Peripheral Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and Medications (Peripheral Nerve and Motor Neuron Disorders October 2020)

Educational Objectives

The goal of this program is to improve diagnosis and management of peripheral nerve and motor neuron disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose overt and subtle presentations of vitamin deficiencies.
2. Define coasting.
3. Critically assess the medication list of a patient with a new or worsening neuropathy.

Summary

Deficiency of vitamin B₁₂: This diagnosis is typically considered in any patient with a peripheral neuropathy; in some cases, laboratory findings are in the normal range, but the patient has cellular deficiency of vitamin B₁₂; testing methylmalonic acid allows assessment of cellular levels of vitamin B₁₂; clinical signs that suggest deficiency in a patient with sensory loss include associated ataxia, cognitive deficits, and onset of symptoms simultaneously in the hands and feet (reflecting the myeloneuropathy at the level of the spinal cord); on cervical MRI, a typical finding is T2 hyperintensity in the dorsal columns.

Deviation from classic presentation: Vitamin B₁₂ levels are routinely measured in patients presenting with neurologic symptoms; for vitamin B₁₂ levels in the marginal-to-low range, vitamin deficiency is less likely to be the cause if the patient shows signs of a small fiber neuropathy than in the setting of, eg, a mild large fiber neuropathy that presents without frank ataxia or cognitive deficit (a late manifestation of subacute combined degeneration); regardless, vitamin B₁₂ levels should be replenished to avoid development of deficiency and further neurologic damage; for neuropathies that do not conform to the classic pattern, alternative causes should be investigated; conversely, deficiency of vitamin B₁₂ should be ruled out in patients who have another condition associated with neuropathy (eg, diabetes).

Etiology of deficiency of vitamin B₁₂: Pernicious anemia is a major cause of deficiency; in elderly patients, atrophic gastritis and use of proton pump inhibitors are more common causes than autoimmune disorders; patients with a gastric bypass may be receiving inadequate supplementation; Crohn disease or gastrointestinal surgery may impair absorption; metformin is associated with poor absorption of vitamin B₁₂.

Replacement of vitamin B₁₂: Parenteral or high-dose oral replacement is reasonable.

Vitamin E: Patients with deficiency typically present with ataxia and large fiber neuropathy, with upper motor neuron signs (presentation may resemble Friedreich ataxia); deficiency in the setting of malabsorption of fat is rare; genetic causes include abetalipoproteinemia and ataxia with vitamin E deficiency.

Pyridoxine (vitamin B₆): Both deficiency and excess are associated with neuropathy; deficiency may develop after prolonged treatment with isoniazid or hydralazine; excessive ingestion of vitamin B₆ is a more common issue and may cause a dorsal root ganglionopathy, which begins with mild paresthesia; with severe and prolonged overuse, the patient may develop an ataxic ganglionopathy and sensory neuronopathy; vitamin B₆ is found in many supplements for “nerve health”; patients should take no more than 25 mg/d; supplementation is unnecessary because the vitamin is readily available in food; exceeding 2 g/d is strongly associated with neuropathy; however, over a long period, even 50 mg/d may lead to paresthesia; symptoms are typically reversible.

Thiamine: Deficiency of thiamine may present as an axonal sensory neuropathy with cranial nerve involvement or symptoms resembling Guillain-Barré syndrome; in Wernicke-Korsakoff syndrome, thiamine should be provided before administering glucose to avoid exacerbating the deficiency.

Alcohol-related neuropathy: Alcohol is toxic to neurons of the dorsal root ganglia; all patients with a neuropathy should limit intake of alcohol; when alcohol is the main cause, it tends to be a painful, small fiber neuropathy; however, establishing that alcohol is the cause of neuropathy can be challenging; alcohol may worsen underlying hereditary neuropathies.

Renal failure: Causes neuropathy, but dialysis prevents uremic neuropathy; renal failure and diabetes may act synergistically to worsen neuropathy; uremic neuropathy is typically reversible.

Heavy metals: The heavy metals most often associated with neuropathy are lead, arsenic, thallium, and mercury; heavy metal neuropathies are uncommon in the United States; lead neuropathy has become rare because this metal has been removed from gasoline and paint; similarly, neuropathies related to arsenic and thallium are seen infrequently because of their removal from manufacturing processes; significant ingestion of arsenic or thallium produces severe gastrointestinal symptoms, a presentation resembling Guillain-Barré syndrome; patients should be examined for hair loss and Mees lines in the nail beds; 24-hour urine testing is used to rule out heavy metal intoxication.

Industrial agents: Hexacarbons are abused as inhalants; these agents may be used in machine shops; the clinician should ask about occupational exposure and hobbies that involve solvents.

Medications: Drugs associated with neuropathies include isoniazid, dapsone, nitrofurantoin, fluoroquinolones, and chemotherapeutic agents; the main classes of chemotherapeutic drugs that cause neuropathy are the platinates, taxanes, vinca alkaloids, and proteasome inhibitors.

Platinum-based compounds: Tend to act at the level of the dorsal root ganglion, producing sensory-predominant neuropathy, sensory ataxia, and minimal pain; platinum compounds may be associated with coasting (worsening of the neuropathy for weeks to months after discontinuation of the drug); oxaliplatin — associated with an acute neuropathy of cold-induced hyperpathia at the time of infusion; patients develop severe pain when they touch cold items or drink cold beverages.

Taxanes and vinca alkaloids: These agents target microtubules; taxanes cause an acute pain syndrome and, eventually, a sensory neuropathy; vinca alkaloids are more likely to cause weakness (especially in children, footdrop may develop).

Prognosis of chemotherapy-induced neuropathies: Milder neuropathies may be reversible; platinum-induced conditions are less likely to be reversible because they cause death of the dorsal root ganglion neurons; neuropathies related to taxanes, vinca alkaloids, and proteasome inhibitors are often reversible; although sensory loss improves, patients may be left with chronic symptoms of pain or imbalance.

Checkpoint inhibitors: These drugs allow the immune system to attack the nervous system, potentially causing myopathy, defects at the neuromuscular junction, chronic inflammatory demyelinating polyradiculoneuropathy(CIDP), or vasculitic neuropathy; these conditions may be severe or fatal; if treated early, some recovery is possible.

Biologic toxins: Seafood-related toxicities are usually associated with plankton that produce toxins affecting voltage-gated sodium channels; these include ciguatera toxin, saxitoxin (from mollusks), and the tetrodotoxin associated with puffer fish; these toxins produce sensory symptoms and, in severe cases, weakness.

Readings

Staff NP. Peripheral neuropathies due to vitamin and mineral deficiencies, toxins, and medications. Continuum (Minneap Minn) 2020;26(5, Peripheral Nerve and Motor Neuron Disorders).

Disclosures

For this program, the following was disclosed: Dr. Staff serves as an associate editor of Stem Cell Research & Therapy and receives research/grant support from BrainStorm Cell Limited; Disarm Therapeutics; the National Institutes of Health (R01 CA 211887); Orion Therapeutics, LLC; and Regenerative Medicine Minnesota (RMM 11215 CT002).

Unlabeled Use of Products/Investigational Use Disclosure: Dr. Staff reports no disclosure.

To view disclosures of planning committee members with relevant financial relationships, visit: legacy.audio-digest.org/continuumaudio/committee. All other members of the planning committee report nothing to disclose.

The material presented in Continuum Audio has been made available by the AAN for educational purposes only and is not intended to represent the only method or procedure for the medical situations discussed but rather to present an approach, view, statement, or opinion of the speaker(s), which may be helpful to others who face similar situations. Opinions expressed by the speakers are not necessarily those of the AAN, its affiliates, or the publisher. The AAN, its affiliates, and the publisher disclaim any liability to any party for the accuracy, completeness, efficacy, or availability of the material contained in this program (including drug dosages) or for any damages arising out of the use or nonuse of any of the material contained in this program.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

CA090507

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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