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Overview of Peripheral Nervous System Disorders


Michael Rubin

, MDCM, New York Presbyterian Hospital-Cornell Medical Center

Reviewed/Revised Apr 2022
Topic Resources

The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior horn cells, although technically part of the central nervous system (CNS), are sometimes discussed with the peripheral nervous system because they are part of the motor unit.

Motor neuron dysfunction results in muscle weakness or paralysis. Sensory neuron dysfunction results in abnormal or lost sensation. Some disorders are progressive and fatal.


A motor unit consists of

  • An anterior horn cell

  • Its motor axon

  • The muscle fibers it innervates

  • The connection between them (neuromuscular junction)

The anterior horn cells are located in the gray matter of the spinal cord and thus are technically part of the CNS. In contrast to the motor system, the cell bodies of the afferent sensory fibers lie outside the spinal cord, in dorsal root ganglia.

Nerve fibers outside the spinal cord join to form anterior (ventral) motor nerve roots and posterior (dorsal) sensory nerve roots. The ventral and dorsal roots combine to form a spinal nerve. Thirty of the 31 pairs of spinal nerves have dorsal and ventral roots; C1 has no sensory root (see figure Spinal nerve Spinal Nerve Spinal Nerve ).

Spinal Nerve

Spinal Nerve

The spinal nerves exit the vertebral column via an intervertebral foramen. Because the spinal cord is shorter than the vertebral column, the more caudal the spinal nerve, the further the foramen is from the corresponding cord segment. Thus, in the lumbosacral region, nerve roots from lower cord segments descend within the spinal column in a near-vertical sheaf, forming the cauda equina. Just beyond the intervertebral foramen, spinal nerves branch into several parts.

Branches of the cervical and lumbosacral spinal nerves anastomose peripherally into plexuses, then branch into nerve trunks that terminate up to 1 m away in peripheral structures (see figure Plexuses Plexuses Plexuses ). The intercostal nerves are segmental.



The term peripheral nerve refers to the part of a spinal nerve distal to the root and plexus. Peripheral nerves are bundles of nerve fibers. They range in diameter from 0.3 to 22 mcm (1 mcm equals 1000 circular mils). Schwann cells form a thin cytoplasmic tube around each fiber and further wrap larger fibers in a multilayered insulating membrane (myelin sheath).


The myelin sheath enhances impulse conduction. The largest and most heavily myelinated fibers conduct quickly; they convey motor, touch, and proprioceptive impulses. The less myelinated and unmyelinated fibers conduct more slowly; they convey pain, temperature, and autonomic impulses.

Because nerves are metabolically active tissues, they require nutrients, supplied by blood vessels called the vasa nervorum.


Peripheral nerve disorders can result from damage to or dysfunction of the one of the following:

  • Cell body

  • Myelin sheath

  • Axons

  • Neuromuscular junction

Disorders can be genetic or acquired (due to toxic, metabolic, traumatic, infectious, or inflammatory conditions—see table Some Causes of Peripheral Nervous System Disorders Some Causes of Peripheral Nervous System Disorders Some Causes of Peripheral Nervous System Disorders ).

Peripheral neuropathies may affect



Because sensory and motor cell bodies are in different locations, a nerve cell body disorder typically affects either the sensory or motor component but rarely both.


Damage to the myelin sheath (demyelination Overview of Demyelinating Disorders Myelin sheaths cover many nerve fibers in the central and peripheral nervous system; they accelerate axonal transmission of neural impulses. Disorders that affect myelin interrupt nerve transmission... read more ) slows nerve conduction. Demyelination affects mainly heavily myelinated fibers, causing large-fiber sensory dysfunction (buzzing and tingling sensations), motor weakness, and diminished reflexes. The hallmark of acquired demyelinating polyneuropathy is severe motor weakness with minimal atrophy.

Because the vasa nervorum do not reach the center of a nerve, centrally located fascicles are most vulnerable to vascular disorders (eg, vasculitis, ischemia). These disorders result in small-fiber sensory dysfunction (sharp pain and burning sensations, decreased temperature sensation), motor weakness proportional to atrophy, and less severe reflex abnormalities than in other nerve disorders. The distal two thirds of a limb is affected most. Initially, deficits tend to be asymmetric because the vasculitic or ischemic process is random. However, multiple infarcts may later coalesce, causing symmetric deficits (polyneuropathy Multiple Mononeuropathy Multiple mononeuropathies are characterized by sensory disturbances and weakness in the distribution of ≥ 2 affected peripheral nerves. (See also Overview of Peripheral Nervous System Disorders... read more ).

Toxic-metabolic or genetic disorders usually begin symmetrically. Immune-mediated processes may be symmetric or, early in rapidly evolving processes, asymmetric.

Damage to the axon transport system for cellular constituents, especially microtubules and microfilaments, causes significant axon dysfunction. First affected are the smaller fibers (because they have greater metabolic requirements) at the most distal part of the nerve. Then, axonal degeneration slowly ascends, producing the characteristic distal-to-proximal pattern of symptoms (stocking-glove sensory loss, followed by weakness).


After axonal damage, the fiber regrows within the Schwann cell tube at about 1 mm/day once the pathologic process ends. However, regrowth may be misdirected, causing aberrant innervation (eg, of fibers in the wrong muscle, of a touch receptor at the wrong site, or of a temperature instead of a touch receptor).

Regeneration is impossible when the cell body dies and is unlikely when the axon is completely lost.


  • Deficits defined by history and examination

  • Attention to clinical clues to peripheral nervous system disorders

  • Usually nerve conduction studies and electromyography

  • Sometimes nerve or skin punch biopsy

  • Genetic testing (for hereditary neuropathies)

Clinical evaluation

History should focus on type of symptom, onset, progression, and location, as well as information about potential causes (eg, family history, toxic exposures, past medical disorders).

Physicians should suspect a peripheral nervous system disorder based on the pattern and type of neurologic deficits, especially if deficits are localized to particular nerve roots, spinal nerves, plexuses, specific peripheral nerves, or a combination. These disorders are also suspected in patients with mixed sensory and motor deficits, with multiple foci, or with a focus that is incompatible with a single anatomic site in the CNS.

Physicians should also suspect peripheral nervous system disorders in patients with generalized or diffuse weakness but no sensory deficits; in these cases, peripheral nervous system disorders may be overlooked because they are not the most likely cause of such symptoms.

Clues that a peripheral nervous system disorder may be the cause of generalized weakness include the following:

Clues that the cause may not be a peripheral nervous system disorder include

  • Hyperreflexia

  • Hypertonia

These deficits suggest an upper motor neuron disorder Symptoms and Signs as the cause of weakness. Hyporeflexia is consistent with peripheral nervous system deficits but is nonspecific. For example, acute cervical transverse myelitis can mimic Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more , particularly in patients with preexisting neuropathy.

Although many exceptions are possible, certain clinical clues may also suggest possible causes of peripheral nervous system deficits (see table Clinical Clues to Causes of Peripheral Nervous System Disorders Clinical Clues to Causes of Peripheral Nervous System* Disorders Clinical Clues to Causes of Peripheral Nervous System* Disorders ).


Clinical assessment narrows diagnostic possibilities and guides further testing.


  • Differentiate peripheral nervous system disorders from neuromuscular junction and muscle disorders

  • Localize site of peripheral nervous system dysfunction (eg, root, plexus, peripheral nerve)

  • Distinguish demyelinating disorders (very slow conduction) from axonal disorders

Patients with weakness but no sensory deficits can be evaluated with electrodiagnostic testing.

Other testing, such as imaging, depends on whether a CNS lesion must be ruled out (eg, MRI if all limbs are affected, to rule out cervical spinal cord compression).

Nerve biopsy is occasionally done to help differentiate demyelinating from vasculitic large-fiber neuropathies. If vasculitis is a consideration, the biopsy specimen should include skin and muscle to increase the likelihood of a definitive diagnosis. If a small-fiber neuropathy is suspected, skin punch biopsy can be done; loss of nerve endings supports that diagnosis.

Pearls & Pitfalls

  • If clinical findings and electrodiagnostic test results are inconclusive, do a biopsy (nerve biopsy for suspected large-fiber neuropathy or skin punch biopsy for suspected small-fiber neuropathy).

  • If all limbs are affected, consider MRI to rule out cervical spinal cord compression.

Genetic testing is indicated if a hereditary neuropathy is suspected.


  • Treatment of underlying disorder

  • Supportive care, often by a multidisciplinary team

Treatment of a peripheral nerve disorder is directed at the underlying disorder when possible. Otherwise, treatment is supportive. A multidisciplinary team approach helps patients cope with progressive neurologic disability:

  • Physical therapists may help patients maintain muscle function.

  • Occupational therapists can recommend adaptive braces and walking devices to help with activities of daily living.

  • Speech and language therapists may provide alternative communication devices.

  • If pharyngeal weakness develops, a speech therapist or a multidisciplinary team that specializes in swallowing problems can help assess risk of aspiration and recommend measures for prevention (eg, precautions for oral feeding and/or need for tube feedings).

  • A gastroenterologist may recommend percutaneous endoscopic gastrostomy.

  • If respiratory weakness develops, forced vital capacity is measured, and pulmonary or intensive care specialists help assess whether intensive care, noninvasive respiratory support (eg, bilevel positive airway pressure), and tracheostomy with full ventilatory support are needed.

Early in fatal disorders, health care practitioners must talk frankly with patients, family members, and caregivers to determine the level of intervention acceptable. Patients are encouraged to put their decisions in writing (advance directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more ) before they become incapacitated. These decisions should be reviewed and confirmed at various stages of the disorder.

Key Points

  • Peripheral nervous system disorders are often suspected based on clinical findings (eg, stocking-glove distribution, hyporeflexia, distal muscle weakness and wasting, localization to a peripheral nerve distribution).

  • If patients have profound motor weakness with minimal atrophy and areflexia, consider acquired demyelinating polyneuropathy.

  • If patients have abnormal pain and temperature sensation and atrophy in proportion to weakness (sometimes with disproportionate preservation of reflexes), consider a vasculitic or ischemic neuropathy.

  • If patients have chronic progressive muscle weakness, fasciculations, muscle atrophy, and no sensory deficits, consider motor neuron disease.

  • Nerve conduction studies and electromyography help identify level of involvement (root, plexus, peripheral nerve, neuromuscular junction, muscle fiber) and help distinguish demyelinating from axonal disorders.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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