Radiology and Imaging Diagnosis of Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory neurological illness common in young adults. The prevalence and incidence of MS are regionally and globally increasing. MRI scans are important for diagnosis and regular follow-up to monitor treatment response and disease progression. Interpretation of MRI scans should be performed by experienced radiologists who are familiar with the patient’s clinical and laboratory data, and who are able to detect evidence supporting or refuting a diagnosis of MS.

multiple sclerosis
radiology
imaging

1. Brain MRI Recommendations

The recommendations for patients with a CIS and/or suspected MS include a baseline gadolinium brain MRI to establish DIT ^[1]. Performing cervical cord and brain MRIs at the same time could be valuable in the diagnosis of myelitis in CIS patients and in reducing the need for subsequent MRI appointments ^[1]. If the patient has myelitis with insufficient features on brain MRI or is above the age of 40 with nonspecific MRI changes, a spinal cord MRI is recommended ^[1]. Finally, patients with severe optic neuritis and poor recovery require orbital MRI imaging ^[1].

MRI Follow-Up

Based on the current McDonald Criteria ^[2], patients with suspected MS and/or CIS should have follow-up MRIs to look for DIT evidence, which includes new T2 lesions or gadolinium-enhancing lesions. Monitoring is recommended at 6–12 months for high-risk CIS, where the patient has two or more ovoid lesions on initial MRI. For low-risk CIS patients with normal brain MRI, less than two lesions on MRI, or undetermined clinical syndromes with suggestive MRI lesions (like RIS), follow-up is recommended at 12–24 months ^[2].

Brain MRI is recommended at presentation for patients with an MS diagnosis if no previous imaging is obtainable, postpartum to determine a new baseline, and before changing or escalating DMT treatment along with close supervision on side-effects, relapses, and current modalities ^[3]^[4].

Moreover, patients on DMT should have imaging done every 1–2 years to evaluate any subclinical disease activity (i.e., gadolinium-enhancing lesions or new T2 lesions). For clinically stable patients with 2 to 3 years of unvaried management, less frequent MRI scans are required ^[5].

Using gadolinium-based contrast agents is not necessary, but may be useful for discovering mild disease activity because new T2 MS lesions could be missed if there is a preexisting large T2 lesion burden obscuring new T2 lesion activity. Gadolinium-based contrast is also recommended in case there is a need for reassessment or unexpected clinical deterioration ^[5].

For pregnant patients, MRI imaging may be cautiously used in pregnancy only if the benefits outweigh the risks in terms of diagnostic performance and medical outcome ^[5].

Due to the minimal distribution of gadolinium-based contrast into the breast milk and subsequently to the infant’s gut, studies recommend continuing breastfeeding after receiving such an agent ^[5].

2. Spinal Cord MRI Recommendations

Consider spinal MRI when:

Spinal cord-specific symptoms (myelitis, progressive myelopathy)
Recurrent myelitis
Older age of start of symptoms
Inability to establish DIT

Typical MRI findings in the spinal cord in MS are short, less than three vertebral segments, peripheral white matter, and constitute less than 50% of the cross-sectional area. Conversely, other inflammatory CNS diseases, such as NMO/MOG, display longitudinally extensive lesions, with at least three vertebral segments and 50% of the cross-sectional area affected, and more grey matter involvement is detected ^[6]. Moreover, in addition to the extensive involvement of grey matter on MRI, NMOSD often displays the characteristic “H-shaped” cord lesion ^[7]. In MOG, “pencil-thin” linear enhancement of the ependymal canal may be spotted ^[8].

MRI Protocols

Brain: 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a diffusion-weighted imaging (DWI) sequence ^[5].

Spinal cord: Sagittal T1-weighted and proton attenuation, short-tau inversion recovery (STIR) or phase-sensitive inversion recovery, axial T2- or T2-weighted imaging through suspicious lesions, and, in some cases, post-contrast gadolinium-enhanced T1-weighted imaging ^[5]. Thoracic and conus imaging is proposed if symptoms spread to this region to exclude a different diagnosis ^[5].

Whenever available, using 3T scanners may offer the advantage of a higher rate of lesion detection and efficiency in regard to acquisition time when compared to scanners of lower magnetic field strength ^[9].

Gadolinium-Based Contrast Agents (GBCAs)

In CIS, the utilization of gadolinium-based contrast agents (GBCAs) is invaluable as it allows for an earlier diagnosis by demonstrating lesions’ DIT (GBCA-enhancing lesion) and DIS. Early diagnosis allows for early management, which may impede disease progression and enhance long-term projection ^[5]. However, the detection of T2 lesions with relapsing–remitting MS predicts a worse diagnosis.

For patients with established MS, GBCA is beneficial for evaluating highly active disease, rapid decline, unexpected or unexplained worsening, or possible alternative diagnoses ^[5].

GBCA is an option for long-term monitoring of patients with MS for detection of mild disease activity, which may cause changes in therapy. The use of GBCA could be useful during the first 2 years of management, but is not necessary in the absence of a large T2 lesion burden because new T2 MS lesions could be detected on high-quality MRI utilizing a standardized protocol ^[5].

Selecting a GBCA could be complicated due to the need for balancing risks vs. benefits for an individual patient, the patient population, and the health care system in general ^[1].

Concerns over the safety of GBCA have been raised in recent years ^[1]. GBCA, which is valuable for the assessment of patients with MS, is not without risk. Nephrogenic systemic sclerosis as a complication of GBCA has been described in patients with preexisting renal dysfunction, requiring assessment of renal function prior to receiving these agents. More recently, gadolinium retention has been detected in patients with MS who have undergone gadolinium-enhanced MRI of the brain ^[1]. This evidence has prompted the U.S. Food and Drug Administration (US FDA) to issue a drug safety alert and request manufacturers to update the medication guide for patients to inform them of this issue ^[1].

The long-term consequences of gadolinium retention in the CNS remain unknown. Additionally, there is variability in the CNS retention of GBCAC based on its chemical structure. GBCA can be categorized as linear or macrocyclic, with linear agents retained at higher concentrations and for longer periods than macrocyclic agents. In all cases, written informed consent should be obtained when GBCA is used to describe the possible complications of nephrogenic systemic fibrosis and gadolinium retention. In addition, radiology departments should be encouraged to use GBCA, which has shorter retention times ^[1].

Recommendations for Communication

MRI requisition:

When making an MRI requisition, the clinician must request a standardized MRI brain and/or spinal cord protocol with questions on diagnosis, monitoring for management decision addressed, relevant medical history, and examination findings addressed. Updates on current DMT status and JCV status (if on natalizumab) should be included. Finally, dates of previous examinations, as well as locations, should be provided if applicable.

This entry is adapted from the peer-reviewed paper 10.3390/ctn7010005

References

McDonald, W.I.; Compston, A.; Edan, G.; Goodkin, D.; Hartung, H.P.; Lublin, F.D.; McFarland, H.F.; Paty, D.W.; Polman, C.H.; Reingold, S.C.; et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc. 2001, 50, 121–127.
Consortium of Multiple Sclerosis Centers. Consortium of MS Centers MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of MS; Consortium of Multiple Sclerosis Centers: Hackensack, NJ, USA, 2018.
Toledano, M.; Weinshenker, B.G.; Solomon, A.J. A Clinical Approach to the Differential Diagnosis of Multiple Sclerosis. Curr. Neurol. Neurosci. Rep. 2015, 15, 57.
Siva, A. Common Clinical and Imaging Conditions Misdiagnosed as Multiple Sclerosis: A Current Approach to the Differential Diagnosis of Multiple Sclerosis. Neurol. Clin. 2018, 36, 69–117.
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Wildner, P.; Stasiołek, M.; Matysiak, M. Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases. Mult. Scler. Relat. Disord. 2019, 37, 101452.
Kim, H.J.; Paul, F.; Lana-Peixoto, M.A.; Tenembaum, S.; Asgari, N.; Palace, J.; Klawiter, E.C.; Sato, D.K.; de Seze, J.; Wuerfel, J.; et al. MRI characteristics of neuromyelitis optica spectrum disorder: An international update. Neurology 2015, 84, 1165–1173.
Denève, M.; Biotti, D.; Patsoura, S.; Ferrier, M.; Meluchova, Z.; Mahieu, L.; Heran, F.; Vignal, C.; Deschamps, R.; Gout, O.; et al. MRI features of demyelinating disease associated with anti-MOG antibodies in adults. J. Neuroradiol. 2019, 46, 312–318.
Wattjes, M.P.; Ciccarelli, O.; Reich, D.S.; Banwell, B.; de Stefano, N.; Enzinger, C.; Fazekas, F.; Filippi, M.; Frederiksen, J.; Gasperini, C.; et al. 2021 MAGNIMS–CMSC–NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol. 2021, 20, 653–670.

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