Basic Science Clinical
Vascular Headache Epilepsy Immunology Movement Neuromuscular Dementia Other Topics Neurosurgery
Clinical
Immunology
9 notes available
1 Last Minute Review 2 Multiple Sclerosis 3 Disease-Modifying Therapies 4 NMOSD & MOGAD 5 Systemic Diseases 6 Autoimmune Encephalitis 7 Paraneoplastic Syndromes 8 CNS Vasculitis 9 Other Neuroimmunology Topics
Clinical › Immunology

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; tissue confirmation of systemic or nervous-system sarcoidosis remains central; both serum and CSF ACE have limited sensitivity and variable specificity — supportive only, not rule-in/rule-out
  • 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. Per 2016 ACR/EULAR criteria, anti-SSA/Ro and minor salivary gland biopsy with focal lymphocytic sialadenitis (focus score ≥1) carry the key classification weight; isolated anti-SSB/La was removed (limited specificity)
  • 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
🚩 Don’t Miss — Test-Day Priorities
  • NPSLE psychosis & anti-ribosomal P: Anti-ribosomal P antibodies correlate with lupus psychosis. In the 2019 EULAR/ACR classification, a positive ANA is the high-sensitivity entry criterion; anti-dsDNA and anti-Sm are specific immunologic criteria that support diagnosis but anti-dsDNA is not mandatory. NPSLE attribution requires excluding mimics and correlating the syndrome with active SLE; anti-NMDAR (anti-N2A/N2B) tracks cognitive dysfunction
  • APS — warfarin standard, DOACs avoided in high-risk APS: Vitamin K antagonists (warfarin INR 2–3) remain standard for thrombotic APS. Avoid DOACs in triple-positive APS (LAC + anticardiolipin + β2-glycoprotein I) and in arterial APS (TRAPS trial showed rivaroxaban inferior in triple-positive); selected lower-risk venous APS scenarios are more nuanced and specialist-dependent
  • Catastrophic APS quadruple therapy: Multi-organ failure within days → IVIG + high-dose steroids + plasma exchange (PLEX) + anticoagulation; livedo reticularis + stroke = think Sneddon syndrome
  • Sjögren sensory ganglionopathy: Non-length-dependent sensory loss + pseudoathetosis + areflexia + sensory ataxia → dorsal root ganglion targeting; lip biopsy focus score ≥1 confirms; anti-Ro/La
  • Neurosarcoid biopsy beats ACE: Serum ACE has only ~60% sensitivity — never rule out with a normal ACE; biopsy from accessible site (skin, conjunctiva, lymph node) + FDG-PET to find target; bilateral facial palsy is the classic clue
  • Neuro-Behçet parenchymal vs CVT: Brainstem-predominant inflammatory lesion (mesodiencephalic) = parenchymal; cerebral venous sinus thrombosis = non-parenchymal; oral + genital aphthae + uveitis + pathergy + HLA-B51
  • RA atlantoaxial subluxation: Cervical pannus + odontoid erosion → cord compression and myelopathy; flexion-extension cervical imaging before any intubation in long-standing RA
  • IgG4 pachymeningitis: Hypertrophic dural thickening + cranial neuropathies + hypophysitis + orbital pseudotumor; storiform fibrosis + obliterative phlebitis + IgG4⁺ plasma cells; rituximab is highly effective
  • GPA vs EGPA vs PAN: GPA = c-ANCA/PR3 + sinus/lung/kidney + pachymeningitis; EGPA = asthma + eosinophilia + p-ANCA/MPO (40%) + mononeuritis multiplex; PAN = ANCA-negative + HBV + medium-vessel + nerve/muscle biopsy
  • Exclude vasculitis BEFORE immunosuppression: Always pursue biopsy (nerve, muscle, brain, dura) when vasculitis is on the differential — empiric steroids can blind the diagnosis and delay definitive therapy
🔍 Buzzwords & Pathognomonic FindingsClinical · Labs / imaging · Treatment
Clinical syndrome by disease
  • Young woman + malar rash + psychosis + seizures → Neuropsychiatric SLE
  • Recurrent miscarriage + arterial & venous thrombosis + livedo reticularis → Antiphospholipid syndrome
  • Livedo racemosa + recurrent stroke (no other APS features) → Sneddon syndrome
  • Multi-organ failure within days + thrombocytopenia + microangiopathy → Catastrophic APS (CAPS)
  • Sicca symptoms + sensory ataxia + pseudoathetosis + areflexia → Sjögren sensory ganglionopathy
  • Bilateral facial palsy + uveitis + parotid swelling + fever → Heerfordt syndrome (neurosarcoidosis)
  • Oral + genital aphthous ulcers + uveitis + brainstem lesion → Neuro-Behçet
  • Long-standing RA + neck pain + Lhermitte + myelopathy → Atlantoaxial subluxation with cervical pannus
  • Asthma + eosinophilia + mononeuritis multiplex + cardiomyopathy → EGPA (Churg-Strauss)
  • Encephalopathy + branch retinal artery occlusion + sensorineural hearing loss → Susac syndrome
Labs / imaging
  • Anti-ribosomal P antibody → Lupus psychosis
  • Triple positive: LAC + anticardiolipin + β2-glycoprotein I → High-risk antiphospholipid syndrome
  • Anti-SSA/Ro + lip biopsy focal lymphocytic sialadenitis (focus score ≥1) ± Schirmer abnormal → Sjögren syndrome (2016 ACR/EULAR; isolated anti-SSB/La is NO longer a serologic criterion)
  • Anti-Scl-70 (topoisomerase I) / anti-centromere → Scleroderma (diffuse / limited)
  • Anti-U1-RNP (high titer) → Mixed connective tissue disease
  • Dorsal subpial “trident sign” on axial cord MRI + non-caseating granulomas → Neurosarcoid myelitis
  • Basal leptomeningeal enhancement + hypothalamic-pituitary involvement + low CSF glucose → Neurosarcoidosis
  • Central callosal “snowball” lesions on MRI → Susac syndrome (vs peripheral callosal in MS)
  • c-ANCA / anti-PR3 + sinus + lung + kidney + pachymeningitis → GPA (Wegener)
  • p-ANCA / anti-MPO + asthma + eosinophilia → EGPA (Churg-Strauss)
  • HBsAg positive + medium-vessel beading on angiography + ANCA-negative → Polyarteritis nodosa
  • HLA-B51 + positive pathergy test → Behçet disease
  • Storiform fibrosis + obliterative phlebitis + IgG4⁺ plasma cells on biopsy → IgG4-related disease
Treatment / pearls
  • Warfarin INR 2–3 (NOT rivaroxaban — TRAPS trial) → Triple-positive antiphospholipid syndrome
  • IVIG + steroids + plasma exchange + anticoagulation → Catastrophic APS
  • Steroids + cyclophosphamide or MMF → Severe NPSLE / lupus nephritis
  • Steroids + methotrexate/azathioprine; infliximab for refractory → Neurosarcoidosis
  • Rituximab is highly effective (steroid-responsive but relapses) → IgG4-related pachymeningitis
  • Rituximab + cyclophosphamide + steroids → GPA / severe ANCA-associated vasculitis
  • Mepolizumab (anti-IL-5) as steroid-sparing → EGPA (Churg-Strauss)
  • Tocilizumab (anti-IL-6) → Giant cell arteritis (steroid-sparing)
  • Anti-TNF (infliximab/adalimumab) + steroids + azathioprine → Neuro-Behçet (parenchymal)
  • Rituximab + IVIG → Sjögren-associated CNS disease / ganglionopathy
  • Flexion-extension cervical MRI before intubation → Long-standing RA (atlantoaxial subluxation risk)
  • Biopsy gold standard — never rely on ACE alone → Neurosarcoidosis workup
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. Differential for bilateral CN VII palsy: Lyme, sarcoidosis, GBS (including Miller Fisher), HIV / HIV seroconversion, leukemic / lymphomatous infiltration, basal meningitis (TB, syphilis), and bilateral Bell palsy
  • 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%), CSF ACE may be elevated CSF ACE has limited sensitivity and variable specificity for neurosarcoidosis; supportive in context but should NOT be used as a rule-in/rule-out test. Tissue confirmation of systemic or nervous-system sarcoidosis remains central when feasible
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

  • Severe parenchymal disease: Infliximab / anti-TNF agents (infliximab, adalimumab) are preferred for severe parenchymal Neuro-Behçet; high-dose IV corticosteroids for acute attacks → oral taper
  • Less severe parenchymal: Corticosteroids + azathioprine (alternative steroid-sparing); anti-TNF for refractory or progressive disease
  • Non-parenchymal (CVST): Anticoagulation + corticosteroids; avoid anticoagulation alone without immunosuppression
  • Maintenance: Azathioprine is the most studied maintenance agent; treat for ≥2 years minimum
💎 Board Pearl
  • Cyclosporine is CONTRAINDICATED in Neuro-Behçet — paradoxically worsens CNS involvement (classic board distractor); use anti-TNF agents instead for severe parenchymal disease
  • Infliximab is the preferred biologic for severe parenchymal Neuro-Behçet — superior to conventional immunosuppressants for brainstem and progressive disease
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; higher-intensity (INR 3–4) or addition of low-dose aspirin considered for recurrent thrombosis despite therapeutic INR; DOACs are NOT recommended in APS — inferior to warfarin in triple-positive patients (TRAPS trial); warfarin remains standard of care
💎 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 — most strongly associated with antiphospholipid antibodies, but the mechanism is thought to be a direct antibody-mediated effect on basal ganglia neurons (not purely thrombotic); imaging is often normal; treatment may include immunosuppression in addition to antithrombotic therapy
  • 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 (positive in ~70%; carries the classification weight in 2016 ACR/EULAR criteria); anti-SSB/La (~40%) can coexist but isolated anti-SSB/La is no longer a serologic criterion (limited specificity); 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 (with minor salivary gland biopsy showing focal lymphocytic sialadenitis, focus score ≥1) Anti-SSA/Ro carries the key classification weight in 2016 ACR/EULAR criteria; anti-SSB/La can coexist and may be clinically useful, but isolated anti-SSB is no longer sufficient as a serologic criterion (limited specificity)
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 elevated IgG4+ plasma cells/HPF — threshold varies by organ (e.g., >10/HPF for meninges, >50/HPF for pancreas, >100/HPF for salivary gland); IgG4/IgG ratio >40% is a consistent supportive criterion across organs
    • 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-frequency sensorineural hearing loss (apical cochlear 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 sensorineural hearing loss (apical cochlear involvement) 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
Antiphospholipid Syndrome (APS)

Overview

  • Definition: Autoimmune thrombophilia defined by vascular thrombosis and/or pregnancy morbidity in the presence of persistent antiphospholipid antibodies
  • Primary vs. secondary: Primary APS occurs in isolation; secondary APS occurs in the setting of SLE or other autoimmune disease
  • Neurological burden: Stroke, TIA, CVST, chorea, cognitive dysfunction, seizures, myelopathy, migraine

Sapporo / Sydney 2006 Classification Criteria

Domain Criteria (≥1 clinical + ≥1 laboratory required)
Clinical Vascular thrombosis (arterial, venous, or small vessel) OR pregnancy morbidity (≥1 fetal death ≥10 weeks; ≥3 consecutive embryonic losses <10 weeks; or premature birth <34 weeks due to eclampsia/severe preeclampsia/placental insufficiency)
Laboratory Lupus anticoagulant OR moderate-to-high titer anti-cardiolipin IgG/IgM (>40 GPL/MPL or >99th percentile) OR anti-β2-glycoprotein I IgG/IgM (>99th percentile) — positive on 2 occasions ≥12 weeks apart

Key Variants

Variant Features
Catastrophic APS (CAPS) Multi-organ thrombosis (≥3 organs) over <1 week with histologic confirmation; mortality ~50%; requires aggressive triple therapy — anticoagulation + high-dose corticosteroids + plasma exchange and/or IVIg; refractory disease → rituximab or eculizumab
Triple-positive APS Positive lupus anticoagulant + anti-cardiolipin + anti-β2GPI — highest thrombotic risk; DOACs inferior to warfarin (TRAPS trial)
Sneddon syndrome Livedo racemosa/reticularis with recurrent ischemic cerebrovascular events from a noninflammatory thrombotic vasculopathy; young patients; aPL may be positive or negative (aPL+ in ~40–60%); APS is an important association but is NOT required to diagnose Sneddon syndrome

Treatment

  • Venous thrombosis: Warfarin INR 2–3 indefinitely
  • Arterial thrombosis / stroke: Warfarin INR 2–3 (with or without low-dose aspirin) or higher-intensity (INR 3–4) for recurrent events
  • DOACs: Vitamin K antagonists (warfarin) remain the standard for thrombotic APS. Avoid rivaroxaban/DOACs in triple-positive APS and arterial APS (TRAPS trial showed inferiority); selected lower-risk venous APS scenarios are more nuanced and specialist-dependent
  • Pregnancy: Low-molecular-weight heparin + low-dose aspirin (warfarin teratogenic)
  • Primary prophylaxis (asymptomatic aPL): Low-dose aspirin in high-risk patients
💎 Board Pearl
  • Young patient with stroke + livedo reticularis = Sneddon syndrome — check aPL
  • Triple-positive APS → warfarin, not DOACs (TRAPS trial)
  • CAPS = multi-organ thrombosis in <1 week → anticoagulation + steroids + PLEX/IVIg (triple therapy)
  • Persistent aPL requires 2 positive tests ≥12 weeks apart — transient positivity is common with infection
Rheumatoid Arthritis (Neurologic Manifestations)

Overview

  • Rheumatoid arthritis: Chronic symmetric inflammatory polyarthritis; anti-CCP and rheumatoid factor positive; extra-articular manifestations include neurological involvement
  • Neurological burden: Cervical spine instability is the most clinically urgent; peripheral neuropathy is more common but often subclinical

Key Neurological Manifestations

Manifestation Features
Atlantoaxial subluxation Synovitis erodes the transverse ligament and odontoid process at C1–C2 → instability and risk of cervicomedullary compression; obtain flexion–extension cervical radiographs / MRI before any surgery (anesthetic intubation risk)
Compressive cervical myelopathy Subaxial subluxation, pannus formation; progressive long-tract signs; surgical decompression / fusion may be required
Peripheral neuropathy Distal symmetric sensorimotor neuropathy; usually mild and length-dependent
Mononeuritis multiplex Vasculitic mechanism (rheumatoid vasculitis); seropositive long-standing disease; poor prognostic marker
Entrapment neuropathies Carpal tunnel syndrome (most common); ulnar neuropathy at elbow; tarsal tunnel; due to synovial proliferation
Rheumatoid pachymeningitis Rare; thickened, enhancing dura — can mimic IgG4-related disease; biopsy distinguishes
CNS vasculitis Rare; stroke, encephalopathy, seizures
💎 Board Pearl
  • RA + cervical pain or long-tract signs → image C-spine with flexion–extension views before surgery — atlantoaxial subluxation risk
  • Rheumatoid pachymeningitis can mimic IgG4-RD — biopsy distinguishes; treat with steroids + DMARDs
  • Mononeuritis multiplex in RA = rheumatoid vasculitis — aggressive immunosuppression warranted
Scleroderma (Systemic Sclerosis)

Overview

  • Definition: Multisystem connective tissue disease characterized by skin/visceral fibrosis, vasculopathy, and autoimmunity
  • Subtypes: Limited (CREST — anti-centromere) vs. diffuse (anti-Scl-70 / topoisomerase I; anti-RNA pol III)
  • Neurological involvement: Historically thought rare; trigeminal sensory neuropathy is the classic association

Neurological Manifestations

Manifestation Features
Trigeminal sensory neuropathy Most common cranial neuropathy in scleroderma; numbness in V2/V3 distribution; may be bilateral; pure sensory
Myopathy Inflammatory (scleroderma–polymyositis overlap; elevated CK, MRI edema) vs. non-inflammatory (fibrotic, mild CK elevation, fiber atrophy)
Peripheral neuropathy Distal sensorimotor or sensory; small fiber neuropathy increasingly recognized
CNS involvement Rare; reported white matter lesions, headache, rare CNS vasculitis
💎 Board Pearl
  • Bilateral trigeminal sensory neuropathy + Raynaud phenomenon + skin tightening = scleroderma
  • Differential for trigeminal sensory neuropathy: Sjögren, scleroderma, mixed connective tissue disease, sarcoidosis
Mixed Connective Tissue Disease (MCTD)

Overview

  • Definition: Overlap syndrome with features of SLE, systemic sclerosis, and polymyositis — defined by high-titer anti-U1 RNP antibodies
  • Sharp criteria: Raynaud + swollen hands + arthritis + myositis + sclerodactyly with anti-U1 RNP
  • Demographics: Female predominance; peak onset 20–30s

Neurological Manifestations

  • Trigeminal neuropathy: Pure sensory; bilateral involvement classic (shared with Sjögren and scleroderma)
  • Aseptic meningitis: May be a presenting feature; lymphocytic CSF
  • Headache: Common; migraine-like
  • Transverse myelitis: Rare; longitudinally extensive lesions reported (test for AQP4-IgG)
  • Peripheral neuropathy: Sensory or sensorimotor
  • Cognitive dysfunction and rare CNS vasculitis described
💎 Board Pearl
  • High-titer anti-U1 RNP defines MCTD — overlap of SLE + scleroderma + polymyositis
  • Trigeminal neuropathy + Raynaud + puffy hands = think MCTD
  • Aseptic meningitis in a young woman with overlap features → check anti-U1 RNP
Systemic Vasculitides with Neurologic Manifestations

Overview

  • Vasculitis classification (Chapel Hill 2012): by predominant vessel size — large (GCA, Takayasu); medium (PAN, Kawasaki); small (ANCA-associated: GPA, MPA, EGPA; immune-complex: cryoglobulinemic, IgA, anti-GBM)
  • Neurological signature: mononeuritis multiplex (medium-vessel and ANCA-associated); ischemic stroke / AION (large-vessel); pachymeningitis (GPA); CNS vasculitis (rare across subtypes)

Large-Vessel Vasculitis

Disease Features
Giant cell arteritis (GCA) Age >50; ESR ≥50 mm/hr; jaw claudication is the strongest clinical predictor; new-onset temporal headache, scalp tenderness, polymyalgia rheumatica overlap; AION (anterior ischemic optic neuropathy) → permanent vision loss; temporal artery biopsy ≥1–2 cm (skip lesions); start emergent high-dose corticosteroids before biopsy if vision threatened; ACR 1990 + 2022 criteria; treat with prednisone 40–60 mg/day (or IV pulses if vision involved); tocilizumab is steroid-sparing
Takayasu arteritis Aorta and major branches; “pulseless disease” — absent or diminished pulses, BP discrepancy, bruits; young women (Asian predilection); claudication, syncope, stroke; corticosteroids + steroid-sparing (MTX, AZA); biologics for refractory

Medium-Vessel Vasculitis

Disease Features
Polyarteritis nodosa (PAN) Medium muscular arteries; ANCA-negative; renal, GI, skin (livedo, ulcers, nodules), testicular pain; mononeuritis multiplex (~60%); HBV association in classic PAN; rare CNS involvement (late stroke); biopsy / angiography (microaneurysms in renal/mesenteric vessels); corticosteroids + cyclophosphamide (or antiviral for HBV-associated)

ANCA-Associated Small-Vessel Vasculitis

Disease Features
Granulomatosis with polyangiitis (GPA, formerly Wegener) c-ANCA / PR3; upper + lower respiratory tract + renal (sinusitis, saddle-nose, pulmonary nodules/cavitation, RPGN); CNS involvement in ~10% — cranial neuropathies, pachymeningitis (mimics IgG4-RD), mononeuritis multiplex, rare granulomatous CNS mass; rituximab or cyclophosphamide + corticosteroids
Microscopic polyangiitis (MPA) p-ANCA / MPO; pulmonary–renal syndrome (alveolar hemorrhage + RPGN); no granulomas; mononeuritis multiplex; rituximab or cyclophosphamide + corticosteroids
Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg–Strauss) Asthma + eosinophilia + p-ANCA / MPO (positive in 30–50%); allergic rhinitis, nasal polyps, pulmonary infiltrates; mononeuritis multiplex (~75%) — highest of any vasculitis; cardiac involvement is leading cause of mortality; corticosteroids ± mepolizumab; cyclophosphamide for severe
💎 Board Pearl
  • Jaw claudication is the single strongest clinical predictor of biopsy-positive GCA — do not wait for biopsy if vision is threatened, start steroids immediately
  • Asthma + eosinophilia + mononeuritis multiplex = EGPA — ~75% have neuropathy, the highest of any vasculitis
  • c-ANCA / PR3 + pachymeningitis = GPA — on the differential for hypertrophic pachymeningitis along with IgG4-RD
  • HBV-associated PAN → antivirals + plasma exchange + short-course steroids (avoid prolonged immunosuppression)
  • “Pulseless disease” in a young woman → Takayasu arteritis
Whipple Disease

Overview

  • Pathogen: Tropheryma whipplei — gram-positive actinobacterium
  • Systemic features: Chronic diarrhea, malabsorption, weight loss, migratory arthralgia (often precedes GI symptoms by years), low-grade fever, lymphadenopathy
  • Demographics: Middle-aged white men predominate
  • CNS involvement: ~10–40% of patients; may occur without GI symptoms (isolated CNS Whipple)

Neurological Manifestations

Manifestation Features
Oculomasticatory myorhythmia (OMM) PATHOGNOMONIC — slow (~1 Hz) pendular vergence oscillations of the eyes synchronous with masticatory (jaw / face) movements; persists in sleep; no other condition produces this sign
Cognitive decline / dementia Subacute progressive dementia; behavioral and personality change
Supranuclear gaze palsy Vertical > horizontal; can mimic progressive supranuclear palsy
Hypothalamic dysfunction Insomnia, hyperphagia, polydipsia
Myoclonus, ataxia, seizures Variable

Diagnosis

  • Small bowel biopsy: PAS-positive foamy macrophages in lamina propria (classic finding)
  • PCR: T. whipplei PCR on CSF, small bowel, or other tissue — high sensitivity
  • CSF: Mild pleocytosis, elevated protein; PAS-positive macrophages may be seen
  • MRI: Variable — hypothalamic, mesial temporal, brainstem T2 hyperintensities; may enhance

Treatment

  • Induction: Ceftriaxone 2 g IV daily × 2–4 weeks (CNS-penetrant)
  • Maintenance: Oral TMP-SMX (trimethoprim-sulfamethoxazole) × 1–2 years
  • Relapse risk: Significant; long-term follow-up required; immune reconstitution inflammatory syndrome (IRIS) can occur
💎 Board Pearl
  • Oculomasticatory myorhythmia is PATHOGNOMONIC for CNS Whipple disease — pendular vergence + synchronous jaw movements; no other condition causes this
  • Dementia + supranuclear gaze palsy + GI symptoms / arthralgia = Whipple until proven otherwise
  • PAS-positive macrophages on small bowel biopsy + CSF PCR for T. whipplei are the diagnostic backbone
  • Treatment: ceftriaxone induction → long-term TMP-SMX (1–2 years)
Cryoglobulinemia

Overview

  • Cryoglobulins: Immunoglobulins that precipitate at <37°C and redissolve on warming; cause vasculitis via immune-complex deposition and/or hyperviscosity
  • Brouet classification

Brouet Classification

Type Composition Associations Mechanism / Features
Type I Monoclonal Ig (usually IgM or IgG) Multiple myeloma, Waldenström macroglobulinemia, MGUS, CLL Hyperviscosity-driven; Raynaud, livedo, acrocyanosis, digital ischemia; CNS hyperviscosity (headache, blurred vision, encephalopathy)
Type II (mixed) Monoclonal IgM (with rheumatoid factor activity) + polyclonal IgG Hepatitis C (most common — ~90% of mixed cryos); HIV; lymphoproliferative Immune-complex vasculitis; Meltzer triad (palpable purpura + arthralgia + weakness); membranoproliferative GN; peripheral neuropathy
Type III (mixed) Polyclonal IgM + polyclonal IgG Autoimmune disease (SLE, Sjögren, RA), chronic infections Similar to Type II but milder; immune-complex vasculitis

Neurological Manifestations

  • Peripheral neuropathy: Most common neurological manifestation — ~50% of mixed cryoglobulinemia; typically axonal, distal, sensorimotor; may be sensory-predominant or painful small-fiber
  • Mononeuritis multiplex: Vasculitic mechanism; less common than distal symmetric pattern
  • CNS involvement: Rare — stroke (immune-complex vasculitis or hyperviscosity), encephalopathy, cognitive dysfunction
  • Hyperviscosity syndrome (Type I): Headache, blurred vision, retinal hemorrhages, confusion, stroke

Diagnosis & Treatment

  • Serum cryoglobulin testing: Sample collected/transported at 37°C; quantification by cryocrit; immunofixation distinguishes type
  • Supportive labs: Low C4 (out of proportion to C3), positive rheumatoid factor (Types II/III), HCV serology / PCR
  • Treatment:
    • Type I: Treat the underlying plasma cell / lymphoproliferative disorder; plasmapheresis for hyperviscosity
    • Type II / III with HCV: Direct-acting antivirals (DAAs) — cure HCV and frequently resolves vasculitis
    • Severe / refractory mixed cryoglobulinemic vasculitis: Rituximab, corticosteroids, plasmapheresis
💎 Board Pearl
  • HCV + peripheral neuropathy + palpable purpura + low C4 = Type II mixed cryoglobulinemia
  • Type I cryoglobulinemia = monoclonal → myeloma / Waldenström; hyperviscosity-driven (not immune-complex)
  • Peripheral neuropathy is the most common neurological manifestation (~50% of mixed cryo) — axonal sensorimotor > mononeuritis multiplex
  • Meltzer triad (purpura + arthralgia + weakness) suggests mixed cryoglobulinemia
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.

References

  1. Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic analysis of 1,166 patients. BMC Neurol 2016;16(1):220.
  2. Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis — diagnosis and management. QJM 1999;92(2):103–117.
  3. Stern BJ, Royal W, Gelfand JM, et al. Definition and consensus diagnostic criteria for neurosarcoidosis: from the Neurosarcoidosis Consortium Consensus Group. JAMA Neurol 2018;75(12):1546–1553.
  4. Al-Araji A, Kidd DP. Neuro-Behçet’s disease: epidemiology, clinical characteristics, and management. Lancet Neurol 2009;8(2):192–204.
  5. Kalra S, Silman A, Akman-Demir G, et al. Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations. J Neurol 2014;261(9):1662–1676.
  6. Unterman A, Nolte JES, Boaz M, et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011;41(1):1–11.
  7. Govoni M, Bortoluzzi A, Padovan M, et al. The diagnosis and clinical management of the neuropsychiatric manifestations of lupus. J Autoimmun 2016;74:41–72.
  8. Morreale M, Marchione P, Giacomini P, et al. Neurological involvement in primary Sjögren syndrome: a focus on central nervous system. PLoS One 2014;9(1):e84605.
  9. Perzyska-Mazan J, Maslinska M, Gasik R. Neurological manifestations of primary Sjögren’s syndrome. Reumatologia 2018;56(2):99–105.
  10. Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol 2020;72(1):7–19.
  11. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet 2015;385(9976):1460–1471.
  12. Dorr J, Krautwald S, Wildemann B, et al. Characteristics of Susac syndrome: a review of all reported cases. Nat Rev Neurol 2013;9(6):307–316.
  13. Kleffner I, Dorr J, Ringelstein M, et al. Diagnostic criteria for Susac syndrome. J Neurol Neurosurg Psychiatry 2016;87(12):1287–1295.
  14. Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 11th ed. McGraw-Hill; 2019.
🔒

Continue reading — sign in

The full note has more clinical pearls, tables, and board-focused tips. Free account, no fee.

Sign in Create free account