| Screen | Disease/agent tested |
| Section.1 Initial workup | Recommended in most or all patients: - Whole blood/serum: CBC, bacterial and fungal cultures, RPR-VDRL, HIV-1/2 immunoassay with confirmatory viral load if appropriate.
- Serum: IgG and IgM testing (acute and convalescent) for Chlamydia pneumoniae, Bartonella henselae, Mycoplasma pneumoniae, Coxiella burnetii, Shigella species and Chlamydia psittaci.
- Nares or nasopharyngeal swab (the latter preferred): Respiratory viral DFA panel; SARS-CoV-2 PCR.
- CSF:
- Cell counts; protein; and glucose, bacterial, and fungal stains and cultures.
- RT-PCR for HIV; PCR for HSV1, HSV2, VZV, EBV, MTb; consider WNV, VDRL, encephalitis panel.
- PCR for C. pneumoniae and psittaci, B. henselae, M. pneumoniae, C. burnetti and Shigella species.
- Autoimmune epilepsy panel (refer to section 2).
- Consider metagenomics for any nonhuman nucleic acid material.
- Consider cytokine profile (section 7).
- Consider cytology and flow cytometry.
- Serum: IgG Cryptococcus species, IgM and IgG Histoplasma capsulatum, IgG Toxoplasma gondii.
- Sputum: MTb Gene Xpert.
- CSF: Eosinophils, silver stain for CNS fungi, PCR for JC virus, CMV, EBV, HHV6, EEE, enterovirus, influenza A/B, HIV, WNV, parvovirus, listeria Ab, measles (rubeola).
- Stool: Adenovirus PCR, enterovirus PCR.
- Serum buffy coat and peripheral smear.
- Lyme EIA with IgM and IgG reflex.
- Hepatitis C immunoassay and viral load if appropriate.
- Send further serum and CSF samples to CDC DVBID Arbovirus Diagnostic Laboratory, CSF and serum rickettsial disease panel, flavivirus panel, bunyavirus panel.
- Serum testing for Acanthamoeba spp., Balamuthia mandrillaris, Baylisascaris procyonis.
- Other.
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| Section.2 Autoimmune/
paraneoplastic | Recommended: - Serum and CSF paraneoplastic and autoimmune epilepsy antibody panel
To include antibodies to: LGI-1, CASPR2, Ma1, Ma2/TaDPPX, GAD65, NMDA, AMPA, GABA-B, GABA-A, glycine receptor, Tr, amphiphysin, CV-2/CRMP-5, Neurexin-3alpha, adenylate kinase, anti-neuronal nuclear antibody types 1/2/3 (Hu, Yo and Ri), Purkinje cell cytoplasmic antibody types 1,2, GFAP-alpha, anti-SOX1, N-type calcium Ab, PQ-type calcium channel, Acetylcholine receptor (muscle) binding Ab, Ach-R ganglionic neuronal Ab, AQP4, MOG Ab, IgLON5 Ab, D2R Ab. - Additional serologic studies - Serum (likely not pathogenic but hint towards an autoimmune etiology)
ANA (detection and identification), ANCA, anti-thyroid antibodies (anti-thryoglobulin, anti-TPO), anti-endomysial, ESR, CRP, SPEP, IFE, RA, ACE, cold and warm agglutinins, tests for MAS/HLH (serum triglycerides and sIL2-r, ferritin). |
| Suggestion: Store extra frozen CSF and serum for possible further autoimmune testing in a research lab. |
| Section.3 Neoplastic | Recommended: - CT chest/abdomen/pelvis, pelvic or scrotal ultrasound, mammogram, CSF cytology, flow cytometry, cancer serum markers. Pelvic MRI. Whole body PET-CT if above tests are not conclusive.
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| Optional: Bone marrow biopsy. |
| Section.4 Metabolic | Recommended: - Whole blood/serum: BUN/Cr, LDH, liver function tests, electrolytes, Ca/Mg/Phos, ammonia.
- Urine: Porphyria screen (spot urine), UA with microscopic urinalysis.
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| Consider: Vitamin B1 level, B12 level, homocysteine, folate, lactate, pyruvate, CK, troponin; tests for mitochondrial disorder (lactate, pyruvate, MR spectroscopy, muscle biopsy). |
| Section.5 Toxicologic | Recommended: - Benzodiazepines, amphetamines, cocaine, fentanyl, alcohol, ecstasy, heavy metals, synthetic cannabinoids, bath salts.
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| Consider: Extended opiate and overdose panel, LSD, heroin, PCP, marijuana. |
| Section.6 Genetics | Consider: Obtain genetics consult, if possible. Genetic screens for mitochondrial disorders (MERRF, MELAS, POLG1, SURF1, MT-ATP6) and VLCFA screen. Consider ceruloplasmin and 24-hour urine copper. Consider mendeliome or whole exome sequencing (also look for gene polymorphisms in IL-1beta, IL-6, IL-10, TNF-alpha, HMGB1, TLR4, IL-1RN, SCN1A, and SCN2A), mitochondrial genome sequencing, and CGH array. |
| Section.7 Cytokine assay | Serum and CSF: - Cytokine assay for quantitative measure of IL‐1beta, IL-1Ra, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12, IL-17, granulocyte‐macrophage colony stimulating factor, tumor necrosis factor‐alpha, HMGB1, CCL2, CXCL8, CXCL9, CXCL10, CXCL11.
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