Version June 2024
| Indicative signs and symptoms | Suggested evaluation |
| Infectious etiology | |
| Fever | CSF Gram stain and bacterial culture |
| Meningismus | CSF PCR: HSV-1, HSV-2, HHV-6, VZV, CMV, EBV, enteroviruses D68 and EV71 |
| Rash | CSF viral culture |
| Concurrent systemic infection | CSF acid-fast bacilli smear and tuberculous culture |
| Immunocompromised state | CSF HSV, VZV, and HTLV-1 antibodies |
| Recurrent genital infection | CSF VDRL and CSF PCR for HSV |
| Symptoms of zoster radiculopathy | CSF PCR for HSV |
| Adenopathy | CSF India ink and fungal culture |
| Residence in area endemic for parasitic infections | Chest radiograph and cranial CT scan |
| Lymphadenopathy | Serology for antibodies to HIV, HSV, VZV, HTLV-1, B. burgdorferi |
| Serology for hepatitis A, B, C, and Mycoplasma | |
| Consider serology for parasites | |
| Blood cultures | |
| Systemic inflammatory disease (vasculitis, collagen vascular diseases, mixed connective tissue disease) | |
| Rash | Serum ACE |
| Oral or genital ulcers | Autoantibodies: ANA, ds-DNA, Ro/SSA, La/SSB, Sm, RNP |
| Adenopathy | Complement levels |
| Livedo reticularis | Urinalysis with microscopic analysis for hematuria |
| Serositis | Lip/salivary gland biopsy |
| Photosensitivity | Chest CT with intravenous contrast |
| Inflammatory arthritis | Schirmer test |
| Erythema nodosum | Chest radiograph |
| Xerostomia | Gallium scan |
| Keratitis | Antiphospholipid antibodies (anticardiolipin antibodies, Russel viper venom time, partial thromboplastin time) |
| Conjunctivitis | |
| Contractures or thickening of skin | |
| Anemia/leukopenia/thrombocytopenia | |
| Raynaud phenomenon | |
| History of arterial and venous thrombosis | |
| Multiple sclerosis | |
| Previous demyelination event | Brain MRI |
| Incomplete deficit clinically with MRI abnormality ≤2 spinal segments and <50% of cord diameter | CSF oligoclonal bands and IgG index |
| Neuromyelitis optica spectrum disorder (NMOSD) | |
| Optic neuritis | Brain MRI (usually negative) |
| Clinical deficit with MRI abnormality ≥3 spinal segments | Serum anti-AQP4 IgG and anti-MOG IgG autoantibodies |
| Paraneoplastic myelopathies | |
| Spastic paresis with or without bowel and bladder dysfunction, usually with involvement of other areas of the nervous system | Paraneoplastic antibody panel |
| Longitudinally extensive transverse myelitis on spine MRI | Cancer screening |
| Idiopathic transverse myelitis | |
| No clinical or paraclinical features suggestive of another diagnostic category | Rule out infectious etiologies, systemic inflammatory disease, CNS inflammatory disorders, and paraneoplastic myelopathies |
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