Patologie infiammatorie encefaliche e midollari
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1 Patologie infiammatorie encefaliche e midollari Maria Laura Stromillo Department of Medicine, Surgery and Neuroscience
2 Inflammatory disorders of the CNS NMOSD ADEM Multiple Sclerosis
3 Neuro-Myelitis Optica NMO Severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord. Causing recurrent attacks of blindness and paralysis. Wingerchuk et al Other parts of the CNS may also be affected by the inflammatory process: Brainstem: medulla oblongata usually in contiguity with cervical cord lesion. Hypothalamus. Corpus callosum and periventricular location. Specific serum antibodies, known as NMO-IgG, have been detected in NMO, and AQP-4 has been identified as their target antigen. Lennon VA et al. Lancet 2004, J Exp Med 2005
4 NMO: diagnostic criteria Wingerchuk et al. Neurology 2006
5 Wingerchuck 2015 Core Diagnostic clinical criteria characteristics for NMOSD without AQP4-IgG or NMOSD with unknown AQP4-IgG status The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). 1. Optic neuritis 1. At least 1 core clinical characteristic. 1. At least 2 core clinical characteristics occurring as a result of one or more clinical 2. Acute Positive myelitis test for AQP4-IgG using best available detection method (cell-based assay attacks and meeting all of the following requirements: strongly recommended). 3. Area a. at postrema least 1 syndrome: core clinical episode characteristic of otherwise must unexplained be optic hiccups neuritis, or acute nausea myelitis and vomiting with 3. LETM, Exclusion or area of postrema alternative syndrome. diagnoses. 4. Acute b. dissemination brainstem syndrome in space (2 or more different core clinical characteristics) c. fulfillment of additional MRI requirements, as applicable 5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions 2. Negative tests for AQP4-IgG using best available detection method, or testing unavailable. 6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions 3. Exclusion of alternative diagnoses.
6 NMOSD: BRAIN MRI Thalamus Hypothalamus Subcortical WM Area postrema Corticospinal tract Corpus callosum Periependymal Wingerchuk et al. Neurology 2015
7 NMOSD: BRAIN MRI Extensive brain lesions (EBLs) include: Tumefactive-like lesions ADEM-like lesions MS-like lesions Posterior reversible encephalopathy syndrome (PRES)-like lesions Cheng et al. BMC 2013
8 NMOSD: BRAIN MRI Enhancement pattern Brain Gadolinium enhancement is rare Frequently patchy enhancement with blurred margins ( cloudlike enhancement ) or pencil-thin ependymal enhancement (similar to that observed in infectious ependymitis) Very rare solid enhancement pattern (indistinguishable from acute MS) Never incomplete ring enhancement Barnett Y et al. AJNR 2013 Ito S. et al. Ann Neurol 2009
9 NMOSD:Spinal Cord MRI Longitudinally extensive transverse myelitis LETM Extension over 3 vertebral segment Frequent Gd enhancement Often necrotizing lesions (T 1 -ipointensity)
10 NMOSD: Spinal Cord MRI LETM lesions have a predilection for central cord Cervical LETM may extend into the medulla Chronic sequelae of LETM may include spinal cord atrophy. Wingerchuk et al. Neurology 2015
11 Acute Disseminated Encephalo-Myelitis-ADEM ADEM is an immune-mediated inflammatory and demyelinating disorder with acute or subacute onset affecting multifocal areas of the CNS. Spinal involvement is much less frequent than brain involvement. ADEM clinical presentation: must be polysimtomatic must include encepahalopathy Encepahalopathy is defined as one or more of the following: Behavioral change (e.g., confusion, excessive irritability) Alteration in consciousness (e.g., lethargy, coma) unexplained by fever Krupp et al. Neurology 2007, Mult Scler 2013
12 ADEM Diagnostic criteria for ADEM Krupp et al 2013 Mult Scler
13 ADEM: BRAIN MRI Large multifocal, T 2 -hyperintense lesions (>1 to 2 cm in size) located in the supratentorial or infratentorial WM regions. T 1 -hypointense lesions are rare. Bilateral diffuse, multifocal, poorly marginated, large asymmetric lesions of the WM, basal ganglia, and cortical GM. Involvement of the thalami Pohl et al. Neurology 2016
14 ADEM: Spinal Cord MRI Spinal cord involvement has been described in up to 1/3 of patients MRI may show confluent intramedullary lesion(s) Often swelling lesions Predominantly affects the thoracic region. Variable enhancement (patchy or pheripheral)
15 ADEM: MRI Complete resolution of MRI abnormalities after treatment has been described in 37% to 75% Partial resolution in 25% to 53% of patients
16 Differential diagnosis Polman C et al 2011
17 Multiple Sclerosis Brain lesions characteristics Sites: Periventricular Infratentorial Corpus callosum (sagittal) Juxtacortical (U fibers) Distribution: Asymmetric Shape: Irregular Ovoid Evolution: Variable
18 Multiple Sclerosis Spinal Cord lesion characteristics Small size: Location: Shape: < 2 vertebral segments < half of cord cross-sectional area cervical > than the rest lateral lateral + posterior columns central GM not spared cigar-like Signal characteristics: Effect on the cord: enhancement uncommon T 1 hypointense rarely swelling (acute phase) local atrophy (chronic phase) Lycklama et al Lancet Neurol 2003
19 NMOSD vs MS Brain MRI MS NMOSD
20 NMOSD vs MS Brain MRI 7.0 Tesla Sinnecker T et al. 2012
21 NMOSD vs MS Spinal Cord MRI NMO central lesion Long spinal cord lesion over 3 vertebral segment Trasversally extensive lesions involving the grey matter surrounding the central canal. SM peripheral lesions Focal, homogeneuos cord lesion Well marginated on sagittal and axial images Peripheral location without involvement of the central canal Nakamura et al. J Neurol 2009; Yonezu et al. Mult Scler 2013
22 NMOSD vs MS Spinal Cord MRI Longitudinally Extensive Transverse Myelitis > 3 segments Centrally located Majority of transverse axis MS risk <2% Acute Partial Transverse Myelitis < 2 segments Eccentric or asymmetric location MS risk: 10% at 61 months in brain MRI negative 88% in brain MRI positive Fisniku LK, Brex PA, Altmann DR, et al. Brain 2008
23 NMOSD:Spinal Cord MRI BSLs: very hyperintense spotty lesions on axial T2WI. The signal is visually more hyperintense than that of surrounding cerebrospinal fluid without flow void effects. BSLs were more frequently found in patients with NMO (54%) than in those with MS (3%; p< 0.01). (Sensitivity=54% specificity = 97%) BSLs were seen in 63% of the patients without longitudinally extensive spinal cord lesions (LESCL). BSLs or LESCL were found in 88% of the NMO patients Yonezu T et al. Mult Scler 2013
24 ADEM vs MS MRI characteristics ADEM ADEM SM MS Pohl et al. Neurology 2016
25 Grazie per la vostra attenzione
26 ADEM Typically bilateral lesions on T2/FLAIR sequences, but may be asymmetric Lesions tend to be poorly marginated Almost all patients have multiple lesions in the deep and subcortical WM while the periventricular WM is generally spared Thalami and basal ganglia are frequently affected often symmetrical and brainstem and SC abnormalities are common Contrast enhancement is sometimes seen in acute lesions Differential diagnosis with MS and other demyelinating diseases
27 Number and dimensions of the lesions are variable In the spinal cord large confluent intramedullary that extend over multiple segment are common with variable degree of contrast enhancement. Abnormal findings on MRI may progress over a relatively short period of time, consistent with progression of the disease The occurrence of relapses with new lesions on MRI suggest the diagnosis of multiphase ADEM or MS
28
29 Neuroimaging characteristics of NMOSD Brain MRI Lesion features Large, confluent, unilateral, or bilateral, subcortical or deep WM. Long (1/2 of the length of the corpus callosum or greater), diffuse, heterogeneous, or edematous corpus callosum lesions. Involving: dorsal medulla (especially the area postrema), periependymal surfaces of the IV ventricle in the brainstem/cerebellum, hypothalamus, thalamus, or periependymal surfaces of the III ventricle, long corticospinal tract lesions, unilateral or bilateral, contiguously involving internal capsule and cerebral peduncle. Extensive periependymal brain lesions, often with gadolinium enhancement Wingerchuk et al. Neurology 2015
30 Neuroimaging characteristics of NMOSD SPINAL CORD SC MRI, acute Other Increased characteristic signal on features T2-W that (standard may be T2-W, detected PD, or STIR sequences) extending over 3 or more complete vertebral segments. Rostral extension of the lesion into the brainstem. Central cord predominance (more than 70% of the lesion residing within the central GM). Cord expansion/swelling. Gadolinium Decreased signal enhancement on T1-W of corresponding the lesion on T1-W to region (no of specific increased distribution T 2 -W signal. or pattern) SC MRI, chronic Longitudinally extensive cord atrophy (sharply demarcated atrophy extending over 3 complete, contiguous vertebral segments and caudal to a particular segment of the SC), with or without focal or diffuse T 2 signal change involving the atrophic segment OPTIC NERVE Unilateral or bilateral increased T 2 signal or T 1 gadolinium enhancement within ON or optic chiasm; relatively long lesions (e.g., those extending more than half the distance from orbit to chiasm) and those involving the posterior aspects of the ON or the chiasm are associated with NMO Wingerchuk et al. Neurology 2015
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