Systemic Diseases
Neurosarcoidosis & Systemic Autoimmune Diseases
What Do You Need to Know?
- Neurosarcoidosis: Non-caseating granulomas; cranial neuropathies (facial nerve #1) and hypothalamic–pituitary dysfunction are the hallmark presentations; biopsy is the gold standard — serum ACE has only ~60% sensitivity
- Neuro-Behçet: Oral + genital ulcers with CNS involvement — parenchymal (brainstem predilection) vs. non-parenchymal (cerebral venous sinus thrombosis); pathergy test and HLA-B51 support diagnosis
- Neuropsychiatric SLE: 19 ACR-defined syndromes; distinguish inflammatory (immunosuppression) vs. thrombotic (anticoagulation for antiphospholipid syndrome); anti-ribosomal P antibodies correlate with psychosis
- Sjögren syndrome: Peripheral neuropathy (sensory ganglionopathy most characteristic) > CNS involvement; anti-SSA/Ro and anti-SSB/La; Schirmer test + lip biopsy for diagnosis
- IgG4-related disease: Hypertrophic pachymeningitis, orbital pseudotumor, hypophysitis; storiform fibrosis + IgG4+ plasma cells on tissue biopsy; rituximab is highly effective
- Susac syndrome: Triad of encephalopathy + branch retinal artery occlusion (BRAO) + sensorineural hearing loss; central callosal “snowball” lesions on MRI (vs. MS peripheral callosal lesions)
- Key board principle: Each systemic autoimmune disease has a characteristic neurological signature — matching the pattern to the disease is the fastest path to the correct answer
Neurosarcoidosis
Overview & Pathology
- Definition: CNS/PNS involvement by sarcoidosis — a multisystem granulomatous disease of unknown etiology
- Pathology: Non-caseating (non-necrotizing) granulomas composed of epithelioid histiocytes, multinucleated giant cells, and surrounding lymphocytes
- Epidemiology: ~5–15% of sarcoidosis patients develop neurological involvement; may be the presenting feature in up to 50% of neurosarcoidosis cases
- Predilection: African Americans, women, age 25–50 years
Clinical Manifestations
| Manifestation | Frequency | Key Features |
|---|---|---|
| Cranial neuropathies | 50–70% | CN VII (facial nerve) #1 — may be bilateral; CN II (optic nerve) #2 — optic neuritis, papilledema; any CN can be affected |
| Leptomeningeal disease | 10–20% | Basal leptomeningeal enhancement on MRI; chronic meningitis with CSF lymphocytic pleocytosis |
| Hypothalamic–pituitary | 10–15% | Diabetes insipidus (most common endocrine manifestation); hyperprolactinemia; panhypopituitarism |
| Myelopathy | 5–10% | Dorsal subpial enhancement (“trident sign” on axial MRI); longitudinally extensive; mimics NMOSD |
| Peripheral neuropathy | 15–20% | Small fiber neuropathy most common; polyradiculopathy; mononeuritis multiplex |
| Parenchymal mass | 5–10% | Ring-enhancing or solid lesion; mimics tumor or abscess |
| Hydrocephalus | 5–10% | Communicating (leptomeningeal) or obstructive (mass lesion) |
Heerfordt Syndrome (Uveoparotid Fever)
- Classic tetrad: Parotid gland enlargement + anterior uveitis + facial nerve palsy + fever
- Pathognomonic for sarcoidosis — highly specific clinical presentation
- May be the initial presentation of systemic sarcoidosis
💎 Board Pearl
- Bilateral facial palsy + uveitis = sarcoidosis until proven otherwise. The differential for bilateral CN VII palsy is narrow: sarcoidosis, Lyme disease, GBS, HIV, leukemia
- Diabetes insipidus + leptomeningeal enhancement on MRI = think neurosarcoidosis (also consider lymphoma, TB, and carcinomatous meningitis)
- Trident sign on axial spinal MRI = dorsal subpial gadolinium enhancement — characteristic of neurosarcoidosis myelopathy
Diagnostic Workup
| Test | Findings | Pearls |
|---|---|---|
| Serum ACE | Elevated in ~60% of systemic sarcoidosis | Low sensitivity (~60%) and poor specificity; normal ACE does NOT exclude diagnosis; false positives with diabetes, hyperthyroidism, lymphoma |
| Chest CT | Bilateral hilar lymphadenopathy (BHL) in ~90% of sarcoidosis | BHL is the most common thoracic finding; absence significantly lowers probability but does not exclude |
| Gallium-67 / PET scan | “Panda sign” (lacrimal + parotid uptake); “Lambda sign” (bilateral hilar + right paratracheal uptake) | FDG-PET largely replacing gallium; useful for identifying biopsy sites |
| CSF | Lymphocytic pleocytosis (50–70%), elevated protein (50–70%), low glucose (10–20%), elevated CSF ACE | CSF ACE has ~55% sensitivity and ~95% specificity for neurosarcoidosis; more useful than serum ACE for CNS disease |
| MRI brain/spine | Leptomeningeal enhancement (basal predominance), parenchymal lesions, hypothalamic/infundibular thickening, cranial nerve enhancement | Leptomeningeal pattern is the most suggestive imaging feature |
| Biopsy | Non-caseating granulomas = gold standard | Target most accessible tissue: lymph node > lung > skin > meninges/brain; must exclude TB, fungal infection, foreign body |
Zajicek Diagnostic Criteria
| Category | Criteria |
|---|---|
| Definite | Compatible clinical presentation + positive nervous system biopsy (non-caseating granulomas) + exclusion of other causes |
| Probable | Compatible clinical presentation + evidence of CNS inflammation (CSF/MRI) + positive systemic biopsy (non-CNS tissue) + exclusion of other causes |
| Possible | Compatible clinical presentation + exclusion of other causes + no tissue confirmation (supportive labs: ACE, chest imaging, etc.) |
💎 Board Pearl
- Serum ACE is a poor screening test — sensitivity only ~60%, and many false positives; never rely on a normal ACE to rule out neurosarcoidosis
- Always get a chest CT — bilateral hilar lymphadenopathy is present in ~90% and provides a safer biopsy target than CNS tissue
- “Probable” neurosarcoidosis is the most common working diagnosis — CNS biopsy is invasive and often avoided if systemic disease is confirmed
Treatment
| Line | Agent(s) | Details |
|---|---|---|
| First-line | Corticosteroids | IV methylprednisolone 1 g/day × 3–5 days for acute/severe → oral prednisone taper over months; most patients require prolonged therapy |
| Steroid-sparing | Methotrexate, azathioprine, mycophenolate mofetil | Methotrexate is the most commonly used steroid-sparing agent; typically added within 2–3 months to reduce steroid burden |
| Refractory | Infliximab, adalimumab (anti-TNF-α) | Infliximab most studied; effective for CNS and PNS disease; monitor for infection, demyelination |
- Prognosis: ~30% monophasic (self-limited); ~30% relapsing–remitting; ~30% chronic progressive despite therapy
- Mortality: 5–10% in neurosarcoidosis; worse with parenchymal disease, hydrocephalus, chronic meningitis
Neuro-Behçet Disease
Overview
- Behçet disease: Chronic relapsing systemic vasculitis of unknown etiology — affects all vessel sizes
- Classic triad: Recurrent oral ulcers + genital ulcers + uveitis
- Epidemiology: “Silk Road disease” — highest prevalence in Turkey, Iran, Japan, Korea; HLA-B51 positive in 50–70%
- Neuro-Behçet: CNS involvement in 5–10% of Behçet patients; may be the presenting feature
Parenchymal vs. Non-Parenchymal Disease
| Feature | Parenchymal (~80%) | Non-Parenchymal (~20%) |
|---|---|---|
| Pathology | Meningoencephalitis with perivascular inflammation | Venous thrombosis / intracranial hypertension |
| Location | Brainstem > diencephalon > basal ganglia; subcortical white matter; spinal cord | Cerebral venous sinus thrombosis (CVST); dural sinus thrombosis; rarely arterial |
| Presentation | Brainstem syndrome, hemiparesis, behavioral changes, encephalopathy | Headache, papilledema, elevated ICP, cranial nerve palsies |
| MRI | T2/FLAIR hyperintensity in brainstem/diencephalon; may enhance | Venous thrombosis on MRV; empty delta sign |
| CSF | Pleocytosis (neutrophilic early, lymphocytic late), elevated protein | Elevated opening pressure; CSF may be normal |
| Prognosis | Worse — progressive brain atrophy and disability | Better — typically responds to anticoagulation |
Diagnostic Clues
- Pathergy test: Hyperreactivity to skin prick → papule/pustule at 24–48 hours; ~60–70% positive in endemic populations; less reliable in Western patients
- HLA-B51: Strongest genetic association; supports diagnosis but not specific
- No pathognomonic lab test — diagnosis is clinical (International Study Group criteria)
💎 Board Pearl
- Oral + genital ulcers + brainstem lesion on MRI = Neuro-Behçet — the combination of mucocutaneous ulcers with brainstem predilection is the classic board scenario
- Parenchymal Neuro-Behçet loves the brainstem — a brainstem–diencephalic T2 lesion in a young patient from the Silk Road region should trigger this diagnosis
- CVST in a young patient with oral/genital ulcers = non-parenchymal Neuro-Behçet
- Pathergy test is SPECIFIC but not sensitive — a positive test strongly supports, but a negative test does not exclude
Treatment
- Parenchymal: High-dose IV corticosteroids → oral taper + azathioprine (first-line steroid-sparing); anti-TNF agents (infliximab, adalimumab) for refractory disease
- Non-parenchymal (CVST): Anticoagulation + corticosteroids; avoid anticoagulation alone without immunosuppression
- Maintenance: Azathioprine is the most studied maintenance agent; treat for ≥2 years minimum
Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)
ACR Classification: 19 Neuropsychiatric Syndromes
| CNS Syndromes (12) | PNS Syndromes (7) |
|---|---|
| Headache, seizures, cerebrovascular disease, cognitive dysfunction, psychosis, acute confusional state, anxiety, mood disorder, demyelinating syndrome, movement disorder (chorea), myelopathy, aseptic meningitis | Polyneuropathy, mononeuropathy, cranial neuropathy, autonomic neuropathy, myasthenia gravis, plexopathy, Guillain-Barré syndrome |
Most Common Manifestations
- Headache: Most frequent (>50%) but least specific; not always attributable to SLE
- Cognitive dysfunction: 20–80% depending on testing rigor; subtle memory and attention deficits
- Seizures: 7–20%; may be focal or generalized; associated with antiphospholipid antibodies and active disease
- Cerebrovascular disease: 5–15%; ischemic stroke > hemorrhagic; strongly linked to antiphospholipid syndrome
- Psychosis: 2–5%; associated with anti-ribosomal P antibodies
Key Antibody Associations
| Antibody | Neuropsychiatric Association | Clinical Significance |
|---|---|---|
| Antiphospholipid (aPL) | Stroke, CVST, chorea, seizures, cognitive dysfunction | Present in 30–40% of SLE; drives thrombotic manifestations → anticoagulation, not immunosuppression |
| Anti-ribosomal P | Lupus psychosis | Most specific antibody for NPSLE psychosis; 90% specificity |
| Anti-dsDNA | Active SLE flare (general marker) | High titers correlate with disease activity; not specific for neuropsychiatric involvement |
| Anti-NMDA-R (NR2) | Cognitive dysfunction, psychosis | Distinct from anti-NMDA-R encephalitis antibodies; cross-reactive with anti-dsDNA |
Inflammatory vs. Thrombotic: The Critical Distinction
| Feature | Inflammatory NPSLE | Thrombotic NPSLE (Antiphospholipid-Related) |
|---|---|---|
| Mechanism | Autoimmune inflammation, complement activation, vasculitis | Thrombosis of cerebral vessels (arterial or venous) |
| Manifestations | Psychosis, myelitis, optic neuritis, aseptic meningitis, acute confusional state | Stroke, TIA, CVST, multi-infarct cognitive decline, chorea |
| MRI | White matter lesions (MS-like), diffuse changes, meningeal enhancement | Infarcts (territorial or lacunar), cortical atrophy |
| Labs | Low complement (C3/C4), high anti-dsDNA, active urinalysis | Positive aPL (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) |
| Treatment | Immunosuppression: corticosteroids, cyclophosphamide, rituximab | Anticoagulation: warfarin (INR 2–3, or 3–4 for recurrent events); DOACs controversial |
💎 Board Pearl
- Anti-ribosomal P + psychosis = lupus psychosis — the most specific antibody–syndrome pairing in NPSLE
- Stroke in young woman with SLE = check antiphospholipid antibodies → treatment is anticoagulation, NOT immunosuppression
- Chorea in SLE = antiphospholipid syndrome — the most common movement disorder in SLE; mechanism is thrombotic/ischemic to basal ganglia
- Complement levels distinguish: Low C3/C4 = inflammatory flare (immunosuppress); normal complement + positive aPL = thrombotic (anticoagulate)
- Lupus myelitis may mimic NMOSD — longitudinally extensive lesion; test for AQP4-IgG
Clinical Pearl
- Not all neuropsychiatric symptoms in a lupus patient are attributable to SLE — infection, metabolic derangement, medication side effects, and primary psychiatric disease must be excluded. The 2019 EULAR recommendations emphasize attribution as a critical step: symptoms within 6 months of SLE diagnosis or during active disease are more likely SLE-related.
Sjögren Syndrome
Overview
- Definition: Chronic autoimmune disease targeting exocrine glands (salivary + lacrimal) → sicca syndrome
- Sicca symptoms: Dry eyes (keratoconjunctivitis sicca) + dry mouth (xerostomia)
- Demographics: 9:1 female predominance; peak onset 40–60 years
- Antibodies: Anti-SSA/Ro (70%) and anti-SSB/La (40%); ANA positive in ~80%
- Neurological involvement: ~20% of Sjögren patients; PNS far more common than CNS
Peripheral Nervous System Manifestations
| PNS Manifestation | Frequency | Key Features |
|---|---|---|
| Small fiber neuropathy | Most common | Burning pain, allodynia; normal NCS/EMG; diagnosed by skin biopsy (reduced IENFD) or QSART |
| Sensory ataxic neuropathy / ganglionopathy | Characteristic | Dorsal root ganglion attack (ganglionopathy) → asymmetric, non-length-dependent sensory loss + sensory ataxia; most characteristic PNS manifestation |
| Sensorimotor polyneuropathy | Common | Length-dependent; axonal > demyelinating |
| Trigeminal neuropathy | Uncommon but classic | Pure sensory involvement of CN V; may be bilateral; highly suggestive of Sjögren when isolated |
| Mononeuritis multiplex | Uncommon | Vasculitic mechanism |
| Autonomic neuropathy | Underrecognized | Adie pupil, orthostatic hypotension, anhidrosis |
CNS Manifestations (Rare but Board-Relevant)
- Optic neuritis: May mimic MS or NMOSD
- Transverse myelitis: Longitudinally extensive → must test for AQP4-IgG (Sjögren + NMOSD overlap)
- MS-like disease: White matter lesions, relapsing course; controversial whether this is true Sjögren CNS disease or comorbid MS
- Aseptic meningitis
- Cognitive dysfunction
Diagnostic Workup
| Test | Purpose |
|---|---|
| Anti-SSA/Ro, anti-SSB/La | Serological hallmark; SSA more sensitive, SSB more specific |
| Schirmer test | <5 mm wetting in 5 min = abnormal; objective measure of tear production |
| Minor salivary gland (lip) biopsy | Focus score ≥1 (aggregate of ≥50 lymphocytes per 4 mm2); most specific test |
| Skin biopsy (IENFD) | Reduced intraepidermal nerve fiber density confirms small fiber neuropathy |
💎 Board Pearl
- Sensory ataxia + non-length-dependent sensory loss + dry eyes/mouth = Sjögren ganglionopathy — the most characteristic neurological manifestation
- Isolated trigeminal sensory neuropathy (especially bilateral) should prompt evaluation for Sjögren syndrome
- Sjögren + longitudinally extensive myelitis → test for AQP4-IgG — up to 10–20% of NMOSD patients have comorbid Sjögren; AQP4 antibody may be the unifying pathology
- Neuropathy may precede sicca symptoms by years — consider Sjögren in any unexplained sensory ganglionopathy or small fiber neuropathy
IgG4-Related Disease (IgG4-RD)
Overview
- Definition: Chronic fibro-inflammatory condition characterized by tumefactive lesions, storiform fibrosis, and dense IgG4+ plasma cell infiltrate
- Systemic manifestations: Autoimmune pancreatitis (#1 associated), retroperitoneal fibrosis, sclerosing cholangitis, sialadenitis, thyroiditis, interstitial nephritis
- Demographics: Middle-aged to older men predominate
Neurological Manifestations
| Manifestation | Key Features |
|---|---|
| Hypertrophic pachymeningitis | Most common CNS manifestation; thickened, enhancing dura on MRI; headache, cranial neuropathies; IgG4-RD is the #1 cause of idiopathic hypertrophic pachymeningitis |
| Orbital pseudotumor | Orbital mass/swelling; proptosis, diplopia; IgG4-RD is the most common cause of orbital inflammatory pseudotumor |
| Hypophysitis | Pituitary enlargement → hypopituitarism, diabetes insipidus; infundibular thickening |
| Cranial neuropathies | Secondary to pachymeningitis or direct nerve infiltration; any cranial nerve |
| Perineural disease | Trigeminal and infraorbital nerve involvement |
Diagnostic Criteria
- Serum IgG4: Elevated (>135 mg/dL) in ~60–70%; not sensitive or specific alone — can be normal in tissue-confirmed cases and elevated in other conditions
- Tissue biopsy (gold standard):
- Storiform fibrosis (swirling, cartwheel-like pattern)
- Dense lymphoplasmacytic infiltrate with ≥10 IgG4+ plasma cells/HPF (or IgG4/IgG ratio >40%)
- Obliterative phlebitis
Treatment
- First-line: Corticosteroids — dramatic initial response in most patients; rapid improvement is itself a diagnostic clue
- Steroid-sparing / refractory: Rituximab is the most effective steroid-sparing agent; depletes IgG4-producing B cells
- Other: Azathioprine, mycophenolate for maintenance
- Relapse rate: High (~30–50%) after steroid discontinuation → long-term maintenance often needed
💎 Board Pearl
- Hypertrophic pachymeningitis + elevated serum IgG4 = IgG4-RD until proven otherwise — the #1 cause of idiopathic hypertrophic pachymeningitis
- Storiform fibrosis on biopsy is the histopathological hallmark — cartwheel/swirling pattern of fibrosis with IgG4+ plasma cells
- Orbital mass + pachymeningitis + autoimmune pancreatitis = classic IgG4-RD multisystem pattern
- Rituximab > conventional immunosuppressants for steroid-sparing therapy in IgG4-RD
Susac Syndrome
Overview
- Definition: Autoimmune endotheliopathy affecting arterioles of the brain, retina, and cochlea
- Classic triad: Encephalopathy + branch retinal artery occlusion (BRAO) + sensorineural hearing loss
- Pathophysiology: Autoimmune attack on endothelial cells → arteriolar occlusion; anti-endothelial cell antibodies proposed but not validated as diagnostic
- Demographics: Young women (20–40 years); 3:1 female predominance
- Important: Complete triad present at onset in only ~15% — components may emerge over weeks to months
Clinical Features
| Component | Features | Evaluation |
|---|---|---|
| Encephalopathy | Subacute cognitive decline, confusion, personality change, paranoia; headache common; may mimic psychiatric disease | MRI brain (see below) |
| BRAO | Visual field deficits; may be subclinical; often bilateral and multifocal | Fluorescein angiography (FA) is the key diagnostic test → arteriolar wall hyperfluorescence + branch occlusions; OCT shows retinal thinning |
| Sensorineural hearing loss | Low- and mid-frequency loss (cochlear apical involvement); may fluctuate; tinnitus common | Audiometry; may progress to bilateral deafness |
MRI Findings: Susac vs. MS
| Feature | Susac Syndrome | Multiple Sclerosis |
|---|---|---|
| Callosal lesions | Central callosal “snowball” lesions — round, involve the central fibers of the corpus callosum | Peripheral callosal lesions — ovoid, perpendicular to the ventricle (“Dawson fingers”), extend from the calloseptal interface |
| Deep gray matter | Internal capsule, thalamus, basal ganglia involvement common | Less common; cortical and juxtacortical lesions more typical |
| Leptomeningeal enhancement | May occur | Uncommon (though leptomeningeal enhancement is increasingly recognized) |
| Spinal cord | Typically spared | Commonly involved |
💎 Board Pearl
- Central callosal “snowball” lesions = Susac; peripheral callosal “Dawson fingers” = MS — the single most important MRI distinction on boards
- Young woman + encephalopathy + hearing loss + visual loss = Susac triad — even if incomplete at presentation
- Fluorescein angiography is essential — BRAO may be subclinical; FA reveals arteriolar wall hyperfluorescence not seen on fundoscopy alone
- Low-frequency hearing loss distinguishes Susac from most other causes (noise-induced, presbycusis = high-frequency)
Treatment
- Aggressive early immunosuppression is critical — the disease is self-limited (2–4 years) but cumulative damage (hearing loss, cognitive impairment, visual loss) can be devastating
- Induction: IV methylprednisolone + IVIg; PLEX for severe/refractory cases
- Maintenance: Mycophenolate mofetil or azathioprine + low-dose aspirin (antiplatelet for endothelial component)
- Anticoagulation: Not standard; low-dose aspirin is recommended for the vascular component
- Monitoring: Serial audiometry and fluorescein angiography to detect subclinical relapses
Comprehensive Comparison Table
Systemic Autoimmune Diseases with Neurological Manifestations
| Disease | Hallmark Neurological Feature | Key Antibody / Lab | Classic MRI Finding | First-Line Treatment |
|---|---|---|---|---|
| Neurosarcoidosis | Cranial neuropathy (CN VII > II), diabetes insipidus, leptomeningeal disease | ACE (~60% sensitivity); non-caseating granulomas on biopsy | Basal leptomeningeal enhancement; infundibular thickening; trident sign (spinal) | Corticosteroids → MTX/AZA → infliximab |
| Neuro-Behçet | Brainstem meningoencephalitis; CVST | HLA-B51; pathergy test | Brainstem–diencephalic T2 lesions; venous sinus thrombosis | Corticosteroids + azathioprine; anti-TNF for refractory |
| NPSLE | Stroke (aPL), psychosis (anti-ribosomal P), seizures, cognitive dysfunction | Anti-dsDNA, aPL, anti-ribosomal P; low complement | White matter lesions; territorial infarcts | Inflammatory: immunosuppression; Thrombotic: anticoagulation |
| Sjögren | Sensory ganglionopathy; small fiber neuropathy; trigeminal neuropathy | Anti-SSA/Ro, anti-SSB/La | Rarely abnormal (white matter lesions if CNS involved) | Corticosteroids + IVIg; rituximab for severe |
| IgG4-RD | Hypertrophic pachymeningitis; orbital pseudotumor; hypophysitis | Serum IgG4; storiform fibrosis + IgG4+ plasma cells on biopsy | Diffuse dural thickening/enhancement; orbital mass | Corticosteroids → rituximab |
| Susac syndrome | Encephalopathy + BRAO + SNHL | No specific antibody; fluorescein angiography diagnostic | Central callosal “snowball” lesions; deep gray matter involvement | IV steroids + IVIg + aspirin; mycophenolate maintenance |
Differentiating by Meningeal Pattern
| Meningeal Pattern | Diseases to Consider |
|---|---|
| Leptomeningeal enhancement (pia-arachnoid) | Neurosarcoidosis, carcinomatous meningitis, TB meningitis, neurosyphilis |
| Pachymeningeal enhancement (dura) | IgG4-RD (#1 cause of idiopathic), granulomatosis with polyangiitis (GPA), intracranial hypotension, meningioma, metastases |
Differentiating by Neuropathy Pattern
| Neuropathy Type | Disease Association |
|---|---|
| Sensory ganglionopathy (non-length-dependent) | Sjögren (#1 autoimmune cause), paraneoplastic (ANNA-1/Hu), cisplatin, vitamin B6 toxicity |
| Small fiber neuropathy | Sjögren, sarcoidosis, SLE, celiac disease, diabetes |
| Mononeuritis multiplex | Vasculitis (PAN, GPA, EGPA), Sjögren, SLE, sarcoidosis, hepatitis B/C |
| Cranial neuropathies (multiple) | Sarcoidosis, IgG4-RD, GPA, lymphoma, carcinomatous meningitis, Lyme |
💎 Board Pearl
- Leptomeningeal = sarcoid; pachymeningeal = IgG4-RD — the meningeal enhancement pattern immediately narrows the differential
- Non-length-dependent sensory neuropathy + sicca = Sjögren ganglionopathy
- Central callosal = Susac; peripheral callosal = MS
- Brainstem lesion + oral/genital ulcers = Neuro-Behçet; brainstem lesion + BHL = neurosarcoidosis
- Thrombotic complications in SLE = anticoagulate; inflammatory complications = immunosuppress — the most important management distinction in NPSLE
Clinical Pearl
- When facing a board question about systemic autoimmune disease with neurological symptoms, use a two-step approach: (1) identify the systemic disease by its extraneurological features (ulcers → Behçet; sicca → Sjögren; rash + arthritis → SLE; BHL → sarcoidosis), then (2) match the neurological pattern to that disease’s known CNS/PNS signature.
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