Anti MOG Disorders and CNS Vasculitides Flashcards
What are MOGAD and NMOSD?
Both MOGAD (Myelin Oligodendrocyte Glycoprotein Antibody Disease) and NMOSD (Neuromyelitis Optica Spectrum Disorder) are inflammatory, autoimmune disorders affecting the central nervous system. They were historically considered part of multiple sclerosis differential diagnoses, but recent discoveries of specific autoantibodies (anti-MOG and anti-AQP4) have led to their classification as distinct diseases.
Pathogenesis of MOGAD vs NMOSD
MOGAD
• Pathology: Autoantibodies target MOG (Myelin Oligodendrocyte Glycoprotein), a key component of myelin located on the surface of oligodendrocytes.
• Mechanism : the exact pathogenic mechanism is still unclear, complement activation may occur, but as a secondary process. Main damage occurs via direct antibody attack on myelin and oligodendrocytes.
NMOSD (Anti-AQP4 Disease)
• Pathology: Autoantibodies target Aquaporin-4 (AQP4) channels on astrocytes.
• Mechanism: Astrocyte destruction is the primary event. Leads to secondary damage to oligodendrocytes and demyelination. Complement activation occurs early, amplifying inflammation and tissue destruction.
Clinical features of MOGAD? Epidemiology? Diagnostic criteria and treatment?
Typical Clinical Presentations
1. Optic Neuritis
• Unilateral or bilateral vision loss.
• Better prognosis than NMOSD optic neuritis.
• Optic nerve swelling on MRI.
2. Acute Transverse Myelitis
• Inflammation of the spinal cord, causing weakness, numbness, and bladder dysfunction.
• Typically longitudinally extensive (spanning ≥3 vertebral segments) but with better recovery than NMOSD.
3. Acute Disseminated Encephalomyelitis (ADEM-like Presentation)
• More common in children.
• Encephalopathy is a key feature.
• Diffuse brain involvement with multiple white matter lesions.
4. Brainstem Involvement
• Nausea, vomiting, hiccups, and ataxia.
• Similar to NMOSD but less severe.
Disease Course :
• Mostly monophasic.
• Some patients have recurrent episodes, but less frequently than NMOSD.
Epidemiology : rare disorder, 0.16 per 100k, median onset 31 yrs, F:M 2.8:1
Diagnostic criteria and MRI findings.
Key Laboratory Findings :
• Serum anti-MOG antibodies (IgG) → Gold standard for diagnosis.
• Serum anti-AQP4 antibodies negative → Helps differentiate from NMOSD.
MRI Findings :
• Optic Neuritis → Unilateral or bilateral optic nerve inflammation.
• Spinal Cord → Longitudinally extensive lesions (≥3 vertebral segments).
• Brain Lesions → ADEM-like in pediatric cases, but no classic MS-like lesions.
Treatment consists of high dose IV steroids and plasma exchange for acute management. Long term treatments include immunosuppressant. (Avoid complement inhibitors as complement activation is minimal in MOGAD).
When should anti MOG antibody test be done?
The anti-MOG antibody test is crucial for diagnosing MOGAD but should only be performed in clinically suggestive cases to avoid false-positive or false-negative results.
Should only be performed in cases of :
- Monophasic or relapsing episodes of acute optic neuritis, acute transverse myelitis, brain stem encephalitis, other types of encephalitis.
- Radiological or electrophysiological findings suggestive of CNS demyelination like longitudinally extensive transverse myelitis on MRI.
- Additional supporting lab findings like CSF findings, fundoscopic abnormalities.
Optic neuritis in MOGAD?
Key Features of MOGAD Optic Neuritis
• Bilateral involvement is common (~70%) (compared to 24% in NMOSD, rare in MS).
• Severe visual loss that can progress to blindness within days.
• Good response to steroids, with frequent relapses after discontinuation.
• More anterior involvement of the optic nerve compared to anti-AQP4 NMOSD, which affects the optic chiasm more frequently.
MRI Findings in MOGAD Optic Neuritis
• Bilateral, extensive optic nerve lesions (longitudinal involvement).
• Anterior localization of optic nerve swelling (vs. posterior in NMOSD).
• Perioptic nerve sheath enhancement (a hallmark of MOGAD).
• No chiasmatic involvement (NMOSD often involves the optic chiasm).
Irreversible Visual Loss?
• Rare in MOGAD, due to good steroid response.
• More common in NMOSD (AQP4-IgG positive), where patients often become blind over time.
Acute transverse myelitis in MOGAD?
Key Features of MOGAD Myelitis
• Less common at onset (18%), but occurs in 50% of cases over time.
• Longitudinally extensive transverse myelitis (LETM) → lesions spanning ≥3 vertebral segments.
• Lesions can affect both upper and lower limbs, leading to: Paraparesis (48%) or tetraparesis (28%), depending on lesion location. Bladder and sexual dysfunction (70%) (more common than in NMOSD/MS). Pain and dysesthesia (68%) (neuropathic pain due to spinal involvement).
• Incomplete recovery → residual neurological deficits are common, particularly sphincter and sexual dysfunction.
Brainstem involvement in MOGAD?
Key Brainstem Symptoms in MOGAD
• Area postrema syndrome (intractable nausea, vomiting, hiccups).
• Internuclear ophthalmoplegia (eye movement abnormalities).
• Dysarthria & dysphagia (speech and swallowing difficulties).
• Facial numbness and other cranial nerve dysfunctions.
Key Points
• Brainstem involvement is often part of a more severe disease course.
• Rarely occurs in isolation—usually coexists with ON and TM (>75% of cases).
Acute disseminated encephalomyelitis?
Key Features of MOGAD ADEM
• More common in children (~36%) than adults (9%).
• Diffuse, large white matter lesions on MRI (can mimic tumors – “pseudo-tumor” appearance).
• Altered mental status (encephalopathy) is a required feature for ADEM diagnosis.
• Systemic symptoms: fever, malaise, irritability.
• May evolve into optic neuritis or myelitis over time.
Clinical course of MOGAS?
Disease course and prognosis —> MOGAD is typically monophasic (50% of cases), meaning it occurs as a single acute episode with full recovery.
Some patients experience relapses, especially those with optic neuritis (particularly when bilateral), NMOSD like presentation, brain stem involvement
Long term prognosis is generally good. Compared to NMOSD, MOGAD has a better recovery rate and fewer long term disabilities.
Paraclinical examinations in MOGAD to support diagnosis?
- Visual Evoked Potentials (VEP) & Optical Coherence Tomography (OCT). Findings in VEP MOGAD —> prolonged P100 latency, indicating delayed conduction in optic nerve. Findings in OCT MOGAS D —> thinning of peripapillary retinal nerve fiber layer due to atonal loss after acute optic neuritis.
- CSF analysis is not particularly useful. No oligoclonal bands unlike MS, no significant increase in proteins or WBC.
Spinal cord involvement in MOGAS vs NMOSD?
The spinal cord is one of the most commonly affected areas in both MOGAD and NMOSD. Both conditions cause longitudinally extensive transverse myelitis, which means lesions extending over three or more vertebral segments. However, certain MRI findings can help differentiate between MOGAD and AQP4-NMOSD.
Shared features include : LETM of at least >3 vertebral segments, central gray matter involvement and acute spinal cord inflammation.
Specific MRI findings in MOGAD :
1. Axial MRI T2 shows hyperintensity localized to the central gray matter forming and H.
2. Sagittal T2 MRI shows a thin linear hyperintensity along the central spinal cord, extending across multiple vertebral levels.
3. Conus Medullaris involvement, lower spinal cord.
4. Pseudo dilation of ependymal canal.
Specific MRI findings in NMOSD :
1. Bright spotty lesions, T2 weighted MRI lesions show intensely hyperintense lesions during acute phase. In MOGAD lesions are less bright.
2. More posterior and asymmetric lesions.
3. Frequent cord swelling, more pronounced than in MOGAD.
• MOGAD is more likely to affect the conus medullaris, leading to bladder/sexual dysfunction.
• AQP4-NMOSD tends to cause more destructive lesions and worse recovery.
DDX MOGAD vs NMOSD vs MS?
Spinal cord lesions : both MOGAD and NMOSD can present with LETM >3 vertebral segments in central gray matter, MS differs by causing shorter segment lesion <2 usually in lateral or posterior white matter.
Key spinal cord MRI differentiating factors : H sign MOGAD specific, Bright spotty lesions NMOSD specific, Conus medullaris involvement MOGAD specific, MS specific lesions are short segments, small and affect part of the cord rather than full cross sectional.
Brain involvement : both MOGAD and NMOSD can have brain and brain stem lesions, but their patterns differ. In MS is classically known for brain involvement with specific periventricular lesions (dawsons fingers).
Key brain MRI differentiating factors : extensive brain stem lesions in MOGAD, leptomeningeal and gyral enhancement MOGAD specific, diencephalon lesions NMOSD specific, MS classic periventricular lesions.
FLAMES in MOGAD?
FLAMES (FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures) is a specific MRI pattern observed in MOGAD patients who present with seizures. It represents a distinct form of cortical encephalitis associated with anti-MOG antibodies.
Clinical presentation : seizures, encephalopathy, focal neurological deficits.
MRI : FLAIR hyperintense cortical lesions, unilateral or bilateral, no deep white matter involvement unlike MS.
What are CNS vasculitides? Classification?
CNS vasculitides are a group of disorders characterized by inflammation and damage of blood vessels within the central nervous system. This leads to vascular occlusion, ischemia, and subsequent neurological damage. They can be primary (limited to CNS) or secondary (associated with systemic diseases like lupus, sarcoidosis, or vasculitis syndromes).
Classification based on location :
1. Primary CNS vasculitis like PACNS.
2. Secondary CNS vasculitis occurs as part of systemic vasculitis (lupus, Behçet’s).
What is PACNS? Clinical manifestation and diagnostic criteria?
Primary angiitis of the CNS is a rare condition with median age onset of 40-50 yrs. Etiology is still unknown.
It is characterized by three main histological patterns : Granulomatous vasculitis (58%) most common, presents with mononuclear inflammation and granulomas, Lymphocytic pattern (28%) with presence of lymphocytic inflammation and fibrinoid necrosis (15%) with transmural fibrinoid necrosis.
Clinical manifestations : PACNS has a long prodromal phase with mild symptoms before progressing to acute neurological manifestations. Manifestations include headache, altered cognition, hemiparesis, stroke, aphasia, seizures.
Diagnostic criteria : A definitive diagnosis requires all three criteria. Very old criteria from 1988.
1. Clinical criteria:
• Acquired neurological symptoms that cannot be explained by other conditions.
2. Neuroimaging/histopathology criteria:
• MRI/angiographic evidence of CNS vasculitis OR
• Brain biopsy confirmation of vasculitis (gold standard).
3. Exclusion criteria:
• No evidence of systemic vasculitis or alternative conditions (infection, malignancy, demyelinating disease, etc.).
78% of targeted biopsies are diagnostic. A negative biopsy does not exclude the diagnosis (segmental involvement).
MRI and angiographic findings in PACNS? Paraclinical findings?
MRI is the first-line imaging test but lacks specificity, making biopsy the gold standard.
Common MRI freatures : white matter abnormalities (90-100%), multiple infarcts (50%), mass like lesions (15%), leptomeningeal enhancement (15%), LGE (30%), hemorrhages (10%).
Angiographic findings include :
• Irregular vessel narrowing & dilation (“beading”) → Suggests inflammation.
• Multiple stenotic lesions → Can cause recurrent ischemic strokes.
• Distal vessel involvement (vs. large vessel disease in systemic vasculitis).
Paraclinical findings include CSF abnormalities such as mildly increased leukocytes and proteins.
