| Atypical or red flag presentations | Diagnostic considerations |
| General | |
| Deficit developing within minutes | Ischemic stroke; seizure |
| Fevers, weight loss, night sweats, alopecia, and synovitis | Infection; systemic vasculitis; SLE |
| Livedo reticularis, early trimester abortions, and thrombotic events | Antiphospholipid syndrome |
| Headache or meningismus | ADEM, cerebral venous thrombosis; chronic meningitis; lymphoma; glioma; vasculitis; SLE |
| Gradually progressive course from onset | HTLV-1; adrenomyeloneuropathy; adrenoleukodystrophy; metachromatic leukodystrophy; vitamin B12 deficiency |
| Onset before age 20 years | Mitochondrial encephalomyopathy; leukodystrophy; Friedrich ataxia |
| Onset after age 50 years | Cerebral infarction; cerebral amyloid angiopathy; lymphoma |
| Supratentorial | |
| Encephalopathy (alterations in awareness and coma) | ADEM; PRES; MOG-EM; infectious/autoimmune encephalitis |
| Hemianopsia and cortical blindness | Ischemic stroke; PRES; neoplasm; PML |
| Insidious cognitive decline | Neurodegenerative disorders; genetic leukoencephalopathy and leukodystrophy |
| Seizures | Whipple disease; vasculitis; metastases |
| Cranial nerves | |
| Progressive optic neuritis | Neoplasm; neurosarcoidosis; LHON |
| Altitudinal deficit and monocular blindness | Ischemic optic neuropathy |
| Clinically severe or simultaneous bilateral optic neuritis | NMOSD; MOG-EM |
| Neuroretinitis and uveitis | NMOSD |
| Multiple cranial neuropathies or polyradiculopathy | Chronic meningitis; including neurosarcoidosis and tuberculosis; Lyme disease |
| Brainstem | |
| Insidiously progressive brainstem symptoms, especially with persistent enhancement on MRI | Neurosarcoidosis; histiocytosis; Behçet syndrome; malignancy; Whipple disease; tuberculosis; CLIPPERS |
| Intractable nausea and vomiting or intractable hiccups (compatible with area postrema syndrome) | NMOSD; MOG-EM |
| Cerebellum | |
| Progressive cerebellar symptoms | Spinocerebellar ataxia; autoimmune/paraneoplastic syndromes |
| Spinal cord | |
| Anterior spinal syndrome | Ischemia |
| Complete transverse myelitis | NMOSD; idiopathic myelitis; ADEM |
| Radiculitis | Infection; neurosarcoidosis; carcinomatosis/lymphomatosis |
| Progressive spastic paraparesis | HTLV-1; HIV; cobalamin deficiency; PLS; cervical spondylotic myelopathy; dAVF; adrenomyeloneuropathy; progressive solitary sclerosis |
| Longitudinally extensive spinal cord lesion | NMOSD; MOG-EM |
