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].

• Pathologist

  He is also now Associate Pathologist (Neuropathology) at St. Michael’s Hospital, Toronto. Dr. Bilbo is a past Chief Examiner, Section of Neuropathology, for the Royal College of Physicians and Surgeons of Canada. [books.google.de]

• Progressive Dementia

  It are shown by the progressing dementia of subcrustal type, sometimes with disturbance of balance and weakness in legs. [infomeds.net]

• Hypersalivation

  In case of acute poisoning with these substances, the following symptoms occur: sweating, hypersalivation, miosis, gastrointestinal disorders, bronchospasm, urinary incontinence, facial stimuli, convulsions, death is possible. [acikgunluk.net]

  At chronic intoxication gastrointestinal frustration, usually, are absent, but hypersalivation is often observed. [infomeds.net]

• Miosis

  In case of acute poisoning with these substances, the following symptoms occur: sweating, hypersalivation, miosis, gastrointestinal disorders, bronchospasm, urinary incontinence, facial stimuli, convulsions, death is possible. [acikgunluk.net]

  Acute poisoning flows as cholinergic crisis: hypersalivation, perspiration, a miosis, intestinal gripes, vomiting, diarrhea, a headache, fastsikulyation, an urine incontience, a bronchospasm, spasms, a depression of breath, a lump, in hard cases death [infomeds.net]

• 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 is the most common neurological complication in patients with HIV/AIDS with an estimated incidence of nearly one-third of all people with HIV/AIDS: For patients with HIV/AIDS, peripheral neuropathy can be caused by the virus itself [atmph.org]

  Peripheral Nerve Disorders Also called: Neuritis, Peripheral neuritis, Peripheral neuropathy Your peripheral nerves are the ones outside your brain and spinal cord. [icdlist.com]

  Chemotherapy-induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as a clinical model to investigate the association of non-CMT polyneuropathy with CMT genes. [mayoclinic.pure.elsevier.com]

  Peripheral Neuropathy The term peripheral neuropathy is frequently used interchangeably with the terms neuropathy and polyneuropathy. [innovationsstemcellcenter.com]

• Hand Tremor

  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]

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].

• Lymphocytic Infiltrate

  The muscles showed denervation atrophy and focal degenerative myopathic changes, with presence of lymphocytic infiltrates and phagocytosis. [ncbi.nlm.nih.gov]

1. 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.
2. Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad Med J. 2003;79(933):391– 396.
3. Marchettini P, Lacerenza M, Mauri E, Marangoni C. Painful Peripheral Neuropathies. Curr Neuropharmacol. 2006;4(3):175-181.
4. Ludolph AC, Spencer PS. Toxic neuropathies and their treatment. Baillieres Clin Neurol. 1995;4(3):505-527.
5. Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol. 2012;14(4):iv45-iv54.
6. Azhary H, Farooq MU, Bhanushali M, Majid A, Kassab MY. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887-892.
7. 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.
8. Willison HJ, Winer JB. Clinical evaluation and investigation of neuropathy. J Neurol Neurosurg Psychiatry. 2003;74(2):ii3–ii8.