Inflammatory Demyelinating disorders.pptx

Inflammator demyelinating disorders in detail

1. Infection, Inflammation, and Demyelinating Diseases ~Dr. Shalvi Modani

2. Postinfection and Postimmunization Demyelination

3. Acute Disseminated Encephalomyelitis[ADEM] ADEM is a postinfection, postimmunization disorder that is also called parainfectious encephalomyelitis. The immunohistopathologic features of ADEM mimic those of experimental allergic encephalitis, an induced autoimmune disease precipitated by myelin antibodies. ADEM can involve both the brain and spinal cord. White matter lesions usually predominate, but basal ganglia involvement is seen in nearly half of all cases. Spinal cord lesions are found in 10-30%.

4. Gross Pathology Lesion size varies from a few millimeters to several centimeters ("tumefactive" ADEM), and lesions have a punctate to flocculent configuration. Multiple lesions are more common than solitary lesions. Small lesions are often inapparent on gross examination. Large "tumefactive" lesions cause a gray-pink white matter discoloration and often extend all the way to the cortex-white matter junction. Mass effect is minimal compared with lesion size. Gross intralesional hemorrhage is rare and is more characteristic of AHLE than ADEM.

5. Microscopic Features Sleeves of pronounced perivenular demyelination with macrophage-predominant inflammatory infiltrates are typical. The outer margins of ADEM lesions are indistinct compared with the relatively well-delineated edges of multiple sclerosis (MS) plaques. Viral inclusion bodies are generally absent, unlike viral encephalitis.

6. Clinical Aspect ADEM is second only to MS as the most common acquired idiopathic inflammatory demyelinating disease. Unlike MS, there is no female predominance. ADEM occurs most commonly in spring and autumn. ADEM can occur at any age but—perhaps because of the frequency of immunizations and antigen exposure—is more common in childhood, with peak occurrence between 5 and 8 years of age. Symptoms typically occur a few days to a few weeks following antigenic challenge (e.g., infection or vaccination).

7. Natural History Monophasic ADEM is the most common type. However, the disease sometimes follows an atypical course, waxing and waning over a period of several months. Recurrent ADEM is characterized by a second episode occurring within 2 years after the initial illness and involving the same anatomic area(s) as the original illness. Multiphasic ADEM (MDEM) is characterized by one or more subsequent events that involve a different anatomic area as demonstrated by a new lesion on MR or a new focal neurologic deficit. MDEM is more common in children and is frequently associated with myelin oligodendrocyte glycoprotein (MOG) seropositivity.

8. Imaging CT Findings- NECT is usually normal. CECT may show multifocal punctate or partial ring-enhancing lesions.

9. Imaging MR Findings- Multifocal hyperintensities on T2/FLAIR are the most common findings and vary from small round/ovoid foci to flocculent "cotton ball" lesions with very hyperintense centers surrounded by slightly less hyperintense areas with "fuzzy" margins. Bilateral but asymmetric involvement is typical. Basal ganglia and posterior fossa lesions are common. Enhancement varies from minimal to striking. Punctate, linear, ring, and incomplete ring patterns all occur

10. Large "tumefactive" lesions with horseshoe-shaped enhancement resemble "tumefactive" MS. Cranial nerve enhancement is relatively common. Acute lesions may show restriction on DWI. MRS is nonspecific with low NAA and elevated lactate.

11. Differential Diagnosis MS Both show tumefactive lesions with incomplete ring enhancement. ADEM is more common in children and often has a history of viral infection or immunization. MS more commonly involves the callososeptal interface and typically has a relapsing-remitting course, whereas most cases of ADEM are monophasic.

12. Differential Diagnosis Although very rare, treatment-associated demyelinating diseases with TNF-α inhibitors such as etanercept can mimic ADEM and NMOSD on imaging studies. Demyelination associated with anti-TNF agents typically develops from 1 week to 12 months after treatment initiation.

13. Acute Hemorrhagic Leukoencephalitis[AHLE] AHLE is also known as Weston Hurst disease. Some investigators include AHLE as part of the ADEM spectrum—as a hyperacute, exceptionally severe, extremely fulminant manifestation of ADEM. AHLE is a fulminant demyelinating disease of unknown etiology. History of a viral prodrome or flu-like illness is common but not invariably present. Cross reactivity between myelin basic protein moieties and various infectious agent antigens probably causes an acute autoimmune-mediated demyelination.

14. Pathology AHLE predominantly affects the white matter but may involve both the brain and spinal cord. Both the cerebral hemispheres and posterior fossa structures are affected. Basal ganglia involvement is common, but the cortical gray matter is generally spared. AHLE has two distinct manifestations: focal macroscopic parenchymal hemorrhages and innumerable petechial microbleeds.

15. Gross and Microscopic Features Marked brain swelling with diffuse confluent and/or petechial hemorrhages. Hemorrhages are typically present in the leptomeninges, cerebral hemispheres (predominately the white matter), and cerebellum. The large arteries are normal. Fibrinoid necrosis of vessel walls with perivascular hemorrhages and mononuclear inflammatory cell cuffing are the pathologic hallmarks of fulminant AHLE. Diffuse, mostly neutrophilic infiltrates are typical, in contrast to the macrophage-predominant infiltrates typical of ADEM. Perivascular demyelination may occur in cases with a longer duration.

16. Clinical Aspect Less common than ADEM. Occurs at all ages, most patients are children and young adults. Fever and lethargy with increasing somnolence, decreased mental status, impaired consciousness, and long-tract signs are the most common clinical symptoms. Mortality is 60-80%. The disease course is fulminant and almost always fatal if untreated. Aggressive treatment with intravenous high-dose corticosteroids, immunoglobulin, cyclophosphamide, and plasmapheresis has been used.

17. CT Imaging Findings NECT may be normal unless macroscopic confluent hemorrhages are present. Petechial microhemorrhages are generally invisible, but white matter edema with diffuse, relatively asymmetric hypodensity in one or both hemispheres may be present.

18. MR Findings T1 scans are often normal unless lobar hemorrhage is present. T2/FLAIR findings vary from subtle to striking. Multifocal scattered or confluent hyperintensities as well as bilateral confluent hyperintensity of the cerebral white matter are typical but nonspecific findings. Multifocal punctate and linear "blooming" hypointensities in the corpus callosum that extend through the full thickness of the hemispheric white matter to the subcortical U-fibers are typical findings on T2*. Striking sparing of the overlying cortex is common. Enhancement on T1 C+ occurs in 50% of cases and ranges from linear perivascular space enhancement to larger patchy or confluent foci.

19. Differential Diagnosis ANE is most common in young children, is often associated with influenza, and results from a para- or postinfectious "cytokine storm." Strikingly symmetric thalamic necrosis with bilateral T2/FLAIR hyperintensities and bithalamic hemorrhages is common. Basal ganglionic and cortical. hemorrhages are rare in AHLE. Petechial microhemorrhages similar to those seen in AHLE can be found in a number of other disorders, including diffuse vascular injury, disseminated intravascular coagulopathy, fat emboli, thrombotic thrombocytopenic purpura, sepsis, vasculitis, hemorrhagic viral fevers, malaria, and rickettsial diseases.

20. Autoimmune Encephalitis

21. Autoimmune Encephalitis Most—but not all—are characterized by limbic dysfunction and varying involvement of the temporal lobes and neocortex. The autoimmune encephalitides are differentiated by specific antibody subtypes and can be paraneoplastic or nonparaneoplastic. Group I antibodies target intracellular antigens, whereas Group II antibodies target cell surface antigens. Group I antibodies are more closely associated with underlying malignancy.

22. Etiology Antibodies against cell-surface antigens such as AQP4 and voltage-gated potassium channels (VGKC-complex) including the leucine-rich glioma inactivated 1 (LGI1) are among the commonest autoantibodies in patients with nonneoplastic autoimmune-mediated CNS disease. Another common group-ion channel antigens include N-methyl, D-aspartate receptor (NMDAR or NMDAr) and γ-aminobutyric acid receptor (GABAr) encephalitis, which has a higher association with cancer (e.g., small-cell lung cancer) than other group II autoantibodies. Less common subtypes include anti-glutamate receptor 3 (GluR3) autoantibodies (associated with Rasmussen encephalitis) and voltage-gated calcium channel (VGCC) encephalitis.

23. Clinical aspect Most common presentation is subacute cognitive dysfunction and altered mental status. Seizures and medically intractable epilepsy are also common, especially in VGKC-complex encephalitis. NMDAr encephalitis is typically characterized by an initial viral-like prodrome followed by psychiatric symptoms, amnesia, and seizures. Nonneoplastic NMDAr is more common and often occurs in young women. Between 25-50% of older women have an ovarian teratoma or carcinoma.

24. Imaging findings The most common pattern is that of limbic encephalitis. T2/FLAIR hyperintensity in one or both medial temporal lobes is typical. Extralimbic involvement with structures such as the cortex, striatum, and diencephalon varies. Cortical involvement-common in VGCC encephalitis,rare in VGKC encephalitis. Diffusion restriction is variable but often absent. Enhancement on T1 C+ occurs in approximately 25% of cases - frequently associated with subsequent development of mesial temporal sclerosis.

25. Guillain-Barré Spectrum Disorders Miller Fisher syndrome (MFS) (acute ophthalmoplegia and ataxia) and Bickerstaff brainstem encephalitis (BBE) are rare inflammatory disorders that are now considered subtypes of Guillain-Barré syndrome (GBS) (acute onset of limb weakness)- all now considered autoimmune-mediated encephalitides associated with anti-GQ1b antibody syndrome. The disease course is usually monophasic with recurrences in few. The differential diagnosis of GBSD includes NMOSD and Listeria brainstem rhombencephalitis.

26. Imaging findings Brain MR findings are nonspecific. Enhancement of one or more cranial nerves may occur in the acute stage of MFS inflammatory demyelinating neuropathy. Patchy or confluent moderately extensive T2/FLAIR hyperintensity in the midbrain and pons may be present in BBE.

27. Neuromyelitis Optica Spectrum Disorder(NMO) Formerly known as Devic syndrome—is a severe form of acute demyelinating disease that preferentially involves the spinal cord and optic nerves with relative sparing of the cerebral white matter. The most common form of NMOSD is a primary autoantibody-mediated astrocytopathy characterized by the presence of antibodies to aquaporin-4 (AQP4) AQP4 is the most abundant water channel in the CNS and is located in the foot processes of astrocytes surrounding the blood-brain barrier. A specific biomarker of the disease, NMO-IgG, is almost always negative in MS and other autoimmune disorders, such as Sjögren syndrome and systemic lupus erythematosus.

28. Pathology In classic NMOSD one or both optic nerves are involved together with the spinal cord. The cervical cord is most commonly affected, and lesions typically extend over three or more consecutive segments. Brain lesions are not uncommon and tend to cluster around the third and fourth ventricles and the dorsal midbrain/aqueduct of Sylvius.

29. Microscopic Features Selective AQP4 immunoreactivity loss and vasculocentric complement and immunoglobulin deposition are characteristic but the loss also occurs in other demyelinating conditions, namely Balo disease and some cases of MS. It is the immunohistochemical staining pattern of NMO-IgG that is diagnostic. NMO-IgG binds to the abluminal face of microvessels at sites of immune complex deposition in NMOSD lesions. Actively demyelinating NMO lesions demonstrate vessel hyalinization, a finding not present in MS or AD EM. Eosinophils are commonly found in NMOSD biopsies but are rare in MS.

30. Clinical Issues In contrast to the striking geographical distribution of MS, NMOSD is a worldwide disease. Patients with NMOSD are on average 10 years older than patients with MS. Mean age at initial diagnosis is around 40 years. The F:M ratio for AQP4-positive NMOSD is 8-9:1. Seronegative NMO is equally distributed among the sexes. NMOSD follows an unpredictable course, but prognosis is generally worse than for MS. The vast majority of cases (85-90%) are relapsing. Accurate diagnosis is essential because some drugs used for MS can worsen NMOSD.

31. Imaging findings The most common MR findings are (1) a hyperintense, enhancing cord lesion that extends over three or more contiguous vertebral segments and (2) optic nerve hyperintensity and/or enhancement. Dorsal medulla and periependymal posterior fossa lesions are characteristic findings in NMOSD with area postrema syndrome and acute brainstem syndrome, respectively.

32. 2015 REVISED NMOSD DIAGNOSTIC CRITERIA In the past, the criteria for a diagnosis of NMO required both optic neuritis and transverse myelitis. The revised criteria allow other symptoms to be included.

33. The major differential diagnosis of NMOSD is MS. The brain is more involved in MS, whereas multisegmental contiguous spinal cord disease is typical of NMOSD.

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