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    Peripheral Neuropathy

    Cardinal Presentations / Presenting Problems, Environmental Injuries / Exposures, Metabolic / Endocrine, Neurological, Toxicology, Trauma

    Last Updated May 31, 2023
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    By Julian Marsden, Alexander Forrester

    First 5 Minutes

    Suspect Guillain-Barré syndrome (GBS) [1]:

    • Recently ill (upper respiratory tract infection, vaccination), with
    • Asymmetric muscle weakness, reduced reflexes, and
    • Variable sensory involvement.

    Suspect Central Nervous System pathology, with speech disturbance, ataxia, visual deficits, cranial nerve involvement or bladder and bowel incontinence [2].


    Peripheral neuropathies affect 1%-7% of the general population, particularly >50 years old. They can be categorized as [3]:

    • Mononeuropathy
      • Restricted to single nerve, myotome or dermatome.
    • Mononeuropathy multiplex
      • Multiple concurrent mononeuropathies.
    • Polyneuropathy
      • Length dependant; diffuse and symmetric affecting most distal nerve segments first. Signs and symptoms usually reach the knees before finger involvement.
      • Non-length dependant; asymmetric, may involve proximal nerves.
    • Autonomic
      • Orthostatic intolerance, gastroparesis, constipation, diarrhea, neurogenic bladder, erectile dysfunction, pupillomotor and vasomotor symptoms.

    Table 1. Signs and Symptoms of Peripheral Neuropathy [4].

    Common causes or peripheral neuropathy [4]:

    • Diabetes mellitus
    • Nerve compression injury (i.e., carpal tunnel syndrome, radial nerve palsy)
    • Alcohol use
    • Toxin exposure (i.e., heavy metals, carbon monoxide, acrylamide, glue, etc.)
    • Hereditary diseases
    • Nutritional deficiencies (i.e., Vitamin B12 deficiency)

    Diabetic Peripheral Neuropathy

    • Most common cause of distal sensory polyneuropathy (DSP), occurs in ½ of all diabetes patients, and 10%-25% of prediabetic patients [4].
    • Aggressive glycemic control decreases risk and rate of DSP progression in type-1 diabetes, but not type 2 [4]. Not ED issue but helps to educate patient.
    • Typically begins in toes and progresses rostral. Expect finger involvement once neuropathy has reached level of the knees or higher. Commonly known as stocking and glove distribution [5].

    Nerve Compression or Injury [2]:

    • Consider for asymmetric symptoms associated with numbness, imbalance, falls, ataxia or paresthesia.
    • May follow dermatomal pattern.
    • Spinal degeneration may lead to radiculopathy.

    Table 2. Common nerve compression syndromes [6] [7] [8] [9] [10] [11]

    Alcohol Use [12]

    • Slow onset (months to years), lower limbs affected more than upper, distal to proximal.
    • Primarily sensory with paraesthesia, numbness and impaired vibration sensation.

    Toxin Exposure

    • Fulminant symptoms (fatigue, numbness/tingling, vision problems spasticity etc.) with rapid progression, typically associated with toxic substance ingestion, see Table 2. [2].
    • Neurotoxic medications, including chemotherapy drugs, tend to have temporal or chronic onset of symptoms depending on dose. Concomitant involvement of feet and hands [13]. See Table 2.
    • Common peripheral neuropathy causing medications and toxins [2]:
      • Antiepileptic drugs (lithium, phenytoin)
      • Antimicrobial / antiviral drugs (i.e., chloroquine, dapsone, isoniazid)
      • Cardiovascular drugs (i.e., amiodarone, hydralazine, statins)
      • Chemotherapy agents (i.e., bortezomib, cisplatin, epothilones)
      • Other drugs (i.e., amitriptyline, cimetidine, colchicine)
      • Metals (i.e., arsenic, lead, mercury, thallium, gold)
      • Solvents (i.e., glue, carbon monoxide, hexacarbons, acrylamide)

    Nutritional Deficiencies

    Table 3. Common Nutritional Deficiencies Causing Peripheral Neuropathies [4] [13] [14]

    Diagnostic Process

    • History [2] [3] [13]
      • Trauma or compression
      • Recent or chronic exposure to toxins (i.e., in the workplace)
      • Drug and alcohol use
      • Recent infection or illness
      • Vaccination status
      • Family history of neurological disease (i.e., CMT)
      • Sudden, usually painless visual field deficits (not associated with giant cell arteritis)
    • Physical Exam [2] [3] [13]
      • Complete neurological examination including cranial nerves.
      • Fundoscopy[JM1] [AF2] , (pale optic disc swelling with flame hemorrhages indicating anterior ischemic optic neuropathy [15].)
      • Assess for muscle fasciculations.
      • Muscle bulk and tone (i.e., distal calf atrophy)
      • Structural deformities (i.e., hammertoes), indicating congenital / inherited condition.
      • Asymmetrical distribution.
      • External signs of trauma
    • Laboratory Tests [2] [3] [13]
      • Complete blood count (CBC)
      • Thyroid-stimulating hormone level
      • Vitamin B12  +/- methylmalonic acid (elevated in Vit B12 deficiency)
      • Serum protein electrophoresis with immunofixation
      • Initiate metabolic panel and diabetic screening, follow-up by specialist or family physician.

    Imaging if suspect central cause.

    MRI does not have high sensitivity or specificity for peripheral neuropathy diagnosis. MRI better for atypical or idiopathic neuropathies, suspected radiculopathies. or myelopathies [2].

    Figure 1. Simple algorithm for diagnosing common peripheral neuropathy causes.

    Recommended Treatment

    • Primary goal is identification and treatment of underlying cause (i.e. diabetes mellitus, nutrient deficiency, alcohol use etc.) [4] [2] [13]
      • Educate diabetic patients on importance of foot care.
    • Neuropathic pain management [4] [2] [3] [13]
      • First-line medications are anticonvulsants (gabapentin, pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline) and.
      • Number needed to treat to achieve 50% reduction in pain for 1 patient:
        • Tricyclic antidepressants (majority of studies used amitriptyline) = 3.6
        • serotonin-norepinephrine reuptake inhibitors (SNRI) (venlafaxine, duloxetine) = 6.4
        • Gabapentin = 7.2
        • Pregabalin = 7.7
    • Guillain-Barré syndrome (GBS) [1] [16]
      • Airway management for acutely ill GBS patients.
      • Admit to the Intensive Care Unit and seen by a neurologist.

    Criteria For Hospital Admission

    • Severe pain that is not resolving [3] [13].
    • Progressive weakness or sensory loss that affects mobility or self-care [2] [3] [13].
    • Complications such as infection, ulceration, or gangrene in the affected limbs [5].
    • Suspected or confirmed diagnosis of GBS, chronic inflammatory demyelinating polyneuropathy or vasculitis neuropathy that may require immunotherapy [1].
    • Need for specialized diagnostic tests or procedures that are not available in outpatient settings.

    Criteria For Transfer To Another Facility

    Transport to another facility will depend on regional guidelines, and:

    • Required specialty consult not available at current facility.
    • Unable to manage complications associated with acute or subacute conditions requiring specialized ICU staff.

    Criteria For Close Observation And/or Consult

    Consult neurology when [2] [13]:

    • Pure motor or autonomic signs with absence of sensory changes.
    • Urgent referral indicated for acute, subacute, severe or progressive symptoms (i.e., GBS suspected).
    • Multifocal
    • Length independent (polyradiculoneuropathy)
    • Severe dysautonomia
    • Suspected hereditary disease (i.e., Charcot-Marie-Tooth).

    Criteria For Safe Discharge Home

    • Able to ambulate safely.
    • Pain management addressed.
    • Follow up arrangements in place.

    Quality Of Evidence?


    Based on the literature reviewed, there was agreement across studies on the diagnosis and management of patients with Peripheral Neuropathy. Given the heterogeneous nature of the research quality of evidence is Moderate.


    Related Information


    Reference List

    1. Florian et al.  To be, or not to be… Guillain-Barré Syndrome. Autoimmunity Reviews 2021, 20(12), 1-26. doi:10.1016/j.autrev.2021.102983

    2. Castelli et al. Peripheral Neuropathy; Evaluation and Differential Diagnosis. American Family Physician 2020, 102(12), 732-739.

    3. Doughty & Seyedsadjadi. Approach to Periheral Neuropathy for the Primary Care Clinician. The American Journal of Medicine 2018, 131(9), 1010-1016. doi:10.1016/j.amjmed.2017.12.042

    4. Barrell & Smith.  Peripheral Neuropathy. Medical Clinics North America 2018, 103(2), 383-397. doi:10.1016/j.mcna.2018.10.006

    5. Sloan et al. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nature Reviews. Endocrinology 2021, 17(7), 400-420. doi:10.1038/s41574-021-00496-z

    6. Ansari. Saturday Night Palsy. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2023. https://www.ncbi.nlm.nih.gov/books/NBK557520/

    7. Sevy & Varacallo. Carpal Tunnel Syndrome. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. https://www.ncbi.nlm.nih.gov/books/NBK448179/

    8. Chauhan et al. Cubital Tunnel Syndrome. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2023. https://www.ncbi.nlm.nih.gov/books/NBK538259/

    9. Davis et al. Sciatica. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2023. https://www.ncbi.nlm.nih.gov/books/NBK507908/

    10. Lezak et al. Peroneal Nerve Injury. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. https://www.ncbi.nlm.nih.gov/books/NBK549859/

    11. Coffey & Gupta. Meralgia Paresthetica. Retrieved from In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022. https://www.ncbi.nlm.nih.gov/books/NBK557735/

    12. Julian et al. Alcohol-related Peripheral Neuroathy: A Systematic Review and Meta-analysis. Journal of Neurology 2019, 266(12), 2907-2919. doi:10.1007/s00415-018-9123-1

    13. Watson & Dyck. Peripjheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management. Mayo Clinic Proceedings 2015, 90(7), 940-951. doi:10.1016/j.mayocp.2015.05.004

    14. Staff. Vitamin B6. Retrieved May 18, 2023, from Mayo Clinic 2021. https://www.mayoclinic.org/drugs-supplements-vitamin-b6/art-20363468

    15. Effron et al. Fundoscopic Findings. In S. L. Knoop KJ, The Atlas of Emergency Medicine, 4e 2016. (pp. 1-26). McGraw Hill. Retrieved 05 18, 2023, from https://accessmedicine.mhmedical.com/content.aspx?bookid=1763&sectionid=125433189

    16. van Leeuwen N et al. Hospital Admissions, Transfers and Costs of Guillain-Barré Syndrome. PLoS One 2016, 11(2), 1-12. doi:10.1371/journal.pone.0143837


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