Version June 2024
| Condition | Potential clues |
| Bacterial infections | |
| Bacterial meningitis | Meningeal signs; CSF pleocytosis with predominance of polymorphonuclear cells |
| CNS tuberculosis | Residing in, travel to, or exposure to contact from endemic areas (Asia, Africa, Latin America, Eastern Europe); contact with an adult with tuberculosis; lacunar infarction; hydrocephalus; low CSF glucose and elevated CSF protein |
| Parameningeal infection | |
| Listeriosis | Age <1 month; immune compromise; rhomboencephalitis (ataxia, cranial nerve deficits, nystagmus) |
| Cat scratch disease | Cat bite/scratch; regional lymphadenopathy; neuroretinitis |
| Parasitic infections | |
| Amoebiasis | Immune compromise; swimming in lakes/brackish water; travel to an endemic area; change in taste or smell |
| Cerebral malaria | Travel to endemic area without prophylaxis |
| Toxoplasmosis | Immune compromise; extrapyramidal symptoms and signs |
| Cysticercosis | Travel to endemic area; seizures, hydrocephalus; ingestion of undercooked pork |
| Echinococcus (tapeworm) | Hydatid cysts |
| Trichinosis | Gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea); ingestion of bear meat or other potentially contaminated foods |
| Fungal infections | |
| Histoplasmosis | Residing in or travel to endemic area (eastern and central US and Canada) |
| Blastomycosis | Residing in or travel to endemic area (in the US, southeastern, central, and states bordering the Great Lakes) |
| Cryptococcus | Immune compromise; exposure to bird droppings |
| Coccidiomycosis | Residing in or travel to endemic areas, such as the southwestern United States, northern Mexico, and parts of Central and South America. |
| Candidiasis | Immune compromise |
| Rickettsial infection | |
| Rocky Mountain spotted fever | Tick exposure in endemic region; maculopapular/petechial rash; intractable seizures |
| Murine typhus | Flea exposure |
| Q fever | Exposure to cats, sheep, goats (particularly placental tissue, parturient fluids, newborn animals) |
| Ehrlichiosis | |
| Tick exposure, rash, leukopenia, thrombocytopenia | |
| Other central nervous system conditions | |
| Head trauma | History of trauma (may be absent in child abuse) |
| Hypertensive encephalopathy | Hypertension; exclusion of other causes |
| Intracranial hemorrhage | Neuroimaging; intracranial hemorrhage may be an indication for lumbar puncture |
| Intracranial thrombosis | Neuroimaging |
| Idiopathic intracranial hypertension (pseudotumor cerebri) | Visual obscurations, diplopia, cranial nerve palsy; papilledema; increased opening pressure during lumbar puncture |
| Status epilepticus (especially nonconvulsive seizures) | Electroencephalogram |
| Systemic lupus erythematosus | Arthritis, nephritis, dermatitis, leukopenia |
| Polyarteritis nodosa | Fever, weight loss, dermatitis, eosinophilia |
| Acute disseminated encephalomyelitis (ADEM, postinfectious encephalitis) | History of recent infection or immunization; multifocal neurologic signs and symptoms; neuroimaging |
| Tumor | Neuroimaging; increased opening pressure during lumbar puncture (however, lumbar puncture usually is not performed if a tumor is suspected) |
| Acute confusional migraine | History of migraine headaches; exclusion of other causes |
| Anti-N-methyl-D-asparate receptor encephalitis* | No identifiable infectious etiology; encephalitis with psychiatric manifestations |
| Metabolic disorders | |
| Hypoglycemia | Serum glucose |
| Uremic encephalopathy | Elevation of blood urea nitrogen, creatinine |
| Hepatic encephalopathy | Elevation of serum bilirubin and aminotransferases; increased opening pressure during lumbar puncture |
| Toxins | |
| Acute toxic ingestion | Toxicology screening; pupillary changes |
| Lead poisoning | History of lead exposure or pica; elevated blood lead level (confirmatory) |
| Reye syndrome | History of aspirin use; recent viral infection; increased opening pressure during lumbar puncture |
| Inborn errors of metabolism (eg, organic acidemia, urea cycle disorder, mitochondrial disorders, mitochondrial fatty acid oxidation disorders, etc) | |
| Abnormal laboratory findings (eg, hypoglycemia, hyperammonemia, acidosis) | |
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