DIAGNOSIS AND EVALUATION OF MULTIPLE SCLEROSIS: …webcir.org/revistavirtual/articulos/2017/1_febrero/col/esclerosis... · drome, for example: Optic neuritis plus myelitis, optic

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1Radiologist resident, Universidad El Bosque. Bogotá, Colombia.

2Radiologist, Hospital Universitario Fundación Santa Fe. Bogotá, Colombia.

3Clinical neurologist. Radiologist resident. Universidad El Bosque. Bogotá, Colombia.

4Neuroradiologist, University of Ottawa.

Palabras clave (DeCS)

Esclerosis múltipleTécnicas de diagnóstico

neurológicoImagen por resonancia

magnética

Key words (MeSH)

Multiple SclerosisNeurological diagnostic

techiquesMagnetic Resonance

Imaging

DIAGNOSIS AND EVALUATION OF MULTIPLE SCLEROSIS: WHAT THE RADIOLOGIST SHOULD NOW AND REPORT. CURRENT CONCEPTSDIAGNÓSTICO Y EVALUACIÓN DE LA ESCLEROSIS MÚLTIPLE: LO QUE EL RADIÓLOGO DEBE CONOCER E INFORMAR. CONCEPTOS ACTUALES

Ángela Guarnizo1

Sonia Bermúdez2

Óscar Torres2

Andrea Nassar3

Carlos Torres4

SummaryMultiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease characterized by focal areas of demyelination/axonal damage known as “plaques”. The diagnostic criteria currently used include clinical or para-clinical demonstration of the dissemination of these lesions in space and time, and the exclusion of alternative diagnoses. Magnetic resonance imaging (MRI) is the most important para-clinical tool for the diagnosis of MS and allows to demonstrate the dissemination in space based on the presence of at least one criteria in two of the five characteristic locations: one lesion in cortical-yuxtacortical, three in the periventricular white matter, one in the infratentorial nervous tissue, one in the spinal cord and one in the optic nerve. Dissemination in time can be established from the simultaneous detection of lesions with and without contrast enhancement in a single MRI study, or through the demonstration of new lesions in follow-up MRI studies. The course of the disease and its pharmacological treatment lead to characteristic changes in imaging including the development of atrophy, multifocal progressive leukoencephalopathy and immune reconstitution inflammatory syndrome.

ResumenLa esclerosis múltiple (EM) es una enfermedad inflamatoria y neurodegenerativa, de curso crónico, caracterizada por áreas focales de desmielinización/daño axonal, llamadas “placas”. Los criterios actualmente utilizados en su diagnóstico incluyen la demostración clínica o paraclínica de diseminación de estas lesiones en el espacio y en el tiempo, y la exclusión de diagnósticos alternativos. La resonancia magnética (RM) es la herramienta paraclínica más importante para establecer el diagnóstico de EM y permite demostrar la diseminación en el espacio, con base en la presencia de, al menos, un criterio en dos de las cinco localizaciones características: una lesión en cortical-yuxtacortical, tres en la sustancia blanca periventricular, una en el tejido nervioso infratentorial, una en la médula espinal y una en el nervio óptico. La diseminación en tiempo se puede establecer a partir de la detección simultánea de lesiones con y sin realce con el medio de contraste en un mismo examen de RM, o mediante la demostración de nuevas lesiones en estudios de RM de seguimiento. El curso de la enfermedad y el tratamiento farmacológico producen cambios característicos en las imágenes de RM que incluyen el desarrollo de atrofia, la leucoencefalopatía multifocal progresiva y el síndrome inflamatorio de reconstitución inmunológica.

4487Rev. Colomb. Radiol. 2016; 27(4): 4486-91

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IntroductionMultiple sclerosis (MS) is the most common demy-

elinating and neurodegenerative inflammatory disease in adults between 18 and 35 years of age and constitutes the second cause of neurological disability in young adults (1,2). This pathology is considered an autoimmune organ-specific disorder, characterized by multiple focal areas of demyelination called plaques or lesions, which are accom-panied by different degrees of gliosis, inflammation, and neuroaxonal damage (3).

Epidemiology

The annual incidence of MS ranges from 1.5 to 11 cases Per 100,000 people, and the average prevalence is 3 / 100,000; however, improvement in early detection of the disease allows to diagnose more cases (2). It is estimated that in the United States there are between 350,000 and 400,000 People with this disease, and around the world, more than 2,500,000 (2, 4).

Several studies have shown that MS has a heterogeneous geographic distribution, characterized by a «latitudinal gradient», in which prevalence increases as it moves away from the equator (5). Accordingly, Colombia Is considered an area of low risk for the development of multiple sclerosis, with an approximate prevalence of 1.48 to 4.98 cases per 100,000 inhabitants (6).

MS is more frequent in the third or fourth decade of life; However, it may occur in adolescence, as well as in people older than 50 years (2, 7). The relationship woman / man is approximately 2:1 (4).

Clinical variants

The initial presentation of the disease in the form of out-breaks (85-90% of all cases of MS) is called “isolated clinical syndrome”, and the possible types of presentation include:

• Optic neuritis: It is characterized by acute pain and unilateral alteration of vision. It may occur with blu-rred vision or scotomas (8) and their duration varies between a few days and two weeks, with subsequent spontaneous recovery of symptoms (9,10).

• Cerebellar and brain stem syndrome: It can manifest with diplopia secondary to intranuclear ophthalmology, pa-ralysis of the sixth pair, ataxia, nystagmus, sensitive fa-cial symptoms, vertigo and paroxysmal symptoms (8). The paroxystic symptoms are characterized by events with a duration lasting from seconds to minutes, which recur in 24 Hours (11). The onset of symptoms is often subacute and there is a full or partial recovery in a few weeks.

• Marrow syndrome: These patients usually present a par-tial transverse myelitis or altered sphincter control. The

onset of symptoms usually occurs in a period of at least 24 hours (11) with a duration less than three weeks (8).

• Hemispheric and poly-regional syndromes: Constitute other less frequent presentation of the isolated clinical syndrome. The hemispheric syndrome is characterized by hemiparesis or sensory disturbances, quadranta-nopsia and, less frequently, may manifest itself with encephalopathy, seizures and fever (12). The poly-re-gional syndromes are usually presented with the com-bination of typical forms of the isolated clinical syn-drome, for example: Optic neuritis plus myelitis, optic neuritis with brain stem syndrome, myelitis and brain stem syndrome, or the three presentations at the same time (13).

Between 85 and 90% of the patients have periods of relapse-remission (RR), with episodes of sudden onset or recurrent neurological deficits, followed by partial or complete recovery (8). From 25% to 40% of patients with the RR variant develop the secondary progressi-ve form (SP), after approximately 20 years of illness (8). This phenotype is characterized by the progression of the disease, regardless of relapse episodes. The diagno-sis is made by demonstrating progression of the disease, without taking into account relapses during a period of at least six months (14).

Approximately 10% to 15% of patients present pro-gressive primary type MS (PP), characterized by an in-sidious onset of symptoms followed by gradual deterio-ration in time (8) without episodes of relapse-remission; they are usually older patients with an average age of 40 Years (15).

There is a small group of patients in the category relapse-progression, who present progression of the disease from its beginning with acute relapses, with or without complete recovery (8, 16). These patients pre-sent progression of the disease during periods between relapses.

Studies show that the natural history of primary pro-gressive MS is similar to the relapse-progression cate-gory, for which there is a debate about the real difference between these two categories (8,16,17). Figure 1 shows the clinical variants of MS and in Table 1, the evaluation of progression and activity of the disease.

Table 1. Evaluation of progression and activity of the disease

Progressive disease

Primary Secundary

Active with progression Active without progression Not active with progression Not active without progression (stable disease)

4488 Diagnosis and Evaluation of Multiple Sclerosis: What the Radiologist should now and report. Current Concepts. Guarnizo A., Bermúdez S., Torres Ó., Nassar A., Torres C.

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In the consensus carried out in 2013 by Lublin and collaborators (18) the proposed variants for MS were evaluated in 1996 according to clinical evolution, imaging findings, biomarkers and reports of the literature, with the purpose of making a better characterization of the phenotypes. According to the committee, the following modifications were proposed:

• The isolated clinical syndrome was recognized as the first form of clinical presentation of a demyelinating inflammatory disease that could be MS, but which does not yet meet the criteria for dissemination in time. According to clinical studies, it was recognized that the isolated clinical syndrome together with the imaging findings in MRI involve a high risk to meet the diagnostic criteria of MS.

• The isolated radiological syndrome, which is characteri-zed by imaging findings suggestive of a demyelinating inflammatory disease in the absence of signs and symp-toms, was not included as a subtype of MS due to the imaging findings being non-specific. However, it was determined that the isolated radiological syndrome has a high probability of switching to MS according to the

shape and location of the lesions. The recommendation is to make a prospective follow-up in these patients and not include this syndrome as a phenotype of MS.

• With respect to the secondary progressive variant, we found that there are no clinical, imaging, and immunological conditions that define the transition point in which the variant relapse-remission becomes secondary progressive and that the transition tends to be gradual.

• The progressive primary form should be part of the phenotypes of progressive MS; because in the studies about the natural history of the disease it was found that PP and SP forms have a similar decay rhythm; therefore, despite having a different clinical presentation, there are no significant pathophysiological differences of the SP form.

• The term relapse-progression should not be used since it is non-specific and overlaps with other subtypes of the illness.

• The chronic progressive variant should be replaced with more specific terms such as secondary-progressive and primary-progressive.

Based on the evaluation of progression, it was conclu-ded that the disease does not progress evenly and can even remain stable for a while. Thus, progression should be es-tablished by medical history or objective evaluation. In the case of a patient with the PP variant that has remained stable during one year, it should be classified as PP without progression and in the case of a patient with the form SP that has progressively declined and presents lesions that en-hance in MRI, it should be classified as active SP and in progression. Therefore, the activity is determined by clini-cally assessed relapses at least once a year and the pre-sence of new or enhanced lesions in MRI. Progression is determined by clinical assessment, which must be done at least once a year. In the case of not having a clinical evaluation available, activity and progression are classi-fied as indeterminate.

It was suggested to use the term relapse rather than progression in patients that present relapses and that the term progression be only used for those who are in the progressive phase of the disease, independent of activity or relapse.

Imaging protocol in magnetic resonance

The sequences recommended in chronological order in the evaluation of patients with multiple sclerosis are (19,20) (Figure 2):

• Axial single T1 weighted spin echo

• Administration of contrast medium (0.1 mmol / kg)

• Axial T2-weighted spin echo

Figure 1. Clinical variants of multiple sclerosis. a). Isolated clinical syndrome. b) Relapse-remission. c) Secondary progressive. d) Primary progressive.

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• Axial and sagittal T2-FLAIR

• T1-weighted spin echo with contrast medium (Delay between contrast injection and sequence acquisition of 5-15 minutes) in axial and coronal planes.

• Axial diffusion (useful for identifying pathologies not related to MS, such as acute ischemia) (21).

The spin echo sequences weighted in T1, T2 and FLAIR can be obtained in two-dimensional or three-dimensional form. Two-dimensional sequences must be obtained with contiguous cuts of 3 mm of thickness and the three-dimensional with isotropic voxels of 1 × 1 × 1 mm.

In the evaluation of the spinal cord in patients with MS, the recommended sequences are (21):

• Sagittal and axial T2-weighted spin echo

• Sagittal STIR or proton density sequence

• Axial and sagittal T1-weighted spin echo with contrast medium (5 to 15 minutes after administration of contrast medium).

In the evaluation of the spinal cord it is recommended to include at least its cervical segment, because in this segment it is easier to display the plates and it usually presents more asymptomatic lesions (21).

Diagnostic criteria

The McDonald criteria, 2010, used to demonstrate dis-semination in time and space for the diagnosis of MS are based on the studies and proposals made by the MAGNIMS group (a network of European centers that investigate the use of MRI in MS) (22,23), in which they demonstrated that such criteria are more sensitive, without altering specifici-ty, for the diagnosis of the disease in relation to the criteria that were used before (24-26).

According to the McDonald’s criteria, the spread in space requires, at a minimum, a high signal injury in T2-weighted sequences in at least two of the four characteris-tic topographies: periventricular white matter, the yuxta-cortical white matter, the infratentorial nerve tissue (stem or cerebellum) and the spinal cord (25).

The MAGNIMS consensus guidelines of 2015 (27) pro-poses an increase in the number of lesions to confirm pe-riventricular involvement, from one to three lesions, and to add the compromise of the optic nerve; in this way, the number of locations in time spread increases from four to five.

Similarly, it was recommended that intracortical le-sions, leukocorticals and yuxtacorcals are combined into one single term: cortical/yuxtacortical, which indicates the compromise of the white matter close to the cortex, in

the cortex or in both locations. This amendment seeks to expand the yuxtacortical term of the McDonald criteria of 2010 (27).

Likewise, another of the proposed modifications in the cited consensus is to not exclude the symptomatic lesions in the total count of lesions to establish dissemination in time (27). It has been shown that by including symptoma-tic lesions, MRI sensitivity increases without compromi-sing specificity.

Dissemination in time can be demonstrated in two ways: 1) by the simultaneous presence of asymptomatic lesions with enhancement and without enhancement after contrast medium (figure 3 or 2) by a new lesion, or several, in T2-weighted sequences or lesions with contrast medium enhancement in a new MRI compared to one obtained previously, regardless of the time elapsed between them (8,25).

The lesions detected with MRI are relatively characte-ristic, both in appearance and topography (8) (figure 4).

Periventricular lesions typically have an ovoid shape, with radial orientation with respect to the ventricles, which are known as the Dawson`s fingers (28,29). These lesions have a perivenular pattern secondary to migration of the autoimmune cells through the blood-brain barrier, which induces a cascade of inflammation and demyelination (30) (Figure 5). The compromise of the calloso-eptal interface is typical (31,32) and is detected in an optimal fashion using T2-FLAIR sequences in the sagittal plane.

Yuxtacortical lesions, as the name implies, affect the white matter adjacent to the cortical gray matter; they have a ring or U-shape and compromise the interconnection axons between adjacent gyri (U-fibers).

Infratentorial lesions are usually located in the floor of the fourth ventricle or on the surface of the bridge. Its loca-tion in the middle cerebellar peduncles is typical (8).

In the spinal cord, demyelinating lesions are usually peripheral, dorsolateraly localized and oval in shape. They are small, with a longitudinal extension less than two ver-tebral bodies, and occupy less than 50% of the medullary area in the axial plane (33).

In the figure 6 the typical locations of lesions in multi-ple sclerosis can be appreciated.

In the acute form of optic neuritis, MRI shows a thicke-ned optic nerve, with a high signal in T2-weighted sequen-ces with fat saturation, and with enhancement with contrast medium (34,35). The chronic form may show an atrophic optic nerve, sometimes with an increased signal in T2, but without enhancement with contrast medium (34).

Enhancement with contrast medium in T1-weighted sequences reflects a disruption of the blood-brain barrier and infiltration of pro-inflammatory T cells within the cerebral parenchyma (30,36,37). This enhancement repre-sents the development of a new lesion or reactivation of an old plaque (21) and is usually transient, with a duration that varies from 1 to 16 weeks (38,39).


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Black holes correspond to areas of low signal visualized in T-1 weighted spin echo sequences, which, in the acute phase, represent demyelination plaques and inflammation edema with or without axonal destruction. These active black holes show contrast enhancement and are frequent in the early stages of the disease (30). Chronic black holes are defined as those which do not show contrast enhancement and persist at at least six months. They are more frequent in the progressive phases of the disease and are related to irreversible axonal damage (40), and with the neurological disability of the patients. During the late phase of the disea-se they are associated with atrophy (figure 7). The increase in number of these chronic black holes indicates deficits in the repair mechanisms in patients with disease progression (30,41). The number or the increase of black holes has been used to evaluate the therapeutic efficacy in some clinical

trials (42,43) and their presence is an indicator of poor prog-nosis (44).

In recent years, because of the use of new sequences (such as double inversion recovery) and the use of three teslas or larger field equipment, it is possible to visualize intracortical demyelinating plaques, which are included in the now-called cortical-yuxtacortical criterion. Despite these advances, the sensitivity of MRI in detection of cortical lesions remains low.

High signal lesions in T1-weighted sequences without contrast medium are found in patients with MS in advanced stages (figure 8). According to different studies, these injuries are associated with physical disability and atrophy, and are the result of the accumulation of albumin and free radicals due to disruption of the blood-brain barrier (45).

F i g u re 2 . Re co m m e n d e d sequences In the evaluation of patients with multiple sclerosis. a) Start with spin echo in simple T1, administer contrast medium. b) T2-Weighted spin echoes in axial. c) T2-weighted FLAIR axial. d) T2 FLAIR or PD in sagittal. e) Axis T1 spin echo with contrast medium.

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Figure 3. Dissemination in time. a) FLAIR axial image, T2-weighted: Multiple lesions of high signal in periventricular localization. b) Echo image of T1 spin with contrast medium: enhancement of periventricular lesions (arrows).

Figure 4. Characteristic areas in which multiple sclerotic lesions are localized. a) Yuxtacortical. b) Periventricular. c) Infratentorial (arrows).

Figure 6. Typical Locations in multiple sclerosis. a) Callosal-spetal interface. b) Yuxtacortical, fibers in U. c) Periventricular temporal. d) Periphery of the cerebral stem. e) Cortical (arrows). f) Optic nerve. g) Periphery of the spinal cord.

Figure 5. Dawson’s fingers: a) axial images of brain magnetic resonance FLAIR, b) gradient echo in T2, c) spin echo with contrast, d) sagittal FLAIR spin echo, showing an oval lesion with orientation perpendicular to the ventricle and enhancing the contrast by disruption of the blood-brain barrier (arrows).

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Multiple sclerosis variants

• Pseudotumoral It is uncommon, with an approximate frequency of three cases per million inhabitants per year, and is more frequent in women during the second and third decades of life (46,47). In the MRI, one can observe rounded lesions of high signal in T2-weighted sequences, of low signal in T2-weighted sequences, with regular margins, low perilesional edema, and discrete mass effect (46,48). These lesions are located in the subcortical and periventricular regions of the cerebral hemispheres (46); they usually show an incomplete ring highlight, with the open ring segment in contact with the cortical or subcortical gray matter (Figure 9). This enhancement pattern helps differentiate these lesions from brain abscesses or tumors (46,49,50).

• Balo concentric sclerosis. It is presented characteristically as ring lesions with demyelination bands that alternate with myelinated areas that can demonstrate concentric enhancement with administration of contrast medium (Figure 10). These Lesions almost always affect the white matter of the cerebral hemispheres and are very rare in other locations (51).

Figure 7. Black holes. a and b) T2-weighted FLAIR axial images and inversion recovery in T1: high signal lesions in T2-weighted sequences in the periventricular white matter, which are of low signal in T1-weighted sequences in acute phase, secondary to edema by acute inflammation (arrows). c and d) T2-weighted FLAIR axial images and spin echo at T1: high signal lesions in sequences with T2 information in the white matter adjacent to the occipital horn of the lateral ventricles, which are of low signal in sequences with information in T1 (short arrows), associated to signs of atrophy of the parenchyma in a patient with advanced multiple sclerosis.

Figure 8. FLAIR axial images. a and c) Lesions of high signal in yuxtacortical and periventricular localization (arrows). b and d) Axial spin echo images at T1 Simple, high signal yuxtacortical and periventricular lesions (arrows). These findings are related to the appearance of atrophy.

• Schilder`s disease This variant occurs during childhood (52), and consists of a sub-acute or chronic myelinoclastic disorder, which has 1 or 2 symmetric plaques which involve semi-oval centers (51) (Figure 11).

• Marburg`s disease. Corresponds to a rare, acute and fulminating form of MS disease that frequently leads to the death of the patient in weeks or months, usually due to the involvement of the brainstem. From the histopathological point of view, the lesions are more destructive than those found in classic MS. MRI studies show focal lesions of variable size and location, predominantly periventricular, which are enhanced with contrast medium and progressively increase in size to finally become confluent (53,54).

Expected findings in imaging according to treatment

There are several options for the treatment of multiple sclerosis such as parenteral immunomodulators and oral agents. The fin-dings related to the type of therapy are described in Table 2.

MRI evaluation is recommended before starting or changing treatment and approximately 6 months after change of therapy (21). Subsequently, annual surveys, at least during the first 2 to 3 years.

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Table 2. Expected imaging findings according to treatment

TreatmentDecrease in the number of injuries and relapses and

degree of disabilityDecrease of atrophy Pseudoatrophy PML* IRIS**

Corticosteroids No No Yes No No

Interferons Yes No No No No

Teruflunomide Yes No No No No

Fingolimod Yes Yes No No No

Mitoxantrone Yes No No No No

Natalizumab Yes No Yes Yes Yes

* PML: Progressive multifocal leukoencephalopathy** IRIS: Immune reconstitution inflammatory syndrome

Progressive multifocal leukoencephalopathyProgressive multifocal leukoencephalopathy is an

opportunistic infection of the central nervous system by the John Cunningham (JC) virus, which presents significant damage of the oligodendrocytes and marked demyelination. This disease, in the majority of cases occurs in immunocompromised patients, and among them, patients with HIV are the most affected (80% to 85%) (55). It has been found that it may also occur in patients receiving therapy with antimonoclonal antibodies for the treatment of MS such as Natalizumab (56-58). The risk of developing the disease depends on the duration of the treatment (> 24 months), antibody levels anti-JC and previous or current administration of immunosuppressive therapies (59,60).

Natalizumab associated Progressive Multifocal Leu-koencephalopathy (PML). Patients with MS affected by this pathology can present in 55% of the cases cognitive symptoms and behavioral alterations (55). Within the findings in images it can be observed single or multiple, bilateral and asymmetric lesions in the cerebral hemis-pheres, but mainly localized In the white matter of the frontal lobes (48% of the cases), occipital (20%) and pa-rietal (12%) (55).

Injuries can also be found on the subcortical U-fibers and in cerebellar peduncles; However, lesions of the corpus callosum are not frequent. Compromise of the gray matter occurs especially in the thalamus and basal ganglia (5%) (55-58). When the lesion progressively increases in size, it can reach the entire white matter of the gyrus and can even extend to the white matter of the adjacent gyrus, pattern which has been called the heart of the gyrus (61,62).

Adjacent to the larger lesion, one can observe multi-ple lesions of microcystic appearance In T2-weighted se-quences, with a perivascular distribution pattern called milky way (55).

The enhancement of the lesions can occur in 30% to 40% of cases in the early stages, can be linear, punctiform or peripheral and is related to a perivascular distribu-tion of the inflammation in the deep white matter and periventricular. It has been observed that it can represent areas of proliferation of the JC virus or activation of the macrophages (55).

For the follow-up of patients with this pathology, the protocol should include T2-FLAIR sequences and diffu-sion; in which the lesions to be observed are high signal with poorly defined subcortical localization and with the appearance of the heart of the gyrus (21). The enhance-ment of the lesions may be in patches, nodular or diffuse (61,62); However, the enhancement of the lesions has little diagnostic value for the follow-up of this pathology becau-se less than 50% of the lesions enhances in early stages (21).

Immune reconstitution inflammatory syndrome (IRIS) due to Natalizumab. It is characterized by the worse-ning of the neurological deficit after the suspension of the drug. There are visible inflammatory changes in MRI among which include: multiple new lesions of demyeli-nating appearance or reactivation of previously encou-ntered demyelinating plaques. The contrast medium shows nodular or incomplete ring enhancement of the lesions (56,57) (Figure 12). Table 3 describes the characte-ristics of the images for progressive multifocal leukoen-cephalopathy and immune reconstitution inflammatory syndrome due to Natalizumab (52,56,57).


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Figure 9. Multiple sclerosis with pseudo-tumoral presentation. a) FLAIR axial images, b) T2-weighted gradient echo, c) spin echo in T1 with contrast: Expansive lesion of high signal with periventricular distribution, perivenular with disconti-nuous annular enhancement with open border towards the gray matter (arrows).

Figure 10. Concentrated sclerosis of Baló: a) Simple T1-weighted axial images, b) FLAIR In T2, c) T1-weighted spin echo sequence with administration of contrast medium, d) diffusion. Low signal lesion in sequences with T1 information in the right frontal lobe, with low signal halo and ring enhancement with contrast medium (arrows) in a 10-year-old patient with left hemiparesis.

Figure 11. CT. Schilder’s disease. a and b) FLAIR and spin-weighted resonance images, c) sagittal in T1: extensive right hemispheric lesion with compromise of the basal ganglia region and the semiova center l.

Figure 12. Evolution after treatment with Natalizumab. Images with FLAIR information. Top row and spin echo with information in T1 and contrast medium administration: multiple lesions in the periventricular white matter, the which increase by leukoencephalopathy progressive multifocal. When to suspend Natalizumab shows an increase in the number of demyelinating lesions (Progression), some of them with enhancement with the contrast medium, secondary to the development of immune reconstitution inflammatory syndrome (IRIS). In the control of the lesions at six months there is a slight decrease in size, decrease in effect mass and resolution in the Gadolinium (arrows).

Source: Courtesy of Dr. Nancy Richert and Biogen.

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Figure 13. Atrophy associated with multiple sclerosis. Images a) Sagittal spin echo In T1 and b) axial T2-weighted FLAIR. Increased subarachnoid supratentorial space and prominence of the brain grooves secondary to atrophy.

Figure 14. Spectroscopy of a right frontal demyelinating lesion with increase in the choline peak due to membrane replacement (long arrow) and in the lactate (curved arrow), decrease in N-acetyl aspartate peak (short arrow) due to axonal injury.

Figure 16. Disseminated acute encephalomyelitis. Axial magnetic resonance imaging (FLAIR), show bilateral asymmetric signal with diffuse borders that compromise the thalamus and basal ganglia region (arrows). They are characterized by being larger and asymmetric lesions.

Figure 15. Patient with optic neuromyelitis. a) Sagittal T1-weighted image of the cervical spine, (b) axial T2-weighted spin echoes and c) in T1 with contrast me-dium: demyelinating lesions involving more than 3 vertebral bodies and occupy more than 50% of the area in the axial plane of the marrow.

Figure 17. CADASIL. a, b and d) T2-weighted spin echo axial images, c) T2-weighted gradient echo: high-signal confluent areas in the frontal lobe and right anterior temporal (long arrow and short arrow), associated to foci of microhe-morrhagia (curved arrows).

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Figure 18. CNS lymphoma. a and d) Axial T1-weighted spin imaging of cerebral MRI, b and e) FLAIR, c and f) T1 with contrast medium. Left parietal lesion of demyelinating appearance. In the control, one year later (lower row) there is an expansive lesion that has increased in size in the same location.

Figure 19. Vascular leukoencephalopathy. a) Spin echo and FLAIR magnetic resonance, b and c) T2-weighted. One can observe subcortical mul-tifocal lesions of variable size with Ill-defined edges and respectful of the corpus callosum and U-fibers (arrows).

Table 3. Imaging characteristics of progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome due

to Natalizumab

PML due to Natalizumab IRIS – MS IRIS – PML

Localization White matter, basal ganglia, thalamusPeriventricular white matter, corpus callosum, callosal-spetal interface

White matter, thalamus, basal ganglia

Edema No Yes +/−

Mass effect No Yes +/−

Enhancement 30 % to 40 % Anillo nodular Yes

JC serology Positive Negative Positive

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Cerebral atrophyCerebral atrophy occurs early in the course of the di-

sease, is usually progressive and affects the parenchyma in diffuse form (figure 13). It reflects multiple disease proces-ses, including demyelination, inflammation and gliosis. The compromise of gray matter and neurodegenerative mecha-nisms are associated with a greater degree of cognitive im-pairment of the patient (63,64).

Spectroscopy

Anomalies have been identified in the metabolites of plaques in both acute and chronic phases. Choline, a metabolite associated with cell membrane phospholipids, is a marker of cellular transformation and rupture and repair of myelin (63,65). In the acute phase, there is an increase in the choline peaks (membrane replacement), glutamate and lactate. Chronic phase plaques show decrease of the N-acetyl aspartate peak (axonal damage) and an increase in the myoinositol peak (microglial proliferation) (20,63,64) (figure 14).

Differential diagnosis: red flags in MR

• Extensive spinal cord injury (figure 15): optic neuromye-litis or Devic’s disease.

• Lesions affecting the basal ganglia and thalamus (Figure 16): acute disseminated encephalomyelitis (ADEM), la-cunar infarcts.

• Injuries that affect the external capsule and microhemo-rrhagic foci (Figure 17): cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoen-cephalopathy (CADASIL).

• Lesions enhancing simultaneously with the contrast medium or the existence of meningeal enhancement: in-flammation or vasculitis of the central nervous system.

• Full or irregular ring enhancement of lesions (figure 18): may correspond to tumors or abscesses.

• High signal lesions in T2-weighted sequences in the white matter with respect to the U fibers and corpus ca-llosum (Figure 19): may represent a vascular leukoen-cephalopathy.

Conclusion

The imaging findings show that MRI has high sensitivity and specificity for diagnosis and follow-up of MS, which is why it is a very important tool in the evaluation of a patient with suspicion of this disease. According to the type of treatment and the evolution of the disease, both the clinician and the radiologist must be alert, as additional important findings can be found such as atrophy, progressive focal leukoencephalopathy and immune reconstitution inflammatory syndrome.

References

1. Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin. 2011;29:207-17.

2. Goldman L, Schafer A. Tratado de medicina interna. España: Elsevier; 2013.3. Popescu BF, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis:

where do we stand? Continuum (Minneap Minn) 2013;19(4 Multiple Sclerosis):901-21.

4. Simon JH. Update on multiple sclerosis. Radiol Clin North Am. 2006;44:79-100.

5. Toro J, Cárdenas S, Martínez CF, Urrutia J, Díaz C. Multiple sclerosis in Colombia and other Latin American Countries. Multiple Sclerosis Related Disorders. 2013;2:80-9.

6. Toro J, Sarmiento OL, Díaz del Castillo A, Satizábal CL, Ramírez JD, Montenegro AC, et al. Prevalence of multiple sclerosis in Bogota, Colombia. Neuroepidemiology. 2007;28:33-38.

7. Confavreux C, Vukusic S. The clinical epidemiology of multiple sclerosis. Neuroimaging Clin N Am. 2008;18:589-622.

8. Katz Sand IB, Lublin FD. Diagnosis and differential diagnosis of multiple sclerosis. Continuum (Minneap Minn) 2013;19(4 Multiple Sclerosis):922-43.

9. Hickman S, Dalton C, Miller D, Plant G. Management of acute optic neuritis. Lancet. 2002;360:1953-962.

10. Jäger HR, Miszkiel KA. Pathology of the optic nerve. Neuroimaging Clin N Am. 2008;18:243-59.

11. Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol. 2012;11:157-69.

12. Thouvenot É. Update on clinically isolated syndrome. Presse Médicale. 2015;44:e121-e136.

13. Pelayo R, Tintore M, Rovira A, Rio J, Nos C, Grive E, et al. Polyregional and hemispheric syndromes: a study of these uncommon first attacks in a CIS cohort. Mult Scler. 2007;13:731-6.

14. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46:907-11.

15. Thompson AJ, Polman CH, Miller DH, McDonald WI, Brochet B, Filippi M Montalban X, et al. Primary progressive multiple sclerosis. Brain. 1997;120:1085-96.

16. O’Connor P. Key issues in the diagnosis and treatment of multiple sclerosis An overview. Neurology. 2002;59(6 Suppl 3):S1-S33.

17. Kremenchutzky M, Cottrell D, Rice G, Hader W, Baskerville J, Koopman W, et al. The natural history of multiple sclerosis: a geographically based study. 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation. Brain. 1999;122(Pt 10):1941-50.

18. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83:278-86.

19. Sahraian MA, Eshaghi A. Role of MRI in diagnosis and treatment of multiple sclerosis. Clin Neurol Neurosurg. 2010;112:609-15.

20. Bakshi R, Thompson AJ, Rocca MA, Pelletier D, Dousset V, Barkhof F, et al. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol. 2008;7:615-25.

21. Traboulsee A, Simon J, Stone L, Fisher E, Jones D, Malhotra A, et al. Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. Am J Neuroradiol. 2015.

22. Swanton JK, Rovira A, Tintore M, Altmann DR, Barkhof F, Filippi M, et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurology. 2007;6:677-86.

23. Rovira À, Swanton J, Tintoré M, Huerga E, Barkhof F, Filippi M, et al. A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis. Arch Neurol. 2009;66:587-92.

24. Montalban X, Tintore M, Swanton J, Barkhof F, Fazekas F, Filippi M, et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology. 2010;74:427-34.

25. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.

26. Rovira A, Wattjes MP, Tintore M, Tur C, Yousry TA, Sormani MP, et al. MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nature Rev Neurol. 2015;11:471.

27. Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15:292-303.

28. Horowitz AL, Kaplan RD, Grewe G, White RT, Salberg LM. The ovoid lesion: a new MR observation in patients with multiple sclerosis. AJNR Am


original articles

J Neuroradiol. 1989;10:303-5.29. Pretorius P, Quaghebeur G. The role of MRI in the diagnosis of MS. Clin

Radiol. 2003;58:434-448.30. Traboulsee A, Li DK. Conventional MR imaging. Neuroimaging Clin N Am.

2008;18:651-73.31. Chen Z, Feng F, Yang Y, Li J, Ma L. MR imaging findings of the corpus

callosum region in the differentiation between multiple sclerosis and neuromyelitis optica. Eur J Radiol. 2012;81:3491-5.

32. Gean-Marton AD, Vezina LG, Marton KI, Stimac GK, Peyster RG, Taveras JM, et al. Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis. Radiology. 1991;180:215-21.

33. Tartaglino LM, Friedman DP, Flanders AE, Lublin FD, Knobler RL, Liem M. Multiple sclerosis in the spinal cord: MR appearance and correlation with clinical parameters. Radiology. 1995;195:725-32.

34. LeBedis CA, Sakai O. Nontraumatic orbital conditions: Diagnosis with CT and MR imaging in the emergent setting 1. Radiographics. 2008;28:1741-53.

35. Szatmáry G. Imaging of the orbit. Neurol Clin. 2009;27:251-84.36. Nesbit GM, Forbes GS, Scheithauer BW, Okazaki H, Rodríguez M. Multiple

sclerosis: histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy. Radiology. 1991;180:467-74.

37. Lai M, Hodgson T, Gawne-Cain M, Webb S, MacManus D, McDonald WI, et al. A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996;60:339-41.

38. Cotton F, Weiner HL, Jolesz FA, Guttmann CR. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology. 2003;60:640-6.

39. Kermode AG, Tofts PS, Thompson AJ, MacManus DG, Rudge P, Kendall BE, et al. Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement. Neurology. 1990;40:229-35.

40. Van Walderveen MA, Barkhof F, Pouwels PJ, Van Schijndel RA, Polman CH, Castelijns JA. Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy. Ann Neurol. 1999;46:79-87.

41. Truyen L, van Waesberghe JH, van Walderveen MA, van Oosten BW, Polman CH, Hommes OR, et al. Accumulation of hypointense lesions (“black holes”) on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology. 1996;47:1469-76.

42. Filippi M, Rovaris M, Rocca MA, Sormani MP, Wolinsky JS, Comi G, et al. Glatiramer acetate reduces the proportion of new MS lesions evolving into “black holes”. Neurology. 2001;57:731-3.

43. Dalton CM, Miszkiel KA, Barker GJ, MacManus DG, Pepple TI, Panzara M, et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J Neurol. 2004;251:407-13.

44. Sahraian M, Radue E, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand. 2010;122:1-8.

45. Janardhan V, Suri S, Bakshi R. Multiple Sclerosis: Hyperintense Lesions in the Brain on Nonenhanced T1-weighted MR images evidenced as areas of T1 shortening 1. Radiology. 2007;244:823-31.

46. Mauri-Fábrega L, Díaz-Sánchez M, Casado-Chocan JL, Ucles-Sánchez AJ. Pseudotumoral forms of multiple sclerosis: report of 14 cases and review of the literature. Eur Neurol. 2014;72:72-8.

47. Comi G. Multiple sclerosis: pseudotumoral forms. Neurol Sci. 2004;25:s374-9.48. Sagar HJ, Warlow CP, Sheldon PW, Esiri MM. Multiple sclerosis with

clinical and radiological features of cerebral tumour. J Neurol Neurosurg Psychiatry. 1982;45:802-8.

49. Masdeu JC, Quinto C, Olivera C, Tenner M, Leslie D, Visintainer P. Open-ring imaging sign: highly specific for atypical brain demyelination. Neurology. 2000;54:1427-33.

50. Masdeu JC, Moreira J, Trasi S, Visintainer P, Cavaliere R, Grundman M. The open ring. A new imaging sign in demyelinating disease. J Neuroimaging. 1996;6:104-7.

51. Simon JH, Kleinschmidt-DeMasters BK. Variants of multiple sclerosis. Neuroimaging Clin N Am. 2008;18:703-16.

52. Fitzgerald MJ, Coleman LT. Recurrent myelinoclastic diffuse sclerosis: a case report of a child with Schilder’s variant of multiple sclerosis. Pediatr Radiol. 2000;30:861-5.

53. Nunes JC, Radbruch H, Walz R, Lin K, Stenzel W, Prokop S, et al. The most fulminant course of the Marburg variant of multiple sclerosis-autopsy findings. Mult Scler. 2015;21:485-7.

54. Cañellas AR, Gols AR, Izquierdo JR, Subirana MT, Gairin XM. Idiopathic inflammatory-demyelinating diseases of the central nervous system. Neuroradiology. 2007;49:393-409.

55. Wattjes MP, Richert ND, Killestein J, de Vos M, Sánchez E, Snaebjornsson P, et al. The chameleon of neuroinflammation: magnetic resonance imaging characteristics of natalizumab-associated progressive multifocal leukoencephalopathy. Mult Scler. 2013;19:1826-40.

56. Kleinschmidt-DeMasters BK, Miravalle A, Schowinsky J, Corboy J, Vollmer T. Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J Neuropathol Exp Neurol. 2012;71:604-17.

57. Schiess N, Calabresi PA. Natalizumab: bound to rebound? Neurology. 2009;72:392-3.

58. Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9:425-37.

59. Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366:1870-80.

60. Sorensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R, Havrdova E, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler. 2012;18:143-52.

61. Wattjes MP, Barkhof F. Diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy using MRI. Curr Opin Neurol. 2014;27:260-70.

62. Yousry TA, Pelletier D, Cadavid D, Gass A, Richert ND, Radue E, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2012;72:779-87.

63. Miller TR, Mohan S, Choudhri AF, Gandhi D, Jindal G. Advances in Multiple Sclerosis and its Variants: Conventional and Newer Imaging Techniques. Radiol Clin North Am. 2014;52:321-36.

64. Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol. 2006;5:158-70.

65. De Stefano N, Filippi M. MR spectroscopy in multiple sclerosis. J Neuroimag. 2007;17:31S-5S.

66. Charil A, Yousry TA, Rovaris M, Barkhof F, De Stefano N, Fazekas F, et al. MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”. Lancet Neurol. 2006;5:841-52.

67. Wingerchuk DM, Weinshenker BG. Acute disseminated encephalomyelitis, transverse myelitis, and neuromyelitis optica. Continuum (Minneap Minn). 2013;19(4 Multiple Sclerosis):944-67.

Correspondence

Ángela GuarnizoCarrera 7a B bis # 130-07, apto 405Bogotá, [email protected]

Received for evaluation: March 15, 2016Accepted for publication: November 4, 2016

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DIAGNOSIS AND EVALUATION OF MULTIPLE SCLEROSIS: …webcir.org/revistavirtual/articulos/2017/1_febrero/col/esclerosis... · drome, for example: Optic neuritis plus myelitis, optic