What is the role of lab tests in the workup of toxic neuropathy?

Updated: Dec 06, 2017
  • Author: Jonathan S Rutchik, MD, MPH, FACOEM; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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See the list below:

  • See other Medscape Reference articles on neuropathy for workup to rule out common causes of neuropathy.

  • A differential diagnosis for peripheral neuropathy with appropriate lab testing is noted in Table 4.

Table 4. Differential Diagnosis of Peripheral Neuropathy With Selective Lab Testing (Recommended lab tests in bold.) (Open Table in a new window)


Metabolic and Nutritional

Infective and Granulo-matous


Neoplastic and Para-proteinemic

Drug-Induced and Toxic


Acute idiopathic polyneuro-pathy (Anti-Gm1, anti-Gd1a, anti-GQ1b)

Diabetes ( Fasting blood glucose , 2-hour glucose tolerance test)


Mixed CT disease (ESR)

Compression and infiltration ( chest radiograph)



Chronic inflammatory demyelin-ating polyneuro-pathy

Endocrino-pathies: hypo-thyroidism, acromegaly ( TSH , Electrolytes, GH)

Leprosy, syphilis ( RPR , FTA , MHA-TP)

Poly-arteritis nodosa

Paraneo-plastic syndromes (anti-Hu, anti-RII, etc; CBC)

See Table



Uremia ( BUN/CR)

Diphtheria, Lyme ( Serology)

Rheu-matoid arthritis ( RF)

Paraprotein-emias ( SPEP , immuno-fixation , anti-MAG, M protein)


Friedreich ataxia


Liver disease ( LFTs)

Sarcoidosis ( ACE)


Amyloidosis (nerve biopsy)


Familial amyloid (nerve biopsy)


Vitamin B-12 deficiency ( B12)

Sepsis and multi-organ failure ( ESR)




Porphyria (porphobil-inogen, amino-levulinic acid),

meta-chromatic leukodys-trophy, Krabbe, abetalipo-proteinemia, Tangier disease, Refsum disease, Fabry disease


  • Neuropathies with unusual features are listed in Table 5.

Table 5. Neuropathies With Unusual Features (Open Table in a new window)

Small Fiber Neuropathies

Facial Nerve Involvement

Autonomic Involvement

Sensory Ataxia

Pure Motor Involvement

Skin, Nail, or Hair Manifestation





Motor neuron disease

Vasculitis: purpura, livedo reticularis





Multifocal motor neuropathy

Cryoglo-binemia: purpura


Lyme disease


Sjögren syndrome


Fabry disease: angiokera-tomas

Hereditary sensory and autonomic neuropathy


Vincristine, vacor

Cisplatin analogs

Acute motor axonal neuropathy

Leprosy: skin hypopig-mentation

Fabry disease



Vitamin B-6 toxicity


Osteo-sclerotic myeloma: skin hyperpig-mentation

Tangier disease



GBS (Miller-Fisher variant)


Variegate porphyria: bullous lesions

Sjögren syndrome



IgM monoclonal gammopathy of undetermined significance

Osteosclerotic myeloma

Refsum disease: ichthyosis



Hereditary sensory and autonomic neuropathy


Diabetic lumbar radiculoplex-opathy

Arsenic or thallium intoxication: Mees lines





Hereditary motor sensory neuropathy (Charcot-Marie-Tooth)

Thallium intoxication: alopecia






Giant axonal neuropathy: curled hair


  • Quantitative sensory testing includes vibration threshold testing, thermal threshold testing, portable motor and sensory latency tests, and current perception threshold (CPT) testing. These tests are often portable gadgets useful in the field. Each has its limitations, but some may be able to measure functions pertaining to small fiber neuropathy, such as the CPT and thermal testing devices. Others are simple versions of the NCV. The vibration testing device measures large fiber function and may be useful if NCV is not available.

  • Other techniques that help prove the presence of neuropathy include skin biopsy and intraepidermal nerve fiber density (IENF) testing. This is well reviewed in the article by Smith et al (2005). [48]

  • The sympathetic skin reflex is performed with EMG machinery, where the absence of one side's testing suggests an abnormality. This test is technically difficult. A sural nerve biopsy is invasive but may be useful. Laser evoked potential and Quantitative Sudomotor Axon Reflex Test (QSART) have been useful in research. QSART measures sweat volume.

  • IENF testing is relatively easy since it is a small punch biopsy of skin (6 mm). It has a reliable method of measuring small fiber neuropathy and has good interrater reliability. It measures intraepidermal nerve fibers, crossing the dermal, epidermal junction. It is being used in clinical trials for pharmaceuticals.

  • For patients with cryptogenic neuropathies, glucose tolerance testing makes sense because impaired glucose tolerance is prevalent in 14% of those aged 50-65 years. This is well reviewed by Sumner et al (2003). [49] It is associated with a syndrome of insulin resistance, and 25-40% of patients progress to frank diabetes. An abnormal oral glucose tolerance test result is defined as a glucose level of 140-200, 2 hours after a 75-g anhydrous load. Clinically, 86% of patients had exclusively sensory symptoms with pain and one third had otherwise idiopathic neuropathy. Oral glucose tolerance testing is more sensitive than glycosylated hemoglobin HbA1C testing.

  • For cryptogenic neuropathy, the glucose tolerance test result is abnormal in 33-61% of patients. Other important laboratory tests to consider are tests for vitamin B-12, monoclonal gammopathy of unknown significance (3% of those >70 y), axonal neuropathy (1-5%), cryoglobins and hepatitis C evaluation, and immunofixation for paraneoplastic neuropathy.

  • CSF protein level in toxic neuropathy is usually normal.

  • Consider performing serum, urine, or blood testing to assess for evidence of absorption (see Table 2). If evaluating a patient weeks or months after the exposure ceased, biological data may not yield useful information. In the case of arsenic, for example, separating inorganic from organic arsenic is important, since organic arsenic is a component of seafood and may contaminate and confuse clinicians. Patients need to refrain from seafood for 24 hour prior to urine testing. Furthermore, labs need to be instructed to perform testing for inorganic, not organic, arsenic. Some agents do not have indices that can be tested. Most need to be performed relatively soon after exposure.

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