For Physicians

The peripheral nervous system consists of the nerves outside of the brain and spinal cord that carry efferent motor and afferent sensory information. Peripheral nerve disorders and injury can be caused by compression, trauma, tumor, vascular insult or by autoimmune or medical conditions such as diabetes or nutritional deficiencies. Symptoms can manifest as weakness, pain, sensation alteration or loss, and new functional loss and can be isolated to one area of skin or limb, muscle group, or can be more widespread. 

When to Refer

Early referral (as soon after injury or onset of symptoms as possible) of adults with new peripheral nerve symptoms to multidisciplinary specialty clinics can improve overall functional outcomes. Regardless of the etiology of the condition, early specialized evaluation is useful to determine an appropriate diagnostic and treatment plan.

Causes and Symptoms

Axons are long projections from a nerve cell body that is made up by a cell membrane as and a basement membrane. Some axons are encased by sheaths of myelin, insulation which is supplied by Schwann cells. Myelin allows for synaptic propagation along the axon by saltatory conduction. Axons are encased by endoneurium which is a layer of connective tissue. Multiple axons bundled together are called fascicles, and are covered by perineurium.  Epineurium is yet another layer of connective tissues which covers the fascicles that are bundled together to form the peripheral nerves. The peripheral nerve can be damaged in two basic ways; the axon’s myelin sheath can be damaged which results in a lack of signal transmission along the axon, or the axon itself can be damaged. In cases of trauma, tumor or infection, the supporting structures and blood vessels can also be damaged. 

A mononeuropathy refers to damage to a peripheral nerve carrying both afferent and efferent information. Afferent involvement refers to sensory deficits and may include small fiber nerve damage in the unmyelinated and small myelinated fibers that are located in peripheral tissues or large fiber damage which includes pathways for balance and proprioception. Efferent involvement refers to motor deficits which may include muscle weakness and atrophy in the distribution of a peripheral nerve. The chronicity of the peripheral nerve injury can also influence symptoms. For example, chronic compression of the Median nerve at the carpal tunnel may present with slowly progressive sensory changes, pain and eventually weakness whereas acute trauma to the Median nerve at the wrist by a sharp object can result in sudden sensory loss and weakness due to complete axonal disruption. To further the diagnostic challenge, the same disease process can lead to different peripheral nerve injuries. For example, polyneuropathy due to diabetes may present with sensory loss or pain beginning in the toes and feet or with hip or leg weakness without significant sensory abnormalities. When there has been direct nerve trauma including a laceration, immediate recognition may lead to additional treatment possibilities and better surgical outcome.

Symptom presentation can vary significantly based on the etiology and extent of the peripheral nerve insult. A detailed clinical history and physical examination can often point toward the etiology of the peripheral nerve dysfunction. Peripheral nerve injury can lead to sensory changes, weakness and loss of function. The onset, nature and distribution of the patient’s symptoms can help localize their findings to a particular nerve or nerve structures. Past medical history and a detailed review of medications and toxin exposure can also point to a potential etiology. Family history should be reviewed as should social history including employment, substance use and functional status. Physical examination findings may include evidence of fracture or trauma, sensory loss in a dermatomal or non-dermatomal distribution, muscle atrophy in the distribution of one or many peripheral nerves, weakness and loss of active compared to passive joint range of motion, loss of muscle stretch reflexes or positive provocative maneuvers. In the instance of sensory findings, the examiner should determine which sensory function (light touch, pain/temperature, vibration or joint position) is impaired because this can help to determine if small or large fibers are involved.

Peripheral nerve injury etiology can be organized in the following categories:

  • Trauma
  • Acute or Chronic Nerve Compression
  • Ischemia (small or large vessel)
  • Tumor (Peripheral Nerve or Metastatic) 
  • Autoimmune Disorder (i.e. Guillain-Barre, Parsonage-Turner Syndrome, Sjogren’s, Lupus)
  • Medical diseases (i.e. Diabetes, Cancer, Endocrine disease)
  • Metabolic or Nutritional deficiencies (B-12 or folate deficiency, thyroid dysfunction) 
  • Toxin Exposure (i.e. alcohol, heavy metals, medications)
  • Other (i.e. motor neuron disease, genetic disorders, infection, etc.)

In addition to a detailed history and physical examination, laboratory testing including serum, cerebrospinal fluid (CSF) or other body fluid samples may also be helpful in providing a diagnosis through detection of a disease process, nutritional deficiency or genetic mutation. Electrodiagnostic testing (EDX) can be beneficial to determine if there is new or chronic demyelination or axon degeneration present and to help with localization of the lesion(s) within the peripheral nerves. Additionally, EDX can evaluate if there is evidence of axonal regeneration. Imaging modalities such as ultrasound or magnetic resonance imaging (MRI) can provide a detailed picture of the nerves and muscles, compressive structures, edema, ischemia, and evaluate for the presence of tumors or masses. It is also beneficial for surgical planning, if warranted. We have found ultrasound neurography to be particularly useful for identifying edema proximal to an area of nerve compression.

Treatment and Therapy

Neurosurgical intervention may be indicated in certain instances of peripheral nerve injury. For all surgical interventions, the most important factor in producing the optimal result is the coordination of non-operative care including therapies, pain management, bracing and close post-operative follow-up monitoring for complications that may impeded. The expectation of surgery is not to regain “normal” function, but to avoid further progression of symptoms and possibly regain some functionality (perhaps without power) of the affected limb. Nerve decompression is a common surgical intervention for anatomical regions of focal nerve compression leading to nerve injury. Common examples include the ulnar nerve at the cubital tunnel, median nerve at the carpal tunnel, and peroneal nerve at the fibular neck. In the case of an acute nerve transection, an end-to-end repair can be done within hours to days. If such a repair is not possible in a timely manner, within 3-12 months after injury a nerve exploration and reconstruction with allograft may be beneficial in cases of nerve transection as a result of trauma. This repair relies upon regrowth of the normal portions of the nerve through the residual pathways after the injured distal nerve is cleared away (Wallerian degeneration). Nerve transfer may be necessary if nerve reconstruction is not possible to facilitate reinnervation. With either intervention, nerve regeneration occurs slowly with the ultimate functional outcome from nerve reconstruction surgery not be apparent for 1-3 years. Tumor resection may be necessary to reduce compression or limit vascular compromise. When surgical intervention for purposes of reinnervation is not possible, other surgical management options exist including muscle or tendon transfers, arthrodesis or soft tissue releases. Most peripheral nerve disorders are managed non-operatively. In cases where an underlying medical condition leads to peripheral nerve manifestations, specifically addressing and optimizing treatment of that disease process is indicated. Treatment of the peripheral nerve disorder focuses on symptom management, therapy paradigms including strengthening and complication avoidance. Physical Therapy, Occupational Therapy and Hand Therapy are integral members of the treatment team and focus on the neurologic recovery of the muscle and function including maintaining joint range of motion, focused strengthening exercises and the use of modalities including electrical stimulation to stimulate muscle contraction and strengthening. Additionally, therapy can help correct associated biomechanical dysfunction which does not directly result from the peripheral nerve injury but contributes to functional impairment and can teach compensatory strategies for functional tasks. In cases of significant neuropathic pain resulting from the peripheral nerve injury they can be helpful administering pain relieving modalities including desensitization, contrast baths and transcutaneous electrical stimulation. Most importantly, these clinicians empower the patient and their care providers to perform self-directed stretching, exercises and modalities. Orthotics can be helpful in creating supportive or functional braces to avoid complications and help to improve function. Often, pain is a major complication resulting from peripheral nerve disorders and can significantly limit treatment and function. A multimodal approach including medication, interventions such as steroid injections or regional anesthesia, and psychologic interventions like cognitive behavioral therapy can be beneficial.


The outlook for recovery after peripheral nerve injury and dysfunction depends on the etiology of the disorder and the treatment options available to correct the underlying disease process.  Early recognition of the correct diagnosis and tailoring of the appropriate surgical and non-surgical management will provide the best chance for improving function and quality of life. In cases of surgical intervention, recovery is often slow and dependent on the dedicated participation of the patient in therapies and exercises. We highly recommend a multidisciplinary approach for management of these challenging cases to best address and improve all of the associated complications resulting from peripheral nerve injuries.