An excellent diagnostic approach to peripheral neuropathy starts with recognizing the signs and symptoms of the disease. Peripheral neuropathy can be diffuse as in diabetic peripheral neuropathy or focal as in carpal tunnel syndrome. After discovering the typical signs and symptoms of this disease, doctors can also order some further tests to make a diagnosis.

How to Diagnose Peripheral Neuropathy
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The peripheral nervous system consists of cranial nerves (except for the olfactory and optic nerves), nerves originating from the spinal cord (roots, rami, trunk, plexus, and peripheral nerves themselves) components autonomic nerves in the periphery. Some of these peripheral nerve's axons are covered by the myelin sheath formed by Schwann cells, while others are not myelinated.

Peripheral neuropathy is a group of disorders that affect the peripheral nervous system. Clinically, peripheral neuropathy can be divided into focal, multifocal, and diffuse polyneuropathies. The most common focal neuropathies are carpal tunnel syndrome and nerve compression due to herniated nucleus pulposus. Meanwhile, multifocal neuropathy is in leprosy, and polyneuropathy is in the diabetes mellitus case.

Steps How to Diagnose Peripheral Neuropathy

1. Anamnesis History 

Peripheral neuropathy patients usually present numbness, tingling, pain, or weakness in the body's distal part. The first step is to differentiate whether the symptoms are due to a central nervous system's lesion or peripheral nerves. In central nervous system lesions, complaints are usually accompanied by other central symptoms such as speech disorders, double vision, ataxia, defecation, and urination disorders.

In peripheral neuropathy, complaints in the distal part of the body are generally distributed in a "stocking and gloves" pattern, which can progress toward the proximal. The doctor then explores whether the complaint is acute or chronic and asks whether comorbidities can cause peripheral neuropathy. Peripheral neuropathy can be caused by toxins, nutritional problems, metabolic diseases, inflammation, and immune-mediated demyelinating disorders.

2. Physical Examinations 

The physical examinations include general physical examinations and neurological examinations to look for diseases that may be causing neuropathy. The general physical examination can be joint examination to detect inflammation such as rheumatoid arthritis, assessment of nerve enlargement as in leprosy, and assessment of the presence or absence of joint hyperextension and muscle atrophy as these are often found in patients with peripheral neuropathy.

Neurological examination includes the examination of deep tendon reflexes, pathological reflexes, and muscle tone. In central nervous system disorders, deep tendon reflexes are usually elevated, pathological reflexes may appear, and muscle tone is increased. This can help differentiate central nervous system disorders from peripheral neuropathy.

Sensory examination plays an important role in determining the etiology of peripheral neuropathy. Peripheral nerve root lesions usually have asymmetric sensory disturbances with distribution according to the dermatome pattern. In contrast, diabetic polyneuropathies usually have distal symmetrical sensory disorders following the "stocking and gloves" pattern. This sensory examination includes sensations of fine touch, vibration, proprioception, temperature, and pain. The motor examination is also important to assess motor involvement.

3. Laboratory Examinations 

The initial evaluation of a patient with peripheral neuropathy includes:
  • complete blood count,
  • metabolic profile,
  • sedimentation rate,
  • fasting blood glucose,
  • thyroid-stimulating hormone (TSH),
  • and vitamin B12 levels.

It aims to explore possible etiologies of peripheral neuropathy, such as:
metabolic disorders (diabetes mellitus and hypothyroidism), vitamin B12 deficiency, infection, or inflammation such as vasculitis.

Further examinations can be performed, such as:
  • hemoglobin A1C examination in diabetic patients,
  • HIV antibody test,
  • syphilis panel,
  • urinalysis if porphyria toxicity is suspected,
  • a paraneoplastic panel if malignancy is suspected,
  • cerebrospinal fluid analysis if inflammatory demyelinating neuropathy is suspected,
  • or genetic testing if hereditary neuropathy is suspected.

4. Electrodiagnostic Examination 

This examination can assess damage to major nerve fibers. It is also useful to differentiate between peripheral neuropathy, myopathy, plexopathy, and radiculopathy. This examination can also assess the motor involvement, sensory nerve fibers, and the damage severity.

The electrodiagnostic examination can distinguish whether the nerve disorder is axonopathy or myelopathic. If performing the serial examination, the examination can also evaluate and assess peripheral neuropathy progression.

5. Radiological Examinations 

Radiological examination is especially useful for focal neuropathy cases. Ultrasound examination (USG) to diagnose peripheral nerve entrapment and magnetic resonance imaging (MRI) to diagnose radiculopathy and rule out a central nervous system disorder diagnosis.

6. Biopsy 

A nerve biopsy may be performed to confirm the diagnosis before starting aggressive therapy such as neuropathy due to vasculitis for which treatment requires steroids or chemotherapy.

A biopsy is usually performed on the superficial peroneus. Nerve biopsy is rarely done lately because of the development of laboratory tests, electrodiagnostic examinations, and genetic examinations.

Skin biopsy is the gold standard for assessing the innervation of small intraepidermal nerve fibers. These unmyelinated nerve fibers convey sensations of pain and temperature away from the skin and play a role in regulating autonomic function. Examination of these tiny nerve fibers cannot be assessed by electrodiagnostic examination.

Differential Diagnosis of Peripheral Neuropathy

Differential diagnosis of peripheral neuropathy is the central nervous system that can also cause weakness, tingling, or pain. However, central nervous lesions are usually accompanied by central symptoms such as speech disturbances, double vision, ataxia, defecation, and urinary disorders. In cerebral lesions, the distribution of symptoms is usually unilateral. In spinal cord lesions, the distribution of symptoms is usually segmental or follows the spinal cord's distribution.

On physical examination of central nervous system disorders, there are signs of upper motor neuron lesions, namely increased deep tendon reflexes and pathological reflexes. If a central nervous system disorder is suspected, computed tomography or MRI may be performed.

The other differential diagnosis is a peripheral vascular disease (such as deep vein thrombosis, chronic venous insufficiency, or acute limb ischemia). Peripheral vascular abnormalities are usually asymmetrical and may reveal signs of vascular abnormalities (such as venous distension, loss or weakening of arterial pulses, skin color, and temperature).

In certain cases where doctors find it difficult to distinguish peripheral neuropathy from peripheral vascular disorders, tests such as Doppler ultrasound and/or angiography may be performed.

Indications for Referring Patients

Indications for referring peripheral neuropathy patients to neurologists is especially in cases with progressive motor complaints such as:
  • Guillain-Barre syndrome,
  • severe nucleus pulposus hernias,
  • balance disorders with a high risk of falls,
  • the extremities injuries,
  • and the etiologic diagnosis is complicated and requires complex management as in paraneoplastic neuropathy/paraproteinemia.

Peripheral neuropathy is a disorder of the peripheral nervous system with a wide variety of etiologies. The diagnostic approach can be started from recognizing signs and symptoms in the form of numbness, tingling, pain, or weakness in the distal part of the body, which is generally distributed in a "glove and stocking" pattern and can progress toward the proximal.

Initial investigations can be in the form of a complete blood laboratory examination, metabolic profile, fasting blood glucose, thyroid-stimulating hormone, and vitamin B12 levels to determine the common causes. If necessary, the doctor can refer to a neurologist for further tests such as electrodiagnosis, radiology, nerve biopsy, or skin biopsy.