Disorders of the peripheral nervous system (PNS) can manifest in a myriad of ways, often presenting diagnostic challenges to clinicians. This chapter delves into the complexities of peripheral neuropathies, providing a comprehensive overview tailored for those preparing for the In-service exam and ABPN Psychiatry Boards exam.

We begin by defining the broad term “peripheral neuropathy” and its subcategories, including polyneuropathies, radiculopathies, and mononeuropathies. The chapter then transitions to neuromuscular junction disorders, emphasizing conditions like myasthenia gravis and Lambert-Eaton myasthenic syndrome. Lastly, we explore myopathies, both inflammatory and inherited, providing insights into their pathophysiology, presentation, and management.

In sum, this chapter serves as a comprehensive guide to peripheral nervous system disorders, ensuring a robust understanding for those aiming to excel in their exams and clinical practice.

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Peripheral Neuropathies


  • Polyneuropathy is defined as a neuropathic disease that involves many nerves in a generalized distribution.
  • Causes of peripheral polyneuropathy can be either axonal and/or demyelinating.

Small fiber polyneuropathy

  • Presents with burning/tingling pain, usually felt to be more significant while trying to go to sleep.
  • Causes of small fiber neuropathy are diverse but include diabetes, B12 deficiency, chronic alcohol use, autoimmune diseases (Sjörgren syndrome), amyloidosis, chemotherapeutic agents, HIV, leprosy, and Fabry’s disease.
  • Patients with small fiber neuropathy can also have concurrent autonomic neuropathy.
  • Diagnostic testing:
    • Skin biopsy to evaluate small fiber density.
    • Quantitative sudomotor axon test (QSART) to evaluate postganglionic sympathetic sudomotor axons.

Neuropathy of systemic disease


  • Responsible for one-third of all neuropathies (most common cause).
  • Can present as a small fiber polyneuropathy, large fiber peripheral polyneuropathy, multifocal neuropathy, mononeuropathy, and/or lumbosacral plexopathy.
  • EMG testing will show axonal pathology.
  • Patients should be screened with a hemoglobin A1c level, fasting glucose, or a 2-hour glucose tolerance test.

Critical illness neuropathy

  • Presents with distal axonal sensorimotor polyneuropathy which leads to limb weakness or difficulty weaning off of artificial ventilation.
  • Sepsis, SIRS, and multiorgan failure are risk factors.
  • Patients with critical illness neuropathy may also have concurrent critical illness myopathy.
  • Symptoms can take months to years to recover and one-third of patients never walk independently again.

B12 deficiency

  • Seen in patients with poor diets: Chronic alcoholism, post-gastric bypass, and nitrous oxide abuse.
  • If B12 levels are borderline abnormal, you should check methylmalonic acid and homocysteine levels if the concern is high.

Copper deficiency

  • Presentation is similar to B12 deficiency.
  • Seen in patients with a malabsorption disorder or from excessive zinc intake.

Connective tissue disease

  • Peripheral neuropathy can be seen in patients with polyarteritis nodosa, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, giant cell arteritis, lupus, and Wegener’s granulomatosis.


  • HIV-related distal symmetric polyneuropathy is the most common neurological complication of HIV, affecting 50% of patients.


  • Chronic hypothyroidism can present with mono- or polyneuropathy due to compression of nerves.

MGUS/Multiple myeloma

  • Presents as a chronic demyelinating disorder that can be similar phenotypically to those with CIDP.


  • Seen in about 28-50% of hepatitis C patients.

Acute intermittent porphyria

  • Presents with proximal upper extremity weakness due to an axonal motor neuropathy.
  • Concurrent symptoms include psychiatric symptoms, vomiting, abdominal pain, and constipation.

Toxins-related neuropathies

Alcohol-related peripheral neuropathy

  • Classified as a toxic and not a nutritional neuropathy.
  • While patients with chronic alcohol use are at risk of B12 deficiency and the associated peripheral neuropathy, studies have shown that chronic alcohol use can lead to axonal neuropathy independent of B12 or B1 levels.
  • EMG testing will show sensorimotor axonal neuropathy with possible secondary demyelination.


  • The most common antibiotics to cause peripheral neuropathy are:
    • Metronidazole, linezolid, and dapsone.
  • It is also relatively common with  chloroquine, fluoroquinolones, isoniazid, nitrofurantoin, and sulfasalazine


  • Classically caused by platinum agents (cisplatin), vinca alkaloids (vincristine), and taxanes (paclitaxel, docetaxel).

Heavy metals

  • Lead, arsenic, mercury, thallium
  • Chronic lead exposure presents with motor-predominant neuropathy and can present with an ankle or wrist drop.

Autoimmune Neuropathies

Guillain-Barre syndrome (GBS)

  • GBS represents an acute, monophasic immune-mediated polyneuropathy often preceded by infection (such as campylobacter jejuni, which causes a diarrheal illness) or other triggers (i.e. vaccine).
  • Acute inflammatory demyelinating polyneuropathy (AIDP):
    • Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form of GBS in the US (85-90%).
    • Commonly presents with acutely evolving symmetric weakness with hypoactive reflexes, starting distally and then extending proximally.
    • Supportive features include mild sensory loss, a progression of symptoms up to 8 weeks, autonomic dysfunction, and possible cranial nerve involvement.
    • Dysautonomia and respiratory muscle weakness with ventilatory failure are potentially serious complications
    • Spirometry is the most effective measure of respiratory muscle function in these patients. Oxygen saturation is not a sensitive marker for impending respiratory dysfunction in neuromuscular disorders.
  • Diagnostic testing:
    • CSF studies will show an elevated CSF protein and normal WBC count (termed albuminocytologic dissociation).
  • Imaging:
    • Contrast enhancement of the cauda equina and mild thickening of nerve roots.


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