Metabolic Neuropathy Workup

Updated: Jul 20, 2021
  • Author: Emad R Noor, MBChB; Chief Editor: Nicholas Lorenzo, MD, CPE, MHCM, FAAPL  more...
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Laboratory Studies

See the list below:

  • General laboratory tests for metabolic neuropathy

    • Blood glucose, glucose tolerance test and glycosylated hemoglobin levels, vitamin B-12, folate, vitamin E, cryoglobulins, hepatitis profile, and antibodies to antinuclear antigen (ANA), extractable nuclear antigen (ENA), and sulfatide

    • Creatinine

    • Thyroid function tests

    • Liver function tests

    • Serum protein electrophoresis or serum immunofixation, anti-MAG antibodies

  • Suggested studies for disorders of carbohydrate metabolism (when metabolic myopathy is being ruled out)

    • Ischemic forearm exercise test

    • Serum lactate, ammonia, and pyruvate

    • Urine myoglobin

    • Muscle histochemistry

    • Enzyme assays of muscle, blood, and fibroblast

    • Leukocyte glycogen levels to detect acid maltase deficiency

    • Leukocyte, DNA analyses (McArdle disease)

  • Suggested investigations for mitochondrial disorders

    • Resting lactate and pyruvate level

    • Muscle histochemistry and electron microscopy

    • Serum mitochondrial DNA deletion and mutation

    • Enzyme assays of muscle, platelets, liver, and fibroblasts

    • Muscle cytochrome oxidase analysis

  • Other suggested studies

    • Biotinidase levels

    • Aminolevulinic acid synthase in urine (porphyria)

    • Arylsulfatase A and B (leukodystrophies)

    • Hexosaminidases

    • Urine oxalate levels to rule out primary hyperoxaluria, which in patients who are undergoing hemodialysis may present with peripheral neuropathy (direct deposition of oxalate crystals on Schwann cells)


Imaging Studies

Magnetic resonance techniques have demonstrated increased water content in peripheral nerves of patients with diabetes. Its utility remains under investigation. Magnetic resonance imaging and ultrasound can be used in peripheral nerve imaging to demonstrate extrinsic compressive lesions, focal neural lesions such as neural edema and swelling, focal neural scarring (posttraumatic neuroma in continuity) and intraneural ganglia. Ultrasound can be particularly useful in assessing for intrinsic lesions in small peripheral nerves because of the superior spatial resolution of ultrasound in assessing superficial structures. Plain radiography (and sometimes computed tomography scanning) may show significant bone changes and should be the initial imaging modality. [25]

Acute or subacute denervation results in prolonged T2 relaxation time, producing increased signal in skeletal muscle on short tau inversion-recovery and fat-suppressed T2-weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T1-weighted images. [26]

When metabolic myopathy is being ruled out, phosphorus magnetic resonance spectroscopy of muscle may be useful for the investigation of carbohydrate metabolism (McArdle disease, phosphofructokinase deficiency) and mitochondrial disorders.

MRI of the brain is suggested for patients in whom leukodystrophies are suspected.


Other Tests

See the list below:

  • Nerve conduction studies (NCS) and electromyography (EMG) are essential to classify and determine the severity of any neuropathy

    • NCS abnormalities in axonal sensory or sensory motor polyneuropathies consist of small or absent sensory nerve action potentials and compound motor action potentials, but NCS findings may be normal in mild cases or in small-fiber neuropathies. NCS abnormalities in demyelinating polyneuropathies can include prolonged distal and F-wave latencies, decreased conduction velocities, and conduction block.

    • EMG abnormalities are more common in axonal neuropathies and consist of signs of denervation (fibrillations and positive sharp waves and reduced recruitment patterns) and reinnervation (large-amplitude, broad-duration polyphasic motor unit potentials).

  • Quantitative sensory testing (QST): Perform QST to evaluate involvement of small nerve fibers. QST holds promise in metabolic neuropathies as a technique to assess perceptual thresholds to pain, temperature, or vibration.

  • Quantitative sudomotor axonal reflex testing (Q-SART) is very useful to identify autonomic involvement and help in establishing the prognosis.

  • Measurement of nerve excitability by threshold tracking provides complementary information to conventional nerve conduction studies and may be used to infer the activity of a variety of ion channels, energy-dependent pumps, and ion exchange processes activated during the process of impulse conduction. This review highlights recent clinical excitability studies that have suggested mechanisms for nerve involvement in a range of metabolic and toxic neuropathies. While there is growing evidence of their utility to provide novel insights into the pathophysiological mechanisms involved in a variety of neuropathic disturbances, it is too early to know whether they have diagnostic value. [27]



Sural nerve biopsy in diabetic neuropathy may reveal a histologic pattern suggestive of nerve ischemia (selective fascicular involvement, diffuse loss of myelinated fibers). However, sural nerve biopsy rarely is performed now unless evidence is being sought of vasculitic, demyelinating, hereditary, or infectious origin for the neuropathy. Muscle biopsy should always be done with nerve biopsy to increase the diagnostic yield for vasculitic and amyloid neuropathies.

Punch skin biopsy and immunohistochemical staining for peripheral nerve axons can be performed.

  • Advances in immunohistochemical techniques, specifically the development of antibodies to human protein gene product 9.5 (PGP 9.5), an antigen present in peripheral nerve fibers of all calibers, allow assessment of the effect of diseases on peripheral nerve density.

  • Fiber density can be quantified with an interobserver agreement of 96%. Reports exist of excellent correlation between reductions in intradermal nerve fiber density and severity of symptoms in a wide range of neuropathies.


Histologic Findings

Loss of myelinated fibers, epineurial periarteriolar lymphocytic infiltrates, and selective involvement of fascicles can be observed in diabetic radiculoplexopathy or other vasculitic neuropathies. Amyloid birefringent deposits (under polarized light) within the endoneurium are revealed in amyloid neuropathy.