Table 1.
Table summarizing important entities in the differential diagnosis of MS and potential ‘red flags’ in the misdiagnosis of MS.
| Brain white matter | Disease | Cortical gray matter | Disease |
|---|---|---|---|
| Normal | NMO (absent or few lesions), ATM | Cortical/subcortical lesions crossing vascular territories | MELAS |
| Large lesions | AMS (can be confluent with perilesional edema), BCS, PACNS (with mass effect) | Infiltrating lesions that do not remain in gray or white matter boundaries | Abscess |
| Symmetrically distributed lesions | ADEM, AFL | Prevalent involvement versus white matter | Encephalitis |
| Poorly defined lesion margins | ADEM, pattern III MS | Deep gray matter | |
| Absent MRI activity at follow-up | ADEM | Bilateral lesions | ADEM (GM-WM junction), CADASIL |
| Involvement temporal pole, vertex U-fibers, external capsule, insula. | CADASIL | Lacunar infarcts | CADASIL, SVD |
| Bilateral microhemorrhagic foci | CADASIL, SVD, AHEM/AHLE, PACNS | T1-hyperintensity of the pulvinar | FD |
| Frequent sparing of CC and cerebellum | CADASIL, SVD | Multiple discrete lesions in the basal ganglia and thalamus | Susac’s syndrome |
| Predominant CC involvement | Susac’s syndrome | Large and infiltrating basal ganglia lesions | NBD |
| Enhancement of all lesions | ADEM, PACNS, sarcoidosis | Infiltrating lesions without respecting gray-matter or white-matter boundaries | Abscesses |
| Infarcts | SID, PACNS, SVD | T2-hyperintense lesions in the dentate nuclei | AFL (CTX) |
| Punctate parenchyma enhancement | PACNS, sarcoidosis, NBD | Spinal cord | |
| Predominance of lesions at the cortical/subcortical junction | SID | Large and swelling lesions | NMO, ADEM, ATM, Sjögren’s syndrome |
| Diffuse white matter involvement | NBD, encephalitis, SVD, CADASIL | Diffuse posterior column abnormalities | B12D, ACD |
| Cerebral venous sinus thrombosis | NBD | Other | |
| Infiltrating (large) brainstem lesions | NBD | No ‘occult’ changes in the NAWM | NMO, Lyme disease, SID (except in NSLE) |
| Anterior temporal and inferior frontal lobe involvement, associated with enhancement or mass effect | Encephalitis (HSE) | Pontine lacunar infarcts | CADASIL, SVD |
| Isolated lesions with ring enhancement (often complete) | Abscess | Dilation of Virchow–Robin spaces | HHC, PACNS |
| Mass effect | Abscess, metastasis, malignancy, tumefactive MS | Diffuse lactate increase on brain MRS | MELAS |
| Progressively enlarging lesions, asymmetric lesions (juxtacortical origin) | PML | Meningeal enhancement | Susac’s syndrome, PACNS, NBD, meningitis, Lyme disease, sarcoidosis |
| Large lesions, absent or rare mass effect | PML | Hydrocephalus | Sarcoidosis |
| Extensive and bilateral periventricular abnormalities in isolation | B12D, ACD | Absence of optic-nerve lesions | PML |
| Regional atrophy | HHC (hippocampus and amygdala), NBD (brainstem) |
ACD, acquired copper deficiency; ADEM, acute disseminated encephalomyelitis; AFL, adult forms of leukoencephalopathies; AMS, acute multiple sclerosis (Marburg type); ATM, acute transverse myelitis; B12D, vitamin B12 deficiency; BCS, Balo’s concentric sclerosis; CNS, central nervous system; CTX, cerebrotendinous xanthomatosis; FD, Fabry’s disease; HHC, hyper homocystinemia; HIVE, HIV encephalitis; HSE, herpes simplex encephalitis; MELAS, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; MRS, magnetic resonance spectroscopy; MS, multiple sclerosis; NAWM, normal-appearing white matter; NBD, Behçet’s disease with CNS involvement; NMO, neuromyelitis optica; NSLE, neuropsychiatric systemic lupus erythematosus; PACNS, primary angiitis of the CNS; PML, progressive multifocal leukoencephalopathy; SID, systemic immune-mediated disease; SSP, subacute sclerosing panencephalitis; SVD, small-vessel disease.