eMedicine Specialties > Neurology > Neuromuscular Diseases

Diabetic Neuropathy: Differential Diagnoses & Workup

Author: Dianna Quan, MD, Associate Professor of Neurology, Director, Electromyography Laboratory, University of Colorado Health Sciences Center
Contributor Information and Disclosures

Updated: Oct 22, 2009

Differential Diagnoses

Alcohol (Ethanol) Related Neuropathy
Thyroid Disease
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Toxic Neuropathy
Nutritional Neuropathy
Uremic Neuropathy
Sarcoidosis and Neuropathy
Vasculitic Neuropathy

Other Problems to Be Considered

Amyloid polyneuropathy
Spinal cord tumors
Vitamin B-12 deficiency

Differential diagnoses to consider in the following situations:

Cranial mononeuropathy
Intracranial aneurysms
Bell palsy

Thoracoabdominal neuropathy
Herpes zoster
Spinal tumors
Myocardial infarction
Acute cholecystitis
Acute appendicitis
Diverticulitis

Lumbosacral radiculoplexopathy
Anterior disk protrusion
Spinal cord tumors
Malignant nerve root infiltrations
Inflammatory neuropathies

Workup

Laboratory Studies

  • The following basic studies are suggested to exclude common causes of neuropathy other than diabetes:
    • Complete blood cell count
    • Complete metabolic panel (electrolytes and liver function panel)
    • Vitamin B-12 and folate levels
    • Thyroid function tests
    • Erythrocyte sedimentation rate
    • Serum protein electrophoresis with immunofixation electrophoresis
  • Examples of other studies that can be ordered depending on the patient's history and examination findings include the following:
    • Antinuclear antibody
    • Anti-SSA and SSB antibodies
    • Rheumatoid factor
    • Paraneoplastic antibodies
  • Patients with diabetic neuropathies likely have elevated hemoglobin A1c levels, but the test is useful to assess the adequacy of diabetes control. In some cases, especially with asymmetrical syndromes, the severity of the elevation does not always correlate with the severity of the nerve disease. A urinalysis is also helpful to screen for nephropathy and proteinuria.

Imaging Studies

In the appropriate clinical setting, MRI of the cervical, thoracic, and/or lumbar regions may help to exclude another cause for symptoms mimicking diabetic neuropathy. Plexus MRI may be helpful to exclude other problems (eg, tumor) in patients with radiculoplexus neuropathy syndromes. For patients who cannot have MRI, CT myelogram is an alternative to exclude compressive lesions and other pathology in the spinal canal. In cranial nerve palsies, brain imaging, usually with MRI, is helpful to exclude intracranial aneurysms, compressive lesions, and infarcts.

Other Tests

  • Electrophysiologic studies are the most sensitive, reliable, and reproducible measures of nerve function. Electrophysiologic findings usually correlate with morphologic changes on nerve biopsy. Common early findings are abnormal nerve conduction studies or reduced variability of heart rate with deep breathing or Valsalva maneuver. Although electrodiagnostic studies can characterize and quantitate nerve dysfunction, they cannot distinguish diabetic neuropathy from neuropathy of other causes. Composite scores, combining clinical, quantitative sensory, and electrophysiologic measures, are often used in natural history and efficacy studies. Examples include the Neuropathy Impairment Score in the Lower Limbs + 7 and the Michigan Diabetic Neuropathy score.
  • Electromyography and nerve conduction studies
    • Findings on nerve conduction studies depend on the pattern of nerve damage. Patients with distal symmetrical polyneuropathy from predominant axonal loss have reduced or absent sensory nerve action potentials, especially in the legs. With progression of neuropathy, compound motor action potential amplitudes may also be reduced and abnormalities may be observed in the hands. These changes reflect length-dependent degeneration of large-diameter myelinated nerve fibers.
    • Conduction velocities are generally within the normal range or only mildly slowed in distal symmetrical polyneuropathy. If conduction velocities are less than 70% the lower limit of normal, or if conduction block is present, the patient may have superimposed peripheral nerve demyelination in addition to the more typical axonal loss seen in distal symmetrical polyneuropathy. Generalized demyelinating changes on nerve conduction studies should prompt further evaluation for CIDP. Focal slowing of conduction velocity at common sites of entrapment may indicate one of the mononeuropathy syndromes discussed above.
    • Nerve conduction study abnormalities may be found in patients with diabetes even without clinical symptoms of polyneuropathy.
    • Electromyographic sampling of distal lower extremity muscles may reveal acute and ongoing denervation in the form of positive sharp waves and fibrillation potentials (spontaneous discharges). Reinnervation changes such as large-amplitude, long-duration, polyphasic motor unit potentials reflect chronicity. Abnormalities in paraspinal muscles (eg, spontaneous discharges) usually reflect disease in spinal nerve roots.

Procedures

  • Sural nerve biopsy is now rarely indicated in the diagnosis or longitudinal assessment of diabetic peripheral neuropathy. Reasons for this move away from biopsies in clinical trials include the invasive nature of the procedure with its attendant risks, discomfort to the patient, cost, problems with reproducibility due to sampling error, and availability of other methods to obtain similar information.
  • The following new diagnostic approaches for diabetic neuropathy are currently under intense study. Details of these techniques are beyond the scope of this review.
    • Skin punch biopsy/intraepidermal nerve fiber density testing16 and immunohistochemical staining of peripheral nerves
    • Quantitative sensory testing
    • Imaging using MRI and ultrasonography

Staging

Different clinical neurological scales can be used to assess the severity of diabetic polyneuropathy.

A common staging scale of diabetic polyneuropathy is as follows:17

  • NO - No neuropathy
  • N1a - Signs but no symptoms of neuropathy
  • N2a - Symptomatic mild diabetic polyneuropathy; sensory, motor, or autonomic symptoms; patient able to heel walk
  • N2b - Severe symptomatic diabetic polyneuropathy (as in N2a, but patient unable to heel walk)
  • N3 - Disabling diabetic polyneuropathy

More on Diabetic Neuropathy

Overview: Diabetic Neuropathy
Differential Diagnoses & Workup: Diabetic Neuropathy
Treatment & Medication: Diabetic Neuropathy
Follow-up: Diabetic Neuropathy
References
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Further Reading

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Keywords

diabetic polyneuropathy, diabetic amyotrophy, proximal diabetic neuropathy, mononeuropathy multiplex, diabetic autonomic neuropathy, distal symmetric sensorimotor polyneuropathy, painful diabetic neuropathy, generalized sensorimotor polyneuropathy of diabetes mellitus, diabetic peripheral neuropathy, peripheral neuropathies, chronic hyperglycemia, entrapment neuropathies, diabetic neuropathy, carpal tunnel syndrome, numbness, feeling of wearing gloves, lossof balance, electric shocklike feelings, hypersensitivity to touch, foot slapping, toe scuffing, postural lightheadedness, fainting, urinary urgency, urinary dribbling, urinary incontinence, nocturnal diarrhea, constipation

erectile impotence, ejaculatory failure, nighttime painful paresthesias, impaired proprioception, impaired vibratory perception, sensory ataxia, anhidrosis, bladder atony, unreactive pupils, painless electric tingling, snug bandlike sensation around ankles, snug bandlike sensation around feet, absent ankle jerk reflexes, proprioceptive sensory impairment, gait instability, orthostatic hypotension, resting tachycardia, loss of sinus arrhythmia, sluggish light reflex

diabetic neuropathic cachexia, median neuropathy of the wrist, MNW, ulnar neuropathy of the elbow, UNE, single somatic mononeuropathies, multiple somatic mononeuropathies, single monoradiculopathies, multiple monoradiculopathies, diabetic lumbosacral radiculoplexoneuropathy, DLSRPN, diabetic thoracolumbar radiculoneuropathy, DTLRN, diabetic autonomia, cranial mononeuropathy, anterior ischemic optic neuropathy, diabetic oculomotor cranial mononeuropathies, acute periorbital pain, facial neuropathy, mononeuritis multiplex

diabetic polyradiculopathy, thoracoabdominal neuropathy, lumbosacral radiculoplexopathy, thoracolumbar neuropathy, thoracoabdominal radiculopathy, thoracic radiculopathy, truncal neuropathy, asymmetric proximal motorneuropathy, diabetic femoral neuropathy, femorosciatic neuropathy, diabetic myelopathy, Bruhn-Garland syndrome, poorly controlled diabetes, acute painful neuropathy, chronic inflammatory demyelinating polyneuropathy, CIDP, diabetes mellitus-CIDP, demyelinating neuropathy, diabetic neuropathy

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Contributor Information and Disclosures

Author

Dianna Quan, MD, Associate Professor of Neurology, Director, Electromyography Laboratory, University of Colorado Health Sciences Center
Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: e-medicine Honoraria Other

Medical Editor

Milind J Kothari, DO, Professor and Vice-Chair, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Penn State Milton S Hershey Medical Center
Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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