Routine Neurology Lab Panel

Most patients with neurologic symptoms benefit from a focused panel of routine laboratory tests as part of the initial workup. The right panel rules out common reversible causes — vitamin and hormone deficiencies, electrolyte and metabolic disturbances, infection, and end-organ dysfunction — before pursuing more specialized testing. This page covers the standard “screening” lab panel for general neurology evaluation: CBC, comprehensive metabolic panel, thyroid function, vitamin B12 and folate, inflammatory markers, hemoglobin A1c, urinalysis, and HIV/syphilis screening. The panel is tailored to the clinical context, but most patients with cognitive impairment, neuropathy, seizures, or unexplained encephalopathy warrant most of these tests.

Complete Blood Count (CBC) with Differential

Components

• WBC count and differential.
• Hemoglobin / hematocrit.
• Platelet count.
• MCV (mean corpuscular volume) — critical for anemia workup.

Clinical Implications

• Macrocytic anemia (MCV >100): B12 or folate deficiency, alcohol use, thyroid disease, drug effect.
• Microcytic anemia: iron deficiency, thalassemia.
• Thrombocytopenia: TTP (with neurologic symptoms, fever, renal dysfunction, hemolysis — emergency).
• Leukocytosis: infection, inflammation.
• Lymphopenia: HIV, certain malignancies, immunosuppression.
• Eosinophilia: parasitic infection, drug reactions, Churg-Strauss, neurosarcoidosis.

Comprehensive Metabolic Panel (CMP)

Components

• Sodium, potassium, chloride, bicarbonate.
• BUN, creatinine, glucose.
• Calcium.
• Liver function: AST, ALT, alkaline phosphatase, total bilirubin, total protein, albumin.

Sodium

• Hyponatremia: lethargy, confusion, seizures (especially <125 mEq/L or rapid drop).
• Causes: SIADH (common with CNS pathology, drugs — particularly anti-LGI1 encephalitis), hypovolemia, heart failure, adrenal insufficiency.
• Hypernatremia: altered mental status, weakness; consider diabetes insipidus (central or nephrogenic).
• Rapid sodium correction risk: osmotic demyelination syndrome (central pontine myelinolysis) — correct chronic hyponatremia ≤8 mEq/L per 24 hours.

Potassium

• Hypokalemia: weakness, including periodic paralysis (hypokalemic periodic paralysis).
• Hyperkalemia: muscle weakness, paralysis; cardiac arrhythmias.

Calcium

• Hypocalcemia: tetany, Chvostek and Trousseau signs, seizures, basal ganglia calcification (chronic).
• Hypercalcemia: lethargy, confusion, weakness.
• Causes: hyperparathyroidism, malignancy, sarcoidosis, vitamin D toxicity.

Magnesium (Order Separately)

• Critical in: tremor, seizures, weakness, refractory hypokalemia/hypocalcemia.
• Often low in alcohol use disorder, malnutrition, diuretic use, proton pump inhibitor use (chronic).

Glucose

• Hypoglycemia: altered mental status, focal neurologic deficits (can mimic stroke), seizures.
• Hyperglycemia: hyperosmolar nonketotic state, ketoacidosis; chorea-ballism with non-ketotic hyperglycemia.

BUN / Creatinine

• Uremic encephalopathy: confusion, myoclonus, asterixis, seizures (severe).
• Renal function affects medication dosing (levetiracetam, gabapentin, etc.).

Liver Function

• Hepatic encephalopathy: asterixis, confusion (elevated ammonia).
• Affects medication metabolism.
• Hepatitis B/C may have associated neurologic manifestations.

Thyroid Function — TSH

TSH as Screening

• TSH is the most sensitive screen for thyroid dysfunction.
• If TSH abnormal → free T4 and sometimes free T3.

Hypothyroidism — Neurologic Manifestations

• Cognitive slowing, depression, dementia (reversible).
• Neuropathy (carpal tunnel, polyneuropathy).
• Myopathy, myalgia, slow reflex relaxation.
• Cerebellar ataxia (rare).
• Encephalopathy with myxedema coma.
• Hashimoto encephalopathy / SREAT: steroid-responsive encephalopathy with anti-thyroid antibodies; may be euthyroid.

Hyperthyroidism — Neurologic Manifestations

• Tremor, anxiety, restlessness.
• Periodic paralysis (especially in Asian men with hyperthyroidism).
• Myopathy (proximal weakness).
• Chorea (uncommon).
• Encephalopathy in thyroid storm.

Vitamin B12 and Folate

Vitamin B12 (Cobalamin) Deficiency

Neurologic Syndromes

• Subacute combined degeneration (SCD): dorsal column (proprioception, vibration) + corticospinal tract (spasticity, hyperreflexia, Babinski).
• Sensorimotor polyneuropathy (often coexisting).
• Cognitive impairment, dementia (reversible).
• Optic neuropathy (rare).
• Psychiatric: depression, psychosis.

Testing Strategy

• Serum B12 level: insufficient — many patients with normal-range B12 (200-400 pg/mL “low normal”) have functional deficiency.
• Methylmalonic acid (MMA) elevated in B12 deficiency → most sensitive marker.
• Homocysteine elevated in B12 OR folate deficiency.
• If B12 level borderline (200-400 pg/mL) and clinical suspicion — check MMA.

Causes

• Pernicious anemia (autoimmune intrinsic factor deficiency).
• Atrophic gastritis (common in elderly).
• Vegan diet (B12 is animal-source).
• Malabsorption: ileal resection, Crohn disease, celiac.
• Medications: metformin, proton pump inhibitors (chronic), H2 blockers.
• N2O (nitrous oxide) abuse: inactivates B12 → can cause severe SCD even with normal B12 levels.

Treatment

• IM B12 1000 mcg daily × 1 week → weekly × 4 weeks → monthly.
• Oral B12 1000-2000 mcg daily can be effective for many patients including pernicious anemia.
• Early treatment may reverse neurologic symptoms; chronic deficiency may leave permanent deficits.

Folate Deficiency

• Macrocytic anemia; rarely causes neurologic syndromes (unlike B12).
• Treatment of folate-deficient megaloblastic anemia in undiagnosed B12 deficiency can WORSEN neurologic symptoms — always check B12 first.
• Important in neural tube defect prevention (pregnancy).
• Antiepileptic drugs (phenytoin, phenobarbital) can lower folate.

Inflammatory Markers — ESR and CRP

ESR (Erythrocyte Sedimentation Rate)

• Non-specific marker of inflammation; rises slowly, normalizes slowly.
• Critical in giant cell arteritis (GCA): ESR >50 mm/hr supports diagnosis (though up to 20% have normal ESR).
• Other utilities: chronic infection, malignancy, autoimmune disease.

CRP (C-Reactive Protein)

• Acute-phase reactant; rises and falls more rapidly than ESR.
• Use alongside ESR in GCA, CNS vasculitis, autoimmune disease.
• Normal CRP makes acute inflammatory process less likely (but does not exclude it).

Hemoglobin A1c

• Reflects average glucose over ~3 months.
• Indication in neurology: any patient with peripheral neuropathy, cognitive impairment, stroke, or unexplained encephalopathy.
• Diabetic peripheral neuropathy: distal symmetric polyneuropathy, painful neuropathy, autonomic neuropathy.
• HbA1c also reflects vascular risk (cognitive impairment, stroke).
• Pre-diabetes (HbA1c 5.7-6.4%) may also cause neuropathy (impaired glucose tolerance neuropathy).

HIV and Syphilis Screening

HIV

• Routine in any patient with new neurologic symptoms of uncertain etiology.
• HIV causes wide spectrum: dementia, neuropathy, myopathy, opportunistic infections (toxoplasmosis, PML, cryptococcal meningitis), CNS lymphoma.
• Fourth-generation HIV-1/2 antigen-antibody assay is standard.

Syphilis

• RPR or VDRL (non-treponemal screening tests).
• Treponemal test confirmation (FTA-ABS, TP-PA, EIA): treponemal tests remain positive lifelong; non-treponemal tests decline after treatment.
• Neurosyphilis: meningovascular, parenchymatous (general paresis), tabes dorsalis, asymptomatic.
• Routine in cognitive impairment, stroke (especially young), unexplained myelopathy, optic neuropathy.

Urinalysis

• Screening for renal dysfunction.
• Urine drug screen if substance abuse suspected.
• Porphyria evaluation (porphobilinogen, ALA — when porphyria suspected from neuropathy, abdominal pain, psychiatric symptoms).

The Routine Workup by Clinical Setting

Cognitive Impairment / Dementia

• CBC, CMP, TSH, B12, folate, HbA1c, RPR, HIV.
• Consider: ANA, anti-thyroid antibodies (Hashimoto encephalopathy), heavy metals (if exposure history), copper/ceruloplasmin (Wilson, if <55 years), MMA/homocysteine.

Peripheral Neuropathy

• CBC, CMP, TSH, B12 + MMA/homocysteine, HbA1c, SPEP/immunofixation, ANA, ESR.
• Consider: free light chains, anti-MAG (if DADS pattern), anti-GM1 (if multifocal motor), anti-GQ1b (variant), heavy metals, B6 (excess can cause neuropathy too).

Seizures

• CBC, CMP, magnesium, glucose, calcium, ammonia.
• Toxicology screen, drug levels.
• If first seizure: routine panel; if status epilepticus: comprehensive metabolic workup.

Encephalopathy / Altered Mental Status

• CBC, CMP, magnesium, ammonia, TSH, B12, glucose, toxicology screen.
• If clinical picture suggests: paraneoplastic antibodies, autoimmune encephalitis panel, thyroid antibodies (Hashimoto encephalopathy).

Stroke (Young Patient)

• Routine + lipid panel + HbA1c.
• Hypercoagulability workup: lupus anticoagulant, anticardiolipin, β2-GP1, factor V Leiden, prothrombin, protein C/S/antithrombin.
• Vasculitis panel: ANA, ANCA, RPR, ESR/CRP.

Pitfalls in Routine Lab Interpretation

“Normal” B12 May Not Be Adequate

• B12 levels 200-400 pg/mL (“low normal”) may represent functional deficiency.
• Check MMA/homocysteine if borderline level + neurologic syndrome.

“Normal” ESR Does Not Exclude GCA

• Up to 20% of GCA patients have normal ESR — clinical syndrome remains critical.
• Both ESR and CRP often elevated; one or the other may be normal.

Hyponatremia Correction

• Chronic hyponatremia → osmotic demyelination if corrected too quickly.
• Limit correction to ≤8 mEq/L per 24 hours; even slower in high-risk patients.

Drug-Related B12 Deficiency

• Metformin, long-term PPIs, H2 blockers can cause B12 deficiency.
• Routine B12 screening in metformin users with neurologic symptoms.

Pitfalls and Pearls

• CBC + CMP + TSH + B12 + folate: minimum panel for cognitive impairment, neuropathy, encephalopathy.
• Macrocytic anemia: think B12, folate, thyroid, alcohol.
• Borderline B12 (200-400): check MMA and homocysteine.
• SCD: dorsal column + corticospinal — B12 deficiency.
• N2O abuse: severe SCD with normal B12 levels.
• Hyponatremia: lethargy, confusion, seizures; correct slowly to prevent osmotic demyelination.
• SIADH: common with CNS pathology, drugs; classical with anti-LGI1 encephalitis.
• Hypocalcemia: tetany, Chvostek, Trousseau, seizures.
• Hypercalcemia: lethargy, weakness, confusion; consider hyperparathyroidism, malignancy, sarcoidosis.
• Magnesium: order separately in tremor, seizures, refractory hypokalemia/calcemia.
• Hypothyroidism: reversible dementia, neuropathy, myopathy.
• Hashimoto encephalopathy: anti-thyroid antibodies; may be euthyroid; steroid-responsive.
• ESR + CRP: in GCA, vasculitis, autoimmune disease; 20% of GCA has normal ESR.
• HbA1c: in peripheral neuropathy, stroke, cognitive impairment, encephalopathy.
• HIV + RPR: routine in unexplained neurologic syndromes.
• Metformin + chronic PPI + neuropathy: think B12 deficiency.
• Don’t treat folate deficiency without checking B12 — can worsen neurologic symptoms.
• Routine workup before exotic workup: rule out reversible causes first.

References

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3. England JD, Gronseth GS, Franklin G, et al. Practice parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Neurology. 2009;72(2):185-192.
4. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581-1589.
5. Sterns RH. Disorders of plasma sodium — causes, consequences, and correction. N Engl J Med. 2015;372(1):55-65.
6. Salomão SR. Vitamin B12 deficiency in adults. Nutrients. 2020;12(3):812.