Mimics of MS in MRI copy for neurologist

a ppt about multiple sclerosis mimics

1. Neuroimaging of Multiple Sclerosis - Mimics S. Arun Saravanan N3 Prof S. Balasubramanian

2. Multiple Sclerosis Primary demyelinating disease of unknown etiology (autoimmune category), characterized by perivenular inflammation/demyelination with relative axon preservation, manifesting as periventricular, juxtacortical, infratentorial, and spinal cord lesions at magnetic resonance (MR) imaging. MRI is very sensitive to inflammatory and demyelinating lesions in the white matter, giving it a central role in the modern process of diagnosing multiple sclerosis (MS) and its mimics

3. Features of MS in MRI Imaging The typical yet nonspecific pathology of MS shows plaques—well-defined, elongated, or oblate, following a perivenular distribution. MR imaging is the most important paraclinical tool for diagnosing and monitoring MS Dissemination in space Dissemination in time Requires - One white matter hyperintensity (WMH) in at least two typical locations such as periventricular, juxtacortical, infratentorial, and spinal cord Requires - both contrast-enhancing and nonenhancing lesions in a single MR imaging examination or development of new lesions at follow-up MR imaging

4. Specific findings in MS   Ependymal dot-dash sign - Corpus callosum lesions in early MS are characteristically found at the callososeptal interface - seen as tiny (~1 mm) dots of high signal along the ependymal surface that may coalesce into short dashes Dawson fingers- Periventricular WMHs in MS are usually ovoid and perpendicular to the ventricle, with perivenular topography MS lesions can also be located around the temporal horn of the lateral ventricle, a region usually spared by small-vessel disease.

5. IMAGING OF MS LESIONS MRI MS T1WI Typically hypo- or isointense ○ Hypointensity correlates with axonal destruction ("black holes") ○ T1 hypointense lesions suggest worse prognosis T2WI Hyperintense, linear foci radiating from ventricles ○ > 85% periventricular / perivenular ○ 50-90% callososeptal interface ○ May also commonly involve subcortical U- fibers , Cerebellum,middle cerebellar peduncle , brainstem, spinal cord (Cervical sc). ON

6. MRI MS FLAIR a) b) c) d) Earliest finding: Alternating linear hyperintensity along ependyma on sagittal FLAIR – Ependymal "dot-dash" sign - Bilateral, asymmetric, linear/ovoid hyperintensity - Perivenular extension; "Dawson fingers" - Hyperintensities become confluent with severity DWI Majority of acute plaques: Normal or↑ diffusivity(Facilitated diffusion) ○ Few acute MS plaques may show restricted diffusion – Often at the margins of acute plaque ○ Subacute /chronic plaques show↑ diffusivity

7. MRI MS SWI the association between brain WM venules and lesions (perivenular lesions- central vein sign MRS ↓ NAA (NAA/Cr), ↑ choline (Cho/Cr), ↑ myoinositol ○ MRS abnormalities found in normal-appearing white matter (NAWM) ○ Only secondary progressive MS shows ↓ NAA in normal appearing gray matter (NAGM) – May allow early distinction between relapsing Remitting and secondary-progressive

8. Mimics of MS

9. Neuromyelitis Optica Demyelinating disease of autoimmune etiology induced by NMO–immunoglobulin G, an autoantibody against aquaporin-4 water channels The spinal cord and optic nerve are preferential targets Brainstem lesions in NMO are typically dorsal and periaqueductal regions due to the higher concentration of aquaporin-4.

10. NMO NMO has a higher frequency of medulla oblongata lesions but lower frequency of pons lesions compared with MS Unlike MS, myelitis in NMO is longitudinally and transversally extensive, often involving three or more vertebral segments, Corpus callosum lesions in NMO preferentially involve the splenium

11. NMO MS

12. NMO - Axial FLAIR MR in a patient with neuromyelitis optica shows characteristic periependymal lesions surrounding the 3rd ventricle, involving the thalamus NMO - Autopsy specimen shows areas of demyelination in the prechiasmatic portions of the optic nerves

13. Bridge-arch sign Oedema of the corpus callosum giving rise to a “marbled” pattern of signal intensity is an infrequent finding, but highly characteristic feature of NMO.

14. Acute Disseminated Encephalomyelitis ADEM is also mediated by antigen-antibody complexes and usually occurs in children within 2 weeks of infection or vaccination The course is monophasic in 90% of cases - complete remission at follow-up MR imaging, Diffuse perivenular inflammation as the underlying process - leading to confluent areas of demyelination

15. ADEM The lesions in ADEM are multiple and bilateral – involves both white matter and gray matter ADEM lesions can be more rounded and larger with poorly defined margins Corpus callosum involvement in ADEM - lesions are larger than in MS and do not usually arise from the callososeptal interface

16. ADEM - Coronal T2-weighted FLAIR image show extensive periventricular and subcortical white matter involvement (can be confused with Tumefactive Demyelinating Lesions) ADEM – Axial T2-weighted FLAIR image shows bilateral hyperintense lesions involving the deep gray matter nuclei and periventricular-subcortical white matter

17. Infectious White Matter Diseases The infectious leukoencephalopathies can be Multifocal - Lyme disease Confluent - PML and human immunodeficiency virus [HIV] encephalopathy

18. Lyme Disease Borreliosis (Lyme disease) is a zoonosis transmitted by tick bite - caused by the spirochete Borrelia burgdorferi CNS involvement seems to be the result of an abnormal autoimmune reaction and occurs in 10%–15% of patients Multifocal WMH with variable enhancement, most commonly in the frontal and parietal regions, sometimes in the basal nuclei and brainstem.

19. Lyme disease Corpus callosum lesions may sometimes occur – calloso septal involvement is less common. Leptomeningeal and cranial nerve enhancement may also be present - help in differentiation from MS

20. Lyme disease

21. Progressive Multifocal Leukoencephalopathy Reactivation of John Cunningham (JC) virus in the context of cellular immunodeficiency JC virus is present in circulating B lymphocytes and is responsible for infection and lysis of oligodendrocytes, - large geographic areas of demyelination. Confluent asymmetric lesions with a predilection for peripheral white matter and subcortical U- fibers .

22. HIV Encephalopathy Consequence of direct infection of microglia by HIV. Diffuse and marked periventricular demyelination, neuronal loss and vaculor changes are observed Imaging studies show diffuse bilateral and symmetric periventricular WMH, preferentially affecting the more central white matter without mass effect or enhancement

23. PML - Axial T2-weighted image shows a large asymmetric confluent WMH, with involvement of the subcortical U- fibers and without mass effect (Asymmetric and Peripheral) HIV - Axial T2- weighted FLAIR image shows symmetric periventricular white matter involvement (Symmetric and central)

24. Vascular White Matter Diseases: Type 1 Arteriolosclerosis Type 2 cerebral amyloid angiopathy Type 3 inherited vasculopathies ( eg , CADASIL, MELAS [ m itochondrial myopathy, e ncephalopathy, l actic a cidosis, s trokelike episodes], Fabry disease); Type 4 inflammatory vasculitides ( eg , primary angiitis of the central nervous system [PACNS], Susac syndrome, connective tissue disorders such as systemic lupus erythematosus [SLE] and Sjögren syndrome); Type 5 venous collagenosis Type 6 Others ( eg , Migraine, radiation therapy)

25. Small-Vessel Disease Related to Arteriolosclerosis WMHs occur in 80% over the age of 60 years, with a predilection for the frontal and parietal regions (MS – Temporal horn) WMHs occur in vascular end zones: supratentorial level - basal nuclei, corona radiata, and centrum semiovale (MS – rarely affects basal ganglia) In the brainstem- deeper brainstem (centrally due to the centripetal pattern of feeding vasculature)

26. Small-Vessel Disease Lacunes are defined as round/ovoid cavities of 3–15 mm Small subcortical infarcts occur in the territory of perforating arterioles Cerebral microhemorrhages are defined as small (up to 5-mm) areas of signal void/blooming

27. Small-vessel disease Axial T2-weighted FLAIR images show the WMH rating scale for small-vessel disease.

28. Cerebral Amyloid Angiopathy Vasculopathy caused by β-amyloid deposition in the media and adventitia of cortical and leptomeningeal arteries Involve the occipital and frontal regions more frequently The vascular fragility explains the propensity to bleed, while the chronic hypoperfusion leads to leukoencephalopathy

29. Cerebral Amyloid Angiopathy CAA - Axial susceptibility-weighted image shows microbleeds at the cortico-subcortical interface can also show lobar, cortico-subcortical, and cortical hemorrhages of different ages and sizes, as well as signs of previous subarachnoid hemorrhage ,

30. CADASIL Inherited (AD) non-arteriosclerotic and amyloid-negative small-vessel disease Common manifestations are migraines, recurrent ischemic strokes, and progressive cognitive impairment in young adults Deposition of granular osmiophilic material around the vascular smooth muscles of small and medium-sized leptomeningeal arteries

31. Imaging findings in CADASIL 3 rd decade WMHs in the temporal pole, which is a differentiating feature from other microvascular diseases 4 th decade WMHs progress to the posterior temporal, frontal, and parietal regions, as well as the basal nuclei and thalami ( relative sparing of the occipital lobe) Subcortical U- fibers can be involved, and subcortical lacunar infarcts become a common finding. 5 th decade microbleeds develop 6 th decade extensive WMHs, lacunes , and microbleeds are often present Angiography should be avoided if possible

32. CADASIL - Axial T2-weighted FLAIR image shows confluent periventricular WMHs, with typical involvement of the external capsule CADASIL - T2 FLAIR showing patchy periventricular white matter changes Followed by  numerous microbleeds scattered throughout the bilateral cerebral hemispheres, cerebellum, bilateral basal ganglia and thalamus

33. 4)Primary Angiitis of the Central Nervous System Definition - Primary arteritis confined to intracranial CNS without any evidence of systemic vasculitis CLINICAL PRESENTATION Headaches, encephalopathy, seizures, signs of meningeal irritation, and focal neurologic deficits resulting from ischemic or hemorrhagic lesions Pathology fibrinoid necrosis of the small arteries and veins in the meningeal and the parenchymal regions of the CNS - Imaging findings- - multiple cortical-subcortical infarcts, hemorrhages , and parenchymal and leptomeningeal enhancement.

34. RED FLAG SIGNS for PACNS 1) Hemorrhage , 2)infarcts 3) Large lesions with mass effect 4)leptomeningeal enhancement at presentation or follow-up 5)Simultaneously enhancing parenchymal masses 6)Pattern of enhancement

35. PATTERN OF ENHANCEMENT PACNS - The pattern of enhancement is typically described as linear or in a radial fashion as opposed to ring-like configuration as seen in MS. ( seen in Balo concentric sclerosis variant of MS)

36. Susac Syndrome Small-vessel disease that occurs in young adults - form of vasculitis produced by anti-endothelial antibodies to specific neural vessels Immune attack results in endotheliopathy that involves the cochlea, retina, and brain – microinfarction Clinical triad : SN hearing loss, visual loss, and encephalopathy Ophthalmoscopy : Branch retinal artery occlusion

37. Image findings in Susac Syndrome Multiple microinfarcts with diffusion restriction and contrast enhancement. Corpus callosum involvement is the rule. central region is more frequently affected, classically described as “snowball” (MS - callososeptal interface) Leptomeningeal enhancement can be seen

38. Images of the typical features of Susac syndrome : intracallosal snowball-shaped T2‑FLAIR hyperintense lesions and lesions in the posterior limb of the internal capsule, appearing as a ‘string of beads’ in an axial FLAIR image

39. Toxic-Metabolic White Matter Diseases Osmotic Myelinolysis involves the pons and is typically central with sparing of the periphery. Posterior Reversible Encephalopathy Syndrome (PRES) T2 hyperintense edema , more frequently involving the parieto-occipital regions Methotrexate Leukoencephalopathy involves the frontoparietal white matter and centrum semiovale . commonly shows no contrast enhancement or mass effect Ethanol-related Marchiafava-Bignami Disease preferentially involves the middle layers of the body of the corpus callosum . Diffusion restriction is recognised. Heroin -induced leukoencephalopathy posterior white matter, internal capsule, brainstem, and cerebellar peduncles Carbon Monoxide Leukoencephalopathy globi pallidi are typically involved, but periventricular white matter injury is a late manifestation Radiation Leukoencephalopathy necrotic changes with contrast enhancement.

40. PRES Most commonly identified in patients with hypertension, pre-eclampsia, eclampsia, immunosuppression, and sepsis during chemotherapy. Accepted theory proposes-- Rapid development of severe hypertension (over 160 mmHg) leading to disturbance in cerebral autoregulation and resultant brain hyperperfusion , endothelial damage, fluid extravasation, and vasogenic oedema Although generally reversible with rapid treatment, PRES may be complicated by infarcts or hemorrhages .

41. Osmotic myelinolysis - Axial T2- weighted FLAIR image shows extensive central pontine hyperintensity sparing the periphery Methotrexate leukoencephalopathy –Axial T2-weighted image shows extensive areas of high signal intensity involving the bilateral periventricular and deep white matter, without mass effect or atrophy. PRES -Axial T2-weighted FLAIR image shows subcortical edematous areas involving the bilateral occipital regions

42. Marchiafava-Bignami Disease Characterized by demyelination followed by necrosis of the corpus callosum secondary to toxic (alcohol) and metabolic (vitamin B deficiency). Neurologic manifestations include dementia, dysarthria , aphasia, hemiparesis , ataxia, or apraxia . Pathology - Microscopically, the lesion proved to be confined to the middle lamina (which makes up about two-thirds of the thickness of the corpus callosum ), in which there was a loss of myelin and, to some degree of axonal loss.

43. Marchiafava-Bignami disease – Sagittal T1W Image shows with a thinned corpus callosum and hypointensity in the middle layers . Note that the genu , body, and splenium are all involved Predominant corpus callosum involvement with lesions inside cc with diffusion restriction As a rule, the internal capsule and corona radiata, subcortical arcuate fibers , and cerebellum are spared

44. Migraine Small, focal areas of T2 hyperintensity that are peripherally located ( ie , centrum semiovale and corona radiata) have been demonstrated in 20% to 50% of patients with migraine Migraine – FLAIR images at three different Axial levels showing Non specific tiny T2 hyperintensities in subcortical white matter. Changes usually stable over years

45. Differentiating features in Migraine Smaller than 1 cm (often they are punctate), Few in number, and scattered throughout the peripheral white matter Spares U fibres Central vein sign usually absent Absence of cortical & spinalcord lesions Remaining stable for years.

46. Demyelinating diseases NMO, ADEM Infectious White Matter Diseases Lyme disease PML and HIVencephalopathy Vascular White Matter Diseases Type 1) Arteriolosclerosis Type 2) Cerebral amyloid angiopathy Type 3) Inherited vasculopathies ( eg , CADASIL, MELAS) Type 4) Inflammatory vasculitides ( eg , PACNS, Susac syndrome, SLE and Sjögren syndrome) Type 5) Venous collagenosis Type 6) Others ( eg,Migraine , radiation therapy) Toxic-Metabolic White Matter Diseases Osmotic Myelinolysis, PRES, Methotrexate Leukoencephalopathy, Heroin & CO leukoencephalopathy, Ethanol related Marchiafava-Bignami Disease Others Neuro Bachet , Limbic Encephalitis, Neurosarcoidosis , CLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids)

47. Favours MS Against MS (Red Flags) The proportion of lesions that exhibit the central vein sign Presence of cortical lesions can be useful in differentiating MS from some of its mimics Meningeal enhancement, indistinct (ill-defined) lesions that increase in size over time, Macrobleeds and Microbleeds, Infarcts, cavities, Symmetrical lesions that spare U-fibres, siderosis and extensive spinal cord lesions suggest diagnoses other than MS

48. Red-flag imaging features summarized by the MIMICs mnemonic

49. Thank You