Toxic polyneuropathy is a term encompassing the injury of the peripheral nerves by pharmacological agents, drugs of abuse, and toxic compounds found in different occupations. Sensory loss, motor weakness, and pain are typical signs. The differential diagnosis is quite broad, which is why a detailed patient history, a complete physical exam, and a thorough laboratory workup are vital in order to identify the underlying cause.
Presentation
The list of substances that may cause toxic polyneuropathy is quite long with some of the most important being [1] [2] [3] [4] [5] [6]:
- Therapeutic drugs - Chemotherapeutics, lithium, antimicrobial agents (isoniazid, metronidazole, nitrofurantoin), cardiovascular (amiodarone, digoxin, hydralazine, nitroprusside), vinca alkaloids, misoprostol, and phenytoin are listed as some of the most common drugs that might induce toxic polyneuropathy [1] [3] [4] [6].
- Occupational pollutants and substances - Heavy metals (arsenic, lead, thallium, mercury) and a number of industrial agents (ethylene oxide, organophosphates, hexacarbons, acrylamide, and several other) [1] [2] [7].
- Drugs of abuse - Alcohol and heroin are the two main substances of abuse that can cause polyneuropathy [1] [6].
The clinical presentation, usually appearing weeks after exposure to the harmful agent, is centered around two main components - sensory and motor deficits [1] [4]. A tingling sensation or numbness in the distal extremities is considered to be one of the first signs of sensory involvement, particularly after the use of chemotherapeutic drugs, which may lead to disturbances in gait, pruritus, and moderate to severe sharp pain [5]. Conversely, motor weakness, typical for heavy metal exposure, manifests as weakness in the extremities (eg. wrist drop) and loss of deep tendon reflexes [1] [5].
Entire Body System
- Agent Orange
Orange and peripheral neuropathy. [foundationforpn.org]
Other causes include certain infections (eg, Lyme disease ), drugs (eg, nitrous oxide), and exposure to certain chemicals (eg, Agent Orange, n -hexane) or heavy metals (eg, lead, arsenic, mercury). [merckmanuals.com]
- Myxedema
[…] nodosa Systemic lupus erythematosus Sjögren's syndrome Sarcoidosis Leprosy HIV/AIDS Multifocal variant of CIDP Hereditary predisposition to pressure palsies TABLE 1 Neuropathies by Pattern of Involvement Focal Entrapment Common sites of compression Myxedema [aafp.org]
Respiratoric
- Pneumonia
These include hydroxycarbamide ( Hydrea ), a drug that has been used to boost the activity of ddI and slow the replication of HIV; isoniazid for tuberculosis; dapsone for Pneumocystis pneumonia; ethambutol ( Myambutol ) for Mycobacterium avium intracellulare [aidsmap.com]
Symptoms of the disease manifest themselves either in the first week (especially dangerous with heart failure and pneumonia), or after the 4th week from the moment of infection. [acikgunluk.net]
The early period of polyneuropathy with threat of a cardiac standstill as a result of defeat of cordial branches of a vagus nerve or heavy aspiration pneumonia in connection with a dysphagia is dangerous. [infomeds.net]
Musculoskeletal
- Muscular Atrophy
This study confirms the noxious effect of n-hexane on the peripheral nerve, with development, in our cases, of a toxic polyneuropathy and denervation muscular atrophy with consistent myopathic changes. [ncbi.nlm.nih.gov]
At most of patients pains and paresthesias, muscular atrophies in distal departments of extremities, decrease in a tone, fading of tendon jerks, vasculomotor and trophic disturbances (change of coloring, temperature of skin, sweating, thinning of skin [infomeds.net]
There is also a variant that involves only lower motor neurons (progressive muscular atrophy) and one that selectively involves the cranial musculature (termed progressive bulbar palsy). [dartmouth.edu]
Psychiatrical
- Hunger
Malnutrition When we think of malnutrition, we typically think of third-world countries, where hunger and starvation run rampant. We don’t commonly think of America, the land of abundance, as being a country stricken with malnutrition, but it is. [nervedoctor.info]
Neurologic
- Polyneuropathy
Abstract Four cases of toxic polyneuropathy due to glue-sniffing were reported. Neurological examination revealed motor predominant mixed type polyneuropathy. [ncbi.nlm.nih.gov]
Drugs of abuse - Alcohol and heroin are the two main substances of abuse that can cause polyneuropathy. [symptoma.com]
G62.8 Other specified polyneuropathies G62.81 Critical illness polyneuropathy G62.82 Radiation-induced polyneuropathy G62.89 Other specified polyneuropathies G62.9 Polyneuropathy, unspecified G63 Polyneuropathy in diseases classified elsewhere G64 Other [icd10data.com]
Drug toxic polyneuropathy ICD 10 is G62.0. [acikgunluk.net]
Code Information Diagnosis Code: G65.2 Short Description: Sequelae of toxic polyneuropathy Long Description: Sequelae of toxic polyneuropathy The code G65.2 is VALID for claim submission Code Classification: Diseases of the nervous system (G00–G99) Polyneuropathies [healthprovidersdata.com]
- Peripheral Neuropathy
Textbook of Peripheral Neuropathy is a practical but authoritative reference for clinicians in any medical specialty who are evaluating and treating patients with signs and symptoms of a peripheral neuropathy. [books.google.de]
Peripheral Neuropathy The term peripheral neuropathy is frequently used interchangeably with the terms neuropathy and polyneuropathy. [innovationsstemcellcenter.com]
Peripheral neuropathy can be divided into: Acute peripheral neuropathy - this a neuropathy of sudden, or rapid, onset. Chronic peripheral neuropathy - this develops more gradually and becomes persistent. Most peripheral neuropathy is chronic. [patient.info]
Alcohol-Induced Peripheral Neuropathy, Alcohol-Induced Peripheral Neuropathy, Alcoholic Peripheral Neuropathies, Alcohol-Induced Peripheral Neuropathy, Alcohol Induced Peripheral Neuropathy, Alcohol-Induced Polyneuritides, Alcoholic Polyneuritis, Alcoholic [finto.fi]
are not independently associated with a significantly increased risk of peripheral neuropathy. [aidsmap.com]
- Headache
Lead toxic polyneuropathy (ICD code 10 - G62.2) is expressed in the patient in the form of lethargy, high fatigue, "dull" headache, loss of memory and attention, encephalopathy, anemia, colitis, pain in the limbs, hand tremor. [acikgunluk.net]
MSG is a substance that has a toxic effect on nerves and the nervous system that causes a wide range of reactions, from temporary headaches to permanent brain damage. [mcvitamins.com]
Surplus of a pyridoxine (at a daily dose of 50-300 mg) also leads to development of touch polyneuropathy with a headache, irritability, fatigue. Inspection reveals Lermitt's symptom. [infomeds.net]
Associated disorders Pain: Abdominal; Headache; Joint General: Fatigue; Irritability Anemia Sickle cell disease Electrophysiology Motor Axon loss Mild cases: Prolonged distal latencies or Normal Sensory Vibratory thresholds: Increased [slideshare.net]
- Confusion
The immune system launches an attack against the bacteria; but, according to the theory, the immune system confuses the myelin with the bacteria in some cases and attacks the myelin sheath as well. [encyclopedia.com]
Workup
Numerous symptoms involving different systems, including additional neurological manifestations, can be present along with the polyneuropathy, such as gastrointestinal irritation (heavy metal exposure), anemia and constitutional complaints [1] [6]. For this reason, a meticulous clinical workup is necessary. Physicians must obtain a complete patient history that will assess the patient's occupation (and to which substances the individual is exposed), presence of underlying diseases (as several systemic and metabolic diseases can present with polyneuropathy, such as hypothyroidism and diabetes mellitus), and history of alcohol and substance abuse [1] [6]. Additionally, a thorough nutritional evaluation must be conducted, keeping in mind that several vitamin deficiencies (thiamine, B6, B12, and also copper) might manifest as a polyneuropathy [1] [6]. History of drug use, however, is the main focus of history taking. Furthermore, a detailed physical examination, focusing on the neurological system (reflex and sensory perception testing, as well as coordination and proprioception) will confirm the extent of peripheral nerve involvement and possibly detect other neurological symptoms that might lead the physician to a presumptive diagnosis [1] [5]. Laboratory studies should be employed later on, including a complete blood count (CBC), a full metabolic panel, serum inflammatory markers (erythrocyte sedimentation rate, or ESR), serum glucose, vitamin B12, thyroid hormone levels, and urinalysis, which is particularly useful for heavy metal exposure [1] [6] [8]. When the diagnosis is inconclusive, nerve conduction studies and electromyography might be performed [5].
Treatment
Cancer Neurology in Clinical Practice: Neurologic Complications of Cancer and its Treatment, Second Edition provides clinicians from various backgrounds and levels of training with a reference to help focus the differential diagnosis, treatment strategy [books.google.de]
Features of the treatment of the disease Toxic polyneuropathy, the treatment of which primarily comes down to eliminating the causes of its occurrence, should be considered comprehensively. [acikgunluk.net]
Treatment Treatment for diabetic neuropathy focuses on pain management, sugar control and supportive services. There are several medications and other treatments that help alleviate tingling and burning pains. [umm.edu]
Treatment of diabetic neuropathy (polyneuropathy) and alcoholic polyneuritis Treatment of diabetic and alcoholic neuropathy (polyneuropathy, polyneuritis) chosen individually in each case. [minclinic.ru]
In case of cisplatinum, the abnormalities can still keep developing after quitting the treatment. Fortunately, in case of neuropathy due to anti-cancer medicine, treatment and recovery is generally possible. [neuropathie.nu]
Prognosis
What is the Prognosis for Drug-Induced Neuropathy? (Outcomes/Resolutions) The prognosis of Drug-Induced Neuropathy is good with adequate treatment and management of the signs and symptoms. [dovemed.com]
The outlook (prognosis) for peripheral neuropathy depends on the underlying cause. In general, if a problem can be identified early and treated successfully, the prognosis is very good. [patient.info]
Prognosis Each patient's prognosis depends on the severity of the neuropathy when exposure is ceased or reduced to levels that will not affect health negatively. 44. [slideshare.net]
The prognosis for getting rid of the disease is favorable. Arsenic polyneuropathy Arsenic can penetrate into the human body along with insecticides, medicines, paints. This disease is a professional for smelters. [acikgunluk.net]
[…] affected (large-fiber, small-fiber, or both), the most distal portions of axons are usually the first to degenerate, and axonal atrophy advances slowly toward the nerve's cell body, however if the cause is removed, regeneration is possible, although the prognosis [en.wikipedia.org]
Etiology
Code First Code First Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10data.com]
The etiologic factor in common turned out to be consumption, ritually, of gingili oil, which is used in a ritual at menarch and after childbirth. [popline.org]
This survey provided a crude etiological picture of generalized neuropathy on this island. © 1993 S. Karger AG, Basel Article / Publication Details First-Page Preview [karger.com]
The findings raise the possibility that other acquired polyneuropathies may also be codetermined by genetic etiological factors, of which some may be related to genes already known to cause the phenotypically related Mendelian disorders of CMT. [mayoclinic.pure.elsevier.com]
Progressive ascending motor neuron paralysis of unknown etiology, frequently following an enteric or respiratory infection. [icd9data.com]
Epidemiology
Abstract: The epidemiological and clinical aspects of an unusual type of polyneuropathy which reached epidemic proportion in Sri Lanka in 1977-1978 are reported. 20 young women in Sri Lanka were affected by this illness, characterized by pain in the calves [popline.org]
Epidemiological data suggested strongly that methyl N -butyl ketone (MBK) was responsible for the outbreak. [science.sciencemag.org]
Lead Epidemiology of lead toxicity Common in children: Especially black non-hispanic children (22%) Most common in homes built from 1920 to 1950 Identical twins often have concordant lead levels Lead neuropathy: Especially from industrial exposure [slideshare.net]
Causation and causal inference in epidemiology. Am J Public Health 95 (Suppl 1): S144–50, 2005. Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Periph N Syst 6:14-20, 2001. Gaist D, Jeppesen U, Anderson M, et al. [now.aapmr.org]
Some of these have been associated with neuropathy in clinical epidemiologic studies, confirming their ability to injure the human peripheral nervous system (PNS). [emedicine.medscape.com]
Pathophysiology
[ edit ] In regards to the pathophysiology of polyneuropathy, of course, the former depends on which polyneuropathy. [en.wikipedia.org]
Because pathophysiology and symptoms are related, polyneuropathies are often classified by area of dysfunction: Myelin Vasa nervorum Axon Polyneuropathies may be acquired or inherited. [merckmanuals.com]
Pathophysiology Although peripheral neuropathy has multiple etiologies, the nerve has a limited number of ways to respond to injury. 4, 5 The damage can occur at the level of the axon (i.e., axonopathy). [aafp.org]
Back to Top Pathophysiology and Natural History Despite the diverse array of medical disorders that cause peripheral neuropathies, peripheral nerves exhibit only a few distinct pathologic reactions to an insult or disease: wallerian degeneration, axonal [clevelandclinicmeded.com]
Pathophysiology Neuropathy may be categorized by presentation (ie, motor or sensory symptoms), electrodiagnostic features, and neuroanatomical location within the peripheral nerve (ie, demyelinating or axonal, neuronopathy, ion channel neuropathy, neuromuscular [emedicine.medscape.com]
Prevention
This may improve your symptoms and help prevent further nerve damage. [healthline.com]
Knowledge of the pathogenesis, genetics, and molecular biology of neuromuscular disorders is essential both in developing and applying new therapies and preventive measures, and in formulating genetic and prognostic advice. [books.google.com]
Prevention Peripheral neuropathies are preventable only to the extent that the underlying causes are preventable. [encyclopedia.com]
References
- Staff NP, Windebank AJ. Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications. Continuum (Minneap Minn). 2014;20(5 Peripheral Nervous System Disorders):1293-1306.
- Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad Med J. 2003;79(933):391– 396.
- Marchettini P, Lacerenza M, Mauri E, Marangoni C. Painful Peripheral Neuropathies. Curr Neuropharmacol. 2006;4(3):175-181.
- Ludolph AC, Spencer PS. Toxic neuropathies and their treatment. Baillieres Clin Neurol. 1995;4(3):505-527.
- Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol. 2012;14(4):iv45-iv54.
- Azhary H, Farooq MU, Bhanushali M, Majid A, Kassab MY. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887-892.
- Krishnan AV, Phoon RK, Pussell BA, et al. Ischaemia induces paradoxical changes in axonal excitability in end-stage kidney disease. Brain. 2006;129(pt 6):1585– 1592.
- Willison HJ, Winer JB. Clinical evaluation and investigation of neuropathy. J Neurol Neurosurg Psychiatry. 2003;74(2):ii3–ii8.