic, radiotherapy
Metabolic
Leukodystrophies
Neoplastic
Metastatic or primary disease
Normal
Age-related or Virchow-Robin spaces
CADASIL, cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy; CNS, central
nervous system; HIV, human immunodeficiency virus; PML,
progressive multifocal leukoencephalopathy; SLE, systemic
lupus erythematosus; TB, tuberculosis.
Table 4.8
2015 MAGNIMS Standardized Brain and Spine MRI Protocol
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Brain
Mandatory
Axial: proton-density and/or T2-FLAIR/T2-weigted
Sagittal: 2D or 3D T2-FLAIR
2D or 3D contrast-enhanced T1-weighted
Optional
Unenhanced 2D or high-resolution isotropic 3D T1-weighted
2D and/or 3D dual inversion recovery
Axial diffusion-weighted imaging
Spinal cord
Mandatory
Dual-echo (proton-density and T2-weighted) conventional
and/or fast spin-echo
STIR (as an alternative to proton-density-weighted)
Contrast-enhanced T1-weighted spin-echo (if T2 lesions
present)
Optional
Phase-sensitive inversion recovery (as an alternative to STIR
at the cervical segment)
FLAIR, fluid attenuated inversion recovery; MAGNIMS,
Magnetic Resonance Imaging in Multiple Sclerosis; MRI,
magnetic resonance imaging; STIR, short-TI inversion
recovery.
Features have been described that distinguish MS from other
demy elinating syndromes, including NMOSDs and acute
demyelinating encephalomyelitis, as well as anti-myelinoligodendrocyte glycoprotein antibody-related disease. 29 The
location and shape of white matter lesions, as well as their
signal characteristics on different MRI sequences, can be
useful in differentiating MS from other white matter diseases
44
(Table 4.9). Specifically, lesions located in the
juxtacortical/cortical regions, periphery of the brainstem, and
the posterolateral cervical spinal cord are suggestive of MS.
4
In addition, elongated lesions along the subependymal veins
that appear as Dawson fingers or the presence of a central vein
sign is also characteristic of MS lesions.
40,65
Despite the
intrinsic diagnostic challenges of MRI, most typical patients
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