Laboratory investigation of neuromuscular disorders

Post by: hadi Gharebaghian on December 20, 2023 | 0 Comment

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 progressive ataxia are also included.

Motor neuron diseases

Concomitant UMN & LMN involvement	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
UMN only	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)
LMN only	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
Bulbar palsy	AChR Ab Anti-MuSK Ab CPK, aldolase
Suspected infectious etiology (consider endemic areas)	HIV Ab HTLV1 Ab (serum or CSF) HBsAg HCV Ab Borrelia Ab (lyme disease) Wright, 2ME VDRL
Suspected paraneoplastic etiology	Paraneoplastic Ab panel

Peripheral neuropathies

Distal symmetric polyneuropathy	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
Suspected nutritional deficiency	Folate Vitamin E Vitamin B6 Vitamin B12, methylmalonic acid Copper Zinc Anti TTG, Anti gliadin Ab, Anti endomysial Ab
Suspected infectious etiology (consider endemic areas)	HIV Ab HBsAg HCV Ab Borrelia Ab (lyme disease) Wright, 2ME VDRL
Mononeuritis multiplex	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
DADS (distal acquired demyelinating symmetric neuropathy)	Anti-MAG Anti-SPGP Serum & urine protein electrophoresis and immunofixation, serum free light chains
CIDP	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
Suspected POEMS syndrome	Serum VEGF level
Sensory neuropathy or neuronopathy	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
Suspected nodopathy or paranodopathy	Anti NF155 Anti NF186 Anti CNTN1 Anti CASPR1
Suspected inflammatory demyelinating etiology	Ganglioside Ab panel: Anti GM1 (MMN, GBS) Anti GD1a, Anti GT1b (GBS) Anti GQ1b (MFS) Anti GD1b (sensory neuropathy) CSF routine analysis
Polyradiculopathy	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
Polyradiculoneuropathy (AIDP, CIDP)	CSF routine analysis
Suspected paraneoplastic etiology (especially sensory neuronopathy)	Anti-Hu Anti-CV2 Anti-Yo Anti-Ri Anti-amphiphysin
Suspected porphyric neuropathy	Single random urine sample for ALA, PBG (in all cases) Urine and feces coproporphyrin & protoporphyrin (in selected cases) Urine uroporphyrine (in selected cases)
Small fiber neuropathy	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 gangliopathy suspected) Alpha-galactosidase A in plasma or WBCs (if Fabry disease suspected) Lyso-Gb3 in plasma (if Fabry disease suspected in female carriers)
Suspected heavy metal intoxication	Serum or urine lead level Serum or urine arsenic level

Neuromuscular junction disorders

Suspected myasthenia gravis	AChR Ab Anti-MuSK Ab Anti LRP4 Anti titin TSH, free T4
Suspected Lambert-Eaton myasthenic syndrome	Anti VGCC Ab
Suspected Botulism	Detection of toxin in serum, nasogastric secretions or feces
Ophthalmoplegia and ptosis	AChR AbAnti-MuSK Ab CPK, aldolase Lactate, pyruvate
Bulbar palsy	AChR Ab Anti-MuSK Ab CPK, aldolase

Myopathies

For all patients	CPK, aldolase AST, ALT Na, K, Ca, P, Mg BUN, Cr CBC diff FBS ESR, CRP 25(OH) vitamin D TSH, free T4
Suspected Cushing syndrome	24h urine free cortisol
Suspected amyloid myopathy	Serum protein electrophoresis
Suspected infectious etiology	HIV Ab HTLV1 Ab Covid-19 PCR
Suspected osteomalacia, hypervitaminosis D or parathyroid disorders	ALP Ca, P 25(OH) vitamin D PTH
Suspected inflammatory myopathy	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)
Suspected nutritional deficiency	Vitamin E
Suspected carnitine deficiency	Serum and urine carnitine level
Suspected connective tissue disease	ESR, CRP ANA, Anti dsDNA RF Anti SSA, Anti SSB C3, C4, CH50 Anti PM-SCL Anti Ku Anti Ro52 Anti U1 RNP
Suspected mitochondrial disorder	CPK, Aldolase Lactate Pyruvate Urine organic acids Graded exercise stress test
Suspected fatty acid oxidation defect	CPK Serum carnitine level Acylcarnitine profile Urine organic acid Peripheral blood smear (for Jordan anomaly)
Suspected Pompe disease (limb-girdle weakness, respiratory insufficiency or cardiomyopathy)	Dried blood spot test (GAA assay)
Suspected GSD (other than Pompe disease)	CPK, LDH Non-ischemic forearm exercise test Graded exercise stress test
Metabolic myopathy (overall)	CPK, LDH 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
Ophthalmoplegia and ptosis	AChR Ab Anti-MuSK Ab CPK, aldolase Lactate, pyruvate

Progressive Ataxia

For all patients	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
Suspected nutritional deficiency	Vitamin B1 Vitamin B12, methylmalonic acid Folate Vitamin E
Suspected autoimmune etiology	ANA Anti SSA, Anti SSB CSF routine analysis and OCB Anti GAD Anti TPO
Suspected infectious etiology (consider endemic areas)	HIV Ab VDRL Borrelia Ab (lyme disease) CSF routine analysis CSF protein 14:3:3
Suspected Wilson disease	Ceruloplasmin 24 hours urine copper
Suspected mitochondrial cytopathy	Lactate Pyruvate
Suspected adreno leukodystrophy	VLCFA assay
Suspected Refsum disease	Phytanic acid assay
Suspected paraneoplastic etiology	Anti Hu Anti Yo Anti Ri Anti mGluR1 Anti Ma Anti CRMP Anti VGKC Anti VGCC

Categories:neuromuscular disorders

Tagged:Neuromuscular disorders