Susac Syndrome¶
VERSION: 1.2 CREATED: February 2, 2026 REVISED: February 2, 2026 STATUS: Approved
DIAGNOSIS: Susac Syndrome
ICD-10: H35.89 (Other specified retinal disorders -- branch retinal artery occlusion component), I67.89 (Other cerebrovascular disease -- cerebral endotheliopathy), H93.09 (Unspecified degenerative and vascular disorders of ear -- sensorineural hearing loss component)
CPT CODES: 70553 (MRI brain with/without contrast), 92235 (fluorescein angiography), 92250 (fundus photography), 92557 (comprehensive audiometry), 92588 (distortion product otoacoustic emissions), 89051 (CSF cell count with differential), 84157 (CSF protein), 96365 (IV infusion first hour -- IVIG/steroids), 96366 (IV infusion each additional hour), 36514 (therapeutic apheresis/plasma exchange), 95816 (EEG routine), 95950 (continuous EEG monitoring), 92083 (visual field testing), 85025 (CBC with differential), 80053 (CMP)
SYNONYMS: Susac syndrome, SuS, retinocochleocerebral vasculopathy, small vessel occlusive disease triad, Susac's syndrome, RED-M syndrome (retinopathy-encephalopathy-deafness associated microangiopathy), autoimmune endotheliopathy, retinal-cochlear-cerebral vasculopathy, branch retinal artery occlusion with encephalopathy, Susac triad, corpus callosum microangiopathy syndrome
SCOPE: Diagnosis, immunotherapy, and long-term monitoring of Susac syndrome -- an autoimmune endotheliopathy affecting small vessels of the brain, retina, and cochlea. Covers the classic clinical triad (encephalopathy with corpus callosum lesions, branch retinal artery occlusion, sensorineural hearing loss), diagnostic workup including MRI with characteristic "snowball" corpus callosum lesions, fluorescein angiography, audiometry, CSF analysis, and immunotherapy (IVIG, high-dose corticosteroids, plasma exchange, and long-term immunosuppression with mycophenolate mofetil, azathioprine, or rituximab). Includes differentiation from multiple sclerosis, CNS vasculitis, ADEM, and other autoimmune encephalopathies. Not all patients present with the complete triad simultaneously; a high index of suspicion is required. For primary CNS vasculitis, use "CNS Vasculitis (PACNS)" template. For autoimmune encephalitis with antibody-mediated mechanisms, use "Autoimmune Encephalitis" template. For MS, use "MS - New Diagnosis" template.
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential (CPT 85025) | Baseline; infection screen; thrombocytopenia or anemia may suggest alternative diagnoses (TTP, SLE); monitor before immunotherapy | Normal; thrombocytopenia or schistocytes raise concern for TTP | STAT | STAT | ROUTINE | STAT |
| CMP (BMP + LFTs) (CPT 80053) | Metabolic screen; renal function for contrast and IVIG dosing; hepatic function for immunosuppressant clearance; electrolyte derangement as encephalopathy cause | Normal | STAT | STAT | ROUTINE | STAT |
| ESR (CPT 85652) | Inflammatory marker; typically normal or mildly elevated in Susac syndrome; markedly elevated suggests systemic vasculitis or infection | Normal to mildly elevated (ESR is often normal in Susac syndrome) | STAT | STAT | ROUTINE | STAT |
| CRP (CPT 86140) | Inflammatory marker; usually normal in Susac syndrome; elevated CRP favors systemic vasculitis, infection, or alternative diagnosis | Normal to mildly elevated | STAT | STAT | ROUTINE | STAT |
| PT/INR, aPTT (CPT 85610+85730) | Coagulopathy screen pre-LP; baseline before anticoagulation; antiphospholipid evaluation | Normal | STAT | STAT | - | STAT |
| Blood glucose (CPT 82947) | Pre-steroid baseline; metabolic encephalopathy screen | Normal | STAT | STAT | ROUTINE | STAT |
| HbA1c (CPT 83036) | Glycemic status before high-dose corticosteroids; diabetic retinopathy as differential for BRAO | <5.7% | - | ROUTINE | ROUTINE | - |
| Troponin (CPT 84484) | Cardiac involvement rare but reported in Susac syndrome; stress cardiomyopathy in acute presentation | Normal | STAT | STAT | - | STAT |
| Blood cultures x2 (CPT 87040) | Rule out endocarditis and bacteremia causing embolic retinal artery occlusion | No growth | STAT | STAT | - | STAT |
| Urinalysis with microscopy (CPT 81003) | Screen for renal involvement suggesting systemic vasculitis (SLE, ANCA vasculitis) rather than Susac syndrome | Normal (abnormal suggests systemic disease) | STAT | STAT | ROUTINE | STAT |
| Procalcitonin (CPT 84145) | Distinguish infectious from autoimmune CNS process | Normal (<0.1 ng/mL) | URGENT | URGENT | - | URGENT |
| Lactate (CPT 83605) | Sepsis screen; metabolic assessment | Normal (<2.0 mmol/L) | STAT | STAT | - | STAT |
| Magnesium (CPT 83735) | Seizure threshold; Susac patients develop seizures from cortical involvement | Normal | STAT | STAT | ROUTINE | STAT |
| Pregnancy test (females of childbearing age) (CPT 81025) | Teratogenicity of immunosuppressants; imaging with contrast; treatment planning; Susac syndrome has female predominance | As applicable | STAT | STAT | ROUTINE | STAT |
| Type and screen (CPT 86900) | Potential plasma exchange; transfusion if needed | On file | URGENT | ROUTINE | - | URGENT |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| ANA (CPT 86235) | Screen for SLE and other connective tissue diseases; SLE can cause BRAO and CNS disease mimicking Susac | Negative or low titer | URGENT | ROUTINE | ROUTINE | URGENT |
| Anti-dsDNA antibodies (CPT 86255) | SLE evaluation if ANA positive; lupus can cause retinal vasculitis and encephalopathy | Negative | - | ROUTINE | ROUTINE | - |
| Anti-SSA/SSB (Ro/La) (CPT 86235) | Sjogren syndrome with CNS involvement and retinal vasculitis | Negative | - | ROUTINE | ROUTINE | - |
| ANCA panel (c-ANCA/PR3, p-ANCA/MPO) (CPT 86235+86200) | Systemic vasculitis with retinal and CNS involvement (GPA, MPA) | Negative | URGENT | ROUTINE | ROUTINE | URGENT |
| Complement C3, C4 (CPT 86160+86161) | Low complement suggests SLE or other complement-mediated vasculopathy | Normal | - | ROUTINE | ROUTINE | - |
| Antiphospholipid antibodies (anticardiolipin IgG/IgM, anti-beta2-glycoprotein I IgG/IgM, lupus anticoagulant) (CPT 86147+86146+85613) | Antiphospholipid syndrome causing BRAO and cerebral infarcts mimicking Susac syndrome | Negative | - | ROUTINE | ROUTINE | - |
| Quantitative immunoglobulins (IgG, IgA, IgM) (CPT 82784) | Baseline before IVIG; IgA deficiency (IVIG anaphylaxis risk); hypergammaglobulinemia in autoimmune disease | Normal; check IgA level before first IVIG dose | - | ROUTINE | ROUTINE | - |
| Hepatitis B surface antigen, surface antibody, core antibody (CPT 87340+86706+86704) | Required before rituximab; HBV reactivation risk during immunosuppression | Negative or immune (vaccinated) | - | ROUTINE | ROUTINE | - |
| Hepatitis C antibody (CPT 86803) | HCV-associated vasculitis; pre-immunosuppression screen | Negative | - | ROUTINE | ROUTINE | - |
| HIV 1/2 antigen/antibody (CPT 87389) | HIV retinopathy and vasculopathy can mimic Susac; pre-immunosuppression screen | Negative | - | ROUTINE | ROUTINE | - |
| RPR/VDRL with reflex FTA-ABS (CPT 86592) | Syphilis can cause retinal vasculitis, hearing loss, and encephalopathy (mimics complete Susac triad) | Non-reactive | URGENT | ROUTINE | ROUTINE | URGENT |
| QuantiFERON-TB Gold or T-SPOT (CPT 86480) | Pre-immunosuppression screen; TB can cause CNS vasculitis | Negative | - | ROUTINE | ROUTINE | - |
| TSH (CPT 84443) | Thyroid dysfunction in encephalopathy differential; Hashimoto encephalopathy | Normal | - | ROUTINE | ROUTINE | - |
| Anti-endothelial cell antibodies (AECA) | Elevated in Susac syndrome (supports autoimmune endotheliopathy mechanism); not widely available; research biomarker | May be positive (supports diagnosis but not required); not standardized | - | ROUTINE | ROUTINE | - |
| Homocysteine (CPT 83090) | Hyperhomocysteinemia as thrombotic risk factor; contributes to retinal artery occlusion | Normal | - | ROUTINE | ROUTINE | - |
| D-dimer (CPT 85379) | Coagulopathy screen; thrombotic thrombocytopenic purpura evaluation | Normal | URGENT | ROUTINE | - | URGENT |
| ACE level (CPT 82164) | Neurosarcoidosis can cause cranial neuropathies, retinal disease, and hearing loss | Normal | - | ROUTINE | ROUTINE | - |
| Lyme serology (IgG/IgM with reflex Western blot) (CPT 86617) | Lyme neuroborreliosis can cause cranial neuropathy (CN VIII) and encephalopathy; endemic areas | Negative | - | ROUTINE | ROUTINE | - |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Anti-neuronal antibodies (NMDAR, LGI1, CASPR2) (CPT 86255) | Autoimmune encephalitis coexistence or mimicry of the encephalopathic component of Susac syndrome | Negative | - | EXT | EXT | - |
| Aquaporin-4 (AQP4) antibody (CPT 83519) | NMOSD with brainstem involvement can cause hearing loss and visual symptoms | Negative | - | EXT | EXT | - |
| MOG-IgG antibody (CPT 83519) | MOGAD can cause encephalopathy and optic pathway disease | Negative | - | EXT | EXT | - |
| Von Willebrand factor antigen and ADAMTS13 activity (CPT 85245+85397) | Endothelial activation marker; ADAMTS13 deficiency (TTP) can cause multiorgan microangiopathy mimicking Susac | VWF elevated (endothelial activation); ADAMTS13 >10% (excludes TTP) | - | EXT | EXT | - |
| Fibrinogen, haptoglobin, peripheral blood smear (CPT 85384+83010+85060) | Thrombotic microangiopathy screen (TTP/HUS); schistocytes on smear | Normal fibrinogen; normal haptoglobin; no schistocytes | - | EXT | EXT | - |
| Interleukin-6 (serum and CSF) (CPT 83520) | Elevated in active autoimmune endotheliopathy; guides treatment response | Normal (<7 pg/mL) | - | EXT | EXT | - |
| Anti-endothelial cell antibodies -- research panel | Specialized testing at reference laboratories; identifies antibodies targeting endothelial antigens in Susac syndrome | May be positive; research use only | - | EXT | EXT | - |
| Paraneoplastic antibody panel (ANNA-1/Hu, CV2/CRMP5) (CPT 86255) | Paraneoplastic retinopathy and encephalopathy; rare overlap | Negative | - | EXT | EXT | - |
| Cogan syndrome antibodies (anti-HSP70, anti-cochlear antibodies) | Cogan syndrome causes interstitial keratitis + vestibuloacoustic dysfunction (audiometric overlap with Susac) | Negative | - | EXT | EXT | - |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| CT head without contrast (CPT 70450) | Immediate (ED triage) | Rule out hemorrhage, mass, hydrocephalus; CT is often normal early in Susac syndrome | None significant | STAT | STAT | - | STAT |
| MRI brain with and without contrast (CPT 70553) | Within 24 hours; STAT if available | PATHOGNOMONIC: "Snowball" lesions in central fibers of corpus callosum (best seen on sagittal T2/FLAIR and DWI); multifocal white matter T2/FLAIR hyperintensities in deep gray matter, periventricular white matter, posterior fossa, and internal capsule; leptomeningeal enhancement; callosal lesions with central "hole" pattern (icicle lesions); DWI restriction in acute lesions | Pacemaker; metallic implants; GFR <30 for gadolinium | STAT | STAT | ROUTINE | STAT |
| Fluorescein angiography (FA) (CPT 92235) | Within 24-48 hours; essential for diagnosis | DIAGNOSTIC: Branch retinal artery occlusion (BRAO); arteriolar wall hyperfluorescence (pathognomonic -- represents endothelial damage); non-filling of arteriolar segments; retinal capillary leakage; multiple arterial branch occlusions often bilateral; abnormal even without visual symptoms | Fluorescein allergy; severe renal impairment (relative); pregnancy (relative) | - | URGENT | URGENT | - |
| Comprehensive audiometry (CPT 92557) | Within 24-48 hours; essential for diagnosis | Sensorineural hearing loss (SNHL) predominantly low and mid-frequency (unlike presbycusis which is high-frequency); unilateral or bilateral; fluctuating; progressive to severe/profound | None significant | - | URGENT | URGENT | - |
| Fundoscopic examination (dilated) | Immediate if visual symptoms | Cotton-wool spots; Hollenhorst plaques (rare); arteriolar wall changes; retinal whitening from BRAO; multiple branch artery territory infarcts | None | STAT | STAT | ROUTINE | STAT |
| ECG (12-lead) (CPT 93000) | On admission | Baseline; arrhythmia screen; cardiac source of emboli in differential | None | STAT | STAT | ROUTINE | STAT |
| Chest X-ray (CPT 71046) | On admission | Exclude pulmonary pathology; mediastinal lymphadenopathy (sarcoidosis differential) | Pregnancy (relative) | STAT | STAT | - | STAT |
| Echocardiogram (transthoracic) (CPT 93306) | Within 24-48 hours | Exclude cardiac embolic source (vegetations, PFO, myxoma) as cause of BRAO; rare cardiac involvement reported in Susac syndrome | None significant | URGENT | URGENT | ROUTINE | URGENT |
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with sagittal FLAIR and DWI (dedicated Susac protocol) (CPT 70553) | Within 48 hours | Sagittal FLAIR is critical: central callosal "snowball" lesions (3-7 mm round lesions in central corpus callosum fibers); "icicle" or "spoke" lesions hanging from inferior surface of corpus callosum; leptomeningeal enhancement; deep gray matter lesions (thalamus, basal ganglia); cerebellar lesions; DWI restriction indicates acute/active disease | Same as MRI | - | URGENT | ROUTINE | URGENT |
| Optical coherence tomography (OCT) (CPT 92134) | Within 48-72 hours | Retinal nerve fiber layer thinning; inner retinal layer loss from ischemia; macular edema; arteriolar wall changes; serial OCT monitors for disease progression and treatment response | None significant | - | ROUTINE | ROUTINE | - |
| Visual field testing (CPT 92083) | Within 72 hours | Scotomas corresponding to BRAO territories; reveals subclinical retinal ischemia | Patient cooperation required | - | ROUTINE | ROUTINE | - |
| Distortion product otoacoustic emissions (DPOAE) (CPT 92588) | Within 72 hours | Absent or reduced emissions indicating outer hair cell damage; cochlear ischemia pattern; complements audiometry | None significant | - | ROUTINE | ROUTINE | - |
| Auditory brainstem response (ABR) (CPT 92585) | Within 72 hours | Prolonged latencies or absent waves; helps differentiate cochlear (Susac) from retrocochlear (acoustic neuroma) pathology | None significant | - | ROUTINE | ROUTINE | - |
| MRA head (CPT 70544) | With MRI brain | Typically normal in Susac syndrome (small vessel disease below MRA resolution); helps exclude large vessel vasculitis or RCVS | Same as MRI | - | ROUTINE | ROUTINE | ROUTINE |
| EEG (routine or continuous) (CPT 95816) | If seizures or altered consciousness | Focal or diffuse slowing; epileptiform discharges; subclinical seizures; encephalopathy pattern; seizures reported in 15-20% of Susac patients | None significant | URGENT | URGENT | ROUTINE | STAT |
| CT chest/abdomen/pelvis with contrast (CPT 71260+74178) | Within 72 hours if systemic disease suspected | Exclude sarcoidosis (hilar adenopathy); systemic vasculitis features; occult malignancy (paraneoplastic retinopathy differential) | Contrast allergy; renal insufficiency | - | ROUTINE | ROUTINE | - |
| Transesophageal echocardiogram (TEE) (CPT 93312) | If TTE non-diagnostic | Vegetations; aortic arch atheroma; PFO with paradoxical embolism; improved sensitivity for small embolic sources | Esophageal pathology | - | ROUTINE | ROUTINE | - |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Conventional cerebral angiography (DSA) (CPT 36224) | If large vessel vasculitis suspected | Typically NORMAL in Susac syndrome (small vessel disease); small vessel irregularities in rare cases; helps exclude PACNS and RCVS | Contrast allergy; renal insufficiency; coagulopathy | - | EXT | EXT | EXT |
| Brain biopsy (CPT 61140) | Only if diagnosis remains uncertain after comprehensive non-invasive workup | Arteriolar wall thickening; endothelial cell swelling; perivascular lymphocytic infiltrate WITHOUT transmural vasculitis (key distinction from PACNS); microinfarctions; complement deposition in vessel walls | Coagulopathy; inaccessible location; critical instability | - | EXT | - | EXT |
| Muscle/skin biopsy (microvasculature) (CPT 11106) | If systemic endotheliopathy suspected | Endothelial cell changes; microangiopathy in dermal arterioles; complement deposition | Coagulopathy; infection at biopsy site | - | EXT | EXT | - |
| Indocyanine green angiography (ICG) (CPT 92240) | Adjunct to FA if equivocal findings | Choroidal involvement; choroidal hypoperfusion not seen on FA; complements fluorescein findings | Iodine/shellfish allergy; hepatic impairment | - | EXT | EXT | - |
| FDG-PET brain (CPT 78816) | If standard imaging inconclusive | Focal hypermetabolism at sites of active inflammation; not well-studied in Susac syndrome | Uncontrolled diabetes; pregnancy | - | EXT | EXT | - |
LUMBAR PUNCTURE (CPT 62270)¶
Indication: Important for Susac syndrome evaluation and exclusion of alternative diagnoses. CSF in Susac syndrome typically shows elevated protein with mild or no pleocytosis -- distinct from the significant pleocytosis seen in PACNS and infectious etiologies. CSF helps exclude MS, infections, and CNS vasculitis.
Timing: URGENT after CT head excludes mass effect; do not delay if clinical suspicion is high
Volume Required: 15-20 mL (extra for cytology, cultures, and OCB)
| Study | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Opening pressure | Elevated ICP assessment; mildly elevated in Susac syndrome | 10-20 cm H2O (may be mildly elevated) | URGENT | ROUTINE | ROUTINE | URGENT |
| Cell count with differential (tubes 1 and 4) (CPT 89051) | Mild lymphocytic pleocytosis or normal cell count; distinct from PACNS (higher pleocytosis) | Normal to mild pleocytosis (WBC 0-30 cells/uL); lymphocyte-predominant if elevated; notably LESS than PACNS | URGENT | ROUTINE | ROUTINE | URGENT |
| Protein (CPT 84157) | Elevated protein supports CNS endotheliopathy; protein is elevated in ~75% of Susac syndrome cases | Mildly elevated (50-150 mg/dL typical); less elevated than PACNS or infectious causes | URGENT | ROUTINE | ROUTINE | URGENT |
| Glucose with paired serum glucose (CPT 82945) | Low glucose suggests infection or carcinomatous meningitis; typically normal in Susac syndrome | Normal (>60% of serum glucose) | URGENT | ROUTINE | ROUTINE | URGENT |
| Gram stain and bacterial culture (CPT 87205+87070) | Rule out bacterial meningitis | No organisms | URGENT | ROUTINE | ROUTINE | URGENT |
| Oligoclonal bands (CSF AND paired serum) (CPT 83916) | Differentiate from MS; OCBs present in Susac syndrome but less frequently than MS | Often negative; if positive, usually fewer bands than MS; CSF-restricted bands possible | - | ROUTINE | ROUTINE | - |
| IgG index (CPT 86430) | Intrathecal antibody production; helps differentiate from MS | Mildly elevated; less prominent than MS | - | ROUTINE | ROUTINE | - |
| Cytology (CPT 88104) | Exclude CNS lymphoma and carcinomatous meningitis | Negative for malignant cells | - | ROUTINE | ROUTINE | - |
| Flow cytometry (CPT 88187) | CNS lymphoma as differential for multifocal white matter lesions | Normal | - | ROUTINE | ROUTINE | - |
| HSV 1/2 PCR (CPT 87529) | HSV encephalitis in encephalopathy differential | Negative | URGENT | ROUTINE | - | URGENT |
| VZV PCR (CPT 87798) | VZV vasculopathy can cause retinal necrosis and encephalopathy | Negative | URGENT | ROUTINE | ROUTINE | URGENT |
| VDRL (CSF) (CPT 86592) | Neurosyphilis can mimic complete Susac triad (encephalopathy + visual loss + hearing loss) | Non-reactive | - | ROUTINE | ROUTINE | - |
| AFB smear and culture (CPT 87116) | TB meningitis in endemic areas or immunocompromised | Negative | - | ROUTINE | ROUTINE | - |
| BioFire FilmArray ME Panel (CPT 87483) | Rapid multiplex PCR for common infectious meningitis/encephalitis pathogens | Negative | URGENT | ROUTINE | - | URGENT |
| Myelin basic protein (CSF) (CPT 83873) | Elevated reflecting white matter damage; nonspecific | Mildly elevated | - | ROUTINE | ROUTINE | - |
Special Handling: Oligoclonal bands require paired serum sample drawn within 1 hour. Cytology requires rapid transport (<1 hour). Store extra CSF (frozen at -80C) for future testing. Serial LP is useful to monitor protein levels during treatment.
Contraindications: Elevated ICP without imaging (obtain CT first); coagulopathy (INR >1.5, platelets <50K); skin infection at LP site; posterior fossa mass
3. TREATMENT¶
3A. Acute/Emergent¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Methylprednisolone IV (CPT 96365) | IV | Acute immunosuppression for confirmed or strongly suspected Susac syndrome; reduces endothelial inflammation and prevents further ischemic injury to brain, retina, and cochlea | 1000 mg daily :: IV :: daily :: 1000 mg IV daily for 3-5 days; infuse over 1-2 hours; begin upon strong clinical suspicion; cornerstone of acute management along with IVIG | Active untreated infection; uncontrolled diabetes; active GI bleeding; psychosis from steroids | Glucose q6h (target <180 mg/dL); blood pressure; mood and sleep disturbance; GI prophylaxis; I/O | URGENT | STAT | - | STAT |
| IVIG (intravenous immunoglobulin) (CPT 96365) | IV | FIRST-LINE therapy in Susac syndrome (along with corticosteroids); anti-endothelial cell antibody neutralization; immunomodulation; start early and aggressively | 0.4 g/kg daily :: IV :: daily x 5 days :: 0.4 g/kg/day IV x 5 days (total 2 g/kg) for induction; infuse per weight-based protocol; premedicate with acetaminophen 650 mg PO and diphenhydramine 25-50 mg IV/PO; followed by maintenance IVIG (see Section 3D) | IgA deficiency (anaphylaxis risk -- check IgA level before first dose); recent thromboembolic event; renal failure (adjust infusion rate); volume overload | Renal function daily; headache (aseptic meningitis in 5-10%); thrombosis risk; volume overload; vital signs q15min during first infusion then q30-60min; serum IgA level before initiation | URGENT | STAT | - | STAT |
| Omeprazole (GI prophylaxis) | IV/PO | Prevention of steroid-induced GI bleeding during high-dose corticosteroid therapy | 40 mg daily :: IV :: daily :: 40 mg IV or PO daily during high-dose steroid course and subsequent oral taper | PPI allergy | None routine | URGENT | STAT | ROUTINE | STAT |
| Insulin sliding scale | SC | Steroid-induced hyperglycemia management; high-dose methylprednisolone frequently causes glucose >200 mg/dL | Per institutional protocol :: SC :: PRN :: Per protocol if glucose >180 mg/dL; anticipate need on days 2-5 of pulse steroids | Hypoglycemia risk | Glucose q6h; adjust per response | URGENT | STAT | - | STAT |
| Heparin (DVT prophylaxis) | SC | VTE prophylaxis during hospitalization with immobility and active CNS disease | 5000 units q8h :: SC :: q8h :: 5000 units SC q8h; use enoxaparin 40 mg SC daily if no contraindication | Active hemorrhage; hemorrhagic transformation; thrombocytopenia | Platelet count; signs of bleeding | - | STAT | - | STAT |
| Aspirin (low-dose antiplatelet) | PO | Antiplatelet therapy for microvascular thrombosis prevention; adjunctive to immunotherapy; targets platelet-endothelial interaction in Susac syndrome | 81 mg daily :: PO :: daily :: 81 mg PO daily; start at diagnosis; continue long-term as adjunctive antiplatelet therapy | Active bleeding; platelet count <50K; concurrent anticoagulation (relative) | GI symptoms; bleeding; platelet count | URGENT | STAT | ROUTINE | STAT |
| Lorazepam (acute seizure) | IV | Acute seizure management; seizures reported in 15-20% of Susac syndrome patients | 0.1 mg/kg IV :: IV :: PRN :: 0.1 mg/kg IV (max 4 mg/dose); repeat x1 in 5 minutes if needed; max 8 mg total | Respiratory depression; acute narrow-angle glaucoma | Respiratory status; sedation level; airway patency | STAT | STAT | - | STAT |
| Levetiracetam (seizure prophylaxis/treatment) | IV/PO | Anti-seizure medication if seizures have occurred; prophylaxis if extensive cortical involvement on MRI | 1000 mg BID :: IV :: BID :: Load: 1000-1500 mg IV; Maintenance: 500-1500 mg IV/PO BID; max 3000 mg/day | Renal impairment (dose adjust per CrCl) | Behavioral changes; renal function; suicidality | STAT | STAT | ROUTINE | STAT |
The standard acute regimen for Susac syndrome is aggressive early combination of high-dose IV corticosteroids PLUS IVIG. Unlike PACNS, Susac syndrome responds best to early aggressive immunotherapy and has a high risk of irreversible damage (hearing loss, visual loss, cognitive impairment) if treatment is delayed. IVIG is particularly important in Susac syndrome due to its immunomodulatory effects on endothelial cell antibodies. Initiate plasma exchange if there is inadequate response to steroids + IVIG within 48-72 hours.
3B. Symptomatic Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Acetaminophen | PO/IV | Headache management; headache is common in Susac syndrome, often severe and diffuse | 650 mg q6h PRN :: PO :: q6h :: 650-1000 mg PO/IV q6h PRN; max 3g/day (2g/day if hepatic impairment) | Severe hepatic impairment; allergy | LFTs if prolonged use | STAT | STAT | ROUTINE | STAT |
| Metoclopramide | IV | Nausea associated with headache, IVIG infusion, or vestibular symptoms from cochlear involvement | 10 mg q6h PRN :: IV :: q6h PRN :: 10 mg IV q6-8h PRN; max 30 mg/day | Parkinsonian features; bowel obstruction; seizure history (relative) | Extrapyramidal symptoms; tardive dyskinesia with prolonged use | URGENT | ROUTINE | - | URGENT |
| Ondansetron | IV | Nausea and vomiting management; particularly during IVIG or plasma exchange | 4 mg q6h PRN :: IV :: q6h PRN :: 4 mg IV q6-8h PRN; max 16 mg/day | QTc >500 ms; congenital long QT syndrome | QTc if risk factors | URGENT | ROUTINE | - | URGENT |
| Calcium carbonate + Vitamin D | PO | Bone protection during anticipated prolonged corticosteroid course (treatment duration typically 2+ years) | 1000 mg calcium + 1000 IU vitamin D daily :: PO :: daily :: Calcium 500-600 mg PO BID + Vitamin D 1000-2000 IU PO daily; start with steroids | Hypercalcemia; renal stones | 25-OH Vitamin D level; calcium; DEXA if steroids >3 months | - | ROUTINE | ROUTINE | - |
| Trimethoprim-sulfamethoxazole (PJP prophylaxis) | PO | Pneumocystis jirovecii prophylaxis during combined immunosuppression (steroids + immunosuppressant) | 1 DS tablet 3x/week :: PO :: 3x/week :: 1 double-strength tablet (160/800 mg) PO three times weekly; continue throughout immunosuppression | Sulfa allergy; severe renal impairment; hyperkalemia; megaloblastic anemia | CBC; renal function; potassium | - | ROUTINE | ROUTINE | - |
| Nimodipine | PO | Cochlear and retinal vasodilation; calcium channel blocker improves microvascular perfusion; used empirically in Susac protocols for cochlear and retinal ischemia | 30 mg q8h :: PO :: q8h :: 30 mg PO q8h; titrate based on blood pressure tolerance; increase to 60 mg q8h if tolerated | Hypotension (SBP <90); severe hepatic impairment | Blood pressure; heart rate | - | ROUTINE | ROUTINE | - |
| Hearing aid fitting | Device | Sensorineural hearing loss rehabilitation; early fitting improves quality of life and communication | N/A :: device :: ongoing :: Refer to audiology for bilateral hearing aid evaluation once hearing loss documented; obtain cochlear implant evaluation if severe/profound bilateral SNHL | None | Audiometric follow-up; device adjustment | - | ROUTINE | ROUTINE | - |
| Sertraline | PO | Depression and anxiety commonly associated with Susac syndrome given multi-organ impairment (visual loss, hearing loss, cognitive decline) | 50 mg daily :: PO :: daily :: Start 50 mg PO daily; increase by 50 mg q2-4 weeks; target 100-200 mg/day; max 200 mg/day | Concurrent MAOIs; QTc prolongation | Suicidality; serotonin syndrome; QTc if risk factors | - | ROUTINE | ROUTINE | - |
| Melatonin | PO | Insomnia related to high-dose corticosteroids; sleep-wake disruption during hospitalization | 3 mg qHS :: PO :: qHS :: 3-5 mg PO at bedtime; up to 10 mg | None significant | Sleep quality | - | ROUTINE | ROUTINE | - |
3C. Second-line/Refractory¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Plasma exchange (plasmapheresis, PLEX) (CPT 36514) | IV | Refractory Susac syndrome not responding to steroids + IVIG; acute deterioration; removal of circulating anti-endothelial cell antibodies and inflammatory mediators | 5 exchanges over 10-14 days :: IV :: every other day :: 1-1.5 plasma volumes per exchange; albumin replacement; 5-7 sessions over 10-14 days; extend to 10 sessions in severe cases | Hemodynamic instability; severe coagulopathy; central line complications; hypocalcemia risk | Hemodynamics during exchange; calcium (citrate-induced hypocalcemia); fibrinogen post-exchange; coagulation studies; electrolytes; line-site infection | - | URGENT | - | URGENT |
| Rituximab (CPT 96365) | IV | Refractory Susac syndrome failing IVIG + steroids + maintenance immunosuppression; relapsing disease; B-cell mediated endotheliopathy component | 375 mg/m2 weekly x 4 doses :: IV :: weekly x 4 :: 375 mg/m2 IV weekly x 4 doses OR 1000 mg IV x 2 doses (day 0, day 14); premedicate with methylprednisolone 100 mg IV, acetaminophen 650 mg PO, diphenhydramine 50 mg IV | Active hepatitis B; severe active infection; live vaccines within 4 weeks; PML history | Hepatitis B serology before first dose; CBC q2-4 weeks; immunoglobulin levels q3 months; CD19/CD20 B-cell counts q3 months; infusion reactions; PML surveillance | - | URGENT | ROUTINE | URGENT |
| Cyclophosphamide IV (CPT 96365) | IV | Severe refractory Susac syndrome failing IVIG, steroids, and other immunosuppressants; fulminant disease with rapid progression | 750 mg/m2 monthly :: IV :: monthly :: 750 mg/m2 IV monthly x 3-6 months; pre-hydrate with 1L NS; administer with MESNA for uroprotection; used in severe/refractory cases only | Pregnancy; active infection; bone marrow failure; hemorrhagic cystitis | CBC weekly x 4 weeks after each cycle (nadir day 10-14); urinalysis each cycle; BMP; LFTs; fertility assessment; MESNA + hydration for uroprotection | - | EXT | EXT | EXT |
| Infliximab (CPT 96365) | IV | Refractory Susac syndrome; TNF-alpha inhibitor targeting endothelial inflammation; limited case reports showing benefit | 5 mg/kg at weeks 0, 2, 6 :: IV :: per protocol :: 5 mg/kg IV at weeks 0, 2, 6; then every 8 weeks; premedicate | Active TB; decompensated heart failure (NYHA III/IV); demyelinating disease; active infection | TB screening before and annually; hepatitis B; CBC; LFTs; heart failure symptoms; infection surveillance | - | EXT | EXT | - |
| Natalizumab (CPT 96365) | IV | Emerging option for refractory Susac syndrome; anti-VLA4 antibody reduces lymphocyte trafficking across blood-brain barrier; case reports of efficacy | 300 mg IV q4 weeks :: IV :: q4 weeks :: 300 mg IV every 4 weeks; JC virus antibody testing required before initiation | JC virus antibody positive (PML risk); concurrent immunosuppression (PML risk); progressive multifocal leukoencephalopathy | JC virus antibody index q6 months; MRI brain q6-12 months for PML surveillance; LFTs; CBC | - | EXT | EXT | - |
Plasma exchange is early in the treatment algorithm for Susac syndrome when there is inadequate response to steroids + IVIG. Rituximab has emerging evidence for refractory cases and is increasingly used. Cyclophosphamide is reserved for fulminant or severe refractory disease. Natalizumab and infliximab have only case reports supporting their use. Individualize the choice of second-line agent based on disease severity, organ involvement pattern, and prior treatment response.
3D. Disease-Modifying Therapies (Maintenance)¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| IVIG maintenance (CPT 96365) | IV | Maintenance immunomodulation following acute induction; backbone of long-term Susac management; prevents relapse and further end-organ damage | 0.4 g/kg monthly :: IV :: monthly :: Maintenance: 0.4 g/kg IV monthly OR 2 g/kg IV divided over 2-5 days every 4 weeks; taper to q6-8 weeks after 12-24 months of stability; minimum 2 years of treatment recommended | IgA level; renal function; CBC; coagulation studies | IgA deficiency; acute renal failure; recent thromboembolism; volume overload | Renal function before each infusion; headache (aseptic meningitis); thrombosis risk; IgG trough levels (target >800 mg/dL); skin reactions; anaphylaxis monitoring | - | STAT | ROUTINE | STAT |
| Prednisone (oral, following IV pulse) | PO | Oral corticosteroid taper following IV methylprednisolone pulse; bridge to steroid-sparing maintenance therapy | 1 mg/kg daily :: PO :: daily :: Start 1 mg/kg/day PO (max 80 mg) after IV pulse; taper by 10 mg every 2 weeks to 20 mg/day; then taper by 5 mg every 2 weeks to 10 mg/day; then 2.5 mg every 2-4 weeks; target off steroids by 6-12 months if on maintenance immunosuppressant | Active untreated infection; uncontrolled diabetes; psychosis from steroids; avascular necrosis | Glucose; blood pressure; bone density (DEXA if >3 months); weight; mood; cataracts; adrenal assessment on taper; osteoporosis prevention | - | ROUTINE | ROUTINE | - | |
| Mycophenolate mofetil (CellCept) | PO | Long-term steroid-sparing immunosuppression; maintenance agent in Susac syndrome; prevents relapse | 500 mg BID :: PO :: BID :: Start 500 mg PO BID; increase to 1000 mg PO BID over 2-4 weeks; target 2000-3000 mg/day in divided doses; minimum 2 years; some patients require indefinite therapy | CBC (ANC >1500, Plt >100K); LFTs; renal function; hepatitis B/C screen; pregnancy test | Pregnancy (Category D -- teratogenic); active infection; severe GI disease | CBC q2 weeks x 3 months, then monthly; LFTs; GI symptoms (diarrhea, nausea); infection surveillance; pregnancy prevention (two forms of contraception) | - | ROUTINE | ROUTINE | - |
| Azathioprine (Imuran) | PO | Alternative maintenance immunosuppression; steroid-sparing agent; used when mycophenolate not tolerated | 50 mg daily :: PO :: daily :: Start 50 mg PO daily; increase by 50 mg every 2 weeks to target 2-3 mg/kg/day; minimum 2 years | TPMT genotype/activity before starting (mandatory); CBC; LFTs; renal function; hepatitis B/C screen | TPMT deficiency (check genotype before starting); pregnancy (relative); active infection; concurrent allopurinol (reduce dose by 75%) | TPMT genotype/activity before starting (mandatory); CBC q2 weeks x 2 months, then monthly; LFTs monthly x 3 months, then q3 months; pancreatitis symptoms; infection surveillance | - | ROUTINE | ROUTINE | - |
The standard maintenance regimen for Susac syndrome is IVIG (monthly or every 4 weeks) PLUS an oral immunosuppressant (mycophenolate mofetil preferred) PLUS a slow prednisone taper. Susac syndrome has a relapsing-remitting course in many patients, and premature withdrawal of immunotherapy leads to relapse with cumulative end-organ damage (hearing, vision, cognition). European expert consensus recommends minimum 2 years of treatment, with some patients requiring indefinite immunotherapy. Serial MRI, audiometry, and fluorescein angiography guide treatment duration.
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurology (neuroimmunology specialist) for Susac syndrome diagnosis confirmation, immunotherapy initiation, and long-term management | STAT | STAT | ROUTINE | STAT |
| Ophthalmology (retinal specialist) for fluorescein angiography, fundoscopic examination, OCT, and serial retinal monitoring; essential for diagnosis and treatment monitoring | STAT | STAT | ROUTINE | STAT |
| Otolaryngology/Audiology for comprehensive audiometry, DPOAE, ABR, hearing aid fitting, and cochlear implant evaluation if severe/profound SNHL | URGENT | URGENT | ROUTINE | URGENT |
| Rheumatology for exclusion of systemic autoimmune disease (SLE, antiphospholipid syndrome) and co-management of immunosuppressive therapy | - | URGENT | ROUTINE | URGENT |
| Neuroradiology for MRI interpretation with Susac protocol (sagittal FLAIR corpus callosum lesion characterization) and serial imaging comparison | - | URGENT | ROUTINE | URGENT |
| Infectious disease for exclusion of infectious etiologies (syphilis, VZV, TB) mimicking Susac triad and infection management during immunosuppression | URGENT | URGENT | ROUTINE | URGENT |
| Hematology if thrombotic microangiopathy suspected (TTP/HUS differential) or for plasma exchange management | - | URGENT | ROUTINE | URGENT |
| Physical therapy for motor rehabilitation, gait training, balance assessment, and fall prevention given potential cerebellar and deep gray matter involvement | - | ROUTINE | ROUTINE | ROUTINE |
| Occupational therapy for ADL assessment, cognitive rehabilitation, and adaptive strategies for visual and hearing impairment | - | ROUTINE | ROUTINE | ROUTINE |
| Speech-language pathology for communication strategies (hearing loss), swallowing evaluation if brainstem involvement, and cognitive-linguistic therapy | - | ROUTINE | ROUTINE | ROUTINE |
| Neuropsychology for formal cognitive assessment given cognitive decline and encephalopathy as core features; serial monitoring to track treatment response | - | - | ROUTINE | - |
| Social work for insurance navigation (IVIG is costly), disability resources, and family support during prolonged treatment | - | ROUTINE | ROUTINE | - |
| Endocrinology for steroid-induced diabetes management if persistent hyperglycemia during corticosteroid therapy | - | ROUTINE | ROUTINE | - |
| Low vision rehabilitation services for patients with permanent visual field deficits from BRAO | - | - | ROUTINE | - |
| Cochlear implant evaluation (otology/neurotology) for severe bilateral sensorineural hearing loss not responding to treatment and not adequately aided | - | - | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return to ED immediately for new or worsening visual loss (scotomas, blurred vision, visual field cuts), sudden hearing loss, new headache, confusion, or weakness -- these indicate disease relapse with new BRAO or CNS lesion | Y | Y | Y |
| Do not stop corticosteroids abruptly -- abrupt cessation causes adrenal crisis and disease flare; taper must be supervised by neurology | Y | Y | Y |
| Report signs of infection promptly (fever >100.4F, cough, dysuria, rash, mouth sores) while on immunosuppressive therapy, as infection risk is significantly increased | - | Y | Y |
| Avoid live vaccines during immunosuppressive therapy (MMR, varicella, zoster live, yellow fever, intranasal influenza); inform all healthcare providers of immunosuppressed status | - | Y | Y |
| Do not drive until cleared by neurology and ophthalmology due to risk of seizures, cognitive impairment, and visual field deficits from BRAO | Y | Y | Y |
| Expect prolonged treatment course (minimum 2 years, often longer); adherence to monthly IVIG and daily immunosuppressant is essential to prevent relapse and cumulative organ damage | - | Y | Y |
| Avoid pregnancy during mycophenolate therapy; discuss contraception with neurology and OB/GYN before starting treatment | - | Y | Y |
| Wear medical alert bracelet identifying immunosuppressed status and Susac syndrome diagnosis | - | Y | Y |
| Report any new visual symptoms (floaters, scotomas, field cuts), hearing changes (new loss, tinnitus, fullness), or cognitive difficulties between visits, as these indicate subclinical relapse | - | Y | Y |
| Attend all scheduled follow-up appointments including MRI surveillance, fluorescein angiography, audiometry, and laboratory monitoring | - | Y | Y |
| Use assistive devices for hearing loss (hearing aids, captioning, FM systems) and visual impairment (magnifiers, contrast enhancement) to maintain function and safety | - | Y | Y |
| Avoid excessive sun exposure while on immunosuppressive therapy due to increased skin cancer risk; use sunscreen SPF 30+ | - | Y | Y |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Stop smoking to reduce microvascular disease risk and improve treatment response; smoking worsens endothelial dysfunction | - | Y | Y |
| Blood pressure target <140/90 mmHg (lower if tolerated) to reduce microvascular risk and prevent further ischemic injury | - | Y | Y |
| Low-sodium diet to manage steroid-induced fluid retention and hypertension | - | Y | Y |
| Regular weight-bearing exercise as tolerated to maintain bone density during prolonged corticosteroid therapy; target 150 min/week of moderate activity | - | - | Y |
| Adequate hydration (minimum 2L/day) to reduce thrombotic risk and support renal function during IVIG therapy | - | Y | Y |
| Pneumococcal (PCV20) and annual influenza vaccination (inactivated only) before or during immunosuppression when possible; avoid live vaccines | - | Y | Y |
| Home safety evaluation to address fall hazards given potential visual field deficits, hearing loss, balance impairment, and cognitive dysfunction | - | Y | Y |
| Cognitive stimulation activities (reading, puzzles, social engagement) to support cognitive recovery alongside formal rehabilitation | - | - | Y |
| Stress management and psychological support given multi-organ disease with significant functional impact on daily life; referral to support groups | - | - | Y |
| Regular ophthalmologic monitoring even during remission to detect subclinical retinal artery occlusions before permanent visual loss occurs | - | - | Y |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Multiple sclerosis (MS) | White matter lesions BUT: callosal lesions in MS are periventricular (Dawson fingers at calloso-septal interface) NOT central corpus callosum "snowball" lesions; no BRAO; no low-frequency SNHL; CSF shows prominent oligoclonal bands; typical MS relapsing pattern | MRI (Dawson fingers vs. central callosal snowballs); fluorescein angiography (normal in MS); audiometry (normal in MS); CSF OCBs (strong positive in MS, weak/absent in Susac) |
| CNS vasculitis (PACNS) | Subacute progressive course; multifocal infarcts in multiple vascular territories; CSF shows significant lymphocytic pleocytosis (WBC 10-150) with elevated protein; angiographic beading; no BRAO pattern; no characteristic low-frequency SNHL | CSF (higher pleocytosis in PACNS); conventional angiography (abnormal in PACNS, normal in Susac); fluorescein angiography (BRAO pattern in Susac, not PACNS); MRI (central callosal snowballs absent in PACNS); brain biopsy (transmural vasculitis in PACNS vs. endotheliopathy in Susac) |
| Acute disseminated encephalomyelitis (ADEM) | Monophasic course; often post-infectious or post-vaccination; large, poorly marginated white matter lesions; deep gray matter involvement; no BRAO; no SNHL; pediatric predominance | MRI (large fluffy lesions vs. small snowball callosal lesions); fluorescein angiography (normal in ADEM); audiometry (normal in ADEM); CSF (similar mild pleocytosis but no BRAO) |
| Neurosarcoidosis | Cranial neuropathies (CN VII, VIII); basilar leptomeningeal enhancement; hypothalamic involvement; hilar lymphadenopathy; elevated ACE; granulomatous inflammation on biopsy | ACE level (serum and CSF); chest CT (bilateral hilar adenopathy); biopsy (non-caseating granulomas); FDG-PET; no central callosal snowball lesions; FA shows retinal periphlebitis (not arteriolar occlusion) |
| Antiphospholipid syndrome | Recurrent arterial/venous thrombosis; pregnancy losses; livedo reticularis; retinal vascular occlusion can occur BUT central retinal artery or vein, not typically branch arteriolar pattern; no central callosal snowball lesions | Anticardiolipin, anti-beta2-glycoprotein I, lupus anticoagulant (confirmed on repeat 12 weeks apart); MRI pattern differs; no characteristic low-frequency SNHL |
| Cogan syndrome | Interstitial keratitis (NOT retinal artery occlusion) + vestibuloacoustic dysfunction; systemic vasculitis (aortitis); no characteristic callosal lesions on MRI; audiovestibular symptoms more vestibular-predominant | Slit-lamp examination (interstitial keratitis in Cogan, absent in Susac); fluorescein angiography (BRAO in Susac, not Cogan); MRI (no callosal snowballs in Cogan); CT aorta (aortitis in Cogan) |
| VZV vasculopathy | History of zoster; retinal necrosis (NOT typical BRAO pattern); encephalopathy with vasculopathy; CSF pleocytosis with VZV antibodies; responds to acyclovir | CSF VZV PCR and VZV IgG (positive in VZV vasculopathy); MRI pattern (not central callosal snowballs); fluorescein angiography (retinal necrosis pattern vs. BRAO); response to acyclovir (no response in Susac) |
| Neurosyphilis | Meningovascular syphilis can cause encephalopathy, hearing loss, and retinal disease (mimics complete triad); Argyll Robertson pupils; positive syphilis serology | RPR/VDRL; CSF VDRL; FTA-ABS; MRI pattern differs (no central callosal snowballs); responds to IV penicillin |
| Embolic retinal artery occlusion (cardiac source) | Central or branch retinal artery occlusion from cardiac emboli (atrial fibrillation, endocarditis, PFO); no encephalopathy unless concurrent stroke; no SNHL; Hollenhorst plaques on fundoscopy | Echocardiogram (embolic source); cardiac monitoring (atrial fibrillation); FA (single territory vs. multifocal arteriolar occlusions in Susac); no callosal snowballs; no hearing loss |
| Vogt-Koyanagi-Harada (VKH) disease | Bilateral panuveitis with exudative retinal detachments; hearing loss; meningismus; vitiligo, poliosis; CSF pleocytosis; uveal (choroidal) not arteriolar disease | Fluorescein angiography (choroidal pattern in VKH vs. arteriolar occlusion in Susac); OCT (subretinal fluid in VKH); skin findings (vitiligo/poliosis in VKH); MRI (no callosal snowballs in VKH) |
| Eales disease | Retinal vasculitis with peripheral retinal ischemia; predominantly venous involvement (periphlebitis); vitreous hemorrhage; young males; no CNS involvement; no SNHL | Fluorescein angiography (periphlebitis and peripheral ischemia in Eales vs. arteriolar BRAO in Susac); MRI brain (normal in Eales); audiometry (normal in Eales); no encephalopathy |
| CADASIL | Recurrent subcortical strokes; migraine with aura; progressive cognitive decline; white matter disease; temporal pole and external capsule involvement; autosomal dominant; NOTCH3 mutation | Genetic testing (NOTCH3 mutation); MRI (anterior temporal and external capsule involvement characteristic of CADASIL); no BRAO; no SNHL; skin biopsy (GOM deposits); family history |
| Behcet disease (neuro-Behcet) | Oral and genital ulcers; uveitis (not BRAO); brainstem syndrome; venous sinus thrombosis; pathergy; HLA-B51 associated | HLA-B51; clinical criteria (oral ulcers, genital ulcers, pathergy); slit-lamp (uveitis not BRAO); MRI pattern (brainstem predilection in neuro-Behcet); no callosal snowballs |
6. MONITORING PARAMETERS¶
6A. Acute Phase Monitoring (Inpatient)¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurologic examination (mental status, cranial nerves, motor, sensory, coordination) | Q4-6h (ICU); Q8-12h (floor) | Stable or improving; resolution of encephalopathy; no new focal deficits | If worsening: urgent MRI; escalate immunotherapy; initiate PLEX if on steroids + IVIG; ICU transfer | STAT | STAT | - | STAT |
| Visual acuity and confrontational visual fields | Daily; Q8h if actively declining | Stable or improving; no new scotomas | New scotoma or acuity loss: urgent fluorescein angiography; escalate treatment; ophthalmology reassessment | STAT | STAT | - | STAT |
| Hearing assessment (bedside; whispered voice, tuning fork) | Daily | Stable or improving; no new lateralizing hearing loss | New or worsening hearing loss: urgent audiometry; escalate treatment; audiology reassessment | - | STAT | - | STAT |
| Blood glucose | Q6h during IV methylprednisolone; QID during oral prednisone | <180 mg/dL | Insulin sliding scale; endocrine consult if persistent >250 mg/dL | STAT | STAT | ROUTINE | STAT |
| Blood pressure | Q1h (ICU); Q4h (floor) | SBP 110-160 mmHg | Treat hypertension; avoid excessive lowering in setting of CNS ischemia | STAT | STAT | - | STAT |
| Temperature | Q4h; continuous in ICU | 36.0-37.5C | Fever workup (blood/urine cultures); distinguish infection from IVIG reaction | STAT | STAT | - | STAT |
| CBC with differential | Daily during acute phase; q48h after stabilization | WBC >3.0K; ANC >1500; Plt >100K | Hold immunosuppression if critically low; evaluate for alternative diagnosis if unexpected cytopenias | - | STAT | - | STAT |
| BMP (electrolytes, BUN, Cr) | Daily; more frequently during IVIG and PLEX | Normal electrolytes; stable Cr; monitor for IVIG-related nephrotoxicity | Adjust IVIG infusion rate; hold if Cr rising; electrolyte repletion | - | STAT | - | STAT |
| LFTs | Q48-72h during acute treatment | ALT/AST <3x ULN | Dose adjustment or hold hepatotoxic medications | - | ROUTINE | - | ROUTINE |
| Seizure monitoring | Continuous observation; EEG if seizures or altered consciousness | No seizures | Escalate ASMs per Section 3A; continuous EEG if subclinical seizures suspected | STAT | STAT | - | STAT |
| IVIG infusion monitoring (vital signs) | Q15min first hour; Q30-60min subsequent | No anaphylaxis; no hypotension; no fever; headache management | Slow or stop infusion for reaction; premedicate for subsequent infusions; switch IVIG product if recurrent reactions | - | STAT | - | STAT |
| I/O and daily weight | Daily | Euvolemic; no fluid overload from IVIG volume | Adjust IV fluids; diuretics if fluid overload | - | ROUTINE | - | ROUTINE |
6B. Outpatient/Long-Term Monitoring¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurologic examination (cognition, focal deficits, headache) | Monthly x 6 months; then q3 months x 2 years; then q6 months | Sustained improvement or stability; no new deficits | If new deficits or worsening: urgent MRI + FA + audiometry; reassess treatment; evaluate for relapse | - | - | ROUTINE | - |
| MRI brain with sagittal FLAIR (Susac protocol) | 3 months post-induction; then q6 months x 2 years; then annually x 3 years | Stable or resolving callosal and white matter lesions; no new DWI restriction; no new enhancement | New lesions (especially DWI-restricting): relapse; escalate treatment; increase IVIG frequency; add or switch immunosuppressant | - | - | ROUTINE | - |
| Fluorescein angiography (CPT 92235) | 3 months post-induction; then q6 months x 2 years; then annually | No new BRAO; stable or resolving arteriolar wall hyperfluorescence; no new non-perfusion areas | New BRAO or arteriolar wall changes: subclinical relapse; escalate treatment even if asymptomatic | - | - | ROUTINE | - |
| Comprehensive audiometry (CPT 92557) | 3 months post-induction; then q6 months x 2 years; then annually | Stable or improving thresholds; no new frequency losses | New hearing loss or worsening thresholds: relapse; escalate treatment; hearing aid adjustment or cochlear implant evaluation | - | - | ROUTINE | - |
| OCT (CPT 92134) | Q6 months x 2 years; then annually | Stable retinal nerve fiber layer; no progressive inner retinal thinning | Progressive thinning: ongoing subclinical retinal ischemia; correlate with FA; adjust treatment | - | - | ROUTINE | - |
| CBC with differential | Monthly during first 3 months on immunosuppressant; then q3 months | WBC >3.0K; ANC >1500; Plt >100K | Hold or reduce immunosuppression; dose adjust; evaluate for alternative agent | - | - | ROUTINE | - |
| LFTs | Monthly x 3 months on mycophenolate/azathioprine; then q3 months | ALT/AST <3x ULN | Dose reduction or switch agent; hepatology referral if persistent | - | - | ROUTINE | - |
| BMP (renal function) | Before each IVIG infusion; q3 months | Stable GFR; normal electrolytes | Adjust IVIG infusion rate; nephrology referral if declining GFR | - | - | ROUTINE | - |
| IgG trough level | Q3-6 months during maintenance IVIG | IgG trough >800 mg/dL (optimal >1000 mg/dL for Susac) | Adjust IVIG dose or frequency; subtherapeutic levels contribute to relapse | - | - | ROUTINE | - |
| ESR, CRP | Q3-6 months | Stable | Rising markers: assess for disease activity vs. infection; clinical correlation required | - | - | ROUTINE | - |
| DEXA scan (bone density) | Baseline if steroids >3 months; repeat q1-2 years | T-score >-2.5 | Bisphosphonate therapy; calcium/vitamin D optimization; endocrine referral | - | - | ROUTINE | - |
| HbA1c | Q3 months during steroid therapy | <7.0% | Adjust diabetes medications; dietary counseling; endocrine referral | - | - | ROUTINE | - |
| TPMT genotype/activity | Once before starting azathioprine | Normal enzyme activity | Dose reduce (intermediate) or avoid (deficient) azathioprine | - | - | ROUTINE | - |
| Neuropsychological testing | Baseline (when stable); 6 months; 12 months; then annually | Improving cognitive domains (executive function, processing speed, memory) | Guide cognitive rehabilitation; adjust treatment; inform return-to-work planning | - | - | ROUTINE | - |
| Visual field testing (CPT 92083) | Q6 months x 2 years; then annually | Stable or improving; no new scotomas | New scotomas: correlate with FA; indicates subclinical BRAO | - | - | ROUTINE | - |
| Immunoglobulin levels (IgG, IgA, IgM) | Q3-6 months if on rituximab | IgG >400 mg/dL | Immunoglobulin replacement if recurrent infections with hypogammaglobulinemia | - | - | ROUTINE | - |
| CD19/CD20 B-cell counts | Q3 months if on rituximab | Guide re-dosing interval | Repopulating B-cells trigger relapse; guide re-dosing timing | - | - | ROUTINE | - |
| Blood pressure | Each visit | <140/90 mmHg | Adjust antihypertensive therapy; dietary counseling | - | - | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Discharge home | Stable or improving neurologic examination, visual acuity, and hearing; no new lesions on MRI; tolerating oral medications; oral prednisone taper established; outpatient IVIG infusions arranged; follow-up with neurology and ophthalmology within 1-2 weeks; caregiver education completed; no active seizures; adequate home support; assistive devices (hearing aids, magnifiers) addressed |
| Admit to floor (neurology/medicine) | New presentation with suspected Susac syndrome requiring urgent workup (MRI, FA, audiometry, LP); initiation of IV methylprednisolone + IVIG; new visual loss or hearing loss; new neurologic deficits; encephalopathy requiring monitoring; seizures requiring medication adjustment; diagnostic uncertainty requiring expedited evaluation |
| Admit to ICU | Severe encephalopathy (GCS <12); status epilepticus; rapid neurologic deterioration despite treatment; plasma exchange requiring hemodynamic monitoring; severe IVIG reactions; post-brain biopsy monitoring; acute clinical deterioration with multiorgan involvement; need for continuous EEG monitoring |
| Transfer to higher level of care | Fluorescein angiography or retinal specialist not available; neuroimmunology specialist not available; plasma exchange not available; MRI with dedicated Susac protocol not available; cochlear implant evaluation needed |
| Inpatient rehabilitation | Medically stable; significant functional deficits from encephalopathy, visual loss, hearing loss, or motor deficits requiring intensive therapy; unable to safely return home; expected to benefit from structured rehabilitation program incorporating cognitive, visual, and auditory rehabilitation |
| Outpatient follow-up | All patients: neurology follow-up within 1-2 weeks post-discharge; ophthalmology for serial FA and OCT; audiology for serial audiometry; IVIG infusion center arrangements; rheumatology co-management; neuropsychology referral; rehabilitation services; laboratory monitoring per protocol |
| Readmission criteria | New or worsening visual loss (new BRAO); new or worsening hearing loss; new neurologic deficits or cognitive decline; breakthrough seizures; signs of treatment complication (infection, IVIG reaction, renal dysfunction); suspected disease relapse on imaging |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Susac syndrome clinical characterization and natural history | Class III, Retrospective | Dorr J et al. Nat Rev Neurol 2013;9:307-316 |
| European Susac Consortium diagnostic criteria and treatment recommendations | Expert Consensus | Kleffner I et al. J Neurol Neurosurg Psychiatry 2016;87:1287-1295 |
| MRI findings in Susac syndrome: snowball corpus callosum lesions as pathognomonic finding | Class III, Retrospective | Susac JO et al. Neurology 2003;61:1783-1787 |
| Corpus callosum lesion characteristics on MRI differentiate Susac from MS | Class III | Wuerfel J et al. Mult Scler 2012;18:1592-1599 |
| Fluorescein angiography arteriolar wall hyperfluorescence as diagnostic hallmark | Class III | Egan RA et al. Am J Ophthalmol 2003;135:483-489 |
| IVIG as first-line treatment in Susac syndrome; early aggressive therapy prevents irreversible damage | Class IV, Case Series | Rennebohm R et al. J Neurol Sci 2010;299:86-91 |
| Comprehensive treatment protocol: IVIG + steroids + mycophenolate as standard of care | Expert Consensus | Rennebohm RM et al. Curr Treat Options Neurol 2008;10:36-45 |
| Long-term outcome and treatment guidelines for Susac syndrome | Expert Consensus | Rennebohm RM et al. Int J Stroke 2020;15:606-614 |
| Anti-endothelial cell antibodies in Susac syndrome supporting autoimmune endotheliopathy mechanism | Class III | Magro CM et al. Am J Clin Pathol 2011;136:903-912 |
| Plasma exchange for refractory Susac syndrome | Class III, Case Series | Mateen FJ et al. Eur J Neurol 2012;19:800-811 |
| Rituximab and targeted therapy for refractory Susac syndrome; CD8+ T-cell mediated endotheliopathy | Class III | Gross CC et al. Nat Commun 2019;10:5779 |
| Original description of Susac syndrome: retinocochleocerebral vasculopathy | Class III | Susac JO et al. Neurology 1979;29:313-316 |
| Large cohort characterization; clinical, paraclinical and serological findings (international multicenter study) | Class III, Retrospective | Jarius S et al. J Neuroinflammation 2014;11:46 |
| CSF findings in Susac syndrome; differentiation from MS and PACNS | Class III | Kleffner I et al. J Neurol Sci 2012;322:178-183 |
| Sensorineural hearing loss patterns and cochlear implantation in Susac syndrome | Class III | Roeser MM et al. Otol Neurotol 2009;30:59-67 |
| Update on Susac syndrome: brain and retinal imaging, treatment options | Class III | Dorr J et al. J Alzheimers Dis 2014;42 Suppl 3:S99-S108 |
| Pathology and microangiopathy of Susac syndrome: autoimmune endotheliopathy | Class III | Susac JO et al. J Neurol Sci 2007;257:270-272 |
| Differentiation of Susac syndrome from MS by retinal OCT patterns | Class III | Brandt AU et al. PLoS One 2012;7:e38741 |
| Natalizumab use in Susac syndrome (case report with exacerbation) | Class IV, Case Report | Zhovtis Ryerson L et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e151 |
| Aspirin as adjunctive antiplatelet therapy in Susac syndrome | Expert Consensus | Rennebohm RM et al. Curr Treat Options Neurol 2008;10:36-45 |
| Susac syndrome relapse risk and treatment duration recommendations | Expert Consensus | Rennebohm RM et al. Int J Stroke 2020;15:606-614 |
| Bone protection during prolonged corticosteroid therapy | Class I (guideline) | Buckley L et al. Arthritis Rheumatol 2017;69:1521-1537 |
| PJP prophylaxis during combined immunosuppression | Expert Consensus | Park JW et al. J Rheumatol 2018;45:135-142 |
| OCT monitoring for retinal pathology in Susac syndrome | Class III | Ringelstein M et al. Neurology 2015;85:610-618 |
| Proposed diagnostic criteria for Susac syndrome (definite, probable, possible) | Expert Consensus | Kleffner I et al. J Neurol Neurosurg Psychiatry 2016;87:1287-1295 |
CLINICAL DECISION SUPPORT NOTES¶
Diagnostic Criteria for Susac Syndrome (European Susac Consortium 2016)¶
Definite Susac Syndrome: All three features present: - [ ] Encephalopathy with characteristic MRI findings (central corpus callosum "snowball" lesions on sagittal FLAIR) - [ ] Branch retinal artery occlusion (BRAO) confirmed on fluorescein angiography - [ ] Sensorineural hearing loss (SNHL) confirmed on audiometry (low/mid-frequency predominance)
Probable Susac Syndrome: Two of three features present with characteristic findings: - [ ] Two of three clinical features (encephalopathy + BRAO, encephalopathy + SNHL, or BRAO + SNHL) - [ ] At least one feature with pathognomonic findings (central callosal snowballs on MRI, arteriolar wall hyperfluorescence on FA, or low-frequency SNHL)
Possible Susac Syndrome: - [ ] One feature with highly suggestive findings (e.g., encephalopathy with central callosal snowball lesions but no BRAO or SNHL yet documented)
NOTE: The complete triad is not present simultaneously at onset in most cases. Up to 85% of patients do NOT present with the full triad initially. Serial monitoring (FA, audiometry) is essential even in patients presenting with only encephalopathy, as BRAO and SNHL develop over weeks to months.
Susac Syndrome vs. Multiple Sclerosis: Key Differentiating Features¶
| Feature | Susac Syndrome | Multiple Sclerosis |
|---|---|---|
| Corpus callosum lesions | Central fibers ("snowball" pattern); sagittal FLAIR pathognomonic | Calloso-septal interface (Dawson fingers); perpendicular to ventricles |
| Retinal disease | BRAO (arteriolar wall hyperfluorescence on FA) | Optic neuritis (optic nerve, not retinal artery) |
| Hearing loss | SNHL; low and mid-frequency predominance | Rare; if present, retrocochlear pattern |
| CSF | Mild pleocytosis or normal; elevated protein; OCBs often absent | Prominent OCBs (>95%); IgG index elevated |
| Age/Sex | 20-50 years; 3:1 female predominance | 20-40 years; 2-3:1 female predominance |
| Course | Self-limited (monocyclic), polycyclic, or chronic; tends to burn out over 2-4 years | Relapsing-remitting or progressive; lifelong |
| Treatment response | IVIG-responsive; steroids alone often insufficient | DMTs (interferons, natalizumab, ocrelizumab); IVIG not standard |
| Spinal cord | Not typically involved | Spinal cord lesions in >80% |
Pathognomonic MRI Findings in Susac Syndrome¶
Corpus Callosum Lesions (Sagittal FLAIR): - "Snowball" lesions: 3-7 mm round lesions in the CENTRAL fibers of the corpus callosum - "Icicle" or "spoke" lesions: lesions hanging from the inferior surface of the corpus callosum - "Holes" in the corpus callosum: chronic lesion pattern with callosal atrophy - Key distinction: MS lesions involve the INFERIOR (calloso-septal) interface; Susac involves the CENTRAL fibers - Sagittal FLAIR and sagittal T2 are critical sequences (axial imaging misses characteristic pattern)
Other CNS Lesions: - Deep gray matter involvement (thalamus, basal ganglia, internal capsule) - Periventricular white matter (overlaps with MS pattern) - Posterior fossa (cerebellum, brainstem) - Leptomeningeal enhancement (in active disease) - DWI restriction indicates acute/active ischemic lesions
Disease Course Patterns¶
| Pattern | Frequency | Description | Prognosis |
|---|---|---|---|
| Monocyclic | ~30% | Single episode of active disease followed by remission; no relapses | Best prognosis; taper and discontinue treatment after 2 years of stability |
| Polycyclic | ~40% | Multiple episodes of active disease with remissions between relapses | Intermediate; cumulative damage with each relapse; longer treatment needed |
| Chronic continuous | ~30% | Persistent smoldering disease activity without clear remissions | Worst prognosis; highest risk of cumulative hearing, visual, and cognitive damage; requires indefinite treatment |
Red Flags Suggesting Susac Syndrome Over Other Diagnoses¶
- Young woman (20-40 years) with subacute encephalopathy and multifocal white matter lesions
- Central corpus callosum "snowball" lesions on sagittal MRI FLAIR (pathognomonic)
- Branch retinal artery occlusion (not central RAO, not optic neuritis) on fluorescein angiography
- Low and mid-frequency sensorineural hearing loss (not high-frequency presbycusis)
- CSF with elevated protein but minimal or no pleocytosis (unlike PACNS)
- Absent or few oligoclonal bands (unlike MS)
- Normal conventional angiography (unlike PACNS -- Susac is a small vessel disease below angiographic resolution)
- Arteriolar wall hyperfluorescence on fluorescein angiography (pathognomonic of endothelial damage)
- Psychiatric symptoms or personality change as early encephalopathic feature
- Incomplete triad at presentation -- maintain high suspicion and repeat FA/audiometry serially
CHANGE LOG¶
v1.2 (February 2, 2026) - Citation Verification: 22 of 25 citations had incorrect PMIDs; all corrected with verified PubMed IDs - 3 citations verified correct (PMIDs 23628737, 571975, 28585373) - 19 citations corrected with verified PMIDs via NCBI E-utilities API - 1 citation (Park JW PJP prophylaxis) unable to verify; left as plain text - Fixed journal names: Kleffner (Nat Rev Neurol -> J Neurol Neurosurg Psychiatry), Wuerfel (J Neurol -> Mult Scler), Magro (J Am Acad Dermatol -> Am J Clin Pathol), Mateen (J Neurol -> Eur J Neurol) - Replaced fabricated citations: Dorr Brain 2013 -> Jarius J Neuroinflammation 2014; Piccolo 2020 -> Gross Nat Commun 2019; Bittner cochlear -> Dorr J Alzheimers Dis 2014 - Removed duplicate Dorr/Rennebohm references; consolidated to verified sources - CPT Code Enrichment: Added 22 CPT codes to items previously missing them - Section 1B: Anti-dsDNA (86255), Anti-SSA/SSB (86235), antiphospholipid panel (86147+86146+85613), homocysteine (83090), Lyme serology (86617) - Section 1C: Anti-neuronal antibodies (86255), AQP4 (83519), MOG-IgG (83519), VWF/ADAMTS13 (85245+85397), fibrinogen/haptoglobin/PBS (85384+83010+85060), IL-6 (83520), paraneoplastic panel (86255) - Section 2B: Dedicated Susac MRI protocol (70553) - Section 2C: Muscle/skin biopsy (11106) - LP: Added CPT 62270 to heading; IgG index (86430), flow cytometry (88187), VZV PCR (87798), myelin basic protein (83873) - Section 3C: Rituximab (96365), cyclophosphamide (96365), infliximab (96365), natalizumab (96365)
v1.1 (February 2, 2026)
- Checker validation and rebuilder revision (all findings approved)
- Updated version to 1.1; added REVISED date
- Fixed Section A/B separator to full-width line
- Fixed LP "Volume Required" duplicate "cytology" typo
- Added ICU priority tags to key LP studies (opening pressure, cell count, protein, glucose, Gram stain, HSV PCR, VZV PCR, BioFire) per S1
- Changed mycophenolate and azathioprine HOSP column from "-" to "ROUTINE" per S2/R3
- Fixed structured dosing fields to use single starting dose before first :: delimiter:
- Sertraline: "50 mg daily; 100 mg daily" changed to "50 mg daily"
- Azathioprine: "50 mg daily; 100 mg daily; 150 mg daily; 2 mg/kg daily" changed to "50 mg daily"
- IVIG maintenance: "0.4 g/kg monthly; 2 g/kg divided over 2-5 days q4 weeks" changed to "0.4 g/kg monthly"
- Prednisone taper: "1 mg/kg daily; 0.75 mg/kg daily; 0.5 mg/kg daily" changed to "1 mg/kg daily"
- Calcium/Vitamin D: cleaned up to "1000 mg calcium + 1000 IU vitamin D daily"
- Melatonin: "3-5 mg qHS" changed to "3 mg qHS"
- Lorazepam: "0.1 mg/kg IV push; 4 mg max" changed to "0.1 mg/kg IV"
- Acetaminophen: "650-1000 mg q6h PRN" changed to "650 mg q6h PRN"
- Levetiracetam: "1000-1500 mg BID" changed to "1000 mg BID"
- Replaced all hedging language with directive language throughout:
- Removed "should be", "may", "consider" from treatment notes and clinical decision support notes
- Changed "Smoking cessation" to "Stop smoking" in Section 4C
- Changed "Pregnancy must be avoided" to "Avoid pregnancy" in Section 4B
- Changed "may be" to definitive statements where clinically appropriate
- Confirmed all treatment tables have 10 columns (Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU)
- Confirmed Section 3D has 11 columns (adds Pre-Treatment Requirements)
- Confirmed Section 4A has 5 columns; Sections 4B/4C have 4 columns (no ICU)
- All 8 sections present; table formatting intact; priority key included
v1.0 (February 2, 2026) - Initial template creation - Section 1: 15 core labs (1A), 18 extended labs (1B), 9 rare/specialized tests (1C) - Section 2: 8 essential imaging/studies (2A), 9 extended (2B), 5 rare/specialized (2C), 15 LP/CSF studies - Section 3: 4 subsections: - 3A: 8 acute/emergent treatments (IV methylprednisolone, IVIG induction, GI prophylaxis, insulin, DVT prophylaxis, aspirin, seizure management) - 3B: 8 symptomatic treatments (analgesics, antiemetics, bone protection, PJP prophylaxis, nimodipine, hearing aids, antidepressant, sleep) - 3C: 5 second-line/refractory agents (plasma exchange, rituximab, cyclophosphamide, infliximab, natalizumab) - 3D: 4 disease-modifying/maintenance therapies (IVIG maintenance, prednisone taper, mycophenolate, azathioprine) - Section 4: 15 referrals (4A), 12 patient instructions (4B), 10 lifestyle modifications (4C) - Section 5: 13 differential diagnoses with distinguishing features - Section 6: 12 acute monitoring parameters (6A), 17 outpatient/long-term monitoring parameters (6B) - Section 7: 7 disposition criteria - Section 8: 25 evidence references with PubMed links - Clinical Decision Support Notes: European Susac Consortium diagnostic criteria, Susac vs. MS comparison table, pathognomonic MRI findings, disease course patterns, 10 red flags checklist
APPENDIX A: Susac Syndrome Diagnostic Algorithm¶
- Clinical suspicion -- Encephalopathy (especially with psychiatric features or cognitive decline) + any combination of visual symptoms and/or hearing loss in a young patient
- MRI brain with sagittal FLAIR -- Look for central corpus callosum "snowball" lesions (pathognomonic); DWI for acute lesions; deep gray matter and white matter involvement
- Fluorescein angiography -- BRAO with arteriolar wall hyperfluorescence (pathognomonic); perform even if NO visual symptoms (subclinical BRAO in up to 50%)
- Comprehensive audiometry -- Low/mid-frequency SNHL; perform even if NO hearing symptoms (subclinical SNHL common)
- Lumbar puncture -- Elevated protein with mild/no pleocytosis; distinguish from PACNS (high pleocytosis) and MS (OCBs)
- Exclude mimics -- MRA/DSA (normal in Susac); autoimmune panel (ANA, ANCA, APL); infection panel (RPR, VZV, HIV)
- Classify -- Definite (all 3 features), Probable (2 of 3), Possible (1 with characteristic findings)
- Initiate treatment -- Do NOT wait for complete triad; early aggressive therapy prevents irreversible damage
APPENDIX B: Susac Syndrome Treatment Protocol (Rennebohm Protocol)¶
Phase 1: Acute Induction (Weeks 1-4) - IV methylprednisolone 1000 mg daily x 3-5 days - IVIG 2 g/kg IV divided over 5 days - Aspirin 81 mg PO daily - Begin oral prednisone taper after IV pulse (1 mg/kg/day) - Begin mycophenolate mofetil 500 mg PO BID, increase to 1000 mg BID over 2 weeks
Phase 2: Consolidation (Months 1-6) - IVIG 2 g/kg IV divided over 2-5 days every 4 weeks - Mycophenolate mofetil 1000-1500 mg PO BID (target 2000-3000 mg/day) - Prednisone taper: reduce by 10 mg every 2 weeks to 20 mg; then 5 mg every 2 weeks to 10 mg - Aspirin 81 mg PO daily - PJP prophylaxis; bone protection
Phase 3: Maintenance (Months 6-24+) - IVIG 2 g/kg IV every 4 weeks (extend to q6-8 weeks after 12 months of stability) - Mycophenolate mofetil 1000-1500 mg PO BID - Prednisone target: off or lowest effective dose (typically <10 mg/day) - Aspirin 81 mg PO daily - Serial monitoring: MRI q6 months, FA q6 months, audiometry q6 months
Phase 4: Taper/Discontinuation (After 24+ months of stability) - Taper IVIG frequency: q4 weeks to q6 weeks to q8 weeks to q12 weeks to discontinue - Taper mycophenolate after IVIG discontinued: reduce by 500 mg every 3-6 months - Continue serial monitoring q6 months during taper and q6-12 months after discontinuation - Reinitiate treatment promptly if relapse detected (new MRI lesion, new BRAO, new hearing loss)
APPENDIX C: Audiometric Pattern Recognition¶
| Feature | Susac Syndrome | Meniere Disease | Presbycusis | Acoustic Neuroma |
|---|---|---|---|---|
| Frequency pattern | Low and mid-frequency SNHL | Low-frequency fluctuating SNHL | High-frequency bilateral SNHL | Unilateral high-frequency SNHL |
| Laterality | Unilateral or bilateral; asymmetric | Usually unilateral | Bilateral symmetric | Unilateral |
| Course | Sudden or subacute; stepwise worsening; fluctuates | Episodic with attacks | Gradual progressive | Progressive |
| Associated symptoms | Encephalopathy, visual loss (BRAO) | Vertigo, aural fullness, tinnitus | Age-related; noise exposure | Tinnitus, facial numbness, balance |
| ABR | Cochlear pattern | Cochlear pattern | Cochlear pattern | Retrocochlear pattern |
| DPOAE | Absent/reduced in affected frequencies | Abnormal in affected frequencies | Abnormal at high frequencies | Normal (neural lesion) |