MULTIPLE SCLEROSIS a disease in detail.pptx

Ms disease in detail for better management

1. MULTIPLE SCLEROSIS DR. NIKITA SHAHU JR. RADIODIAGNOSIS

2. INTRODUCTION White matter composition : 1) myelinated axons 2) support elements (oligodendrocytes, astrocytes, microglia, and blood vessels). The myelin sheath is formed by the oligodendrocyte. White matter disease is caused by a pathologic process that prevents the normal formation and maintenance of myelin or that selectively destroys the oligodendrocyte and/or myelin sheath.

3. CNS inflammatory syndromes have been classified in numerous ways: by presentation (clinically isolated vs. polysymptomatic disease), pattern ( monofocal or multifocal), geography (brain vs. spinal cord vs. peripheral nervous system), disease severity (from asymptomatic to severe), disease course (monophasic, multiphasic, relapsing-remitting, progressive, etc.). we follow a simplified approach, dividing our discussion into multiple sclerosis (MS) and its variants, postinfection/postvaccination inflammatory disorders, autoimmune/autoantibody-mediated disorders, and inflammatory-like disorders such as neurosarcoidosis and pseudotumors.

4. MULTIPLE SCLEROSIS Introduction and terminology etiology pathology, clinical phenotypes, imaging appearance differential diagnosis Variants

5. Terminology : Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disorder of the CNS characterized pathologically by multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring. Axonal loss is now being recognized as an important pathological feature. It is characterized histo -pathologically by multiple inflammatory demyelinating foci called " plaques ." Etiology: General Concepts : MS is a multifactorial disease whose precise pathogenesis remains unknown. It is influenced by a complex interplay of genetic susceptibility and epigenetic and postgenomic events. Environmental factors with diverse, population-specific levels of prevalence-latitude gradient also play a prominent role

6. Pathological Flowchart of Multiple Sclerosis Genetic & Environmental Predisposition
(EBV, Vitamin D deficiency, HLA-DR2) Activation of autoreactive T-cells
(CD4+ TH1, TH17) Crossing Blood–Brain Barrier (BBB) Immune Cascade Initiation
(Cytokines, B-cells, Macrophages) Demyelination
(Oligodendrocyte injury, Plaques) Inflammation & Axonal Damage
(Perivenular lymphocytes, Microglia) Gliosis & Chronic Plaques
(Astrocytic proliferation) Neurodegeneration
(Axonal loss, Brain atrophy) Clinical Correlation
(Relapsing-remitting → Progressive) Radiology Correlation (MRI)
- T2/FLAIR: Hyperintense plaques
- T1: Black holes
- Gd+ T1: Active lesions
- MRS/DTI: Axonal damage

7. PATHOLOGY Demyelination occurs in discrete perivenular foci, termed plaques Size and Number: Multiple > solitary Mostly small (5-10 mm) Giant "tumefactive" plaques can be several centimeters 30% of "tumefactive" MS lesions solitary Three pathological stages: 1) early acute stage (active plaque) - active myelin breakdown. 2) subacute stage - pale colored plaques with abundant macrophages. 3) chronic stage (inactive plaque)- gliosis with associated volume loss and plaque becoming grey in color.

8. CLINICAL PRESENTATION The first attack of MS (most commonly optic neuritis, transverse myelitis, or a brainstem syndrome) is known as a clinically isolated syndrome. Half of patients with optic neuritis eventually develop MS. Clinical MS Subtypes: Several major MS subtypes are recognized. From least to most severe they are as follows: Radiologically isolated syndrome (RIS), Clinically isolated syndrome (CIS), Relapsing-remitting MS (RR-MS), Relapsing progressive MS (RP-MS), Secondary-progressive MS (SP-MS), Primary-progressive MS (PP-MS)

9. Radiologically isolated syndrome (RIS): RIS refers to MR findings of spatial dissemination of T2/FLAIR lesions suggestive of MS in persons with no history of neurologic symptoms and with a normal neurologic examination. By definition, patients with RIS have dissemination in space. When a clinical attack occurs in these patients, a diagnosis of MS can be made. Until that occurs, most experts agree that MS should not be diagnosed solely on the basis of MR findings.

10. 2. Clinically Isolated Syndrome. CIS refers to a first episode of neurologic symptoms that: (1) lasts at least 24 hours and (2) is caused by inflammation or demyelination in the CNS. CIS can be monofocal or multifocal. In monofocal CIS, a single neurologic sign or symptom (e.g., optic neuritis) is caused by a single lesion. Multifocal CIS is characterized by more than one sign or symptom (e.g., an attack of optic neuritis accompanied by extremity paresthesias ) caused by lesions in more than one location.

11. Relapsing-Remitting MS: A ttacks ("relapses" or "exacerbations") are followed by periods of partial or complete recovery. New MR lesions often occur as part of a relapse but may also occur without symptoms. Relapsing-Progressive MS . RP-MS is also known as secondary progressive MS. In RP-MS, there is progressive worsening of neurologic function (accumulation of disability) over time. Primary-Progressive MS . PP-MS is characterized by worsening neurologic function from the outset and lacks periods of remission.

12. IMAGING APPEARANCE CT Findings: NECT : normal early in the disease course and with mild cases. Solitary or multiple ill-defined white matter hypodensities may be present. CECT : Acute or subacute lesions may show mild to moderate punctate, patchy, or ring enhancement. Enhancement increases with delayed or double-dose scans.

13. Juxtacortical and cortical lesions are specific for MS. They are adjacent to the cortex and must touch the cortex. In small vessel disease the U-fibers are typically spared and on T2 and FLAIR there will be a dark band of normal WM between the WML and the bright cortex. 

14. Dawson fingers Dawson fingers are typical for MS. They are oriented perpendicular to the outer surface of the lateral ventricle surrounding the medullary veins that radiate centripetally away from the lateral ventricle.

15. MR FINDINGS MR is the procedure of choice for both initial evaluation and treatment follow-up. T1WI: Most MS plaques are hypo- or isointense on T1WI. The hypointensity ("black holes") correlates with axonal destruction. A faint, poorly delineated peripheral rim of mild hyperintensity secondary to lipid peroxidation and macrophage infiltration often surrounds sharply delineated hypointense "black holes” giving subacute and chronic lesions a characteristic "beveled" or "lesion-within-a-lesion" appearance. Chronic and severe cases -volume loss and generalized atrophy. The corpus callosum becomes progressively thinner and is best delineated on sagittal T1WI

16. T2/FLAIR: Earliest findings - alternating areas of linear hyperintensity along the ependyma on sagittal FLAIR, known as the "ependymal 'dot-dash '" sign T2WI shows multiple hyperintense linear, round, or ovoid lesions surrounding the medullary veins that radiate centripetally away from the lateral ventricles. Larger lesions often demonstrate a very hyperintense center surrounded by a slightly less hyperintense peripheral area and variable amounts of perilesional edema.

17. T1 C+: MS plaques demonstrate transient enhancement during active demyelination. Punctate, nodular, linear, and rim patterns are seen. A prominent incomplete rim ("horseshoe") of enhancement with the "open" non-enhancing segment facing the cortex can be present, especially in large "tumefactive" lesions. lesion with incomplete ("horseshoe") rim enhancement punctate and ring enhancement in the cerebral white matter. "target" appearance of the left frontal lesion

18. DWI: Majority of acute plaques show normal or increased diffusivity. Occasionally acute MS plaques can demonstrate restriction on DWI, such an appearance is atypical and should not be considered a reliable biomarker of plaque activity. MRS: It allow early distinction between relapsing remitting and secondary-progressive MS. Secondary progressive MS shows decreased NAA in normal-appearing gray matter consistent with axonal/neuronal loss or dysfunction. Myoinositol levels are elevated in acute lesions and are also increased in normal-appearing white matter. "Tumefactive" MS shows nonspecific findings (elevated choline, decreased NAA, and high lactate).

19. DIAGNOSIS

20. MULTIPLE SCLEROSIS – 2024 REVISED McDONALD CRITERIA

21. DIFFERENTIAL DIAGNOSIS Multifocal T2/FLAIR Hyperintensities • ADEM - usually has a history of viral prodrome or recent vaccination. • Lyme disease - . Cranial nerve enhancement is more common in LD than in MS. • Vasculitis - preferentially involves the basal ganglia and spares the callososeptal interface. • Susac syndrome - Lesions in Susac syndrome preferentially involve the middle of the corpus callosum, not the callososeptal interface. Mass-Like ("Tumefactive") Lesion(s) • Neoplasm (Glioblastoma multiforme, Metastases) • PML ( HIV/AIDS, Natalizumab-treated MS) • Medication-related (Enbrel)

22. SMALL VESSEL ISCHEMIC CHANGES: These are white matter hyperintensities seen commonly in the elderly. Foci of hyperintense signal on T2-weighted images, frequently found in subcortical or periventricular white matter in elderly are smoother than the smaller, lobulated ovoid MS lesions. Corpus callosum and spinal cord involvement is not seen in ischemic changes.

23. ADEM Acute Disseminated Encephalomyelitis (ADEM) is another important differential diagnosis of MS. This is a monophasic, immune-mediated demyelinating disease which often presents in children following an infection or vaccination. Many of the patients have MOG antibodies (MOG= Myelin oligodendrocyte glycoprotein). MRI - diffuse and relatively symmetrical lesions in the supra-and infratentorial white matter which may enhance simultaneously. Preferential involvement of the cortical gray matter and the deep gray matter of the basal ganglia and thalami

24. ADEM extensive involvement of the cortical and gray matter - including thalamus. involvement of the basal ganglia 

25. Neuromyelitis Optica A very important differential to keep in mind, especially in patients with a bilateral optic neuritis and myelitis. Neuromyelitis Optica Spectrum Disorder (NMOSD) was previously called Devic's Disease. This is a demyelinating disease caused by antibodies against aquaporin or MOG in which the optic nerves and spinal cord are usually involved.

26. VARIANTS Major MS variants are (1) Marburg disease (acute, severe, fulminant MS) (MD), (2) Schilder disease (SD), (3) Balo concentric sclerosis (BCS).

27. MARBURG DISEASE Axial FLAIR shows a large heterogeneously hyperintense lesion in the right parietal WM with a smaller lesion on the left. Axial T1 C+ FS in the same case shows multiple bilateral incomplete ring-enhancing lesions in the deep and periventricular WM.

28. TUMIFACTIVE SCLEROSIS Tumefactive MS is a variant of Multiple Sclerosis. On MRI it presents as a large intra-parenchymal lesion with usually less mass effect than would be expected for its size. They may show some peripheral enhancement, often with an  incomplete ring  unlike gliomas or intraparenchymal abscesses, which typically have a closed-ring enhancement.

29. SCHILDER DISEASE • Myelinoclastic diffuse sclerosis ○ Rare acute/subacute demyelinating disorder ○ Lesions may resolve; 15% progress to MS Young adults ○ Mean age at onset = 18 years Clinical features atypical for MS, ADEM ○ CSF normal ○ No history of fever, flu, vaccination Imaging: • Solitary > multifocal lesions • Lesions look like "tumefactive" MS Differential diagnosis: neoplasm, abscess  multiple large hemispheric lesions, with an enhancing rim

30. BALO CONCENTRIC SCLEROSIS BCS is generally considered an atypical or variant form of MS and occurs as a discrete, concentrically layered white matter lesion. It is often described as having an "onion ring" or "whorled" appearance. The pathologic hallmark of BCS is its peculiar pattern of lamellar or concentric rings. Large plaques with alternating rims of demyelination and myelin preservation give the lesion its characteristic appearance. Imaging: T2 and post-contrast T1W images show a large lesion in the left hemisphere with alternating T2-hyperintense and isointense bands. Post contrast - alternating linear enhancement. Note that the outermost band shows diffusion restriction

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