eMedicine Specialties > Neurology > Neurotoxicology
Toxic Neuropathy: Differential Diagnoses & Workup
Updated: Feb 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Peripheral neuropathy
Small fiber neuropathy
Infectious neuropathy
Autoimmune neuropathy
Chronic disease polyneuropathy
Carcinogenic neuropathy
Vitamin B-6 deficiency
Vitamin B-12 deficiency
Connective tissue disorder
Glucose intolerance
Workup
Laboratory Studies
- See other eMedicine articles on neuropathy for workup to rule out common causes of neuropathy.
- A differential diagnosis for peripheral neuropathy with appropriate lab testing is noted in Table 4.
- Table 4. Differential Diagnosis of Peripheral Neuropathy With Selective Lab Testing (Recommended lab tests in bold.)
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Inflammatory Metabolic and Nutritional Infective and Granulomatous Vasculitic Neoplastic and Paraproteinemic Drug-Induced and Toxic Hereditary Acute idiopathic polyneuropathy (Anti-Gm1, anti-Gd1a, anti-GQ1b) Diabetes (Fasting blood glucose, 2-hour glucose tolerance test) AIDS (HIV) Mixed CT disease (ESR) Compression and infiltration (chest radiograph) Alcohol HMSN Chronic inflammatory demyelinating polyneuropathy Endocrinopathies: hypothyroidism, acromegaly (TSH, Electrolytes, GH) Leprosy, syphilis (RPR, FTA, MHA-TP) Polyarteritis nodosa Paraneoplastic syndromes (anti-Hu, anti-RII, etc; CBC) See Table HSN Uremia (BUN/CR) Diphtheria, Lyme (Serology) Rheumatoid arthritis (RF) Paraproteinemias (SPEP, immunofixation, anti-MAG, M protein) Friedreich ataxia Liver disease (LFTs) Sarcoidosis (ACE) SLE (ANA) Amyloidosis (nerve biopsy) Familial amyloid (nerve biopsy) Vitamin B-12 deficiency (B12) Sepsis and multiorgan failure (ESR) Porphyria (porphobilinogen, aminolevulinic acid),
metachromatic leukodystrophy, Krabbe, abetalipoproteinemia, Tangier disease, Refsum disease, Fabry diseaseInflammatory Metabolic and Nutritional Infective and Granulomatous Vasculitic Neoplastic and Paraproteinemic Drug-Induced and Toxic Hereditary Acute idiopathic polyneuropathy (Anti-Gm1, anti-Gd1a, anti-GQ1b) Diabetes (Fasting blood glucose, 2-hour glucose tolerance test) AIDS (HIV) Mixed CT disease (ESR) Compression and infiltration (chest radiograph) Alcohol HMSN Chronic inflammatory demyelinating polyneuropathy Endocrinopathies: hypothyroidism, acromegaly (TSH, Electrolytes, GH) Leprosy, syphilis (RPR, FTA, MHA-TP) Polyarteritis nodosa Paraneoplastic syndromes (anti-Hu, anti-RII, etc; CBC) See Table HSN Uremia (BUN/CR) Diphtheria, Lyme (Serology) Rheumatoid arthritis (RF) Paraproteinemias (SPEP, immunofixation, anti-MAG, M protein) Friedreich ataxia Liver disease (LFTs) Sarcoidosis (ACE) SLE (ANA) Amyloidosis (nerve biopsy) Familial amyloid (nerve biopsy) Vitamin B-12 deficiency (B12) Sepsis and multiorgan failure (ESR) Porphyria (porphobilinogen, aminolevulinic acid),
metachromatic leukodystrophy, Krabbe, abetalipoproteinemia, Tangier disease, Refsum disease, Fabry disease - Neuropathies with unusual features are listed in Table 5.
- Table 5. Neuropathies With Unusual Features
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Small Fiber Neuropathies Facial Nerve Involvement Autonomic Involvement Sensory Ataxia Pure Motor Involvement Skin, Nail, or Hair Manifestation Diabetes Guillain-Barré Paraneoplastic Polyganglionopathies Motor neuron disease Vasculitis: purpura, livedo reticularis Amyloid CIDP GBS Paraneoplastic Multifocal motor neuropathy Cryoglobinemia: purpura HIV-associated Lyme disease Porphyria Sjögren syndrome GBs Fabry disease: angiokeratomas Hereditary sensory and autonomic neuropathy Sarcoidosis Vincristine, vacor Cisplatin analogs Acute motor axonal neuropathy Leprosy: skin hypopigmentation Fabry disease HIV Diabetes Vitamin B-6 toxicity Porphyria Osteosclerotic myeloma: skin hyperpigmentation Tangier disease Tangier Amyloid GBS (Miller-Fisher variant) CIDP Variegate porphyria: bullous lesions Sjögren syndrome HIV IgM monoclonal gammopathy of undetermined significance Osteosclerotic myeloma Refsum disease: ichthyosis Hereditary sensory and autonomic neuropathy Diabetic lumbar radiculoplexopathy Arsenic or thallium intoxication: Mees lines Hereditary motor sensory neuropathy (Charcot-Marie-Tooth) Thallium intoxication: alopecia Lead Giant axonal neuropathy: curled hair Small Fiber Neuropathies Facial Nerve Involvement Autonomic Involvement Sensory Ataxia Pure Motor Involvement Skin, Nail, or Hair Manifestation Diabetes Guillain-Barré Paraneoplastic Polyganglionopathies Motor neuron disease Vasculitis: purpura, livedo reticularis Amyloid CIDP GBS Paraneoplastic Multifocal motor neuropathy Cryoglobinemia: purpura HIV-associated Lyme disease Porphyria Sjögren syndrome GBs Fabry disease: angiokeratomas Hereditary sensory and autonomic neuropathy Sarcoidosis Vincristine, vacor Cisplatin analogs Acute motor axonal neuropathy Leprosy: skin hypopigmentation Fabry disease HIV Diabetes Vitamin B-6 toxicity Porphyria Osteosclerotic myeloma: skin hyperpigmentation Tangier disease Tangier Amyloid GBS (Miller-Fisher variant) CIDP Variegate porphyria: bullous lesions Sjögren syndrome HIV IgM monoclonal gammopathy of undetermined significance Osteosclerotic myeloma Refsum disease: ichthyosis Hereditary sensory and autonomic neuropathy Diabetic lumbar radiculoplexopathy Arsenic or thallium intoxication: Mees lines Hereditary motor sensory neuropathy (Charcot-Marie-Tooth) Thallium intoxication: alopecia Lead Giant axonal neuropathy: curled hair - Quantitative sensory testing includes vibration threshold testing, thermal threshold testing, portable motor and sensory latency tests, and current perception threshold (CPT) testing. These tests are often portable gadgets useful in the field. Each has its limitations, but some may be able to measure functions pertaining to small fiber neuropathy, such as the CPT and thermal testing devices. Others are simple versions of the NCV. The vibration testing device measures large fiber function and may be useful if NCV is not available.
- Other techniques that help prove the presence of neuropathy include skin biopsy and intraepidermal nerve fiber density (IENF) testing. This is well reviewed in the article by Smith et al (2005).37
- The sympathetic skin reflex is performed with EMG machinery, where the absence of one side's testing suggests an abnormality. This test is technically difficult. A sural nerve biopsy is invasive but may be useful. Laser evoked potential and Quantitative Sudomotor Axon Reflex Test (QSART) have been useful in research. QSART measures sweat volume.
- IENF testing is relatively easy since it is a small punch biopsy of skin (6 mm). It has a reliable method of measuring small fiber neuropathy and has good interrater reliability. It measures intraepidermal nerve fibers, crossing the dermal, epidermal junction. It is being used in clinical trials for pharmaceuticals.
- For patients with cryogenic neuropathies, glucose tolerance testing makes sense because impaired glucose tolerance is prevalent in 14% of those aged 50-65 years. This is well reviewed by Sumner et al (2003).38 It is associated with a syndrome of insulin resistance, and 25-40% of patients progress to frank diabetes. An abnormal oral glucose tolerance test result is defined as a glucose level of 140-200, 2 hours after a 75-g anhydrous load. Clinically, 86% of patients had exclusively sensory symptoms with pain and one third had otherwise idiopathic neuropathy. Oral glucose tolerance testing is more sensitive than glycosylated hemoglobin HbA1C testing.
- For cryptogenic neuropathy, the glucose tolerance test result is abnormal in 33-61% of patients. Other important laboratory tests to consider are tests for vitamin B-12, monoclonal gammopathy of unknown significance (3% of those >70 y), axonal neuropathy (1-5%), cryoglobins and hepatitis C evaluation, and immunofixation for paraneoplastic neuropathy.
- CSF protein level in toxic neuropathy is usually normal.
- Consider performing serum, urine, or blood testing to assess for evidence of absorption (see Table 2). If evaluating a patient weeks or months after the exposure ceased, biological data may not yield useful information. In the case of arsenic, for example, separating inorganic from organic arsenic is important, since organic arsenic is a component of seafood and may contaminate and confuse clinicians. Patients need to refrain from seafood for 24 hour prior to urine testing. Furthermore, labs need to be instructed to perform testing for inorganic, not organic, arsenic. Some agents do not have indices that can be tested. Most need to be performed relatively soon after exposure.
Other Tests
- Electromyography (EMG) and nerve conduction study (NCV)
- Using EMG and NCV, peripheral neuropathy may be separated into axonal and demyelinating forms.
- Axonal neuropathies are more commonly the result of chronic low-level occupational or environmental toxicity.
- Axonal neuropathies are characterized by sensory amplitude loss in the lower extremities, commonly the sural and or superficial peroneal nerves.
- More severe axonal neuropathies may involve motor fibers and thus motor amplitudes may be small.
- When motor fibers are involved, then fibrillation may be noted as evidence for acute denervation. For more chronic neuropathies, polyphasia and wave forms for large and long duration are evident. EMG needle assessment may then help classify duration of the neuropathy.
- Demyelination-type neuropathies are characterized by sensory and motor slowing.
- Some toxic neuropathies that are the result of high-level acute exposure may result in severe motor demyelinating neuropathies. However, these conditions are rare. “Ginger Jack leg” paralysis from ingestion of organophosphates is one example of this. NCV may reveal prolonged F waves initially, but then later, motor slowing.
- EMG needle testing in these cases may be normal if the condition is purely demyelinating.
- Characterizing a neuropathy into demyelinating or axonal may assist in identifying chemical agents responsible. (See Table 6.)
- The differential diagnosis, however, must include inherited neuropathies as well as other common acquired neuropathies.
- Patients with inherited demyelinating neuropathies are noted to have prolonged and symmetrical sensory and/or motor nerve conduction velocities.
- Those with inherited axonal neuropathies may have small amplitudes that are out of proportion to their relatively minor sensory or motor findings.
- These patients may also have high arches or other congenital physical ailments.
- Patients with other acquired neuropathies, such as diabetes or thyroiditis, may have EMG and NCV findings that are inseparable from those with toxic neuropathy.
- Table 6. Industrial Agents and Pharmaceuticals Associated With Peripheral Neuropathy
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Almitrine (s) “Spanish toxic oil” Arsenic (s)(d) 2-t-Butylazo- 2- hydroxyl- 5 methylhexane Capsaicin Acrylamide Carbamate pesticides (nm) Allyl chloride Carbon disulfide (m)(d) Amiodaron e (d) Chloramphenicol (s) Amitriptyline Cimetidine (m) Carbamates (nm) Cisplatin (s) Carbon monoxide Cyanate Chloroquine Cycloleucine Colchicine Cytarabine Dichloroacetic acid Dapsone (m) Disulfiram (m) Dichloroacetylene (cr) Ethionamide Didoxynucleosides (s) (ddC, ddI, d4T) Ethyl alcohol Dimethylaminopropionitrile Ethylene glycol (cr) Doxorubicin (m) Ethylene oxide Ethambutol (s) Germanium dioxide Etoposide (s) Gold Glutethimide Hexamethylmelamine Hexachlorophene Hydrazine Hydralazine (s) Indomethacin Hyperinsulinemia/ hypoglycemia (m) Isoniazid Imipramine (m) Lincomycin (nm) Interferon alpha (nm) Lithium Lead (m) L-Tryptophan Lidocaine Mercury, inorganic Methyl n-butyl ketone (m)(d) Mercury, organic Metronidazole (s) Methaqualone Misonidazole (s) Methyl bromide Muzolimine Methyl methacrylate Nitrous Oxide (s) N hexane (d) Organophosphates (m) Naproxen Organophosphorus compounds (nm) Nitrofurantoin (m) Polychlorinated biphenyls (s) Penicillamine (nm) Polymyxin (nm) Perhexiline (d) Pyrethroids (ic) Phenol Pyridoxine (s) Phenytoin Sarin Pyriminil Succinylcholine (nm) Quinine (nm) Sulfonamides (m), sulfasalazine Statins Tacrolimus Stilbamidine (cr) Taxanes (paclitaxel, docetaxel) (s) Suramin Thalidomide (s) Tetrachloroethane Thallium (s) Tetracyclines (nm) Trimethaphan (nm) Trithiozine Vidarabine Tubocurarine (nm) Vincristine (m) Vincristine (m), Vinca alkaloids Zimeldine Vinyl chloride (s): Predominantly sensoryAlmitrine (s) “Spanish toxic oil” Arsenic (s)(d) 2-t-Butylazo- 2- hydroxyl- 5 methylhexane Capsaicin Acrylamide Carbamate pesticides (nm) Allyl chloride Carbon disulfide (m)(d) Amiodaron e (d) Chloramphenicol (s) Amitriptyline Cimetidine (m) Carbamates (nm) Cisplatin (s) Carbon monoxide Cyanate Chloroquine Cycloleucine Colchicine Cytarabine Dichloroacetic acid Dapsone (m) Disulfiram (m) Dichloroacetylene (cr) Ethionamide Didoxynucleosides (s) (ddC, ddI, d4T) Ethyl alcohol Dimethylaminopropionitrile Ethylene glycol (cr) Doxorubicin (m) Ethylene oxide Ethambutol (s) Germanium dioxide Etoposide (s) Gold Glutethimide Hexamethylmelamine Hexachlorophene Hydrazine Hydralazine (s) Indomethacin Hyperinsulinemia/ hypoglycemia (m) Isoniazid Imipramine (m) Lincomycin (nm) Interferon alpha (nm) Lithium Lead (m) L-Tryptophan Lidocaine Mercury, inorganic Methyl n-butyl ketone (m)(d) Mercury, organic Metronidazole (s) Methaqualone Misonidazole (s) Methyl bromide Muzolimine Methyl methacrylate Nitrous Oxide (s) N hexane (d) Organophosphates (m) Naproxen Organophosphorus compounds (nm) Nitrofurantoin (m) Polychlorinated biphenyls (s) Penicillamine (nm) Polymyxin (nm) Perhexiline (d) Pyrethroids (ic) Phenol Pyridoxine (s) Phenytoin Sarin Pyriminil Succinylcholine (nm) Quinine (nm) Sulfonamides (m), sulfasalazine Statins Tacrolimus Stilbamidine (cr) Taxanes (paclitaxel, docetaxel) (s) Suramin Thalidomide (s) Tetrachloroethane Thallium (s) Tetracyclines (nm) Trimethaphan (nm) Trithiozine Vidarabine Tubocurarine (nm) Vincristine (m) Vincristine (m), Vinca alkaloids Zimeldine Vinyl chloride
(m): Predominantly motor
(d): Possibly demyelination with conduction block
(cr): Associated with cranial neuropathy
(nm): Associated with neuromuscular transmission syndromes
(ic): Associated with axon ion channel syndromes
Bold: A rating for common or strong association
Unbolded: B rating for less common or less than strong association
- Neurophysiologic abnormalities in workers exposed to ethylene oxide
- In 1993, Ohnishi and Murai reviewed polyneuropathy cases caused by EtO. Needle EMG revealed neurogenic changes in 8 of 11 patients. Conduction studies of limb nerves were abnormal in 8 of 10 patients. Relatively mild decreases of motor and sensory NCVs with decreases in the amplitudes of nerve and muscle action potentials indicated axonal degeneration of both motor and sensory nerve fibers.39
- In 1983, Kuzuhara et al reported 2 patients with occupationally induced EtO polyneuropathy and their EMG and NCV results. In one patient, EMG of the limb muscles was normal except for long-duration and high-amplitude units recorded from the triceps. Motor NCVs were relatively well preserved. In the second patient, only an EMG was performed, which revealed denervation patterns in distal limb muscles.14
- Finelli et al reported electrophysiological findings in 3 patients with EtO-induced neuropathy; they demonstrated mild slowing of motor conduction with positive sharp waves and fibrillation potentials on EMG during the active disease state, indicating axonal neuropathy.15
- In patient 1, nerve conduction studies showed no response to stimulation of the left peroneal nerve, slowing of motor conduction over the right peroneal and the right posterior tibial nerves, and absence of the right tibial H reflex and the right sural nerve sensory potential. The EMG showed scattered positive sharp waves and fibrillation potentials with increased polyphasic activity in the intrinsic foot muscles and, to a lesser extent, in the leg muscles. Repeated examinations 5 weeks and 7 months later showed return of normal conduction velocity and disappearance of denervation potentials and the recording of giant potentials as signs of reinnervation. The left H reflex remained suppressed.
- In patient 2, the EMG initially showed positive sharp-wave fibrillation potentials and small-amplitude motor unit potentials in leg and foot muscles. Follow-up studies showed the disappearance of the denervation potentials and the appearance of giant potentials indicating reinnervation.
- Patient 3 showed absent potentials from the extensor digitorum brevis muscle on stimulation of the right peroneal nerve. Right tibial conduction was slowed, and the tibial H reflex was absent on the right and delayed on the left. The right sural nerve sensory potential amplitude was normal but delayed. Leg and foot muscle EMG studies showed denervation potentials. Repeat studies 7 months later showed mild slowing and active denervation on EMG with some polyphasic giant potentials.
- In 1979, Gross et al reported 4 patients with EtO neurotoxicity and results of their nerve conduction studies. One patient had acute CNS symptoms and normal NCV. Another 2 had milder CNS symptoms with symptoms of a generalized sensorimotor polyneuropathy with fibrillations in the intrinsic muscles of the feet and abnormal NCVs (patient 2), and decreased numbers and increased amplitude and duration of motor unit potentials in the distal muscles (patient 3). Patient 4 was asymptomatic. Patients 2, 3, and 4 had decreased amplitudes of motor action potentials, moderately decreased NCVs, and signs of denervation compatible with axonal degeneration as the cause of neuropathy.11
- In 1985, Schroeder et al also reported a case of EtO-induced polyneuropathy. This patient had nerve conduction study findings that showed slowed NCVs; the mean tibial NCV was 26 m/s, with normal amplitudes, 2.5 mV.13
- Fukushima et al reported a 19-year-old patient with 20 days of EtO exposure who had numbness and weakness of his extremities and was noted to have a steppage gait on examination at the time of admission 1 month later. Nerve conduction study findings were abnormal; mean peroneal and tibial NCVs were 37.7 and 37.1 m/s (no normals were included), respectively. No latency potential was demonstrable for the right peroneal nerve. Neurogenic changes were demonstrated on EMG in the anterior tibial muscles.12
- Deschamps et al reported a case of persistent asthma after accidental EtO exposure. They performed EMG and NCVs after an examination of the patient's lower extremities revealed abnormal findings. EMG and NCV findings were normal, but maximum amplitudes of the right and left H reflex responses were reduced significantly (ie, 6% and 2% of the maximum amplitude elicited from the direct response) without a decrease in the proximal conduction velocity. These results suggested axonal neuropathy.40
- Neurophysiologic abnormalities associated with mercury exposure (inorganic and organic)
- Inorganic mercury is noted to produce a sensory or sensorimotor polyneuropathy similar to that produced by arsenic. Chloralkali plant workers (n=138) with long-term inorganic mercury vapor exposure were noted to have elevated urine mercury levels and reduced sensation on quantitative testing, prolonged distal latencies with reduced sensory-evoked response amplitudes, and increased likelihood of abnormal needle EMG findings. Factory workers exposed to elemental mercury vapor with elevated urine mercury concentrations had prolonged motor and sensory ulnar distal latencies. Slowing of the median motor NCV was found to correlate with both increased levels of mercury in blood and urine and with increased numbers of neurological symptoms. Sensory deficits found with short-term exposure to mercury vapor, whereas motor nerve impairment occurred with longer periods of exposure.
- Chloralkali workers exposed to inorganic mercury vapors for an average of 12.3 years were found to have median motor and sensory NCVs that were slightly reduced among the highly exposed subjects. Seventeen thermometer factory workers had high urine and blood mercury levels but no symptoms; 88% had subclinical neuropathy, mainly distal and axonal neuropathy. In another study, a sensory polyneuropathy was found in 11% of workers exposed to inorganic mercury, while a sensorimotor polyneuropathy was found in 27% of workers.
- Chloralkali workers who were exposed to inorganic mercury for an average of 7.9 years and had ceased working in that environment an average of 12.3 years prior to the study were found to have both median sensory NCV and amplitude of the sural nerve associated with measures of cumulative exposure to mercury. A study reviewing the relationship between exposure-related indices and neurological and neurophysiological effects in workers previously exposed to mercury vapor revealed that, of 298 dentists with long-term exposure to mercury amalgam vapor evaluated for peripheral neuropathy, 30% had polyneuropathies. Another paper reported that one dentist apparently had an unelicitable sensory superficial peroneal nerve action potential that returned to normal following penicillamine treatment.
- Industrial workers with long-term exposure to mercury were found to have performance decrements in neuromuscular functions that were reversible and correlated with blood and urine mercury levels.
- Neurophysiological abnormalities in workers exposed to xylene
- Nerve conduction testing was utilized in 8 studies evaluating the PNS in workers with occupational exposure to mixed organic solvents including xylene. One of these noted a prolonged refractory period in lower extremity motor and sensory nerves of 28 exposed painters compared with age-matched controls. In 1980, Elofsson found a slight decrease in NCV in the distal sensory nerves of the lower extremities of an exposed population. He concluded that these findings were consistent with an axonal polyneuropathy.
- In 1978, Seppalainen noted that 12 of 59 car painters had abnormally slow motor and sensory NCVs, while none of the controls had slowing.41 In 1980, Seppalainen reported that at least one abnormally slow NCV was noted in 48 of 107 subjects with a diagnosis of solvent poisoning.42 A third publication by the same author reported a different cross-sectional study and noted that 26 of 44 (59%) subjects with a diagnosis of organic solvent intoxication, who had been exposed exclusively to mixed solvents including dimethyl benzene, were diagnosed with peripheral neuropathy by EMG.31 Follow-up questionnaires of all subjects of the previous study, including those with mixed solvent exposure, noted that 57 of 87 subjects had symptoms referred to the PNS.
- EMG revealed sensorimotor neuropathy in 5 of 7 painters tested in a study by Linz. Four of these 5 painters had evidence of mild distal neuropathy with reduced 2-point discrimination on neurologic examination. Temporal dispersion noted in sural SNAPs was a statistically significant finding in 50 male painters compared with controls.43
Histologic Findings
Muscle and nerve pathology findings associated with ethylene oxide or mercury exposure include the following:
- Muscle and nerve biopsies were carried out by Kuzuhara et al on 2 patients who developed distal symmetrical polyneuropathies after being exposed to EtO while working as employees of a factory that produced medical supplies. The nerve biopsies of both patients implied axonal degeneration and regeneration. Swollen Schwann cell processes with numerous filaments, myelin figures, debris, and vacuoles with and without granules were seen on the electromicrogram of the sural nerve of patient 1. Growth cones of damaged axons were seen on the sural nerve of patient 2.14
- Muscle biopsies revealed smearing and distortion of the Z bands. Some revealed absence of mitochondria and target or targetoid structures. Transverse sections showed atrophic fibers, scattered or grouped with many target fibers. Enzyme histochemistry of muscle from patient 2 revealed atrophy of both type 1 and type 2 fibers in the myosin adenosine triphosphatase (ATPase) reaction and dark angulated fibers, target, targetoid, and moth-eaten fibers on nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) reaction.
- In 1993, Ohnishi and Murai reported that histologic studies of the sural nerves biopsied in 3 patients revealed decreased density of large myelinated fibers, reduction of the cross-sectional area of axons, reduction of axonal circularity, and presence of myelin ovoid and Bunger bands, which are compatible with a mild degree of axonal degeneration.39
- Experimental EtO neuropathy was produced by Ohnishi in rats exposed to a one-time dose of 500 ppm for 6 hours or 5 doses of 250 ppm for 6 hours at a time over a week. In both experiments, distal axonal degeneration was found both in peripheral and central myelinated axons of lumbar primary sensory neurons of rats. In hind leg nerves and in the fasciculus gracilis, myelinated fibers showed axonal degeneration sparing the nerve cell body of the lumbar dorsal root ganglion and myelinated fibers of lumbar dorsal and ventral roots. The rats exposed to 250 ppm also showed a retardation of growth and maturation of myelinated fibers in the presence of mild axonal degeneration.
- In a patient with EtO polyneuropathy after 5 months of exposure, Schroder et al performed a sural nerve biopsy that revealed nerve fiber degeneration of the wallerian type associated with reduction of axonal cross-sectional areas and some degree of nerve fiber regeneration. Conspicuous paranodal vesicular disintegration of individual myelin lamella also was present. Unusual cisternae with introverted hemidesmosomes were noted in endoneural fibroblasts.13
- Nerve pathology was investigated in those exposed to organic mercury. Miyakawa et al reported selective swelling and degeneration of the Schwann cells, noticeable changes of both myelin sheaths and the axon. Pathologic changes began at the nodes of Ranvier. Primary site of damage was noted to be in the cell bodies of the sensory ganglion cells, with axonal degeneration occurring later in rats poisoned by methylmercury hydroxide. The largest myelinated fibers were affected to a greater extent than the smaller caliber fibers in the dorsal root.44
- An autopsy performed on a descendant of a woman exposed to mercury at Minimata Bay demonstrated segmental demyelination of the PNS. In both humans and animals, the major pathologic effect of methylmercury appears to be on the dorsal root ganglion cells. Similar data are not available for inorganic or metallic mercury poisoning.
More on Toxic Neuropathy |
| Overview: Toxic Neuropathy |
 Differential Diagnoses & Workup: Toxic Neuropathy |
| Treatment & Medication: Toxic Neuropathy |
| Follow-up: Toxic Neuropathy |
| References |
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References
Hoitsma E, Reulen JP, de Baets M, et al. Small fiber neuropathy: a common and important clinical disorder. J Neurol Sci. Dec 15 2004;227(1):119-30. [Medline].
Kimura J. Polyneuropathies. In: Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. 1989. 2nd ed. Philadelphia: FA Davis; 462-81.
Kimura J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. 2nd ed. Philadelphia: FA Davis; 1989:149-162.
Feldman RG. Occupational and Environmental Neurotoxicology. Philadelphia: Lippincott-Raven; 1999.
Albers J, Bromberg MB. Chemically induced toxic neuropathy. In: Rosenberg NL, ed. Occupational and Environmental Neurology. Boston: Butterworth-Heinemann; 1995:175-234.
Schaumberg HH. Human neurotoxic disease. In: Spencer P, Schaumberg HH, eds. Experimental and Clinical Neurotoxicology. 2nd ed. New York: Oxford University Press; 2000.
Seppalainen AM, Tolonen E. Neurotoxicity of long term effects of carbon disulfide in the viscose rayon industry. Scand J Work Environ Health. 1974;1:145-153.
Ruijten MW, Salle HJ, Verberk MM, Muijser H. Special nerve functions and colour discrimination in workers with long term low level exposure to carbon disulphide. Br J Ind Med. Sep 1990;47(9):589-95. [Medline].
Ruijten MW, Salle HJ, Verberk MM. Verification of effects on the nervous system of low level occupational exposure to CS2. Br J Ind Med. Apr 1993;50(4):301-7. [Medline].
Johnson BL, Boyd J, Burg JR, et al. Effects on the peripheral nervous system of workers' exposure to carbon disulfide. Neurotoxicology. 1983;4(1):53-65. [Medline].
Gross JA, Haas ML, Swift TR. Ethylene oxide neurotoxicity: report of four cases and review of the literature. Neurology. Jul 1979;29(7):978-83. [Medline].
Fukushima T, Abe K, Nakagawa A, et al. Chronic ethylene oxide poisoning in a factory manufacturing medical appliances. J Soc Occup Med. 1986;36(4):118-23. [Medline].
Schroder JM, Hoheneck M, Weis J, Deist H. Ethylene oxide polyneuropathy: clinical follow-up study with morphometric and electron microscopic findings in a sural nerve biopsy. J Neurol. 1985;232(2):83-90. [Medline].
Kuzuhara S, Kanazawa I, Nakanishi T, Egashira T. Ethylene oxide polyneuropathy. Neurology. Mar 1983;33(3):377-80. [Medline].
Finelli PF, Morgan TF, Yaar I, Granger CV. Ethylene oxide-induced polyneuropathy. A clinical and electrophysiologic study. Arch Neurol. Jul 1983;40(7):419-21. [Medline].
Andersen A, Ellingsen DG, Morland T, Kjuus H. A neurological and neurophysiological study of chloralkali workers previously exposed to mercury vapour. Acta Neurol Scand. Dec 1993;88(6):427-33. [Medline].
Barber TE. Inorganic mercury intoxication reminiscent of amyotrophic lateral sclerosis. J Occup Med. Oct 1978;20(10):667-9. [Medline].
Adams CR, Ziegler DK, Lin JT. Mercury intoxication simulating amyotrophic lateral sclerosis. JAMA. Aug 5 1983;250(5):642-3. [Medline].
Ross AT. Mercuric polyneuropathy with albumino-cytologic dissociation and eosinophilia. JAMA. Jun 1 1964;188:830-1. [Medline].
Warkany J, Hubbard DM. Acrodynia and mercury. J Pediatr. 1953;42:365-386.
Yoshida Y, Kamitsuchibashi H, Hamada R, et al. Truncal hypesthesia in patients with Minamata disease. Intern Med. Feb 1992;31(2):204-7. [Medline].
Bleecker ML, Bolla KI, Agnew J, Schwartz BS, Ford DP. Dose-related subclinical neurobehavioral effects of chronic exposure to low levels of organic solvents. Am J Ind Med. 1991;19(6):715-28. [Medline].
Bleeker ML. Clinical presentations of selected neurotoxic compounds. In: Bleeker ML, Hansen JA, eds. Occupational Neurology and Clinical Neurotoxicology. Baltimore: Williams & Wilkins; 1994:207-234.
Demers RY, Markell BL, Wabeke R. Peripheral vibratory sense deficits in solvent-exposed painters. J Occup Med. Oct 1991;33(10):1051-4. [Medline].
Bove FJ, Letz R, Baker EL. Sensory thresholds among construction trade painters: a cross-sectional study using new methods for measuring temperature and vibration sensitivity. J Occup Med. Apr 1989;31(4):320-5. [Medline].
Padilla SS, Lyerly DP. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells. Toxicol Appl Pharmacol. Dec 1989;101(3):390-8. [Medline].
Feldman RG. Effect of toxins and physical agents on the nervous system. In: Bradley WG et al, eds. Neurology in Clinical Practice. Boston: Butterworth-Heinemann; 1991:1185-207.
Feldman RG. The recognition and differentiation of neurotoxic and non-neurotoxic syndromes. In: Chang LW, Slikker W, eds. Neurotoxicology: Approaches and Methods. San Diego: Academic Press; 1995:689-694.
Juntunen J, Antti-Poika M, Tola S, Partanen T. Clinical prognosis of patients with diagnosed chronic solvent intoxication. Acta Neurol Scand. May 1982;65(5):488-503. [Medline].
Antti-Poika M. Overall prognosis of patients with diagnosed chronic organic solvent intoxication. Int Arch Occup Environ Health. 1982;51(2):127-38. [Medline].
Seppalainen AM, Antti-Poika M. Time course of electrophysiological findings for patients with solvent poisoning. A descriptive study. Scand J Work Environ Health. Feb 1983;9(1):15-24. [Medline].
Herruzo Perez A, Linares del Rio F, Moniche García-Pumarino M. [Sensitive painful polyneuropathy probably caused by poisoning by perchloroethylene. Apropos of 1 case]. Rev Esp Anestesiol Reanim. May-Jun 1989;36(3):180-1. [Medline].
Baker EL. A review of recent research on health effects of human occupational exposure to organic solvents. A critical review. J Occup Med. Oct 1994;36(10):1079-92. [Medline].
Orbaek P, Rosen I, Svensson K. Electroneurographic findings in patients with solvent induced central nervous system dysfunction. Br J Ind Med. Jun 1988;45(6):409-14. [Medline].
Maizlish NA, Fine LJ, Albers JW, Whitehead L, Langolf GD. A neurological evaluation of workers exposed to mixtures of organic solvents. Br J Ind Med. Jan 1987;44(1):14-25. [Medline].
Feldman RG. Neurotoxic effects of trichloroethylene in drinking water. In: Isaacson RL, Jensen KF, eds. The Vulnerable Brain and Environmental Risks: Toxins in Air and Water. Vol 3. Plenum Press; 1994.
Smith AG, Howard JR, Kroll R, et al. The reliability of skin biopsy with measurement of intraepidermal nerve fiber density. J Neurol Sci. Jan 15 2005;228(1):65-9. [Medline].
Sumner CJ, Sheth S, Griffin JW, et al. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology. Jan 14 2003;60(1):108-11. [Medline].
Ohnishi A, Murai Y. Polyneuropathy due to ethylene oxide, propylene oxide, and butylene oxide. Environ Res. Feb 1993;60(2):242-7. [Medline].
Deschamps D, Rosenberg N, Soler P, Maillard G, Fournier E, Salson D, et al. Persistent asthma after accidental exposure to ethylene oxide. Br J Ind Med. Jul 1992;49(7):523-5. [Medline].
Seppalainen AM, Husman K, Martenson C. Neurophysiological effects of long-term exposure to a mixture of organic solvents. Scand J Work Environ Health. Dec 1978;4(4):304-14. [Medline].
Seppalainen AM, Lindstrom K, Martelin T. Neurophysiological and psychological picture of solvent poisoning. Am J Ind Med. 1980;1(1):31-42. [Medline].
Linz DH, de Garmo PL, Morton WE, et al. Organic solvent-induced encephalopathy in industrial painters. J Occup Med. Feb 1986;28(2):119-25. [Medline].
Miyakawa T, Deshimaru M, Sumiyoshi S, et al. Experimental organic mercury poisoning--pathological changes in peripheral nerves. Acta Neuropathol (Berl). 1970;15(1):45-55. [Medline].
Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract. Jan-Feb 2003;16(1):47-57. [Medline].
Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology. Jan 11 2005;64(1):26-31. [Medline].
Adams RD, Victor M, Ropper AH. Principles of Neurology. 6th ed. New York: McGraw-Hill; 1997:1278-1369.
Albers JW, Cavender GD, Levine SP, Langolf GD. Asymptomatic sensorimotor polyneuropathy in workers exposed to elemental mercury. Neurology. Oct 1982;32(10):1168-74. [Medline].
Albers JW, Kallenbach LR, Fine LJ, et al. Neurological abnormalities associated with remote occupational elemental mercury exposure. Ann Neurol. Nov 1988;24(5):651-9. [Medline].
American Conference of Governmental Industrial Hygienist. Threshold Limit Values and Biological Exposure Indices. 1999.
Angotzi G, Battistini N, Carboncini F, et al. Impairment of nervous system in workers exposed to inorganic mercury. Toxicol Eur Res. Nov 1981;3(6):275-8. [Medline].
ATSDR. Toxicological profile for carbon disulphide. US Department of Health and Human Services;1994.
Berger AR, Schaumberg HH. Disorders of the peripheral nervous system. In: Rosenstock L, Cullen MR, eds. Textbook of Clinical Occupational and Environmental Medicine. Philadelphia: Saunders; 1994:482-513.
Bernad PG, Newell S, Spyker DA. Neurotoxicity and behavior abnormalities in a cohort chronologically exposed to trichloroethylene. Vet Hum Toxicol. 1987;29:475.
Dyck PJ. Diabetic Neuropathy. Philadelphia: WB Saunders Co; 1998.
Dyck PJ. Peripheral Neuropathy. Philadelphia: WB Saunders Co; 1993.
Ellingsen DG, Morland T, Andersen A, Kjuus H. Relation between exposure related indices and neurological and neurophysiological effects in workers previously exposed to mercury vapour. Br J Ind Med. Aug 1993;50(8):736-44. [Medline].
Elofsson SA, Gamberale F, Hindmarsh T, et al. Exposure to organic solvents. A cross-sectional epidemiologic investigation on occupationally exposed care and industrial spray painters with special reference to the nervous system. Scand J Work Environ Health. Dec 1980;6(4):239-73. [Medline].
Eto K, Oyanagi S, Itai Y, et al. A fetal type of Minamata disease. An autopsy case report with special reference to the nervous system. Mol Chem Neuropathol. Feb-Apr 1992;16(1-2):171-86. [Medline].
Feldman RG, White RF. Role of the neurologist in hazard identification and risk assessment. Environ Health Perspect. Apr 1996;104 Suppl 2:227-37. [Medline].
Gilioli R, et al. Horvath M, ed. Adverse Effects of Environmental Chemicals and Psychotropic Drugs. Vol 2. Amsterdam: Elsevier Science; 1976:157-164.
Iyer K, Goodgold J, Eberstein A, Berg P. Mercury poisoning in a dentist. Arch Neurol. Nov 1976;33(11):788-90. [Medline].
Juntunen J. Neurotoxic syndromes and occupational exposure to solvents. Environ Res. Jan 1993;60(1):98-111. [Medline].
Levine SP, Cavender GD, Langolf GD, Albers JW. Elemental mercury exposure: peripheral neurotoxicity. Br J Ind Med. May 1982;39(2):136-9. [Medline].
Miller JM, Chaffin DB, Smith RG. Subclinical psychomotor and neuromuscular changes in workers exposed to inorganic mercury. Am Ind Hyg Assoc J. Oct 1975;36(10):725-33. [Medline].
National Institute for Occupational Safety and Health (NIOSH). Tetrachloroethylene. Current Intelligence Bulletin; January 1978;number 20.
Pleasure DE, Schotland DL. Peripheral neuropathies. In: Rowland LP, ed. Merritt's Textbook of Neurology. 8th ed. Philadelphia: Lea & Febiger; 1989:601-26.
Rowland LP, ed. Merritt's Textbook of Neurology. 8th ed. Philadelphia: Lea & Febiger; 1989.
Rutchik JS. The occupational medicine physician's guide to neuropathy in the workplace. J Occup Environ Med. In Press: Spring 2009.
Schaumberg HH, Spencer PS. Clinical and experimental studies of distal axonopathy- A frequent form of brain and nerve damage produced by environmental chemical hazards. Ann NY Acad Sci. 1979;14-29.
Schaumburg HH, Spencer PS. The neurology and neuropathology of the occupational neuropathies. J Occup Med. Nov 1976;18(11):739-42. [Medline].
Shapiro IM, Cornblath DR, Sumner AJ, et al. Neurophysiological and neuropsychological function in mercury-exposed dentists. Lancet. May 22 1982;1(8282):1147-50. [Medline].
Singer R, Valciukas JA, Rosenman KD. Peripheral neurotoxicity in workers exposed to inorganic mercury compounds. Arch Environ Health. Jul-Aug 1987;42(4):181-4. [Medline].
Somjen S, Mercury. Schaumberg HH and Spencer PS, eds. Clinical Neurotoxicology. Baltimore: Lippincott Williams & Wilkins; 1980.
Wang MS, Fang G, Culver DG, et al. The WldS protein protects against axonal degeneration: a model of gene therapy for peripheral neuropathy. Ann Neurol. Dec 2001;50(6):773-9. [Medline].
Zampollo A, Baruffini A, Cirla AM, et al. Subclinical inorganic mercury neuropathy: neurophysiological investigations in 17 occupationally exposed subjects. Ital J Neurol Sci. Jun 1987;8(3):249-54. [Medline].
Further Reading
Keywords
drug neuropathy, chemical neuropathy, toxins, industrial chemicals, organic solvents, occupational exposure, environmental exposure, pollutants
