Susac, NPSLE, NBD and NS Flashcards
What is Susan syndrome?
Susac Syndrome is a rare autoimmune disorder characterized by inflammation and occlusion of microvessels in the brain, retina, and inner ear. The disease is progressively increasing in reported cases due to improved recognition and diagnostic techniques.
Key Features :
• Autoimmune-mediated microangiopathy leading to vascular occlusion.
• Age range: 7 to 72 years, but most commonly affects young women (M:F = 1:3) between 20-40 years.
• Clinical Triad :
1. Encephalopathy (headache, cognitive impairment).
2. Branch retinal artery occlusion (BRAO).
3. Sensorineural hearing loss.
Pathophysiolgy of Susac syndrome?
Pathophysiology :
• It is an immune-mediated damage to the microvascular endothelium, particularly in the central nervous system, retina, and inner ear.
• This occurs through a T-cell and antibody-mediated process
Histopathology :
• Microangiopathic changes → endothelial swelling, lymphocytic infiltration, leaky vessel walls, and thrombotic occlusions.
• The brain lesions resemble small-vessel ischemia but are inflammatory rather than embolic.
• Demyelination, gliosis, and neuronal damage occur due
to ischemia in affected regions.
Diagnostic criteria of Susan syndrome? DDX for Susac syndrome?
A definitive diagnosis requires all three of the following:
1. Brain Involvement
• Clinical symptoms (headache, cognitive impairment, neurological deficits).
• MRI findings: Hyperintense, multifocal, round lesions on T2/FLAIR. At least one lesion in the corpus callosum (a hallmark feature).
2. Retinal Involvement
• Fluorescein angiography: Retinal artery occlusions.
• Patients may be asymptomatic but show paraclinical evidence of vascular compromise.
3. Vestibulocochlear Involvement
• Audiometry showing sensorineural hearing loss.
• Clinical signs: Tinnitus, vertigo, hearing impairment.
DDX includes systemic immune mediated diseases like SLE, behçets, sarcoidosis and sjogren.
Key MRI findings in Susac syndrome?
- Corpus Callosum Involvement (Hallmark Feature)
• Lesion distribution: The most characteristic lesions are found in the central portion of the corpus callosum (unlike MS or NMOSD, which affect different regions).
• Lesion types:
• Snowball lesions: Small, round, hyperintense lesions (T2-weighted) in the central corpus callosum (most specific feature).
• Icicle lesions: Wedge-shaped lesions extending from the upper corpus callosum towards the ventricles.
• Spoke lesions: Linear lesions representing microinfarcts of obliquely radiating axons.
• “Riddled” corpus callosum: Residual punched-out holes in the corpus callosum from previous lesions. - Multifocal Lesions in Other Brain Regions
• Periventricular, centrum semiovale, and subcortical regions (100%) → Similar to MS but different in distribution.
• Deep gray matter (basal ganglia and thalamus) (70%) → Unlike MS, which rarely involves deep gray matter.
• Brainstem and cerebellar peduncles (33%) → Can cause ataxia and cranial nerve symptoms. - White Matter and Cortical Involvement
• Small, multifocal T2 hyperintense lesions seen in both white and gray matter.
• Lesions can resemble small ischemic strokes but are non-ischemic in nature.
• The lesions do not follow a clear vascular distribution, unlike strokes. - Leptomeningeal and Parenchymal Enhancement (70%)
• Leptomeningeal enhancement is present early in the disease.
• It represents perivascular inflammation and leakage of contrast due to small vessel endothelial damage.
• Can involve the cerebellum, brainstem, and cortical regions. - Atrophy
• Whole-brain atrophy may be seen in later stages, particularly affecting the corpus callosum and cerebellum.
• This occurs due to chronic microvascular damage.
Angiographic findings in Susac syndrome? Laboratory findings?
- Fluorescein Angiography (FA) for Retinal Involvement :
• Branch Retinal Artery Occlusions (BRAO).
• Pathognomonic feature of Susac Syndrome.
• Multiple, small, segmental occlusions of retinal arteries.
• Can be asymptomatic or present as scotomas, visual loss.
Arteriolar Wall Hyperfluorescence (AWH) :
• Diffuse or focal hyperfluorescence of affected vessels.
• Suggests endothelial damage and vascular leakage. - Magnetic Resonance Angiography (MRA) & Digital Subtraction Angiography (DSA) for Brain Involvement
• Absence of Large Vessel Vasculitis. Unlike other CNS vasculitides (e.g., PACNS, SLE vasculitis), Susac does not involve medium/large arteries.
• Microvascular Occlusions in Small Arterioles. - Inner Ear Perfusion Abnormalities (Rarely Studied)
• Cochlear Microvascular dysfunction.
• May contribute to sensorineural hearing loss.
Lab findings : no specific serological markers, ANA described but not more than in healthy controls. CSF analysis shoes unspecific elevation of total proteins, mild pleocytosis.
Treatment for Susac syndrome?
Since Susac Syndrome is a rare and newly recognized immune-mediated endotheliopathy, there is no standardized treatment based on clinical trials. However, management is based on early, aggressive, and prolonged immunosuppression to prevent relapses and irreversible damage.
- First-Line Treatment: High-Dose Corticosteroids
• Methylprednisolone 1000 mg/day IV for 5 days, followed by:
• Oral prednisone 1 mg/kg/day, with slow tapering (over months). - Additional immunosuppressive therapy may include IVIG, cyclophosphamide, mycophenolate mofetil, rituximab.
- Antithrombotic therapy may include aspirin, and anticoagulation with heparin or warfarin.
What is neuropsychiatric SLE? CNS and PNS manifestations?
Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to neurological and psychiatric symptoms occurring in SLE patients due to autoimmune-mediated inflammation, vascular damage, and autoantibody effects on the CNS and PNS. The American College of Rheumatology (ACR) has proposed 19 neuropsychiatric manifestations of SLE.
The ACR expanded the recognition of 19 neuropsychiatric syndromes in SLE, classified into CNS and PNS involvement.
CNS manifestations include :
1. Diffuse CNS dysfunction : cognitive dysfunction, acute confusion state, psychiatric syndromes like depression and anxiety.
2. Focal CNS syndrome like seizures, cranial neuropathies, cerebrovascular diseases, demyelinating syndromes.
PNS manifestations :
1. Peripheral neuropathy.
2. Acute inflammatory demyelinating poly neuropathy, GBS like presentation.
3. Chronic relapsing poly neuropathy.
4. Myasthenia syndromes, MG like.
Pathophysiology and diagnostic approach to NPSLE?
NPSLE has a multifactorial pathogenesis, involving:
• Autoimmune-mediated microvascular damage (vasculitis, thrombosis)
• Autoantibody effects (anti-NMDAR, anti-phospholipid, anti-ribosomal P antibodies)
• Cytokine-mediated neuroinflammation
• Choroid plexus dysfunction → altered CSF composition
Key Autoantibodies in NPSLE
1. Antiphospholipid antibodies → Stroke, thrombosis
2. Anti-NMDAR antibodies → Cognitive dysfunction, seizures, psychosis
3. Anti-ribosomal P antibodies → Psychosis, depression
4. Anti-neuronal antibodies → Peripheral neuropathy
Diagnosis is based on :
1. Clinical criteria —> presence of SLE (> 4 ACR criteria), presence of one or more neuropsychiatric involvement, exclusion of other causes.
2. Lab tests for ANA, Anti dsDNA, Antiphospholipid, anti ribosomal P.
3. Imaging : MS like WM lesions, cerebrovascular infarcts or hemorrhages.
MRI findings in NPSLE?
- White Matter lesions :
• Multiple small hyperintense WM lesions on T2-weighted and FLAIR sequences.
• These lesions can mimic multiple sclerosis or other white matter diseases, leading to a broad differential diagnosis.
• Typically smaller and more scattered than in MS.
• Periventricular, subcortical, or centrum semiovale involvement is common. - Vascular involvement :
• Microinfarcts & macroinfarcts: ischemic strokes due to vasculitis or antiphospholipid syndrome (APS).
• Cerebral hemorrhages: due to vasculitis-related vessel fragility or anticoagulant complications.
• Venous thrombosis: cerebral venous sinus thrombosis (CVST) is a possible presentation.
• Leptomeningeal enhancement: common in vasculitic forms of NPSLE. - Spinal Cord Involvement :
• Thoracic spinal cord > Cervical spinal cord
• Longitudinally extensive transverse myelitis (LETM), lesions extend >3 vertebral segments, unlike short lesions in MS.
• Can resemble NMOSD (anti-AQP4 disease).
• Acute myelitis → severe weakness, sensory loss, bladder dysfunction. - Basal Ganglia & Deep Gray Matter Involvement
• Hyperintense lesions in basal ganglia, thalamus
• Can result in movement disorders (chorea, dystonia, tremors). - Leptomeningeal Enhancement
•Seen in 33% of cases.
•Indicates vasculitis or blood-brain barrier disruption.
Therapy for Neuropsychiatric SLE?
- Corticosteroids (First-line for Acute Episodes)
• Methylprednisolone 1g IV/day for 3-5 days, followed by:
• Oral prednisone 1mg/kg/day for 1 month, then slow tapering over 12 months. - Immunosuppressants (For Maintenance & Severe Cases)
• Cyclophosphamide (Severe cases, vasculitis)
• Azathioprine, Mycophenolate mofetil, Methotrexate
• Rituximab (For refractory cases, especially in APS or vasculitis) - Anticoagulation (For APS-related Stroke)
• If antiphospholipid syndrome (APS) is present:
• Lifelong anticoagulation with warfarin or DOACs, aspirin or heparin in acute phases.
What is Neuro-Behçet’s Disease?
It is a idiopathic multi systemic disease with vascular and inflammatory involvement. It most commonly affects Mediterranean, middle eastern and Japanese men in their 3-4th decade of life.
It presents with neurological involvement and can affect both CNS and PNS.
Two main forms:
1. Parenchymal NBD (P-NBD) (80%) → Meningoencephalitis
2. Non-Parenchymal NBD (NP-NBD) (20%) → Vascular complications (venous thrombosis, stroke)
Clinical features of NBD?
- Parenchymal NBD (P-NBD)
• Most frequent form (80%), subacute onset (days to weeks), lasting several weeks.
• Systemic symptoms often present (fever, oral/genital ulcers, uveitis, skin lesions).
• Headache is common before/during attack.
• Common Syndromes: brainstem syndrome (most typical), hemiparesis, spinal cord involvement, cognitive dysfunction & behavioral changes (frontal lobe involvement). - Non-Parenchymal NBD (NP-NBD)
• 20% of NBD cases, involves large vessels → “vasculo-Behçet’s disease”
• Venous thrombosis → Cerebral venous sinus thrombosis (CVST) (transverse sinus, sagittal sinus)
• Arterial thrombosis/infarcts (less common)
• Symptoms:
• Intracranial hypertension (due to venous thrombosis), false localizing signs (CN III, VI palsy), headache, papilledema, focal neurological deficits due to infarction.
MRI findings in NBD?
- Parenchymal Form (P-NBD)
• Single lesion in acute phase, more widespread involvement in chronic phase.
• T2 Hyperintense lesions : Brainstem involvement (most common) → midbrain, pons, thalamus, large lesions with enhancement & edema, resolving after treatment, bilateral thalamic, basal ganglia involvement, cerebral white matter lesions (frontal, temporal, subcortical), pseudotumoral lesions (mass effect, enhancement), spinal cord involvement such as
• Long transverse myelitis (>2-3 segments)
• Thoracic > Cervical involvement - Non-Parenchymal Form (NP-NBD)
• Cerebral venous sinus thrombosis (CVST) → hyperintense thrombosed sinus on T2.
• Ischemic infarcts in venous territories.
• Intracranial hemorrhages (rare, due to vasculitis).
Diagnostic criteria for Neuro-Behçet’s Disease?
Systemic Behçet’s disease + Neurological symptoms/signs.
• No standardized criteria exist, but common features:
• Parenchymal involvement: Brainstem/thalamus/basal ganglia lesions.
• Non-parenchymal involvement: CVST, ischemic infarcts.
• CSF findings: Increased protein, pleocytosis, cytokine changes.
• MRI findings: T2 lesions in brainstem, thalamus, basal ganglia, or spinal cord.
• Exclusion of other conditions (MS, NMOSD, vasculitis, stroke, infection
Treatment for Neuro-Behçet’s Disease?
A. Acute Treatment
1. High-dose IV corticosteroids (Methylprednisolone 1g/day for 5 days)
• Followed by oral prednisone 1mg/kg/day, slowly tapered over 12 months.
2. Immunosuppressants:
• Oral: Azathioprine, Mycophenolate Mofetil, Methotrexate.
• IV: Cyclophosphamide (severe cases).
3. TNF-alpha inhibitors (Infliximab, Adalimumab) → for steroid-resistant cases.
- Treatment for Cerebral Venous Thrombosis (CVT)
• Immunosuppressants + Steroids + Anticoagulation (Heparin/Warfarin).
