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Imaging in multiple sclerosis and related disorders Shelley Renowden Correspondence to Dr Shelley Renowden, Department of Neuroradiology, Frenchay Hospital, NHS Trust, Bristol, UK

To cite: Renowden S. Pract Neurol Published Online First: [ please include Day Month Year] doi:10.1136/ practneurol-2014-000856

INTRODUCTION Demyelinating disorders of the central nervous system (CNS) may be divided into primary (cause unknown, eg, multiple sclerosis (MS)) and secondary (eg, infective, hypoxic–ischaemic, metabolic, toxic) processes. The underlying cause damages the myelin sheath and/or oligodendrocyte. MRI is the imaging modality of choice because of its high spatial and contrast resolution, but imaging features are often non-specific. The most common causes of multifocal white matter lesions are perivascular spaces (not discussed here), ischaemia (small vessel disease) and MS. Small vessel disease is much more common than MS, hence, their distinguishing features are discussed first. SMALL VESSEL DISEASE Vascular white matter lesions are age-related, asymptomatic foci of ischaemic demyelination (unidentified bright objects or ‘UBOs’), myelin pallor or gliosis. They are uncommon in those below age 40 years (figure 1), thereafter, increasing in frequency with age. These white matter changes occur in 5–10% of those aged 20–40 years. Most patients are neurologically normal. At all ages, the incidence and lesion load increase with cardiovascular risk factors (figure 2). The white matter lesions are small and have high T2 signal but differ from MS plaques because of their irregular shape, poor definition and peripheral location and are most common in the frontal and parietal lobes. Posterior fossa lesions are uncommon, and callosal lesions are rare because of a dual blood supply. Patients with multiple cardiovascular risk factors may have larger, more confluent, deep white matter lesions around the trigones of the lateral ventricles—the white matter watersheds—and their vascular aetiology is often suppported by the presence of cortical infarctions, arterial

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borderzone/watershed lesions, lacunes and multifocal basal ganglia lesions (figure 3). Binswanger’s disease (subacute arteriosclerotic encephalopathy) is a heterogeneous disorder; most cases represent severe hypertensive microangiopathy, or more rarely, undiagnosed CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy). These patients show progressive cognitive difficulties, gait instability, subtle long tract signs and cortical release signs, and have prominent white matter abnormalities on MRI. MULTIPLE SCLEROSIS MS is the most common primary inflammatory demyelinating disease of the CNS. Notwithstanding the increasing role of MRI, and the emergence of (ever changing) MRI-centred ‘diagnostic criteria’, the fundamental basis of the diagnosis remains clinical—episodes of neurological dysfunction in time and space, with exclusion of other conditions that can mimic this clinical picture. MRI plays an increasing role in the diagnosis and management of MS. Combined with clinical information, MR provides an earlier and more confident diagnosis, helps prognostically to a limited extent in the clinically isolated syndrome, and is used widely to monitor effects of therapy in the clinic and in clinical trials. MRI can show dissemination in time (with serial scans) and space. Conventional MRI is 5–10 times more sensitive to disease activity than clinical assessment. This review does not discuss the various MR criteria for diagnosis. Interestingly, neurologists pre-MRI and neuroradiologists achieve 90–99% specificity in diagnosis of MS without using the strict published diagnostic MR criteria.

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Figure 1 T2W axial MR image of a neurologically normal 45-year-old shows small ill-defined foci of high T2 signal in the frontal subcortical white matter. These are almost certainly age-related changes of no significance.

MRI is abnormal in at least 95% of MS patients. In our experience, it approaches 100% such that a normal MRI is a red flag that it is not MS. Standard MR sequences include T2W, proton density and/or fluid attenuated inversion recovery (FLAIR) sequences. FLAIR and proton density sequences make

periventricular lesions more conspicuous, though FLAIR underestimates lesion load in the posterior fossa. This review does not discuss magnetisation transfer, spectroscopy and diffusion tensor imaging. T2W lesions are typically multiple, small, welldefined and ovoid, occurring wherever there is myelin (figure 4), preferentially involving the undersurface of the corpus callosum (red flag: central callosal lesions, sparing the periphery, think Susac’s syndrome) and periventricular white matter. They also occur along the veins in the perivascular spaces, reflecting the perivenular pattern of inflammation—the radially oriented ‘Dawson’s fingers’ (figure 5). Their long axis is perpendicular to the long axis of the cerebral hemispheres and lateral ventricles. The optic nerves and pathways, posterior fossa and cervical cord are often involved. Lesions also occur in the subcortical white matter, but should not predominate in MS (red flag: think age-related change, small vessel disease, vasculitis, progressive multifocal leukoencephalopathy). T2 hyperintensity is non-specific, reflecting oedema, inflammation, demyelination, remyelination, gliosis and axonal loss. Active plaques show perivascular inflammatory cuffing with T-lymphocytes and B-lymphocytes, oedema and myelin fragmentation. Inactive lesions are hypocellular and without perivascular inflammation. Five to ten per cent of lesions involve grey matter, such as cortex, thalami and basal ganglia (figure 6). Grey matter lesions are usually small, and of intermediate T2 signal, reflecting less severe inflammation. Cortical lesions are difficult to detect with

Figure 2 T2W axial (A) and axial apparent diffusion coefficient MR images (B) in a 63-year-old man with sudden onset right hemiparesis, showing multiple small peripheral, poorly defined foci of high T2 signal in the frontal lobes and adjacent to the trigones of both lateral ventricles—more numerous than in the patient in figure 1. He is a smoker. The cause of his right hemiparesis is an ischaemic stroke in the deep white matter: the result of small vessel disease. This appears as an area of decreased diffusion on the apparent diffusion coefficient map (B).

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Figure 3 Axial T2W MR images in a 70-year-old man with diabetes mellitus and hypertension, showing diffuse high T2 signal in the deep white matter bilaterally, resulting from white matter hypoperfusion due to vascular disease. There are areas of ischaemic damage in the basal ganglia and pons.

conventional MR due to their small size and partial volume effects. Double inversion recovery sequences may make them more conspicuous (figure 7). Double inversion recovery involves two inversion times to suppress signal from white matter and CSF and thereby increase detection of cortical lesions (in fact, all lesions seem to be better delineated). Cortical lesions are more common in secondary progressive MS than relapsing–remitting MS, and their volume correlates with progression of disability. Less typical lesions are more confluent, several centimetres in diameter (figure 8) and can mimic tumours and other white matter disorders. Acute lesions may also have a more complex appearance with central spherical or elliptical T2 hyperintensity surrounded by isointense or hypointense rings (figure 9). The rings may result from paramagnetic free radicals, produced by macrophages; the rings enhance with gadolinium. T2 lesions may become smaller with time but rarely disappear, unless in the brainstem or cord.

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T2 lesion volume increases by 5–10% per year in patients with relapsing–remitting and secondary progressive MS. T2 lesion volume is higher in secondary progressive than in benign, relapsing–remitting, or primary progressive MS. The correlation between T2 lesion burden and disability, however, is low—the so-called clinical–radiologic paradox. Pathological iron deposition may occur in the red nuclei, thalami, dentate, lentiform and caudate nuclei and Rolandic cortex, appearing as low T2 signal. There may be T1 hypointense lesions, which can enhance when active. The number of enhancing lesions increases shortly before and during clinical relapses and can precede T2 lesions by hours or days. Enhancement lasts around 4–6 weeks. Enhancement beyond 6 months should suggest an alternative diagnosis (red flag: persistent enhancement, think lymphoma, glioma, vasculitis and sarcoidosis, especially if they increase in size). All the lesions should not simultaneously enhance (red flag: 3

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Figure 4 Two patients with multiple sclerosis (MS) (A, B) and (C, D). T2 W axial MR images (A–C) and fluid-attenuated inversion recovery coronal (D) MR image show the typical appearance of MS plaques: multiple, small, well defined, ovoid, in the periventricular and subcortical white matter, involving the corpus callosum, particularly the calloseptal interface. The long axis of the plaques is perpendicular to the long axis of the ventricles and cerebral hemispheres.

think acute demyelinating encephalomyelopathy, vasculitis, lymphoma, sarcoidosis). Enhancing lesions vary in size, shape and pattern of enhancement. Most are clinically silent, small and homogeneously enhancing. About 25% show ring enhancement (figure 10) and 10% show other enhancement patterns. Ring-enhancing lesions have

higher levels of tissue destruction and tend to resolve more slowly. Open ring/partial ring enhancement— where the ring is incomplete, a C rather than an O— may help to distinguish demyelinating lesions from tumour and abscess. Open ring enhancement occurs in 66–90% of demyelinating lesions compared with only 6–17% of tumours or abscess.

Figure 5 T2W parasagittal MR images show the demyelinating multiple sclerosis plaques, coursing along the deep medullary veins reflecting the perivenular inflammation—the ‘Dawson’s fingers’.

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Figure 6 T2W (A–C) and fluid-attenuated inversion recovery coronal (D) MR images show a plaque in the right thalamus—10% of multiple sclerosis plaques involve the cortex, thalami and basal ganglia. These lesions are of intermediate signal, reflecting less severe inflammation.

Some T1W hypointensities disappear as the oedema resolves and remyelination occurs, while some remain and develop into ‘black holes’, reflecting more aggressive tissue destruction and axonal loss. There may be progressive brain and cord atrophy. Progressive brain atrophy involving grey and white matter develops at a rate of 0.60–1.35% per year— highest in patients with active relapsing–remitting MS.

Figure 7 Axial double inversion recovery MR image, showing small plaques in the cortex (arrows), not visible on other sequences. The white matter lesions show particularly well.

Renowden S. Pract Neurol 2014;0:1–20. doi:10.1136/practneurol-2014-000856

Grey matter is affected more than white matter, and particularly deep grey nuclei. SPINAL CORD IN MS Cord imaging is important to exclude compressive lesions in patients presenting acutely with myelopathy, or to help diagnosis where there is uncertainty. Cord plaques occur in 90–97% of established MS, and in 83% of recently diagnosed patients even without clinical features. Asymptomatic cord lesions occur in 30–40% of those with a clinically isolated syndrome. Screening spinal MR might, therefore, help diagnostically in patients aged >50 years because T2 hyperintense cord lesions do not usually develop in small vessel disease, hypertension, diabetes mellitus, and are rare in other immune-mediated disorders and progressive multifocal leukoencephalopathy. MS plaques occur more frequently in the cervical cord than in the thoracic cord. The T2 hyperintense plaques are typically peripheral, commonly dorsolateral (figure 11), fewer than two vertebral segments in length and occupy less than half the cross-sectional area of the cord. T1 hypointense and cavitating cord lesions are rare in MS. Acute plaques cause cord swelling and may enhance. Cord atrophy commonly develops in advanced MS, probably reflecting axonal loss. MS VARIANTS Balo’s concentric sclerosis is a rare demyelinating process, reflecting recurrent demyelination at the

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Figure 8 T2W axial MR images show typical demyelinating plaques: well defined, ovoid, and periventricular, with the long axis perpendicular to the long axis of the ventricles. There is also a large plaque involving the white matter of the right occipital lobe, initially misinterpreted as a tumour.

same location, producing multiple concentric rings of demyelinated and remyelinated white matter. Schilder’s disease is a rare variant, an aggressive diffuse, bilateral but asymmetric disorder, usually beginning in childhood. Symptoms may include dementia, aphasia, seizures, personality changes, poor attention, headache and vomiting. Marburg’s disease is a rare, rapidly progressive variant, with severe widespread white matter lesions, with acute onset and death within weeks/months. Classically, the initial MR may show large, sometimes confluent lesions, involving the brainstem and or cerebral white matter (figure 12). There may be enhancement and oedema. MRI is unfortunately poor at identifying patients at risk of this aggressive course of disease. TUMEFACTIVE DEMYELINATING LESIONS These are solitary focal areas of demyelination, larger than 2 cm, often mimicking neoplasm (figure 13). Not all patients have MS or will progress to MS. Tumefactive lesions are located perivascularly, tend to have less mass effect than expected from their size, and show an arc-like incomplete ring of enhancement (not typical of tumour or abscess). Veins may course through the lesion (whereas neoplasms displace veins). Spectroscopy cannot reliably distinguish it from a tumour: both show low N-acetyl aspartate, raised choline, lipid and lactate peaks. Repeat imaging after a trial of corticosteroids may help, showing regression in tumefactive demyelinating lesions (figure 9). CLINICALLY ISOLATED SYNDROME Patients presenting with a first neurological episode due to suspected inflammatory demyelinating disease

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—most commonly sensory symptoms, optic neuritis, acute transverse myelitis or an acute brainstem syndrome—are said to have a clinically isolated syndrome (with no dissemination in time). Two or more typical white matter lesions on MRI have a conversion rate to clinically definite MS of 80–90% (figure 14) after 20 years; 56% of optic neuritis patients convert after 10 years. The risk of conversion is low at 11% if brain MR imaging is normal. CSF unmatched oligoclonal bands in a patient with clinically isolated syndrome also increases the risk of future clinical conversion to MS. The initial baseline MRI only weakly predicts long-term clinical disability. RADIOLOGICALLY ISOLATED SYNDROME This refers to the cerebral lesions on MRI, characteristic of MS, in asymptomatic people without other explanation (figure 15); 0.7–0.8% of brain MRIs may show these incidental lesions. Perhaps one-third to one-half clinically convert over 0.1–12.5 years, but more progress radiologically. Disease activity can, therefore, remain silent for a very long time, even a lifetime; radiologically isolated syndromes may represent different disease severity. In trials of diseasemodifying therapy in clinically isolated syndromes, conversion rates are lower than in placebo groups. CSF oligoclonal bands or elevated IgG index do not increase the risk of radiological or clinical progression. However, there is a higher risk of clinical conversion with more cerebral white matter lesions (>9), gadolinium enhancement and the presence of asymptomatic spinal cord lesions. Appropriately trained neuroradiologists must interpret the imaging. Some clinicians advocate a ‘wait and see’ strategy for patients with radiologically isolated syndromes,

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Figure 9 T2W axial (A–C at presentation, and 2 months later: G–I) and fluid-attenuated inversion recovery coronal (D–F at presentation and 2 months later: ( J) MR images in a 38-year-old woman with a progressive hemiparesis. T1W gadolinium enhanced axial scans were also obtained at follow-up (K). On the initial scans, there is a large area of high T2 signal in the deep white matter of the left paracentral area, extending to the corpus callosum. There is only a little mass effect with distortion of the left frontal horn. It contains an isointense ring (arrows). Note the small typical multiple sclerosis plaque adjacent to the trigones of the lateral ventricles. Follow-up scans after a course of corticosteroids show a significantly smaller left paracentral lesion and a small additional enhancing lesion in the deep white matter of the right frontal lobe.

while others schedule MR, clinical and neuropsychology follow-up. The outcome from no treatment versus treatment with disease-modifying drugs is

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uncertain. However, in long-term follow-up, cohorts of early versus late disease-modifying treatment in clinically isolated syndromes, there were no significant 7

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Figure 10 Patient with known multiple sclerosis. T2W axial (A–C) and T1W gadolinium enhanced (D) MR images show diffuse high T2 signal in the periventricular white matter, together with more discrete cystic ring enhancing lesions, with partial ring enhancement, in keeping with inflammatory lesions rather than abscesses or metastases. There are also a few small discrete foci of nodular enhancement.

Figure 11 T2W (A) and STIR (B) sagittal and T2W axial (C) MR images show a typical multiple sclerosis plaque in the cervical cord at C4. It is peripherally located, less than one vertebral body in height, less than half the cross-sectional area of the cord, and seen best on the STIR image (more diffuse lesions in the cord involving the posterior columns can be seen with B12 and copper deficiency).

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Figure 12 T2W axial (A–C) and fluid-attenuated inversion recovery coronal (D) MR images in a 47-year-old man with the Marburg variant show more diffuse high signal in the cerebral white matter and brainstem, together with more discrete plaques.

changes in clinical disability, conversion rates to secondary progressive MS or indeed MRI measures 10 years from presentation (CHAMPIONS 10-year data). Therefore, it seems very unlikely that early disease-modifying treatment in radiologically isolated syndromes will help or be cost effective. The widespread availability and use of MRI (eg, screening for acoustic neuromas) increasingly identify patients with radiologically isolated syndromes. The long-term anxiety and distress for the patient and their family should remind the neurologist not to undertake unnecessary MRI investigations. ‘RED FLAGS’ AND DIAGNOSIS OF MS Red flags (clinical and imaging) should alert clinicians to possible alternative diagnoses (see Charil et al 2006; Miller et al 2008). Some clinical features are red flags that should make you contemplate other diagnoses. These include family history, prominent or persistent headache, relentlessly progressive course particularly in younger

individuals, prominent cortical features, encephalopathy, symptoms lasting minutes/hours, peripheral neuropathy, fever and involvement of other systems (cardiac, haematological, rheumatological, genitourinary). Table 1 shows red flags for imaging. Normal MRI is a BIG red flag for ‘not MS’! NEUROMYELITIS OPTICA (DEVIC’S DISEASE) Neuromyelitis optica (NMO) is an autoimmune aquaporinopathy, an acquired relapsing–remitting demyelinating CNS disease with some features similar to MS. Distinguishing it from MS is important because of prognostic and therapeutic implications. NMO, rare in Caucasians, comprises 3 vertebral segments (figure 16), are located centrally, involve more than half the cord area and may cavitate, so distinguishing them from MS plaques. Acutely, the cord is oedematous, and the lesions may enhance with gadolinium. Lesions may appear T1 hypointense—an uncommon feature in MS. Persistent T1 hypointensity indicates axonal loss; transient T1 hypointense lesions reflect remyelination. Haemorrhagic cord lesions occur in 2%. Optic nerve lesions may be unilateral or bilateral; the swollen optic nerves have high T2 signal on MRI. Brain lesions—featuring in 60% of NMO—may appear as non-specific T2 hyperintensities. Medullary lesions are usually in continuity with a cervical cord lesion. The hypothalamus and brainstem (areas with high expression of aquaporin-4), as well as the corpus callosum and periventricular areas may be involved, but the lesions are usually linear and lack the Dawson’s finger configuration. NMO brain lesions are indistinguishable from MS in 10% of cases. Blood pressure fluctuations in NMO and immunomodulatory therapies can predispose to posterior reversible leukoencephalopathy; these changes may be superimposed. The diagnosis of NMO is made with 99% sensitivity and 90% specificity by the combination of optic neuritis, acute myelitis (with typical MR appearance), brain MRI not meeting diagnostic criteria for MS, and NMO IgG seropositivity. ACUTE DISSEMINATED ENCEPHALOMYELITIS This is an uncommon inflammatory, usually monophasic demyelinating disease of the CNS: a perivenous encephalomyelitis, affecting grey and white matter, resulting from an allergic or autoimmune crossreaction. Activated B-cells and T-cells enter the CNS and react against a myelin protein similar in structure to the invading pathogen. In up to 75%, it follows 1–3 weeks after a viral or bacterial infection, mostly upper respiratory tract, and mostly in children. Vaccination also predisposes. Encephalopathy (irritability to coma) and multifocal symptoms suggest the diagnosis. No clinical, paraclinical or imaging criteria reliably distinguish fulminant initial episodes of MS from acute disseminated encephalomyelitis (ADEM), although severe encephalopathy, fever

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and drowsiness are more specific for ADEM. It bears a possible relationship to MS especially in rare cases with a multiphasic course, and sometimes the imaging is indistinguishable from MS. About 30% of patients who meet ADEM criteria at initial presentation are later diagnosed as MS. The rate of conversion from ADEM to MS is higher in adults. The presentation may be acute, with seizures and coma, or more insidious with behavioural disturbance, headaches, vomiting, fever, drowsiness and variable focal deficits. Meningism develops in up to one-third. Unilateral optic neuropathy is rare. There is usually a favourable response to corticosteroids and/or plasma exchange, with recovery in 1–6 months, although up to 20% have permanent deficits. MRI shows multiple asymmetrical, poorly marginated (whereas, most MS plaques are well defined), amorphous T2 hyperintense lesions, often larger than 1.5–2.0 cm and, hence, bigger than most MS plaques. The subcortical and deep white matter are more often affected than periventricular regions. The lesions are not orientated perpendicularly to the lateral ventricles and are not well seen on T1W. The basal ganglia, thalami (both often symmetrically involved) and cortex may also be affected (though rarely in isolation)—structures that are less commonly involved in MS. Enhancement is variable and probably uncommon, but when present, most lesions enhance simultaneously. Mass effect is usually negligible except in brainstem lesions. Diffusion imaging is variable. Acute lesions (within 7 days) show restricted diffusion (reflecting swelling of the myelin sheath, reduced vascular supply and dense inflammatory cell infiltration). Subacute lesions show increased diffusion (reflecting axonal loss, demyelination and oedema). MS gives similar diffusion changes. The lesions usually resolve gradually and completely in up to 75%, though occasionally some persist. New lesions appearing after 6 months raise the possibility of MS. One-third have cord lesions involving either grey matter, white matter or both. The lesions are usually large, may extend over 2–3 vertebral bodies in length, may expand the cord (and so differ from MS plaques) but do not usually enhance. Relapsing and remitting ADEM may represent an intermediate form between ADEM and MS. Relapsing–remitting ADEM is a second episode more than 3 months after the first, at least 1 month after corticosteroid completion, and involves the same anatomic area. Multiphasic disseminated encephalomyelitis requires a second episode involving new anatomical areas. Acute haemorrhagic leucoencephalomyelitis (Hurst’s disease) is a rapidly progressive haemorrhagic variant. This inflammatory process is complicated by a necrotising vasculitis and is usually rapidly fatal. 11

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Imaging red flags—? MS consider alternate diagnosis* Consider

Cortical infarctions Embolic, vasculitis Haemorrhages/microhaemorrhages Amyloid, CADASIL, vasculitis Meningeal enhancement Meningitis, sarcoidosis, lymphoma, vasculitis Calcification on CT Cysticercosis, toxoplasmosis, mitochondrial cytopathy Selective anterior temporal/inferior frontal lobe involvement CADASIL Lacunar infarctions Small vessel disease, CADASIL, Susac’s syndrome Persistent gadolinium enhancement Lymphoma, glioma, vasculitis Continued lesion enlargement Sarcoidosis Simultaneous enhancement of all lesions Vasculitis, lymphoma, sarcoidosis Dentate T2 high signal Cerebrotendinous xanthomatosis Pulvinar high T1 signal Fabry’s disease, hepatic encephalopathy, manganese toxicity Large/infiltrating brain stem lesion Behçet’s disease, glioma Mainly cortical/subcortical Infarctions, vasculitis, PML White matter lesions Hydrocephalus Meningitic processes (malignant, infective, granulomatous) Punctiform parenchymal enhancement Sarcoidosis, vasculitis T2 high signal in external capsule/insular CADASIL Regional brainstem atrophy Behçet’s disease Marked hippocampal/amygdala atrophy Hyperhomocysteinaemia Symmetrical lesions Leukodystrophy T2 hyperintensities in basal ganglia, Behçet’s disease, mitochondrial cytopathy, Susac’s syndrome Thalamus, hypothalamus ADEM Diffuse high T2 signal in posterior B12 and copper deficiency Columns of the cord Paraneoplastic, HIV Lesions across grey/white boundary Hypoxic–ischaemic process, vasculitis, systemic lupus erythematosus T2 high signal anterior temporal pole CADASIL Central brainstem lesion Central pontine myelinolysis, hypoxic–ischaemic Central callosal lesions, sparing the periphery Susac’s syndrome Large lesions PML, lymphoma *Adapted from Miller et al Multiple Sclerosis, 2008, 14, 1157–74. ADEM, acute disseminated encephalomyelitis; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy; MS, multiple sclerosis; PML, progressive multifocal leucencephalopathy.

OTHER CONDITIONS Causes of optic neuritis and myelitis (clinically isolated syndrome) other than MS, NMO and ADEM, are much rarer, and include systemic vasculitis, systemic lupus erythematosus, Sjögren’s syndrome, Behçet’s disease, primary CNS angiitis, sarcoidosis, nutritional opticomyelopathy, neurosyphilis, tuberculosis, HIV, West Nile virus infection, varicella zoster and adrenomyeloneuropathy. Autoimmune and inflammatory disease, such as systemic lupus erythematosus, Sjögren’s syndrome, gluten sensitivity, myasthenia gravis, syphilis and dengue fever can coexist with NMO. NON-MS AUTOIMMUNE DEMYELINATION Connective tissue disorders have diverse CNS involvement and can mimic MS by a combination of inflammatory demyelinating and vascular insults. The latter are more common in connective tissue disorders with multiple microinfarctions, non-inflammatory thickening of small vessels by intimal proliferation,

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thrombotic occlusion of major vessels (arteries and veins), intracranial haemorrhage, emboli or true vasculitis with inflammatory cell infiltrates and fibrinoid necrosis. White matter lesions are usually peripheral and look ischaemic (figure 17). However, systemic lupus erythematosus, Behçet’s disease, Sjögren’s syndrome (figure 18), vasculitides, antiphospholipid syndrome, systemic sclerosis (figure) and rheumatoid arthritis may all have areas of demyelination that are difficult to differentiate from MS in the absence of multiorgan involvement. Systemic lupus erythematosus may also have migratory white matter lesions. Cord lesions however are rare. VASCULITIS Most cases of CNS vasculitis are manifestations of systemic disease, such as polyarteritis nodosa, Wegener’s granulomatosis (granulomatosis with polyangiitis), lupus, Sjögren’s syndrome, Behçet’s disease are secondary to meningitis or drug abuse.

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Figure 16 Two women (A, B and C, D) with neuromyelitis optica (NMO). T2W sagittal (A, C), T2W axial (D) and gadolinium-enhanced T1W sagittal MR (B) images of the cervical and thoracic cord, show extensive areas of high T2 signal within the cord, located centrally, occupying more than half the cross-sectional area, and associated with cord swelling. Signal is low on T1W, and there is peripheral enhancement. The patients presented with backache, gait disturbance, perianal numbness, reduced awareness of bladder filling and constipation. Their legs were mildly weak (4/5), plantars were extensor, and there were mid-thoracic sensory levels. NMO antibody was positive. CSF showed a lymphocytosis. Patient (A, B) developed optic neuritis 3 months later. Brain imaging was otherwise normal.

Isolated angiitis of the CNS, a rare disorder of unknown aetiology, is restricted to the brain and characterised by non-specific granulomatous inflammation of small cerebral parenchymal and leptomeningeal arteries and veins. Most patients have severe headache (unlike MS) and focal neurological signs. MRI findings vary from being normal, (unlike MS), or having

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focal lesions similar to MS (figure 19), diffuse white matter changes, infarctions, haemorrhages, leptomeningeal and parenchymal enhancement. There is no predilection for the periventricular regions. Meningeal enhancement in MS is extremely rare: its presence effectively excludes the diagnosis or invokes dual pathology. 13

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Figure 17 Acute demyelinating encephalomyelitis. T2W axial (A–D), apparent diffusion coefficient maps (E–G) and T1W gadolinium-enhanced (H–K) MR images in a 26-year-old woman. Two weeks before her admission, she had a flu-like illness and had started to slur her speech, become confused and to develop left-sided weakness. CSF protein was raised, glucose was normal, there were no organisms and only a mild lymphocytosis. The MR images show multiple, bilateral, poorly defined large inhomogeneous T2 hyperintense lesions in the periventricular and subcortical white matter. There is restricted diffusion in the more acute lesions. Most of the lesions are partially enhancing. She was treated with corticosteroids but did not recover completely, and is currently cortically blind. This was a monophasic illness.

In isolated CNS angiitis, cerebral angiography is often negative because small blood vessels are affected. SUSAC’S SYNDROME This is rare, but probably underdiagnosed and misdiagnosed. It is characterised by the clinical triad of multifocal encephalopathy, branch retinal artery

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occlusion and hearing loss, with a female predominance of 3:1. The usual age at diagnosis is 20–40 years, but the reported age range varies from 7 to 72 years. Its cause is uncertain, but the leading hypothesis is immune-mediated injury affecting retina, cochlea and cerebral vasculature, with a predilection for small precapillary arterioles

Imaging in multiple sclerosis and related disorders.

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