The Relationship between MRI and Multiple Sclerosis. Carlos Rangel, RT UNMC MRI Program

Transcription

1 1 The Relationship between MRI and Multiple Sclerosis Carlos Rangel, RT UNMC MRI Program

2 2 Abstract This paper will explain Multiple Sclerosis and how imaging is used to diagnose it, with the help of multiple resources that were found from various books and journals. The overall object of this paper is to review the current and relevant literature pertaining to the origin, imaging, and treatment for Multiple Sclerosis in order to obtain information beneficial for radiologic technologists. This manuscript will first define what Multiple Sclerosis (MS) is as a disease and how it reacts with the body until its final stages. The two main points that will be focused on in this manuscript are the origin and imaging of MS and how the radiologic technologist should be prepared when imaging this patient as well as caring for this patient while they are in the department getting their exam done.

3 3 Multiple Sclerosis (MS) is a chronic disease characterized by inflammation, demyelination, gliosis (scarring), and neuronal loss; the course can be relapsing-remitting or progressive. 1 Lesions of MS typically occur at different times and in different central nervous locations. Manifestations of MS vary from a benign illness to a rapidly evolving and incapacitating disease requiring profound lifestyle adjustments. The origins of MS affect three hundred and fifty thousand individuals in the United States and two point five million individuals worldwide. 2 The information presented in this article will explain the origin, structure, clinical presentation, imaging, and management of MS, and establishes the vital role that imaging plays in the care of diagnosing and treating such a disease. Methods A literature review was conducted on the origin, imaging characteristics, and management of Multiple Sclerosis. Terms related to the MS were entered into an electronic database with the subject Multiple Sclerosis and imaging. The terms included clinical findings of Multiple Sclerosis, treatment for Multiple Sclerosis, and imaging of Multiple Sclerosis. The initial focus of the literature review was on large studies that included historical data and follow-up information, including treatment options. A more refined search was then performed for available articles published within the past six years. Approximately fifty articles were chosen for their usefulness initially, although only twenty were used as references in this review. Results

4 4 New MS lesions begin with perivenular cuffing by inflammatory mononuclear cells, predominantly T cells and macrophages, which also infiltrate the surrounding white matter. 3 At sites of inflammation, the blood-brain barrier is disrupted and the vessel wall is preserved. Involvement of the humoral immune system is also evident; small numbers of B lymphocytes also infiltrate the nervous system, and myelin-specific autoantibodies are present on degenerating myelin sheaths. 3 As lesions evolve, there is prominent astrocytic proliferation (gliosis). Surviving oligodendrocytes or those that differentiate from precursor cells can partially remyelinate the surviving naked axons, producing socalled shadow plaques. In many lesions, oligodendrocyte precursor cells are present in large numbers but fail to differentiate and remyelinate. 2 Over time, ectopic lymphocyte follicles appear in perivascular and perimeningeal regions, consisting of aggregates of T and B cells and resembling secondary lymphoid structures. Although relative sparing of axons is typical of MS, partial or total axonal destruction can also occur, especially within highly inflammatory lesions. Thus, MS is not solely a disease of myelin, and neuronal pathology is increasingly recognized as a major contributor to irreversible neurologic disability. 4 Inflammation and plaque formation are present in the cerebral cortex, and significant axon loss indicating death of neurons is widespread, especially in advanced cases. Manifestations of MS vary from a benign illness to a rapidly evolving and incapacitating disease requiring profound lifestyle adjustments. MS is approximately threefold more common in women than men. The age of onset is typically between twenty and forty years (slightly later in men than in women), but the disease can present across the life span. In ten percent of cases it begins before age eighteen years and in a

5 5 small percentage it begins before the age of ten years. 5 Caucasians are inherently at higher risk for MS than Africans or Asians, even when residing in a similar environment. MS also aggregates within some families, and adoption, half-sibling, and twins. 5 The onset of MS may be abrupt or insidious. Symptoms may be severe or seem so trivial that a patient may not seek medical attention for months or years. In fact, at autopsy, approximately zero point one percent of individuals who were asymptomatic during life will be found, unexpectedly, to have pathologic evidence of MS. Symptoms of MS are extremely varied and depend on the location and severity of lesions within the central nervous system. Examination often reveals evidence of neurologic dysfunction, often in asymptomatic locations. For example, a patient may present with symptoms in one leg but signs in both. Weakness of the limbs may manifest as loss of strength, speed, or dexterity, as fatigue, or a disturbance of gait. Exercise-induced weakness is a characteristic symptom of MS. 6 The weakness is of the upper motor neuron type and is usually accompanied by other pyramidal signs such as spasticity, hyperreflexia, and Babinski's signs. 5 Occasionally a tendon reflex may be lost (simulating a lower motor neuron lesion) if an MS lesion disrupts the afferent reflex fibers in the spinal cord. Another common symptom is spasticity which is commonly associated with spontaneous and movement-induced muscle spasms. More than thirty percent of MS patients have moderate to severe spasticity, especially in the legs. 7 This is often accompanied by painful spasms interfering with ambulation, work, or self-care. Occasionally spasticity provides support for the body weight during ambulation, and in these cases treatment of spasticity may actually do more harm than good.

6 6 Sensory symptoms are varied and include both paresthesias (e.g., tingling, prickling sensations, formications, pins and needles, or painful burning) and hypesthesia (e.g., reduced sensation, numbness, or a dead feeling). Unpleasant sensations (e.g., feelings that body parts are swollen, wet, raw, or tightly wrapped) are also common. 8 Sensory impairment of the trunk and legs below a horizontal line on the torso (a sensory level) indicates that the spinal cord is the origin of the sensory disturbance. It is often accompanied by a bandlike sensation of tightness around the torso. Pain is a common symptom of MS, experienced by more than fifty percent of patients. 5 Pain can occur anywhere on the body and can change locations over time. Ataxia usually manifests as cerebellar tremors. 9 Ataxia may also involve the head and trunk or the voice, producing a characteristic cerebellar dysarthria (scanning speech). 10 Axonal damage occurs in every newly formed MS lesion, and cumulative axonal loss is considered to be the major cause of progressive and irreversible neurologic disability in MS. As many as seventy percent of axons are lost from the lateral corticospinal tracts in patients with advanced paraparesis from MS, and longitudinal MRI studies suggest there is progressive axonal loss over time within established, inactive lesions. 5 Knowledge of the mechanisms responsible for axonal injury is incomplete and, despite the fact that axonal transactions are most conspicuous in acute inflammatory lesions, it is still unclear whether demyelination is a prerequisite for axonal injury in MS. 11 Demyelination can result in reduced trophic support for axons, redistribution of ion channels, and destabilization of action potential membrane potentials, (See Figures 1 and 2). 5 Axons can adapt initially to these injuries; with time distal and retrograde degeneration often occurs. Therefore, promotion of remyelination and preservation of

7 7 oligodendrocytes early in the disease course remain important therapeutic goals in MS. 12 Some evidence suggests that axonal damage is mediated directly by resident and invading inflammatory cells and their toxic products, in particular by microglia, macrophages, and CD8 T lymphocytes. 13 Activated microglia are particularly likely to cause axonal injury through the release of NO and oxygen radicals and via glutamate, which is toxic to oligodendrocytes and neurons. Interestingly, NMDA (glutamate) receptors are expressed on naked axon membranes that have undergone demyelination, perhaps providing a mechanism for glutamate-mediated calcium entry and cell death. 14 Figure 1. Showing how an actual nerve unchanged by MS. 5

8 8 Figure 2. Showing a nerve changed by MS. 5 Imaging Magnetic Resonance Imaging (MR) revolutionized the research, diagnosis and treatment of MS. With sensitivity in detecting MS at approximately eighty five percent and excellent tissue contrast, MR far surpasses computed tomography (CT) scanning in imaging the presence of plaques or scarring caused by MS. 15 Brains that appear normal on CT images show MS plaques on MR images. On T2 images, brain tissue is dark, cerebrospinal fluid is bright and MS plaques are bright areas or spots. On MS images, the distribution of lesions are random in the central nervous system white matter of the supratentorium, infratentorium and spinal cord. The most common locations are periventricular white matter, corpus callosum, visual system from optic nerve to occipital

9 9 lobe and spinal cord. Spinal cord involvement is often symptomatic, while brain lesions are more likely to be asymptomatic. 16 Gadolinium is used as an enhancement to show inflammation-induced permeability changes to the blood-brain barrier and distinguish active from inactive lesions (See Figure 3 A, B). 17 It also objectively monitors disease activity at the CNS level and assesses the effectiveness of treatment modalities. Gadolinium enhancement is used in relapsing-remitting and secondary progressive MS during relapse stage. Enhancement is rare in primary progressive MS. A B Figure 3. Post gadolinium contrast image demonstrating enhancing MS plaques. A. Sagittal T1 image. B. Coronal T1 image. 17 MR sensitivity for detecting active brain lesions can be increased by injecting larger doses of contrast material, up to a triple dose (0.3 mmol/kg). Sensitivity can be further improved by delaying scanning by as much as forty to sixty minutes after injection. 18 MS plaques in the brain are commonly ovoid or round in shape and can have a lesion-within-a-lesion, bull s-eye appearance. 19 The most common lesions in MS are

10 10 Dawson fingers, which are ovoid lesions perpendicular to the ventricles that occur along the path of the deep medullary veins, and corpus callosum lesions occurring at the interface with the septum pellucidum. 9 Another paradox of MS is that the distribution and number of plaques seen on MR images may not be representative of the severity of the clinical disease state. A finding of three or more lesions of at least five mm in size in a periventricular location is considered suggestive of MS. 11 Despite the sensitivity and superiority of MR as a diagnostic tool, a definitive diagnosis of MS cannot be made solely on the basis of MR imaging. Other neurologic diseases, such as glioma, cause lesions in the brain that appear similar to MS plaques on MR images. 11 Abnormalities not related to any disease process, called unidentified bright objects (UBOs), are sometimes found in healthy older individuals. 12 Conversely, a normal MR does not rule out a diagnosis of MS. Approximately five percent of patients confirmed to have multiple sclerosis on the basis of other criteria do not show any plaques or lesions in the brain on MR images. 11 Their lesions may be in the spinal cord or they may have plaques that cannot be detected by MR. Eventually, the majority of people with MS will have brain and/or spinal lesions that will be visible on MR. However, an initial diagnosis of MS becomes more questionable the longer an MR examination remains negative. 20 T2-weighted images are used to assess edema and tissue destruction early in the inflammatory stage of MS. T2-weighted images have limited sensitivity and specificity in measuring disease burden when demyelination and gliosis occur in later stages of disease progression. 1 Lesions are more easily identified with proton density (PD)-weighted MR as opposed to standard T2 imaging. In a PD series, MS lesions remain hyperintense,

11 11 while the cerebrospinal fluid signal is suppressed. Depending on the PD technique, the cerebrospinal fluid signal can be suppressed to a variable degree, rendering it isointense to hypointense relative to the brain parenchyma. Such a sequence results in substantial suppression of perivascular spinal fluid spaces that may penetrate to the subcortical white matter. These spaces, called Virchow-Robin spaces, may appear as hyperintense spots on standard T2-weighted MR images. 20 A fluid-attenuated inversion recovery (FLAIR) sequence is a widely used variant of T2 imaging. (See Figure 4 A, B). Ventricles are starkly differentiated from periventricular white matter lesions on FLAIR imaging and FLAIR suppresses the T2 hyperintensity of fluid. Parenchymal hemisphere lesions stand out more prominently with FLAIR imaging, and the ability to detect juxtacortical lesions is improved as opposed to conventional T2 scans. 19 A B Figure 4. Fluid-attenuated inversion recovery (FLAIR) MR image showing abnormal areas. Hyperintense signal in periventricular white matter demonstrates characteristic pattern of a perivascular distribution (long axis perpendicular to body of lateral ventricle). A. Axial FLAIR image. B. Sagittal FLAIR image. 2

12 12 On T1-weighted scans, hypointense lesions that do not persist may indicate a reversible change such as edema. Persistent lesions are indicative of axonal loss and demyelination. 18 Severe disease progression can be gauged by the presence of black holes on hypointense T1-weighted images. Black holes emit very low signals, and some evidence suggests they may represent iron deposits in the brain. 20 Spinal Cord Imaging Spinal cord imaging is technically challenging because of the thin, longitudinal anatomy of the spinal cord and the introduction of artifacts by voluntary and involuntary motions. 6 MS plaques, depending on their age, appear as areas of slightly low to low signal intensity on unenhanced T1-weighted images. The plaques are shaped like nodules, rings or arcs, generally less than two vertebral bodies in length. 7 Active disease responds rapidly to gadolinium enhancement. The enhancement may last two to eight weeks and steroids (used in treatment) typically do not suppress the enhancement of active plaques. Chronic lesions do not respond to contrast enhancement. On T2-weighted images, MS plaques appear hyperintense and the spinal cord may or may not be focally enlarged (See Figure 5). Cord enlargement is characteristic of active disease. Larger active lesions may have extensive edema with associated cord expansion. Chronic lesions often demonstrate focal cord atrophy. Spinal lesions usually coexist with more severe concomitant brain plaques. As many as twenty percent of spinal MS lesions are isolated. 19 Spinal cord narrowing due to atrophic changes is present in ten percent of patients with spinal cord involvement. A demyelinating process should always be considered if any mass-like lesions are present because MS may mimic a neoplasm. 11

13 13 Figure 5. Sagittal MR image of the cervical spine showing MS lesions at the craniocervical junction and posterior to C3 (arrows). Because artifacts are a concern in spinal imaging, FLAIR techniques are not as useful as conventional T2 to evaluate the spinal cord or posterior fossa. More effective imaging in these anatomic areas are PD or spin echo sequences. 1 Conclusion This article describes the origins, clinical presentation, and imaging of MS. MRI plays a significant role in the timely detection of MS. It is imperative that an imaging professional be well versed in the origins and diagnostic characteristics of MS in order to focus care toward the lesions unique qualities and positively affect a patient s outcome. The literature suggests that the recent advances in MRI scans may improve the doctors understanding of the patient s condition and help with the prognosis of the patient.

14 14 Technologist need to know this information to be able to assist not only the patients but the doctors as well.

15 15 AMA References 1. Bonnier G, Roche A, Romascano D, et al. Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis. Ann Clin Transl Neurol. 2014;1(6): Choo EK DR. Chapter e magnetic resonance imaging. In: Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T, ed. Tintinalli's emergency medicine: A comprehensive study guide. 7th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 15, Cormier JN, Gronchi A, Pollock RE. Soft tissue sarcomas. In: Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE, ed. Schwartz's principles of surgery. 10th ed. New York,NY: McGraw-Hill; &Se ctionid= Accessed October 10, Cunningham F, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS. Neurologic disorders. In: KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS., ed. Williams obstetrics. New York, NY: McGraw-Hill; &Sectionid= Accessed October 12, Dixon RL WC. Chapter 2. the physical basis of diagnostic imaging. In: Chen MM, Pope TL, Ott DJ., ed. Basic radiology. 2nd ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 20, Fan AP, Govindarajan ST, Kinkel RP, et al. Quantitative oxygen extraction fraction from 7-tesla MRI phase: Reproducibility and application in multiple sclerosis. J Cereb Blood Flow Metab Greenberg DA, Aminoff MJ, Simon RP. Laboratory investigations. In: Clinical neurology. 8th ed. New York, NY: McGraw-Hill; &Sectionid=

16 16 8. Hauser SL GD. Multiple sclerosis and other demyelinating diseases. In: Principles of internal medicine. 18th ed. ; &Sectionid= Kedia S, Knupp K, Schreiner T, Yang ML, Levisohn PM, Moe PG. Neurologic & muscular disorders. In: Hay WW, Jr., Levin MJ, Deterding RR, Abzug MJ, ed. CURRENT diagnosis & treatment: Pediatrics. 22nd ed. New York, NY: McGraw- Hill; &Sectionid= Accessed October15, Lagana MM, Chaudhary A, Balagurunathan D, et al. Cerebrospinal fluid flow dynamics in multiple sclerosis patients through phase contrast magnetic resonance imaging. Curr Neurovasc Res Lal G CO. Thyroid, parathyroid, and adrenal. In: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE, ed. Schwartz's principles of surgery. 10th ed. New York,NY: McGraw-Hill; &Sectionid= Accessed October 18, LeBlond RF, Brown DD, DeGowin RL. Chapter 14. the neurologic examination. In: LeBlond RF, Brown DD, DeGowin RL., ed. DeGowin's diagnostic examination. 9th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 17, Levinson W. Tolerance & autoimmune disease. In: Levinson W., ed. Review of medical microbiology and immunology. 13th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 17, Riordan-Eva P HW. Chapter 14. neuro-ophthalmology. In: Riordan-Eva P, Cunningham ET, Jr, ed. Vaughan & asbury's general ophthalmology. 18th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 20, 2014.

17 Ropper AH, Samuels MA, Klein JP. Chapter 36. multiple sclerosis and other inflammatory demyelinating diseases. In: Ropper AH, Samuels MA, Klein JP, ed. Adams & victor's principles of neurology. 10th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 19, Ross JJ RA. Ross J.J., ropper A.H. ross, john J., and allan H. ropper.chapter 213. multiple sclerosis. In: Dressler DD, Brotman DJ, Ginsberg JS, ed. Principles and practice of hospital medicine. New York, NY: McGraq-Hill; &Sectionid= Accessed October 19, 's-gravenmade EJ, Minderhoud JM. MRI and MRS diagnosis. application in multiple sclerosis patients and research animals with experimental allergic encephalomyelitis. Ned Tijdschr Tandheelkd. 1993;100(4): Simon J, Kinkel R, Kollman C, et al. Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS multiple sclerosis prevention trial. Mult Scler Sloan EP, Handel DA, Gaines S. Chapter 167. chronic neurologic disorders. In: Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T., ed. Tintinalli's emergency medicine: A comprehensive study guide. 7th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 19, Waxman SG. Chapter 22. imaging of the brain. In: Waxman SG, ed. Clinical neuroanatomy,. 27th ed. New York,NY: McGraw-Hill; &Sectionid= Accessed October 26, Waxman SG. Chapter 6. the vertebral column and other structures surrounding the spinal cord. In: Waxman SG., ed. Clinical neuroanatomy. 27th ed. New York, NY: McGraw-Hill; &Sectionid= Accessed October 28, 2014.