Neurosarcoidosis¶
VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review
DIAGNOSIS: Neurosarcoidosis
ICD-10: D86.82 (Sarcoid meningitis), D86.89 (Sarcoidosis of other sites), D86.9 (Sarcoidosis, unspecified), G53 (Cranial nerve disorders in diseases classified elsewhere)
SYNONYMS: Neurosarcoidosis, neurosarcoid, CNS sarcoidosis, sarcoid neuropathy, sarcoid meningitis, sarcoid myelopathy, sarcoid cranial neuropathy, sarcoid optic neuropathy, granulomatous meningitis, sarcoid hypothalamic-pituitary dysfunction, sarcoid hydrocephalus, sarcoid mass lesion, neuro-sarcoid, sarcoidosis with nervous system involvement, central nervous system sarcoidosis
SCOPE: Diagnostic workup and management of suspected or confirmed neurosarcoidosis across all neurological presentations: cranial neuropathies, aseptic meningitis, hypothalamic-pituitary dysfunction, myelopathy, peripheral neuropathy, hydrocephalus, and mass lesions. Covers Zajicek diagnostic criteria (definite, probable, possible), acute immunotherapy, steroid-sparing agents, and long-term immunosuppression. For isolated pulmonary or systemic sarcoidosis without neurological involvement, defer to pulmonology. For other granulomatous CNS diseases (e.g., granulomatosis with polyangiitis, TB meningitis), use respective templates.
DEFINITIONS: - Definite Neurosarcoidosis (Zajicek criteria): Biopsy of nervous system tissue demonstrating non-caseating granulomas, with other causes excluded - Probable Neurosarcoidosis: CNS inflammation (elevated CSF protein/cells, MRI abnormalities, or positive brain/spine biopsy consistent with neurosarcoidosis) PLUS evidence of systemic sarcoidosis (biopsy-confirmed) - Possible Neurosarcoidosis: Clinical and MRI findings suggestive of neurosarcoidosis without tissue confirmation of systemic or nervous system sarcoidosis
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; leukopenia in sarcoidosis; pre-immunotherapy | Normal; lymphopenia common | STAT | STAT | ROUTINE | STAT |
| CMP (BMP + LFTs) (CPT 80053) | Metabolic screen; hepatic involvement (granulomatous hepatitis); renal function; hypercalcemia screening | Normal; elevated ALP/GGT suggests hepatic involvement | STAT | STAT | ROUTINE | STAT |
| Calcium (total and ionized) (CPT 82310+82330) | Hypercalcemia from granulomatous 1,25-dihydroxyvitamin D production; present in 10-17% of sarcoidosis | Normal (8.5-10.5 mg/dL) | STAT | STAT | ROUTINE | STAT |
| ESR (CPT 85652) | Inflammatory marker; often elevated in active sarcoidosis | Elevated (non-specific) | URGENT | ROUTINE | ROUTINE | URGENT |
| CRP (CPT 86140) | Inflammatory marker; infection screen | Normal to mildly elevated | URGENT | ROUTINE | ROUTINE | URGENT |
| Serum ACE level (CPT 82164) | Elevated in ~60% of systemic sarcoidosis but only ~30-50% of neurosarcoidosis; limited sensitivity; false positives in DM, hyperthyroidism, lymphoma | Elevated (>52 U/L; varies by lab) | URGENT | URGENT | ROUTINE | URGENT |
| TSH (CPT 84443) | Hypothalamic-pituitary dysfunction screen; central hypothyroidism | Normal | URGENT | ROUTINE | ROUTINE | URGENT |
| Free T4 (CPT 84439) | Central hypothyroidism from hypothalamic-pituitary sarcoidosis | Normal | URGENT | ROUTINE | ROUTINE | URGENT |
| Prolactin (CPT 84146) | Elevated with hypothalamic/pituitary stalk involvement; usually mild elevation (<100 ng/mL) | Normal (<25 ng/mL) | URGENT | ROUTINE | ROUTINE | URGENT |
| AM cortisol (CPT 82533) | Adrenal insufficiency from HPA axis involvement; central hypoadrenalism | Normal (>10 mcg/dL at 8AM) | URGENT | ROUTINE | ROUTINE | URGENT |
| Blood glucose (CPT 82947) | Diabetes insipidus screen; pre-steroid baseline | Normal | STAT | STAT | ROUTINE | STAT |
| HbA1c (CPT 83036) | Glycemic status before high-dose steroids | <5.7% | - | ROUTINE | ROUTINE | - |
| Urinalysis with culture (CPT 81003+87086) | Infection screen; 24h urine calcium if hypercalcemia | Negative | STAT | STAT | ROUTINE | STAT |
| Blood cultures (x2 sets) (CPT 87040) | Rule out infection (particularly TB, fungal before immunosuppression) | No growth | STAT | STAT | - | STAT |
| PT/INR, aPTT (CPT 85610+85730) | Coagulation status pre-LP; pre-procedure | Normal | STAT | STAT | - | STAT |
| Magnesium (CPT 83735) | Seizure threshold; metabolic screen | Normal | STAT | STAT | ROUTINE | STAT |
| Phosphorus (CPT 84100) | Metabolic screen | Normal | STAT | STAT | ROUTINE | STAT |
| LDH (CPT 83615) | Marker of granulomatous activity; lymphoma screen | Normal | URGENT | ROUTINE | ROUTINE | URGENT |
| Uric acid (CPT 84550) | Elevated in active sarcoidosis | Normal | - | ROUTINE | ROUTINE | - |
| Procalcitonin (CPT 84145) | Distinguish bacterial infection from granulomatous inflammation | Normal (<0.1 ng/mL) | URGENT | URGENT | - | URGENT |
| Serum protein electrophoresis (SPEP) (CPT 86334) | Polyclonal hypergammaglobulinemia common in sarcoidosis; lymphoma screen | Polyclonal pattern or normal | - | ROUTINE | ROUTINE | - |
| Quantitative immunoglobulins (IgG, IgA, IgM) (CPT 82784) | Baseline before immunotherapy; hypergammaglobulinemia | Normal or elevated IgG | - | ROUTINE | ROUTINE | - |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| 1,25-dihydroxyvitamin D (calcitriol) (CPT 82652) | Elevated due to granulomatous production by activated macrophages; more specific than calcium alone | Elevated (supports sarcoidosis) | - | ROUTINE | ROUTINE | - |
| 25-hydroxyvitamin D (CPT 82306) | May be low (consumed by granulomatous conversion to 1,25-D); guides supplementation | Normal (>30 ng/mL) | - | ROUTINE | ROUTINE | - |
| 24-hour urine calcium (CPT 82340) | Hypercalciuria (more common than hypercalcemia); nephrolithiasis risk | <300 mg/24h | - | ROUTINE | ROUTINE | - |
| Serum lysozyme (CPT 86318) | Elevated in active sarcoidosis; marker of macrophage activity | Normal | - | ROUTINE | ROUTINE | - |
| Soluble IL-2 receptor (sIL-2R) (CPT 86235) | Elevated in active sarcoidosis; may be more sensitive than ACE; correlates with disease activity | Normal | - | ROUTINE | ROUTINE | - |
| ANA (CPT 86235) | Lupus/vasculitis screen | Negative or low titer | URGENT | ROUTINE | ROUTINE | URGENT |
| Anti-dsDNA (CPT 86225) | If ANA positive; lupus cerebritis exclusion | Negative | - | ROUTINE | ROUTINE | - |
| ANCA (c-ANCA and p-ANCA) (CPT 86235) | Granulomatosis with polyangiitis exclusion (CNS vasculitis mimic) | Negative | - | ROUTINE | ROUTINE | - |
| Anti-SSA/SSB (Ro/La) | Sjogren syndrome with CNS involvement | Negative | - | ROUTINE | ROUTINE | - |
| RPR/VDRL (CPT 86592) | Neurosyphilis exclusion (granulomatous meningitis mimic) | Negative | - | ROUTINE | ROUTINE | - |
| Lyme serology (CPT 86618) | Lyme neuroborreliosis (cranial neuropathy, meningitis mimic) | Negative | - | ROUTINE | ROUTINE | - |
| QuantiFERON-TB Gold or PPD (CPT 86480) | TB exclusion before immunosuppression; TB meningitis is critical differential | Negative | - | URGENT | ROUTINE | URGENT |
| HIV (CPT 87389) | Immunocompromised screen; CNS lymphoma risk | Negative | - | ROUTINE | ROUTINE | - |
| Hepatitis B surface antigen + core antibody (CPT 80074) | Reactivation risk before immunosuppression (rituximab, methotrexate) | Negative | - | ROUTINE | ROUTINE | - |
| Hepatitis C antibody (CPT 80074) | Screen before immunosuppression | Negative | - | ROUTINE | ROUTINE | - |
| LH, FSH | Hypogonadotropic hypogonadism from pituitary involvement | Normal | - | ROUTINE | ROUTINE | - |
| Testosterone (males) or estradiol (premenopausal females) | Central hypogonadism screen | Normal | - | ROUTINE | ROUTINE | - |
| IGF-1 (CPT 84305) | Growth hormone deficiency from pituitary involvement | Normal | - | ROUTINE | ROUTINE | - |
| Serum osmolality + urine osmolality (CPT 83930+83935) | Diabetes insipidus screen (central DI from hypothalamic/posterior pituitary involvement) | Serum 275-295 mOsm/kg; urine concentrated | URGENT | ROUTINE | ROUTINE | URGENT |
| Water deprivation test (supervised) | Confirm central diabetes insipidus if polyuria/polydipsia | Normal concentration ability | - | ROUTINE | ROUTINE | - |
| Anti-AQP4 (NMO-IgG) (CPT 86255) | NMOSD exclusion if longitudinally extensive transverse myelitis | Negative | - | ROUTINE | ROUTINE | - |
| Anti-MOG IgG | MOGAD exclusion if optic neuritis or myelitis | Negative | - | ROUTINE | ROUTINE | - |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Chitotriosidase (CPT 82657) | Elevated in active sarcoidosis; macrophage activation marker; may monitor treatment response | Normal | - | EXT | EXT | - |
| Serum amyloid A (SAA) | Inflammatory marker in refractory sarcoidosis; monitor activity | Normal | - | EXT | EXT | - |
| Bronchoalveolar lavage (BAL) with CD4/CD8 ratio | CD4/CD8 ratio >3.5 supports sarcoidosis; helps differentiate from other granulomatous diseases | CD4/CD8 >3.5 | - | EXT | EXT | - |
| Kveim test | Historical; rarely available; skin biopsy 4-6 weeks after injection of sarcoid tissue extract | Granuloma formation | - | EXT | EXT | - |
| Anti-neuronal antibody panel | Paraneoplastic/autoimmune encephalitis exclusion if atypical presentation | Negative | - | EXT | EXT | - |
| 14-3-3 protein (CSF) | Prion disease exclusion if rapidly progressive | Negative | - | EXT | EXT | - |
| RT-QuIC (CSF) | Prion disease exclusion | Negative | - | EXT | EXT | - |
| CSF metagenomics (next-generation sequencing) | Occult infection exclusion when standard testing negative | No pathogens detected | - | EXT | EXT | - |
| Genetic testing (BTNL2, HLA-DRB1) | Sarcoidosis susceptibility genes; research/atypical cases | Informational | - | - | 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 mass, hemorrhage, hydrocephalus; calcified granulomas | None significant | STAT | STAT | - | STAT |
| MRI brain with and without gadolinium (CPT 70553) | Within 24h | Leptomeningeal enhancement (most common); pachymeningeal enhancement; hypothalamic/pituitary enhancement; cranial nerve enhancement (especially CN II, VII); parenchymal granulomas; periventricular white matter lesions; hydrocephalus | GFR <30; gadolinium allergy; pacemaker | URGENT | URGENT | ROUTINE | URGENT |
| MRI spine (cervical and thoracic) with and without contrast (CPT 72156+72157) | Within 24-48h if myelopathy suspected | Intramedullary lesions; leptomeningeal enhancement; cord expansion; dorsal subpial enhancement ("trident sign"); longitudinally extensive lesions | GFR <30; gadolinium allergy | URGENT | URGENT | ROUTINE | URGENT |
| CT chest (with or without contrast) (CPT 71260) | Within 24-48h | Bilateral hilar lymphadenopathy (Scadding stages); pulmonary infiltrates; mediastinal lymphadenopathy -- present in up to 90% of sarcoidosis | Contrast allergy; renal insufficiency | URGENT | URGENT | ROUTINE | URGENT |
| ECG (12-lead) (CPT 93000) | Immediate | Conduction abnormalities (cardiac sarcoidosis); QTc prolongation; heart block | None | STAT | STAT | ROUTINE | STAT |
| Chest X-ray (CPT 71046) | Immediate | Bilateral hilar lymphadenopathy; pulmonary infiltrates | Pregnancy (relative) | STAT | STAT | ROUTINE | STAT |
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| FDG-PET/CT (whole body) (CPT 78816) | Within 1-2 weeks | FDG-avid lymph nodes, pulmonary infiltrates, or other sites for biopsy targeting; disease activity assessment; identify biopsy-accessible sites | Uncontrolled diabetes; pregnancy | - | ROUTINE | ROUTINE | - |
| Gallium-67 scan | Within 1-2 weeks | Lambda sign (bilateral hilar + right paratracheal uptake); panda sign (lacrimal + parotid uptake); largely replaced by FDG-PET | Pregnancy | - | ROUTINE | ROUTINE | - |
| Cardiac MRI (CPT 75561) | Within 1-2 weeks | Cardiac sarcoidosis (late gadolinium enhancement, myocardial edema); conduction disease; cardiomyopathy | Pacemaker; GFR <30 | - | ROUTINE | ROUTINE | - |
| Echocardiogram (CPT 93306) | Within 48h | Cardiac sarcoidosis; wall motion abnormalities; systolic/diastolic dysfunction | None significant | - | ROUTINE | ROUTINE | URGENT |
| CT orbits with contrast | If orbital/optic nerve involvement | Optic nerve/sheath enhancement; orbital mass; lacrimal gland enlargement | Contrast allergy | - | ROUTINE | ROUTINE | - |
| EMG/NCS (electromyography/nerve conduction studies) (CPT 95907-95913) | Within 1-2 weeks | Small fiber neuropathy; axonal polyneuropathy; mononeuritis multiplex; polyradiculopathy | Anticoagulation (relative for needle EMG) | - | ROUTINE | ROUTINE | - |
| Pulmonary function tests (PFTs) (CPT 94010) | Within 1-2 weeks | Restrictive pattern; reduced DLCO; pulmonary sarcoidosis staging | Unable to cooperate | - | ROUTINE | ROUTINE | - |
| Ophthalmologic slit lamp examination | Within 24-48h | Anterior uveitis; posterior uveitis; optic disc edema; lacrimal gland enlargement; keratoconjunctivitis sicca | None | URGENT | URGENT | ROUTINE | URGENT |
| Visual evoked potentials (VEPs) (CPT 95930) | Within 1-2 weeks | Optic neuropathy assessment; P100 latency prolongation | None significant | - | ROUTINE | ROUTINE | - |
| Holter monitor/event monitor (CPT 93224) | Within 1 week | Cardiac arrhythmias from cardiac sarcoidosis | None | - | ROUTINE | ROUTINE | - |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Meningeal biopsy (open or stereotactic) | When tissue diagnosis required | Non-caseating granulomas with multinucleated giant cells; exclusion of infection/malignancy; definite neurosarcoidosis diagnosis | Coagulopathy; inaccessible location | - | EXT | - | - |
| Lymph node biopsy (mediastinal or peripheral) | When systemic tissue confirmation needed | Non-caseating granulomas; probable neurosarcoidosis diagnosis | Coagulopathy | - | EXT | EXT | - |
| Transbronchial lung biopsy (TBLB) | If hilar lymphadenopathy present | Non-caseating granulomas; high yield (60-90%) with EBUS guidance | Coagulopathy; severe pulmonary hypertension | - | EXT | EXT | - |
| Endobronchial ultrasound (EBUS) with biopsy | Preferred for mediastinal lymph node sampling | Non-caseating granulomas; diagnostic yield >90% for stage I-II sarcoidosis | Same as TBLB | - | EXT | EXT | - |
| Skin biopsy (if skin lesions present) | When cutaneous sarcoidosis suspected | Non-caseating granulomas; easiest biopsy site | Coagulopathy | - | ROUTINE | ROUTINE | - |
| Minor salivary gland biopsy (lip biopsy) | Alternative biopsy site when other sites not accessible | Non-caseating granulomas; yield ~30-60% | Coagulopathy | - | EXT | EXT | - |
| Conjunctival biopsy | If lacrimal/conjunctival nodules present | Non-caseating granulomas | None significant | - | EXT | EXT | - |
| Brain biopsy (stereotactic) | Last resort; when diagnosis uncertain and treatment-critical | Non-caseating granulomas; definite neurosarcoidosis | Coagulopathy; deep lesion location | - | EXT | - | - |
| FDG-PET brain | If brain MRI equivocal | Focal or diffuse hypermetabolism; meningeal uptake | Uncontrolled diabetes | - | EXT | EXT | - |
LUMBAR PUNCTURE¶
Indication: Essential for diagnosis of neurosarcoidosis; CSF abnormalities support diagnosis (lymphocytic pleocytosis, elevated protein, low glucose); CSF ACE level; rules out infectious meningitis (TB, fungal, bacterial); rules out CNS lymphoma and carcinomatous meningitis
Timing: URGENT in ED/hospital setting; ROUTINE for outpatient workup. Perform after CT head to rule out mass effect/hydrocephalus
Volume Required: 15-20 mL (sufficient for comprehensive infectious, inflammatory, and cytology studies)
| Study | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Opening pressure (CPT 89050) | Elevated ICP assessment; hydrocephalus from meningeal involvement | 10-20 cm H2O (often elevated in neurosarcoidosis) | URGENT | ROUTINE | ROUTINE | - |
| Cell count with differential (tubes 1 and 4) (CPT 89051) | Lymphocytic pleocytosis (50-70% of neurosarcoidosis); distinguish from infection | WBC 10-100 (lymphocyte-predominant); RBC 0 | STAT | STAT | ROUTINE | STAT |
| Protein (CPT 84157) | Elevated in 50-70% of neurosarcoidosis; usually 50-200 mg/dL | Normal to elevated (often 50-200 mg/dL) | STAT | STAT | ROUTINE | STAT |
| Glucose with paired serum glucose (CPT 82945) | Low in ~18% of neurosarcoidosis; also low in TB, fungal, bacterial meningitis | Normal or low (>40 mg/dL; >60% of serum) | STAT | STAT | ROUTINE | STAT |
| CSF ACE level (CPT 82164) | Elevated in ~50-70% of neurosarcoidosis; limited sensitivity (50%) but reasonable specificity (~90%); NOT diagnostic alone | Elevated supports diagnosis (normal does not exclude) | URGENT | URGENT | ROUTINE | URGENT |
| Oligoclonal bands (CSF AND paired serum) (CPT 83916) | Intrathecal IgG synthesis; present in ~30-40% of neurosarcoidosis; helps differentiate from MS | May show CSF-specific bands | URGENT | ROUTINE | ROUTINE | - |
| IgG index (CPT 83787) | Intrathecal antibody synthesis | May be elevated | URGENT | ROUTINE | ROUTINE | - |
| Gram stain and bacterial culture (CPT 87205+87070) | Rule out bacterial meningitis | No organisms | STAT | STAT | ROUTINE | STAT |
| AFB smear and culture (CPT 87116) | TB meningitis exclusion (CRITICAL differential for granulomatous meningitis) | Negative | URGENT | URGENT | ROUTINE | URGENT |
| Fungal culture (CPT 87102) | Fungal meningitis exclusion (cryptococcal, coccidioidomycosis) | Negative | URGENT | URGENT | ROUTINE | - |
| Cryptococcal antigen (CPT 87327) | Cryptococcal meningitis exclusion | Negative | URGENT | URGENT | - | URGENT |
| CSF VDRL (CPT 86592) | Neurosyphilis exclusion | Negative | - | ROUTINE | ROUTINE | - |
| Cytology (CPT 88104) | Carcinomatous/lymphomatous meningitis exclusion | Negative for malignant cells | - | ROUTINE | ROUTINE | - |
| Flow cytometry (CPT 88184) | CNS lymphoma exclusion | Normal | - | ROUTINE | ROUTINE | - |
| HSV PCR (CPT 87529) | Viral encephalitis exclusion | Negative | STAT | STAT | - | STAT |
| TB PCR (GeneXpert) | Rapid TB meningitis exclusion; more sensitive than AFB smear | Negative | URGENT | URGENT | ROUTINE | - |
| CSF CD4/CD8 ratio | Elevated CD4/CD8 ratio supports neurosarcoidosis (similar to BAL) | Elevated (>3.0 suggestive) | - | ROUTINE | ROUTINE | - |
| Adenosine deaminase (ADA) (CPT 86235) | Elevated in TB meningitis (>10 IU/L); helps differentiate TB from sarcoid | Normal (<10 IU/L) | URGENT | ROUTINE | ROUTINE | - |
Special Handling: CSF ACE level requires prompt processing; send AFB and fungal cultures in sufficient volume (minimum 2 mL each). Cytology requires rapid transport (<1 hour). Store extra CSF (frozen at -20C) for future testing.
Contraindications: Elevated ICP without imaging (get CT first); coagulopathy (INR >1.5, platelets <50K); skin infection at LP site; obstructive hydrocephalus with risk of herniation
3. TREATMENT¶
3A. Acute/Emergent¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Methylprednisolone | IV | Acute severe neurosarcoidosis (optic neuropathy, myelopathy, cranial neuropathy, acute hydrocephalus, mass lesion with edema) | 1000 mg :: IV :: daily :: 1000 mg IV daily for 3-5 days; infuse over 1-2 hours | Active untreated infection (especially TB); uncontrolled diabetes; active GI bleeding; psychosis from steroids | Glucose q6h (target <180 mg/dL); BP; mood/sleep; I/O; GI prophylaxis; electrolytes | STAT | STAT | - | STAT |
| Omeprazole | PO | GI protection during high-dose corticosteroid therapy | 40 mg :: PO :: daily :: 40 mg PO daily during steroid course and oral taper; IV if NPO | PPI allergy | None routine | URGENT | STAT | ROUTINE | STAT |
| Insulin sliding scale | SC | Steroid-induced hyperglycemia management | Per protocol :: SC :: PRN :: Per sliding scale if glucose >180 mg/dL; adjust per glucose trends | Hypoglycemia risk | Glucose q6h; adjust per response | URGENT | STAT | - | STAT |
| Dexamethasone | IV | Cerebral edema from granulomatous mass lesion; acute elevated ICP | 10 mg :: IV :: q6h :: 10 mg IV loading dose, then 4 mg IV q6h; taper over days-weeks as clinically improving | Active untreated infection; uncontrolled diabetes | Glucose; BP; neurological status; GI prophylaxis | STAT | STAT | - | STAT |
| Lorazepam | IV | Seizure secondary to cortical/meningeal sarcoidosis | 4 mg :: IV :: PRN seizure :: 0.1 mg/kg IV push (max 4 mg/dose); may repeat x1 in 5 minutes | Respiratory depression; acute narrow-angle glaucoma | Respiratory status; sedation level; airway patency | STAT | STAT | - | STAT |
| Desmopressin | IV | Central diabetes insipidus from hypothalamic/posterior pituitary sarcoidosis | 1-2 mcg :: IV :: q12h :: 1-2 mcg IV/SC q12h; or 10-20 mcg intranasal BID; titrate to urine output and serum sodium | Hyponatremia; type IIb von Willebrand disease | Sodium q4-6h initially; urine output; urine specific gravity; serum osmolality; weight | STAT | STAT | ROUTINE | STAT |
| Mannitol | IV | Acute elevated ICP from mass lesion or obstructive hydrocephalus pending surgical intervention | 1 g/kg :: IV :: PRN ICP :: 1 g/kg IV bolus over 15-20 minutes; may repeat 0.5 g/kg q6h; maintain serum osmolality <320 mOsm/kg | Anuria; severe dehydration; active intracranial hemorrhage | Serum osmolality q6h; electrolytes; renal function; I/O | STAT | STAT | - | STAT |
| Hypertonic saline 3% | IV | Acute elevated ICP from obstructive hydrocephalus or mass effect | 250 mL :: IV :: PRN ICP :: 250 mL 3% NaCl IV over 15-30 minutes; may repeat; target sodium 145-155 mEq/L | Hypernatremia >155 mEq/L; severe CHF | Sodium q2-4h; serum osmolality; central line preferred for concentrations >3% | STAT | STAT | - | STAT |
Note: High-dose IV corticosteroids are the mainstay of acute neurosarcoidosis treatment. Do NOT delay steroids if neurosarcoidosis is clinically suspected -- tissue confirmation can proceed in parallel. Always exclude TB meningitis before or concurrently with initiating immunosuppression (send AFB cultures + TB PCR before starting steroids).
3B. Symptomatic Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Gabapentin | PO | Neuropathic pain from peripheral neuropathy or radiculopathy | 300 mg :: PO :: TID :: Start 300 mg qHS; titrate by 300 mg q1-3d; target 900-1800 mg TID; max 3600 mg/day | Renal impairment (adjust dose per CrCl) | Sedation; dizziness; peripheral edema; renal function | - | ROUTINE | ROUTINE | - |
| Pregabalin | PO | Neuropathic pain; alternative to gabapentin | 75 mg :: PO :: BID :: Start 75 mg BID; may increase q1wk; max 600 mg/day | Renal impairment (adjust dose); Class V controlled substance | Sedation; weight gain; peripheral edema; renal function | - | ROUTINE | ROUTINE | - |
| Duloxetine | PO | Neuropathic pain; comorbid depression | 30 mg :: PO :: daily :: Start 30 mg daily x 1 week, then increase to 60 mg daily; max 120 mg/day | Severe hepatic impairment; concurrent MAOIs; uncontrolled narrow-angle glaucoma | BP; hepatic function; serotonin syndrome risk; suicidality monitoring | - | ROUTINE | ROUTINE | - |
| Carbamazepine | PO | Trigeminal neuralgia from CN V sarcoidosis | 100 mg :: PO :: BID :: Start 100 mg BID; titrate by 200 mg/day q3-7d; target level 4-12 mcg/mL; max 1200 mg/day | AV block; bone marrow suppression; HLA-B*1502 positive (SJS risk); hepatic porphyria | CBC q2 weeks x 2 months, then q3 months; LFTs; sodium (SIADH); drug level; HLA-B*1502 before starting in at-risk populations | - | ROUTINE | ROUTINE | - |
| Levetiracetam | IV | Seizures secondary to cortical or meningeal neurosarcoidosis | 500 mg :: IV :: BID :: Start 500 mg BID (IV or PO); increase by 500 mg/day q1-2wk; max 3000 mg/day; transition to PO when tolerated | Renal impairment (adjust dose per CrCl) | Behavioral changes (rage, irritability); suicidality; renal function | STAT | STAT | ROUTINE | STAT |
| Lacosamide | IV | Seizures; second-line ASM or adjunctive therapy | 100 mg :: IV :: BID :: Start 100 mg BID (IV or PO); increase by 50 mg/dose q1wk; max 400 mg/day; transition to PO when tolerated | Second/third degree AV block; severe hepatic impairment | ECG (PR prolongation); dizziness; cardiac monitoring during IV load | URGENT | URGENT | ROUTINE | URGENT |
| Levothyroxine | PO | Central hypothyroidism from hypothalamic-pituitary sarcoidosis | 25 mcg :: PO :: daily :: Start 25-50 mcg daily (lower in elderly/cardiac disease); titrate q6-8 weeks by 12.5-25 mcg; target free T4 in upper half of normal range (NOT TSH-guided for central hypothyroidism) | Adrenal insufficiency (must correct cortisol FIRST); acute MI | Free T4 (NOT TSH) q6-8 weeks; monitor for adrenal crisis if cortisol not replaced | - | ROUTINE | ROUTINE | - |
| Hydrocortisone (physiologic replacement) | PO | Central adrenal insufficiency from HPA axis sarcoidosis | 10 mg :: PO :: BID :: 10 mg on waking + 5 mg in early afternoon; stress dosing: double or triple during illness/surgery | Active infection (relative); peptic ulcer | AM cortisol (before dose); ACTH stimulation test; stress dose education | - | ROUTINE | ROUTINE | ROUTINE |
| Testosterone cypionate (males) | IM | Hypogonadotropic hypogonadism from pituitary sarcoidosis | 200 mg :: IM :: q2wk :: 100-200 mg IM every 2 weeks; titrate based on testosterone trough levels | Prostate cancer; breast cancer; polycythemia (Hct >54%); OSA (untreated); desire for fertility | Testosterone level; PSA; Hct q3 months initially; DRE annually; lipids | - | - | ROUTINE | - |
| Testosterone gel 1% (males) | TOP | Hypogonadotropic hypogonadism from pituitary sarcoidosis; alternative to IM injection | 50 mg :: TOP :: daily :: 50 mg (5g gel) applied to shoulders/upper arms daily; wash hands after application; avoid skin-to-skin transfer | Prostate cancer; breast cancer; polycythemia (Hct >54%); women/children skin contact | Testosterone level; PSA; Hct q3 months initially; DRE annually; lipids | - | - | ROUTINE | - |
| Calcium + Vitamin D (bone protection) | PO | Bone protection during chronic corticosteroid therapy; AVOID vitamin D supplementation if hypercalcemia | 500 mg :: PO :: BID :: Calcium 500-600 mg PO BID + Vitamin D 800-1000 IU daily; HOLD vitamin D if serum calcium elevated | Hypercalcemia; hypercalciuria; nephrolithiasis (avoid vitamin D in active sarcoid hypercalcemia) | Serum calcium; 25-OH vitamin D; 24h urine calcium; DEXA if steroids >3 months | - | ROUTINE | ROUTINE | - |
| Acetazolamide | PO | Communicating hydrocephalus; elevated ICP from meningeal sarcoidosis (adjunct to steroids) | 250 mg :: PO :: BID :: Start 250 mg BID; may increase to 500 mg BID; max 2000 mg/day | Sulfa allergy; severe renal/hepatic failure; hypokalemia; metabolic acidosis | BMP (potassium, bicarbonate); renal function; paresthesias; kidney stones | - | ROUTINE | ROUTINE | - |
| Artificial tears | TOP | Keratoconjunctivitis sicca from lacrimal gland sarcoidosis | 1-2 drops :: TOP :: q2-4h PRN :: 1-2 drops in each eye q2-4h PRN for dryness; preservative-free preferred for frequent use | None significant | Symptom relief; ophthalmology follow-up | - | ROUTINE | ROUTINE | - |
Note: Hormonal replacement is essential when hypothalamic-pituitary involvement is documented. Always correct adrenal insufficiency BEFORE starting thyroid replacement to avoid precipitating adrenal crisis. Vitamin D supplementation should be used cautiously in sarcoidosis due to risk of exacerbating hypercalcemia through granulomatous 1,25-D overproduction.
3C. Second-line/Refractory¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Prednisone | PO | Transition from IV steroids; maintenance corticosteroid therapy | 60 mg :: PO :: daily :: Start 1 mg/kg/day (max 60 mg) after IV pulse; taper by 10 mg every 2 weeks to 20 mg, then by 5 mg every 2-4 weeks to lowest effective dose (goal 5-10 mg daily or off); total taper over 6-12 months | Active infection; uncontrolled diabetes; avascular necrosis; psychosis from steroids | Glucose; BP; weight; mood; bone density (DEXA if >3 months); ophthalmology (cataracts, glaucoma); adrenal function on taper | - | ROUTINE | ROUTINE | - |
| Methotrexate | PO | Steroid-sparing immunosuppression; relapsing neurosarcoidosis; inability to taper steroids below 10 mg/day | 10 mg :: PO :: weekly :: Start 7.5-10 mg PO once weekly; increase by 2.5-5 mg q2-4wk; target 15-25 mg weekly; always co-prescribe folic acid 1 mg daily (except MTX day) | Pregnancy (Category X -- teratogenic); severe hepatic/renal disease; active infection; bone marrow suppression; significant pleural effusion/ascites | CBC q2 weeks x 2 months, then monthly; LFTs monthly; renal function q3 months; chest X-ray annually; hepatic fibrosis screen (FibroScan or liver biopsy if cumulative dose >1.5g); pulmonary toxicity (cough, dyspnea) | - | ROUTINE | ROUTINE | - |
| Mycophenolate mofetil | PO | Steroid-sparing agent; alternative to methotrexate; relapsing neurosarcoidosis | 500 mg :: PO :: BID :: Start 500 mg PO BID; increase by 500 mg every 2 weeks; target 1000-1500 mg BID (2000-3000 mg/day total) | Pregnancy (Category D -- teratogenic); active infection; concurrent live vaccines | CBC q2 weeks x 3 months, then monthly; LFTs; GI symptoms (diarrhea, nausea); infection surveillance; pregnancy prevention | - | ROUTINE | ROUTINE | - |
| Azathioprine | PO | Steroid-sparing agent; alternative to methotrexate/mycophenolate | 50 mg :: PO :: daily :: Start 50 mg PO daily; increase by 50 mg every 2 weeks to target 2-3 mg/kg/day; onset of action 3-6 months | TPMT deficiency (check before starting); concurrent allopurinol (reduce dose 75%); pregnancy (relative) | TPMT genotype/activity before starting; CBC q2 weeks x 2 months, then monthly; LFTs monthly; amylase if abdominal pain (pancreatitis) | - | ROUTINE | ROUTINE | - |
| Hydroxychloroquine | PO | Mild neurosarcoidosis; cutaneous sarcoidosis with mild CNS involvement; adjunctive therapy | 200 mg :: PO :: BID :: 200 mg PO BID (max 5 mg/kg/day based on actual body weight); onset 2-3 months | Retinal disease; G6PD deficiency; QTc prolongation | Baseline and annual ophthalmologic exam (OCT + visual fields) after 5 years (or earlier if risk factors); CBC; LFTs; ECG | - | ROUTINE | ROUTINE | - |
| Leflunomide | PO | Steroid-sparing agent; alternative to methotrexate (similar mechanism) | 20 mg :: PO :: daily :: Loading dose: 100 mg PO daily x 3 days (optional); then 20 mg PO daily | Pregnancy (Category X); severe hepatic impairment; immunodeficiency | LFTs monthly x 6 months, then q2 months; CBC; BP; cholestyramine washout if pregnancy desired (11g TID x 11 days) | - | - | ROUTINE | - |
Note: Steroid-sparing agents should be initiated early (within 1-3 months) for patients requiring prolonged corticosteroid therapy. Methotrexate is the most commonly used and best-studied steroid-sparing agent in neurosarcoidosis. Allow 2-3 months for onset of steroid-sparing effect before concluding failure. Folic acid supplementation is mandatory with methotrexate to reduce toxicity.
3D. Disease-Modifying / Biologic Therapies (Refractory)¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| Infliximab | IV | Refractory neurosarcoidosis failing methotrexate/mycophenolate; severe/progressive disease; CNS mass lesions; optic neuropathy not responding to steroids | 5 mg/kg :: IV :: q6-8wk :: 3-5 mg/kg IV at weeks 0, 2, and 6 (induction), then every 4-8 weeks (maintenance); may increase to 7-10 mg/kg if inadequate response; infuse over 2 hours minimum | TB testing (QuantiFERON); Hepatitis B/C screening; CBC, LFTs, CMP; chest X-ray; age-appropriate cancer screening; heart failure assessment (NYHA class); pregnancy test | Active or latent TB (treat first); active serious infection; decompensated CHF (NYHA III-IV); demyelinating disease; live vaccines within 4 weeks | CBC with differential q2-4 months; LFTs q3 months; ANA/anti-dsDNA annually (drug-induced lupus); infection surveillance; infusion reactions; skin cancer screening annually; heart failure symptoms | - | URGENT | ROUTINE | URGENT |
| Adalimumab | SC | Refractory neurosarcoidosis; alternative to infliximab; may be preferred for outpatient self-administration | 40 mg :: SC :: q2wk :: 80 mg SC at week 0, then 40 mg SC every other week; may increase to 40 mg weekly or 80 mg q2wk if inadequate response | TB testing (QuantiFERON); Hepatitis B/C screening; CBC, LFTs; chest X-ray; pregnancy test | Active or latent TB (treat first); active serious infection; decompensated CHF; demyelinating disease; live vaccines within 4 weeks | CBC q2-4 months; LFTs q3 months; ANA annually; infection surveillance; injection site reactions; skin cancer screening | - | - | ROUTINE | - |
| Rituximab | IV | Refractory neurosarcoidosis failing anti-TNF therapy; B-cell-mediated disease component | 1000 mg :: IV :: q2wk x2 :: 375 mg/m2 IV weekly x 4 doses OR 1000 mg IV x 2 doses (day 0 and day 14); re-dose based on CD19/CD20 repopulation or clinical relapse; premedicate with methylprednisolone 100 mg, acetaminophen, diphenhydramine | Hepatitis B serology; CBC, CMP; quantitative immunoglobulins; JCV antibody (PML risk); pregnancy test; vaccination update | Active hepatitis B; severe active infection; live vaccines within 4 weeks; severe hypogammaglobulinemia | Hepatitis B surveillance; CBC q2-4 weeks initially; immunoglobulin levels q3 months; CD19/CD20 B-cell counts q3 months; infusion reactions; PML surveillance; infection monitoring | - | URGENT | ROUTINE | URGENT |
| Cyclophosphamide | IV | Severe refractory neurosarcoidosis with progressive neurological decline despite other therapies; last resort | 750 mg/m2 :: IV :: monthly x6 :: 750 mg/m2 IV monthly for 6 cycles; pre-hydrate with 1L NS; administer with MESNA for uroprotection; consider dose reduction for renal impairment | Pregnancy (Category D); CBC, CMP, UA before each cycle; fertility counseling | Pregnancy; active infection; bone marrow failure; bladder outlet obstruction | CBC weekly x 4 weeks after each cycle (nadir day 10-14); urinalysis (hemorrhagic cystitis); BMP; LFTs; fertility preservation discussion; malignancy risk (bladder cancer) | - | URGENT | ROUTINE | URGENT |
Note: Anti-TNF agents (infliximab, adalimumab) are the most effective biologic therapies for refractory neurosarcoidosis. Infliximab has the most evidence. ALWAYS exclude latent TB before starting anti-TNF therapy (granulomatous infection can be catastrophically reactivated). Treatment duration is typically 1-2 years minimum; relapse is common on discontinuation. Rituximab and cyclophosphamide are reserved for cases refractory to anti-TNF agents.
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurology (neuroimmunology/neurosarcoidosis specialist) for diagnosis confirmation, immunotherapy guidance, and long-term management | STAT | STAT | ROUTINE | STAT |
| Pulmonology for pulmonary sarcoidosis staging, PFTs, and bronchoscopy/EBUS biopsy coordination | - | URGENT | ROUTINE | URGENT |
| Ophthalmology for comprehensive eye examination including slit lamp (uveitis screen), visual acuity, OCT, and visual fields | URGENT | URGENT | ROUTINE | URGENT |
| Endocrinology for hypothalamic-pituitary axis evaluation and hormonal replacement management if pituitary involvement documented | - | ROUTINE | ROUTINE | - |
| Rheumatology for systemic sarcoidosis co-management and steroid-sparing immunosuppression coordination | - | ROUTINE | ROUTINE | - |
| Neurosurgery for VP shunt placement if obstructive hydrocephalus, or for meningeal/brain biopsy if tissue diagnosis required | URGENT | URGENT | - | URGENT |
| Interventional pulmonology for EBUS-guided lymph node biopsy to confirm systemic sarcoidosis diagnosis | - | ROUTINE | ROUTINE | - |
| Cardiology for cardiac MRI interpretation and management if cardiac sarcoidosis suspected (conduction abnormalities, cardiomyopathy) | - | URGENT | ROUTINE | URGENT |
| Physical therapy for gait training, balance assessment, and fall prevention given myelopathy or peripheral neuropathy | - | ROUTINE | ROUTINE | ROUTINE |
| Occupational therapy for ADL adaptation and energy conservation given fatigue and functional impairment | - | ROUTINE | ROUTINE | ROUTINE |
| Speech-language pathology for swallowing evaluation given cranial nerve involvement (CN IX, X) and cognitive-linguistic rehabilitation | - | ROUTINE | ROUTINE | ROUTINE |
| Neuropsychology for cognitive assessment and rehabilitation planning given neurocognitive impairment | - | - | ROUTINE | - |
| Pain management for refractory neuropathic pain not responding to first-line agents | - | - | ROUTINE | - |
| Social work for insurance navigation, disability resources, and long-term care planning | - | ROUTINE | ROUTINE | - |
| Dermatology for skin biopsy if cutaneous lesions present (erythema nodosum, lupus pernio, papules, plaques) as accessible biopsy site | - | ROUTINE | ROUTINE | - |
| Infusion center coordination for IV methylprednisolone, infliximab, rituximab, or cyclophosphamide infusions | - | ROUTINE | ROUTINE | - |
| Fertility specialist for reproductive counseling before initiating teratogenic immunosuppressants (methotrexate, mycophenolate, cyclophosphamide) | - | - | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Return to ED immediately for sudden vision loss, new weakness, difficulty walking, severe headache, seizures, or difficulty breathing (may indicate disease progression or complications) | Y | Y | Y | - |
| Neurosarcoidosis is a chronic, treatable condition -- improvement may be gradual over weeks to months with appropriate immunotherapy | Y | Y | Y | - |
| Do NOT stop corticosteroids abruptly as this may cause adrenal crisis and disease flare; always taper under physician supervision | - | Y | Y | - |
| Report signs of infection immediately (fever >100.4F, cough, dysuria, rash, wound redness) as immunosuppressive therapy increases infection risk | - | Y | Y | - |
| Avoid live vaccines while on immunosuppressive therapy (inform all physicians and pharmacists of immunosuppression status) | - | Y | Y | - |
| Monitor blood sugars if diabetic or if on corticosteroids -- steroids significantly elevate blood glucose | Y | Y | Y | - |
| Do not drive until cleared by neurology if visual impairment, seizures, or significant neurological deficits are present | Y | Y | Y | - |
| Keep a symptom diary tracking visual changes, weakness, numbness, headaches, fatigue, and pain to monitor treatment response | - | Y | Y | - |
| Take methotrexate on the same day each week; take folic acid daily EXCEPT on methotrexate day to reduce side effects | - | Y | Y | - |
| Report excessive thirst or urination (may indicate diabetes insipidus from hypothalamic involvement requiring treatment adjustment) | - | Y | Y | - |
| Pregnancy must be avoided during methotrexate, mycophenolate, or cyclophosphamide therapy; discuss contraception with neurology and OB/GYN | - | Y | Y | - |
| Attend all follow-up appointments -- neurosarcoidosis requires regular monitoring with MRI, labs, and clinical assessments | - | Y | Y | - |
| Wear medical alert identification (bracelet/card) indicating neurosarcoidosis, immunosuppressive medications, and adrenal insufficiency if applicable | - | Y | Y | - |
| Sun protection is important while on methotrexate and immunosuppressive therapy due to increased skin cancer risk | - | Y | Y | - |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Smoking cessation to improve pulmonary function and reduce infection risk during immunosuppression | Y | Y | Y | - |
| Alcohol avoidance or strict limitation while on methotrexate due to additive hepatotoxicity | - | Y | Y | - |
| Low-sodium diet to reduce fluid retention and hypertension from corticosteroid therapy | - | Y | Y | - |
| Calcium-rich diet (dairy, leafy greens) for bone protection during chronic steroid use; AVOID excessive vitamin D supplementation unless calcium is normal | - | Y | Y | - |
| Regular weight-bearing exercise as tolerated (walking, resistance training) to prevent steroid-related osteoporosis and deconditioning | - | Y | Y | - |
| Adequate hydration (2-3 L/day) especially if on methotrexate or if hypercalciuria present to prevent nephrolithiasis | - | Y | Y | - |
| Fall prevention measures at home (remove loose rugs, adequate lighting, grab bars in bathroom) given myelopathy and balance impairment | - | Y | Y | - |
| Stress management and adequate sleep (7-8 hours nightly) as stress may exacerbate symptoms and fatigue | - | Y | Y | - |
| Vaccinations should be up to date before initiating immunosuppressive therapy (especially pneumococcal, influenza, hepatitis B); avoid live vaccines on immunosuppression | - | Y | Y | - |
| Sun protection (SPF 50+, protective clothing) during immunosuppressive therapy due to increased skin cancer risk | - | Y | Y | - |
| Energy conservation techniques (pacing activities, scheduled rest periods) to manage sarcoidosis-related fatigue | - | Y | Y | - |
| Annual ophthalmologic examination even if asymptomatic due to risk of subclinical uveitis and steroid-related cataracts/glaucoma | - | - | Y | - |
═══════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Tuberculosis meningitis | Subacute meningitis; basilar meningeal enhancement; caseating granulomas; CSF low glucose, high protein, elevated ADA; risk factors (endemic areas, immunosuppression) | AFB culture/smear; CSF TB PCR (GeneXpert); QuantiFERON-TB; chest CT (apical disease vs. hilar adenopathy); tissue biopsy (caseating vs. non-caseating) |
| CNS lymphoma (primary) | Progressive encephalopathy; periventricular enhancement; homogeneous enhancing mass; immunocompromised | CSF cytology/flow cytometry; brain biopsy; FDG-PET (intense uptake); HIV testing |
| Multiple sclerosis | Relapsing-remitting course; periventricular/juxtacortical/infratentorial/spinal cord lesions (Dawson fingers); oligoclonal bands; young female predominance | MRI (MS vs. sarcoid pattern); CSF oligoclonal bands; no systemic involvement; no hilar adenopathy |
| Neuromyelitis optica spectrum disorder (NMOSD) | Optic neuritis and longitudinally extensive transverse myelitis; area postrema syndrome | AQP4-IgG (positive); no hilar adenopathy; different MRI pattern |
| CNS vasculitis (primary or secondary) | Headache; multifocal strokes; beading on angiography; CSF pleocytosis | Cerebral angiography (beading); brain/leptomeningeal biopsy; ANCA; no hilar adenopathy |
| Granulomatosis with polyangiitis (GPA/Wegener) | Sinusitis; pulmonary nodules/cavities; glomerulonephritis; pachymeningeal enhancement | c-ANCA (PR3); biopsy showing necrotizing vasculitis with granulomas; renal function |
| Lyme neuroborreliosis | Cranial neuropathy (CN VII bilateral); meningitis; radiculopathy; erythema migrans; endemic area | Lyme serology (two-tier); CSF Lyme antibody index; travel history |
| Neurosyphilis | Cranial neuropathies; meningitis; Argyll Robertson pupils; cognitive decline; positive serology | RPR/VDRL; CSF VDRL; FTA-ABS; HIV co-testing |
| Histoplasmosis/Coccidioidomycosis (CNS fungal) | Chronic meningitis; basilar enhancement; endemic area; immunocompromised | Fungal cultures; Histoplasma/Coccidioides antigen; CSF antibodies; biopsy |
| Meningeal carcinomatosis | Known malignancy; cranial neuropathies; headache; progressive; CSF cytology positive | CSF cytology (serial LPs increase yield); MRI (nodular leptomeningeal enhancement); whole-body staging |
| IgG4-related disease | Mass-forming lesions; pachymeningeal or orbital involvement; elevated serum IgG4; multi-organ fibrosis | Serum IgG4 level; tissue biopsy (storiform fibrosis, IgG4+ plasma cells >40%); no non-caseating granulomas |
| Histiocytic disorders (Erdheim-Chester, Langerhans cell histiocytosis) | Hypothalamic-pituitary involvement; orbital masses; bone lesions; skin involvement | Tissue biopsy (CD68+ foamy histiocytes in ECD; CD1a+/Langerin+ in LCH); BRAF V600E mutation; PET/CT |
| Lymphomatoid granulomatosis | Pulmonary nodules; CNS involvement; EBV-associated; angiocentric lymphoid proliferation | Lung biopsy; EBV in-situ hybridization; angiocentric/angiodestructive pattern |
| Behcet disease | Oral/genital ulcers; brainstem involvement; CSF neutrophilic pleocytosis; pathergy test | Clinical criteria; pathergy test; HLA-B51; no hilar adenopathy |
| Chronic meningitis (idiopathic) | Persistent CSF pleocytosis and meningeal enhancement without identifiable cause after exhaustive workup | Comprehensive infectious, inflammatory, and neoplastic workup; brain/meningeal biopsy if refractory |
6. MONITORING PARAMETERS¶
6A. Acute Phase Monitoring (Inpatient)¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurologic examination (cranial nerves, motor, sensory, gait, cognition) | Q4-6h (ICU); Q8-12h (floor) | Stable or improving | If worsening: urgent re-imaging; escalate immunotherapy; neurosurgery consult if hydrocephalus | STAT | STAT | - | STAT |
| Visual acuity testing | Daily if optic neuropathy | Stable or improving | Worsening: urgent ophthalmology; escalate steroids; consider PLEX | URGENT | URGENT | ROUTINE | URGENT |
| Blood glucose | Q6h during IV steroids | <180 mg/dL | Insulin sliding scale; endocrine consult if persistent >250 mg/dL | STAT | STAT | - | STAT |
| Blood pressure | Q1h (ICU); Q4h (floor) | SBP <160 mmHg; MAP >65 | Antihypertensive therapy; steroid dose adjustment if severe | STAT | ROUTINE | - | STAT |
| Temperature | Q4h; continuous in ICU | 36.0-37.5C | Rule out infection; blood cultures if febrile on immunosuppression | STAT | ROUTINE | - | STAT |
| Serum sodium | Q6-12h if diabetes insipidus | 135-145 mEq/L | Desmopressin titration; fluid balance adjustment | URGENT | ROUTINE | - | URGENT |
| Urine output | Q1h (ICU); Q4h (floor) | 0.5-1.0 mL/kg/hr | If polyuria (>3 L/day): check sodium, osmolality; diabetes insipidus workup | URGENT | ROUTINE | - | STAT |
| Calcium (total and ionized) | Daily during steroid therapy | 8.5-10.5 mg/dL (total) | If hypercalcemia: IV normal saline hydration; hold vitamin D; consider calcitonin | URGENT | ROUTINE | - | URGENT |
| Renal function (BUN/Cr) | Daily during acute treatment | Stable | Adjust renally-dosed medications; hydration | URGENT | ROUTINE | - | URGENT |
| ICP monitoring (if VP shunt or EVD) | Continuous if EVD | ICP <20 mmHg | CSF drainage; escalate ICP management; repeat imaging | - | - | - | STAT |
6B. Outpatient/Long-Term Monitoring¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurologic examination (comprehensive) | Monthly x 6 months; then q3 months x 2 years; then q6 months | Stable or improving; no new deficits | If relapse: repeat MRI; escalate immunotherapy; consider biopsy if diagnosis uncertain | - | - | ROUTINE | - |
| MRI brain with and without gadolinium | 3-6 months after treatment initiation; then q6-12 months x 2-3 years; then annually | Stable or decreased enhancement and lesion burden | New/worsening lesions: treatment failure; escalate; re-evaluate diagnosis | - | - | ROUTINE | - |
| MRI spine (if myelopathy) | 3-6 months; then annually x 2-3 years | Stable or improved cord lesions | Worsening: escalate therapy | - | - | ROUTINE | - |
| CT chest | Annually | Stable or improved hilar adenopathy | Progression: pulmonology consult; adjust systemic treatment | - | - | ROUTINE | - |
| CBC with differential | Q2 weeks x 2 months on methotrexate/azathioprine; then monthly; q2-4 months on infliximab | WBC >3.0; ANC >1.5; Plt >100 | Hold/reduce immunosuppression; growth factor support if needed | - | - | ROUTINE | - |
| LFTs (ALT, AST, ALP, bilirubin) | Monthly on methotrexate; q3 months on other agents | ALT/AST <3x ULN | Dose reduction or switch agent; hepatology consult if persistent elevation | - | - | ROUTINE | - |
| Renal function (BUN/Cr) | Q3 months | Stable | Dose adjustment of renally-cleared drugs; evaluate nephrocalcinosis if hypercalcemia | - | - | ROUTINE | - |
| Serum calcium | Q3-6 months (more frequent if history of hypercalcemia) | Normal (8.5-10.5 mg/dL) | If elevated: hold vitamin D; increase hydration; consider disease activity | - | - | ROUTINE | - |
| Serum ACE level | Q3-6 months | Trending down with treatment | Rising ACE: consider disease relapse; repeat imaging | - | - | ROUTINE | - |
| Endocrine panel (TSH, free T4, cortisol, prolactin) | Q6-12 months if pituitary involvement | Normal or appropriately replaced | Adjust hormone replacement; endocrinology follow-up | - | - | ROUTINE | - |
| DEXA scan (bone density) | Baseline if steroids >3 months; repeat q1-2 years | T-score >-2.5 | Bisphosphonate therapy; calcium/vitamin D optimization (if not hypercalcemic); endocrinology referral | - | - | ROUTINE | - |
| Ophthalmologic examination | Q6-12 months; more frequent if uveitis history or on steroids | No uveitis; no cataracts; no glaucoma | Topical/systemic treatment per ophthalmology; IOP management | - | - | ROUTINE | - |
| Pulmonary function tests (PFTs) | Annually if pulmonary involvement | Stable FVC and DLCO | Pulmonology adjustment; consider escalation of systemic therapy | - | - | ROUTINE | - |
| Quantitative immunoglobulins | Q6 months on rituximab or prolonged immunosuppression | IgG >400 mg/dL | Immunoglobulin replacement if recurrent infections with hypogammaglobulinemia | - | - | ROUTINE | - |
| TB screening (QuantiFERON) | Annually on anti-TNF therapy | Negative | If positive: infectious disease consult; TB prophylaxis; hold anti-TNF | - | - | ROUTINE | - |
| Skin cancer screening | Annually on immunosuppression | No suspicious lesions | Dermatology referral | - | - | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Discharge home | Stable or improving neurological exam; able to perform basic ADLs; seizure-free (if applicable); diabetes insipidus well-controlled on desmopressin; oral medications tolerated; steroid taper plan established; follow-up with neurology within 1-2 weeks; outpatient labs and imaging scheduled; family/caregiver education completed |
| Admit to floor (neurology) | New-onset or worsening neurosarcoidosis requiring IV methylprednisolone; diagnostic workup requiring expedited imaging and LP; new cranial neuropathy with visual threat; new seizures requiring medication optimization; diabetes insipidus requiring titration; need for tissue biopsy coordination |
| Admit to ICU | Acute hydrocephalus requiring EVD/VP shunt; severe elevated ICP; status epilepticus; severe myelopathy with respiratory compromise; rapid neurological decline; autonomic instability; severe hyponatremia or hypercalcemia requiring close monitoring |
| Transfer to higher level of care | Neurosurgery not available (hydrocephalus, biopsy); neuroimmunology specialist not available; interventional pulmonology for EBUS biopsy; infusion center for biologic therapy not available |
| Inpatient rehabilitation | Significant functional deficits from myelopathy or multifocal disease; medically stable; expected to benefit from intensive PT/OT/ST; unable to safely return home |
| Outpatient follow-up | All discharged patients: neurology follow-up within 1-2 weeks; ophthalmology within 2-4 weeks; pulmonology if pulmonary involvement; endocrinology if pituitary involvement; labs per monitoring schedule; MRI per protocol |
| Readmission criteria | New or worsening neurological symptoms (vision loss, weakness, seizures); infection on immunosuppression; suspected relapse; uncontrolled diabetes insipidus; severe steroid side effects |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Zajicek diagnostic criteria for neurosarcoidosis (definite, probable, possible) | Expert Consensus, Class III | Zajicek JP et al. J Neurol Neurosurg Psychiatry 1999;67:517-521 |
| Updated consensus diagnostic criteria for neurosarcoidosis (Stern et al.) | Expert Consensus | Stern BJ et al. JAMA Neurol 2018;75:1546-1553 |
| High-dose IV methylprednisolone as first-line acute treatment | Class III, Expert Consensus | Fritz D et al. J Neuroimmunol 2016;299:146-151 |
| Prednisone oral taper following IV pulse therapy | Expert Consensus | Tavee JO, Stern BJ. Neurol Clin 2015;33:553-577 |
| Methotrexate as first-line steroid-sparing agent | Class III, Retrospective | Lower EE, Broderick JP. Neurology 2004;62:2198-2202 |
| Methotrexate efficacy in neurosarcoidosis | Class III, Retrospective | Scott TF et al. Neurology 2007;68:1405-1407 |
| Mycophenolate mofetil as steroid-sparing agent | Class IV, Case Series | Moravan M, Segal BM. Arch Neurol 2009;66:1144-1145 |
| Infliximab for refractory neurosarcoidosis | Class III, Retrospective | Gelfand JM et al. Neurology 2017;89:2092-2100 |
| Infliximab safety and efficacy in sarcoidosis | Class III | Judson MA et al. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:49-57 |
| Adalimumab for refractory sarcoidosis | Class IV, Case Series | Erckens RJ et al. Ophthalmology 2012;119:2020-2028 |
| Rituximab for refractory neurosarcoidosis | Class IV, Case Reports | Bomprezzi R et al. J Neurol 2010;257:1108-1110 |
| Cranial neuropathy (CN VII most common) in neurosarcoidosis | Class II, Retrospective | Stern BJ et al. Arch Neurol 1985;42:909-917 |
| Optic neuropathy in neurosarcoidosis | Class III | Koczman JJ et al. Ophthalmology 2008;115:890-896 |
| CSF ACE levels -- sensitivity and specificity in neurosarcoidosis | Class II | Dale JC, O'Brien JF. Mayo Clin Proc 1999;74:535-540 |
| Serum ACE -- limited sensitivity in neurosarcoidosis (~30-50%) | Class II | Miyoshi S et al. Clin Biochem 2010;43:1004-1008 |
| MRI patterns in neurosarcoidosis (leptomeningeal enhancement most common) | Class III, Retrospective | Shah R et al. AJR Am J Roentgenol 2009;193:1317-1332 |
| Hypothalamic-pituitary involvement in neurosarcoidosis | Class III | Anthony J et al. QJM 2016;109:643-648 |
| Diabetes insipidus as presenting feature of neurosarcoidosis | Class IV, Case Series | Stuart CA et al. Am J Med 1978;65:585-594 |
| Scadding staging for pulmonary sarcoidosis | Class II | Scadding JG. Br Med J 1961;2:1165-1172 |
| FDG-PET for biopsy site identification in sarcoidosis | Class III | Teirstein AS et al. Sarcoidosis Vasc Diffuse Lung Dis 2007;24:85-92 |
| Small fiber neuropathy in sarcoidosis | Class III | Hoitsma E et al. Lancet Neurol 2004;3:349-353 |
| Neurosarcoidosis clinical features and outcomes | Class II, Retrospective | Joubert B et al. Medicine (Baltimore) 2017;96:e8340 |
| Hypercalcemia mechanism in sarcoidosis (1,25-dihydroxyvitamin D) | Class II | Bell NH et al. J Clin Invest 1979;64:218-225 |
| Cyclophosphamide for refractory neurosarcoidosis | Class IV, Case Series | Doty JD et al. Chest 2003;124:2023-2027 |
| Long-term outcomes of neurosarcoidosis treatment | Class III | Bitoun S et al. Medicine (Baltimore) 2016;95:e3241 |
CLINICAL DECISION SUPPORT NOTES¶
Zajicek Diagnostic Criteria for Neurosarcoidosis¶
Definite Neurosarcoidosis: - [ ] Nervous system biopsy demonstrating non-caseating granulomas - [ ] Other causes of granulomatous inflammation excluded (TB, fungal, foreign body)
Probable Neurosarcoidosis: - [ ] Evidence of CNS inflammation (CSF abnormalities: elevated protein, pleocytosis, oligoclonal bands) AND/OR MRI abnormalities consistent with neurosarcoidosis AND/OR positive brain/spine biopsy - [ ] Evidence of systemic sarcoidosis confirmed by tissue biopsy (lung, lymph node, skin, etc.) - [ ] Other causes excluded
Possible Neurosarcoidosis: - [ ] Clinical and/or MRI features suggestive of neurosarcoidosis - [ ] No tissue confirmation of sarcoidosis (systemic or nervous system) - [ ] Other causes excluded to the extent possible
Updated Stern/Sarcoidosis Consortium Criteria (2018)¶
- Type 1 (Definite): Nervous system pathology consistent with neurosarcoidosis + exclusion of other causes
- Type 2 (Probable): Systemic biopsy-proven sarcoidosis + typical neurological syndrome + exclusion of other causes
- Type 3 (Possible): Typical neurological syndrome + no tissue confirmation + exclusion of other causes
Common Presentations of Neurosarcoidosis¶
| Presentation | Frequency | Key Features |
|---|---|---|
| Cranial neuropathy | 50-70% | CN VII (facial palsy) most common; CN II (optic neuropathy) second; may be bilateral; any CN can be involved |
| Aseptic meningitis | 10-25% | Headache, meningismus; CSF lymphocytic pleocytosis; may be chronic/relapsing |
| Hypothalamic-pituitary | 5-15% | Diabetes insipidus; hyperprolactinemia; central hypothyroidism; hypogonadism; SIADH |
| Myelopathy | 5-10% | Subacute; thoracic predominance; dorsal subpial enhancement; may mimic MS or NMOSD |
| Hydrocephalus | 5-10% | Communicating (meningeal) or obstructive; may require VP shunt |
| Mass lesion (granuloma) | 5-10% | Mimics tumor; dural-based or parenchymal; may cause seizures, focal deficits |
| Peripheral neuropathy | 15-40% | Small fiber neuropathy (most common); mononeuritis multiplex; polyradiculopathy |
| Seizures | 5-10% | From cortical/meningeal involvement; may be presenting feature |
| Cognitive/psychiatric | 5-20% | Memory impairment; confusion; depression; personality changes |
Red Flags Suggesting Neurosarcoidosis¶
- Bilateral facial nerve palsy (especially in young African American patient)
- Cranial neuropathy + bilateral hilar lymphadenopathy on chest imaging
- Chronic meningitis with lymphocytic pleocytosis + elevated CSF ACE
- Diabetes insipidus + hypothalamic/pituitary stalk enhancement on MRI
- Leptomeningeal enhancement on MRI (especially basilar) + systemic sarcoidosis
- Optic neuropathy + hilar adenopathy + elevated serum ACE
- Myelopathy with dorsal subpial enhancement ("trident sign") on spine MRI
- Small fiber neuropathy with multisystem granulomatous disease
- Erythema nodosum or lupus pernio + new neurological symptoms
Scadding Staging (Chest Imaging)¶
| Stage | Findings | Frequency in Sarcoidosis |
|---|---|---|
| 0 | Normal chest imaging | 5-10% |
| I | Bilateral hilar lymphadenopathy (BHL) only | ~50% |
| II | BHL + pulmonary infiltrates | ~25% |
| III | Pulmonary infiltrates without BHL | ~15% |
| IV | Pulmonary fibrosis | ~5% |
CHANGE LOG¶
v1.1 (January 30, 2026)
- Checker/Rebuilder pipeline: validated against 6 quality domains; applied all approved revisions
- R6: Reordered ALL lab tables (1A, 1B, 1C) and imaging tables (2A, 2B, 2C) and LP table to place venue columns (ED/HOSP/OPD/ICU) as last 4 columns per style guide CSS requirements
- R1: Standardized structured dosing format across ALL treatment sections (3A, 3B, 3C, 3D) to use [dose] :: [route] :: [frequency] :: [full_instructions] with exactly 4 fields
- R2: Cleaned up Route column in all treatment tables to show single primary route instead of multi-route (e.g., "IV" instead of "IV/SC/IN")
- R3: Split testosterone replacement into two separate rows (testosterone cypionate IM and testosterone gel topical) for proper order sentence generation
- R5/R8: Added ICU column to Section 4B (Patient Instructions) and Section 4C (Lifestyle & Prevention) for 4-column venue consistency
- M1-M4: Fixed structured dosing format across all treatment rows -- each now has standard_dose, route, frequency, and full_instructions fields
- Updated version to 1.1; added REVISED date
- No clinical content changes; all medication dosing and clinical recommendations unchanged
v1.0 (January 30, 2026) - Initial creation - Section 1: 22 core labs (1A), 22 extended labs (1B), 9 rare/specialized tests (1C) - Section 2: 6 essential imaging/studies (2A), 10 extended (2B), 9 rare/specialized (2C), 18 LP/CSF studies - Section 3: 4 subsections: - 3A: 8 acute/emergent treatments (IV methylprednisolone, dexamethasone, GI prophylaxis, insulin, lorazepam, desmopressin, mannitol, hypertonic saline) - 3B: 12 symptomatic treatments (neuropathic pain, seizures, hormonal replacement, bone protection, acetazolamide, artificial tears) - 3C: 6 second-line/steroid-sparing agents (prednisone taper, methotrexate, mycophenolate, azathioprine, hydroxychloroquine, leflunomide) - 3D: 4 disease-modifying/biologic therapies with Pre-Treatment Requirements (infliximab, adalimumab, rituximab, cyclophosphamide) - Section 4: 18 referrals (4A), 14 patient instructions (4B), 12 lifestyle/prevention items (4C) - Section 5: 15 differential diagnoses with distinguishing features - Section 6: 10 acute monitoring parameters (6A), 16 outpatient/long-term monitoring parameters (6B) - Section 7: 7 disposition criteria - Section 8: 25 evidence references - Clinical Decision Support Notes: Zajicek criteria checklist, Stern 2018 updated criteria, common presentations table, red flags checklist, Scadding staging