Laboratory investigation of neuromuscular disorders
Laboratory investigation is important in diagnostic approach to neuromuscular disorders.
They help find treatable underlying causes or confirm the possible clinical diagnosis.
In this article, we review laboratory tests used for diagnosis of neuromuscular disorders.
Neuromuscular disorders are anatomically divided into 4 levels:
- motor neuron diseases
- peripheral neuropathies
- neuromuscular junction disorders
- myopathies
Recommended laboratory workup for each level as well as their different clinical subtypes are included
Laboratory tests for patients with neuromuscular hyperexcitability syndromes and progressive ataxia are also included.
Motor neuron diseases
Concomitant UMN & LMN involvement UMN only LMN only Bulbar palsy Suspected infectious etiology (consider endemic areas) Suspected paraneoplastic etiology Distal symmetric polyneuropathy Suspected nutritional deficiency Suspected infectious etiology (consider endemic areas) Mononeuritis multiplex DADS (distal acquired demyelinating symmetric neuropathy) CIDP Suspected POEMS syndrome Sensory neuropathy or neuronopathy Suspected nodopathy or paranodopathy Suspected inflammatory etiology Polyradiculopathy Polyradiculoneuropathy (AIDP, CIDP) Suspected paraneoplastic etiology (especially sensory neuronopathy) Suspected porphyric neuropathy Small fiber neuropathy Suspected heavy metal intoxication Suspected myasthenia gravis Suspected Lambert-Eaton myasthenic syndrome Suspected Botulism Ophthalmoplegia and ptosis Bulbar palsy For all patients Suspected Cushing syndrome Suspected amyloid myopathy Suspected infectious etiology Suspected osteomalacia, hypervitaminosis D or parathyroid disorders Suspected inflammatory myopathy Suspected nutritional deficiency Periodic paralysis Suspected connective tissue disease Suspected mitochondrial disorder Suspected fatty acid oxidation defect Suspected Pompe disease (limb-girdle weakness, respiratory insufficiency or cardiomyopathy) Suspected GSD (other than Pompe disease) Metabolic myopathy (overall) Ophthalmoplegia and ptosis For all patients Neuromyotonia Tetany Suspected stiff-person syndrome Suspected metabolic myopathy Cramp For all patients Suspected nutritional deficiency Suspected autoimmune etiology Suspected infectious etiology (consider endemic areas) Suspected Wilson disease Suspected mitochondrial cytopathy Suspected adreno leukodystrophy Suspected Refsum disease Suspected paraneoplastic etiology
CBC
BUN, Cr
FBS, HbA1c
AST, ALT, ALP
Na, K, Ca, P
ESR, CRP
TSH, free T4
Vitamin B12, methylmalonic acid
Folic acid
Copper, ceruloplasmin
Zinc
RF
ANA, Anti dsDNA
Anti SSA, Anti SSB
ACE
CSF analysis for OCB
VLCFA assay, ASA assay, beta galactosidase (when suspected)
Hex A assay in WBCs or skin fibroblasts (when suspected)
HIV Ab
HTLV1 Ab
VDRL
CBC
BUN, Cr
FBS, HbA1c
AST, ALT, ALP
Na, K, Ca, P
ESR, CRP
Vitamin B12, methylmalonic acid
Copper
Zinc
VLCFA assay, ASA assay, beta galactosidase (when suspected)
HIV Ab
HTLV1 Ab
CSF analysis for OCB, IgG index, HTLV1 Ab
Paraneoplastic Ab pane (when suspected)
CBC
BUN, Cr
FBS, HbA1c
TSH, free T4
AST, ALT, ALP
Na, K, Ca, P
PTH
CPK, aldolase
ESR, CRP
Vitamin B12
Serum protein electrophoresis and immunofixation
ANA
Lead level (serum or urine)
Hex A assay in WBCs or skin fibroblasts (when suspected)
Anti GM1
HIV Ab (in high risk patients)
CSF routine analysis and cytology
AChR Ab
Anti-MuSK Ab
CPK, aldolase
HIV Ab
HTLV1 Ab (serum or CSF)
HBsAg
HCV Ab
Borrelia Ab (Lyme disease)
Wright, 2ME
VDRL
Paraneoplastic Ab panel
Peripheral neuropathies
FBS, HbA1c, 2HPP
TSH, free T4
Cholesterol, LDL, HDL, TG
CBC diff
Na, K, Ca, P
AST, ALT
Bun, Cr
Vitamin B12, methylmalonic acid
Serum & urine protein electrophoresis and immunofixation, serum free light chains
Folate
Vitamin E
Vitamin B6
Vitamin B12, methylmalonic acid
Copper
Zinc
Anti TTG, Anti gliadin Ab, Anti endomysial Ab
HIV Ab
HBsAg
HCV Ab
Borrelia Ab (Lyme disease)
Wright, 2ME
VDRL
CBC
FBS, HbA1c
ESR, CRP
ANA, Anti dsDNA
RF, anti CCP
Anti SSA, Anti SSB
P-ANCA, C-ANCA
C3, C4, CH50
Cryoglobulin
HBsAg
HCV Ab
HIV Ab
ACE
Anti-MAG
Anti-SPGP
Serum & urine protein electrophoresis and immunofixation, serum free light chains
HbA1c
CBC
Na, K, Ca, P
AST, ALT
Bun, Cr
TSH, free T4
Vitamin B12, methylmalonic acid
Serum & urine protein electrophoresis and immunofixation, serum free light chains
CSF routine analysis
Serum VEGF level
Paraneoplastic panel (Anti-Hu)
Anti SSA, Anti SSB
ESR,CRP
ANA, Anti dsDNA
HIV Ab
Pyridoxine (when suspected)
Serum & urine protein electrophoresis and immunofixation, serum free light chains
Anti TTG, Anti gliadin Ab, Anti endomysial Ab
Anti GD1b
Anti NF155
Anti NF186
Anti CNTN1
Anti CASPR1
Ganglioside Ab panel:
Anti GM1, Anti GM1: GalC (MMN)
Anti GD1a, Anti GM1 (AMAN)
Anti GQ1b, Anti GT1a (MFS)
Anti GD1b, Anti GQ1b (sensory ataxic neuropathy)
Anti GT1a, Anti GQ1b (PCB variant of GBS)
Anti GD3, GD1b, GT1b, GQ1b (CANOMAD/ CANDA as a paraproteinemia)
CSF routine analysis
CSF routine analysis
CSF cytology or Ab testing when needed
HIV Ab
HTLV1 Ab
Wright, 2ME
Borrelia Ab (Lyme disease)
VDRL
ACE
RF
ANA, Anti dsDNA
Anti SSA, Anti SSB
CSF routine analysis
Anti-Hu
Anti-CV2
Anti-Yo
Anti-Ri
Anti-amphiphysin
Single random urine sample for ALA, PBG (in all cases)
Urine and feces coproporphyrin & protoporphyrin (in selected cases)
Urine uroporphyrine (in selected cases)
FBS, HbA1c, 2HPP
TSH, free T4
Cholesterol, LDL, HDL, TG
CBC diff
Na, K, Ca, P
AST, ALT, ALP
Bun, Cr
Vitamin B12, methylmalonic acid
Folate
ESR, CRP
ANA
Anti SSA, Anti SSB
ACE
Serum & urine protein electrophoresis and immunofixation, serum free light chains
Serum copper
HIV Ab
HCV Ab
Anti TTG, Anti gliadin Ab, Anti endomysial Ab (when celiac disease suspected)
Paraneoplastic panel (when suspected)
Ganglionic acetylcholine receptor Ab (when autoimmune autonomic ganglionopathy suspected)
Alpha-galactosidase A in plasma or WBCs (if Fabry disease suspected)
Lyso-Gb3 in plasma (if Fabry disease suspected in female carriers)
Serum or urine lead level
Serum or urine arsenic level
Neuromuscular junction disorders
AChR Ab
Anti-MuSK Ab
Anti LRP4
Anti titin
TSH, free T4
Anti VGCC Ab
Detection of toxin in serum, nasogastric secretions or feces
AChR Ab, Anti-MuSK Ab
CPK, aldolase
Lactate, pyruvate
AChR Ab
Anti-MuSK Ab
CPK, aldolase
Myopathies
CPK, aldolase
AST, ALT
Na, K, Ca, P, Mg
BUN, Cr
CBC diff
FBS
ESR, CRP
25(OH) vitamin D
TSH, free T4
24h urine free cortisol
Serum protein electrophoresis
HIV Ab
HTLV1 Ab
Covid-19 PCR
ALP
Ca, P
25(OH) vitamin D
PTH
Mi-2, TIF1-γ, NXP-2, MDA-5, SAE (dermatomyositis)
Jo-1, PL-7, PL-12, OJ, EJ (anti synthetase syndrome)
SRP, HMGCR, anti mitochondrial Ab (necrotizing autoimmune myopathy)
NT5c1A (inclusion body myositis)
Vitamin E
K
BUN, Cr
CPK
TSH, free T4
Glucose loading test (hypoKPP)
Potassium load test (hyperKPP)
ESR, CRP
ANA, Anti dsDNA
RF
Anti SSA, Anti SSB
C3, C4, CH50
Anti PM-SCL
Anti Ku
Anti Ro52
Anti U1 RNP
CPK, Aldolase
Lactate
Pyruvate
Urine organic acids
Graded exercise stress test
CPK
Serum carnitine level
Acylcarnitine profile
Urine organic acid
Peripheral blood smear (for Jordan anomaly)
Dried blood spot test (GAA assay)
CPK, LDH
Non-ischemic forearm exercise test
Graded exercise stress test
CPK, LDH
Dried blood spot test (GAA assay)
Acylcarnitine profile
Urine organic acids
Uric acid
Lactate
Pyruvate
Serum aminoacids
Peripheral blood smear (for Jordan anomaly)
Non-ischemic forearm exercise test
Graded exercise stress test
AChR Ab
Anti-MuSK Ab
CPK, aldolase
Lactate, pyruvate
Neuromuscular hyperexcitability syndromes
CPK
Anti VGKC including CASPR2 & LGI1
Ca, P, Mg
ALP
PTH
FBS, HbA1c, 2HPP
Anti-GAD Ab
Anti-amphiphysin Ab
Metabolic myopathy panel
Na, K, Ca, P, Mg
Ferritin
Zinc
FBS
BUN, Cr
AST, ALT
TSH, free T4
Progressive Ataxia
CBC diff
ESR, CRP
FBS
Na, K
BUN, Cr
AST, ALT
Cholesterol, LDL, HDL
TSH, free T4
Vitamin B12, methylmalonic acid
Vitamin E
Anti TTG, Anti gliadin Ab, Anti endomysial Ab
HIV Ab
Vitamin B1
Vitamin B12, methylmalonic acid
Folate
Vitamin E
ANA
Anti SSA, Anti SSB
CSF routine analysis and OCB
Anti GAD
Anti TPO
HIV Ab
VDRL
Borrelia Ab (lyme disease)
CSF routine analysis
CSF protein 14:3:3
Ceruloplasmin
24 hours urine copper
Lactate
Pyruvate
VLCFA assay
Phytanic acid assay
Anti Hu
Anti Yo
Anti Ri
Anti mGluR1
Anti Ma
Anti CRMP
Anti VGKC
Anti VGCC