2. Revised criteria for MRI diagnosis of MS have improved sensitivity while maintaining specificity.[1] However, it is important to identify atypical foci that might suggest an alternate diagnosis. Chronic MS plaques appear on T2-weighted images as well-demarcated, ovoid lesions, such as the one seen in this slide.[2]
1. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69;
2. Ropper AH, Samuels MA. Chapter 36. In: Ropper AH, Samuels MA, eds. Adams and Victor's Principles of Neurology. 9th ed. New York: McGraw-Hill; 2009.

3. A range of conditions may present with symptoms that mimic aspects of MS.[1] Here, MRI of a migraineur reveals lesions that could be confused with those seen in a patient with MS. Other rule-outs in differential diagnosis include:
Anti-phospholipid syndrome
Behçet disease
CADASIL
CNS lymphoma
Infection
Inflammation
Ischemic white matter disease
Lyme disease
Metabolic
Neurosyphilis
Other vasculitides
Primary angiitis of the CNS
Sarcoidosis
Sjögren syndrome
Systemic lupus erythematosus
Vitamin B12 deficiencies
Before a diagnosis of MS can be made, especially in the context of atypical clinical presentations, laboratory studies are advisable to exclude disorders whose symptoms and signs might mimic those of MS.[2] Some of these include:
Genetic syndrome
Infectious diseases
Lesions of the posterior fossa and spinal cord
Metabolic disorders
Neoplastic illnesses
Psychiatric disorders
Systemic autoimmune diseases
Variants of MS: Balo concentric sclerosis, Devic disease, Schilder's diffuse sclerosis, Marburg multiple sclerosis
Vascular disorders
1. Cohen J, Rensel M. In: Burks J, Johnson K, eds. Multiple Sclerosis Diagnosis, Medical Management and Rehabilitation. New York: Demos; 2000:
2. Noseworthy JN, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:

4. EM is a 35-year-old female who presented to the hospital with difficulty walking and gradual worsening of numbness involving the right face. Over the next several days, she also noted clumsiness involving her left side, weakness of her left arm, and occasional diplopia.
Her exam showed a diplopia on right lateral gaze, diminished sensation to pinprick in the right upper lip, normal motor survey, and dysmetria on finger-to-nose and heel-knee-shin on the left side with ataxia of gait. Her imaging shows multiple focal areas of enhancement involving the brain stem.
She was treated with 5 days of high-dose intravenous methylprednisolone with marked improvement of symptoms.
Neurosarcoidosis is uncommon and usually involves the cranial nerves[1] or meninges rather than the parenchyma. Neurosarcoidosis may present with simultaneous enhancement of multiple punctate lesions often along Virchow-Robin spaces.[2] A similar pattern can be seen with neurologic Behçet disease.[2] Bickerstaff encephalitis might also be included in the differential diagnosis.
Neuroborreliosis[3] and treponemal infections of the CNS[4] (eg, syphilis) also usually involve the meninges and only rarely the parenchyma
1. Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis -- diagnosis and management. QJM. 1999;92:
2. Hoitsma E, Drent M, Sharma OP, et al. A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st century. Curr Opin Pulm Med. 2010;16:
3. Halperin JJ. Nervous system Lyme disease: diagnosis and treatment. Rev Neurol Disease. 2009;6:4-12.
4. Halperin JJ. A tale of two spirochetes: Lyme disease and syphilis. Neurol Clin. 2010;28:

5. Ring-enhancing lesions can be observed in MS, though often there is incomplete ring formation.[1] Note that in this image, in addition to the incomplete ring-enhancing lesion, there are multiple lesions more characteristic of disease. Additionally, T2-weighted images show a hypointense rim, possibly resulting from iron-containing macrophages,[2] which corresponds to the ring seen on T1 Gd-enhanced imaging. This low intensity rim on T2WI could potentially be mistaken for an abscess. Large ring-enhancing lesions located beneath the cortex with edema may be suspicious f
1. Masdeu JC, Quinto C, Olivera C, et al. Open-ring imaging sign: highly specific for atypical brain demyelination. Neurology. 2000;54:
2. Llufriu S, Pujol T, Blanco Y, et al. T2 hypointense rims and ring-enhancing lesions in MS. Mult Scler. 2010;16:
or primary CNS tumor or metastasis. Enhancement in primary CNS lymphoma may persist for a longer duration than typically observed in MS.

6. This image is from a patient who has Balo’s concentric sclerosis
This image is from a patient who has Balo’s concentric sclerosis. Note the large lesion with minimal edema and concentric appearance. The site most commonly affected in Balo variant of MS is the cerebral white matter, although lesions within the basal ganglia, pons, and spinal cord also have been documented.[1] Lesions are characterized by large areas of demyelination surrounded by smaller areas of preserved myelin.[1] Histopathological features of these areas of preserved myelin vary; some authors report normally myelinated axons[1,2] while others have reported either remyelinated or partially demyelinated myelin[3] and still others suggest that the alternating areas are merely a stage in the process of demyelination.[4] Additionally, factors contributing to the concentric pattern have yet to be fully determined; some experts feel that periplaque tissue might contain increased levels of stress proteins, making it more resistant to damage.[5]
Balo's concentric rings have been described in isolation associated with a fulminant clinical decline,[6] but they have also been documented to coexist in patients with an initial diagnosis of MS.[1,7] The paucity of cortical gray involvement and usual sparing of subcortical U fibers can be observed on imaging.[6] Additionally, contrast enhancement, which is often heterogeneous, can sometimes be seen limited to the outer rings,[7] though this might be in part dependent upon the timing of MRI scans.[4] No enhancement was observed in this patient.
1. Moore GRW, Berry K, Oger JJF, et al. Balo’s concentric sclerosis: surviving normal myelin in a patient with a relapsing-remitting clinical course. Mult Scler. 2001;7:
2. Yao DL, Webster HF, Hudson LD, et al. Concentric sclerosis (Balo): morphometric and in situ hybridization study of lesions in six patients. Ann Neurol. 1994;35:18-30.
3. Moore GR, Neumann PE, Suzuki K, et al. Balo’s concentric sclerosis: new observations on lesion development. Ann Neurol. 1985;17:
4. Iannucci G, Mascalchi M, Salvi F, et al. Vanishing Balo-like lesions in multiple sclerosis. J Neurol Neurosurg Psychiatry, 2000;69:
5. Stadelmann C, Ludwin S, Tabira T, et al. Tissue preconditioning may explain concentric lesions in Balo’s type of multiple sclerosis. Brain. 2005;128:
6. Kira J. Astrocytopathy in Balo’s disease. Mult Scler. 2011;17:
7. Wang C, Zhang KN, Wu XM, et al. Balo’s disease showing benign clinical course and co-existence with multiple sclerosis-like lesions in Chinese. Mult Scler. 2008;14:

7. Case Study: Patient C
CM is a 34-year-old female with a history of SLE. Previous exam showed cutaneous manifestations and laboratory confirmed diagnosis with high titers of antinuclear and double-stranded DNA antibodies. She had presented with transient quadraparesis that significantly improved with high-dose intravenous steroids.
Imaging of her CNS revealed a hyperintense focus involving the upper cervical spine and the foci in the brain indicated by the arrows.
Parenchymal lesions are not unique to MS and might also be seen in a variety of other conditions, including SLE, Sjögren syndrome, and Adamantaiades-Behçet disease.[1] Lesions are often subcortical with an appearance of vascular pathology (thin arrows) but in rare cases might also be adjacent to ventricles (thick arrows) or involve the corpus callosum.[2,3] Similar findings have been observed in anti-phospholipid syndrome.[2]
Antinuclear antibody positivity may be seen in MS, but persistent high titers and/or presence of systemic involvement should increase suspicion for diagnosis of connective tissue disease.[4]
1. Theodoridou A, Settas L. Demyelination in rheumatic diseases. J Neurol Neurosurg Psychiatry. 2006;77:
2. Hughes GR. Migraine, memory loss, and "multiple sclerosis". Neurological features of the antiphospholipid (Hughes') syndrome. Postgrad Med J. 2003;79:81-83.
3. Rovaris M, Viti B, Ciboddo G, et al. Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study. J Neurol Neurosurg Psychiatry. 2000;68:
4. Ferreira S, D'Cruz DP, Hughes GR. Multiple sclerosis, neuropsychiatric lupus and antiphospholipid syndrome: where do we stand? Rheumatology. 2005;44:

8. T2-hyperintensities located in subcortical or deep white matter areas often may not be specific to any disorder or may represent small vessel ischemic disease. Such lesions can be seen in disorders such as migraine headache where an association between headache, especially with aura, and increased stroke risk has been documented.[1] Evaluating lesion characteristics, as previously described, may assist in differentiating non-specific T2 foci from those consistent with MS.
1. Pezzini A, Del Zotto E, Giossi A, et al. The migraine-ischemic stroke connection: potential pathogenic mechanisms. Curr Mol Med. 2009;9:

9. Gd within developmental venous abnormalities can be mistaken for parenchymal enhancement. This image shows a venous angioma. Note that the area of enhancement appears tortuous and that corresponding hyperintensity in the T2-weighted images is linear and follows the contour of the vessel.