1. Neurotoxicology A. H. Mehrparvar, MD Occupational Medicine department
Yazd University of Medical Sciences

2. Introduction The nervous system:
vulnerable to a wide range of insults from environmental or occupational toxins
selective permeability barriers
metals, gases, solvents, and other chemicals penetrate sufficiently to cause deleterious effects

3. Historical preview
lead poisoning described by Greek physicians before the birth of Christ
homicidal use of arsenic by Nero
glue-sniffer's neuropathy (hexacarbons).

4. Disorders of the nervous system manifest in a diverse manner
brain, spinal cord, peripheral nerve, or muscle respond differently to toxic injuries
Pathophysiology:
is not well understood
Much of our current knowledge is gained from clinical observations of intense exposures during accidents or chronic heavy occupational exposures

5. General principles dose-toxicity relationship
threshold level
Individual susceptibility
a nonfocal or symmetric neurologic syndrome
temporal relationship
Recovery
Delayed or persistent neuro­logic deficits

6. Exclusion of non-toxic causes
Few toxins present with a pathognomonic neurologic syndrome
Symptoms and signs may be mimicked by many psychiatric, metabolic, inflamma­tory, neoplastic, and degenerative diseases of the nervous system

7. CNS Acute encephalopathy (many toxins)
Chronic encephalopathy (many toxins)
Parkinsonism (Mn, CO)
Motor neuron disease (Pb, Mn)

8. PNS
sensory disturbances and weakness, often accompanied by impairment of the deep tendon reflexes
the peripheral nerve: the most vulnerable
the resulting syndrome: a symmetric peripheral neuropathy (polyneuropathy)
toxic myopathy: uncommon
Hallmark:
distal distribution

9. The most common syndrome:
subacute onset of tingling or numbness in a symmetric stocking-and-glove distribution

10. Toxic neuropathies
Mostly sensory or sensorimotor polyneuropathy (little or no weakness)
Acrylamide
Carbon disulfide
Ethylene oxide
Metals: arsenic, lead, mercury, thallium
Methyl bromide
Polychlorinated biphenyls (PCBs)
Thallium Predominantly motor

11. polyneuropathy or sensorimotor polyneur­opathy with significant weakness
Hexacarbons: n-hexane, methyl n-butyl ketone
Metals: lead, arsenic, mercury
Organophosphates
Pyridoxine abuse

12. Cranial neuropathy
Thallium
Trichloroethylene (trigeminal neuropathy)

13. Prominent autonomic dysfunction
Acrylamide
n-Hexane (glue-sniffer)
Thaliium
Benzene
Carbon monoxide
Dioxin
Methyl methacrylate
Pyrethrin

14. Acrylamide
workers who handle monomeric acrylamide in the production of polyacrylamides
inhalation or skin absorption
local skin irritation, weight loss, cen­tral and peripheral nervous system involvement
Acute exposure:
confusional state, disorientation, memory loss, and gait ataxia.

15. Acrylamide Chronic exposure:
dizziness, increased irritability, emotional changes, and sleep disturbances
The primary site: peripheral nerve
Both sensory and motor nerves are affected
sensory loss, weakness, ataxia, and loss of tendon reflexes
Autonomic involvement, such as hyperhidrosis and urinary reten­tion, is common.

16. Arsenic
Acute:
nausea, vomiting, abdominal pain, and diarrhea, dermatologic lesions
Peripheral neuropathy is the most common neurologic manifestation
mimics Guillain-Barre syndrome
Symmetric paresthesias and pain, distal weakness, sensory and motor deficits spread proximally

17. Carbon monoxide headache and mild confusion Somnolence, stupor
prolonged or severe hypoxia:
tremor, chorea, spasticity, dystonia, rigidity, and bradykinesia
Residual dementia, spasticity, cortical blindness, and parkinsonian features are relatively common

18. Hexacarbones
widely used volatile organic compounds employed in homes and industries as solvents and adhesives
inhalation, especially in poorly ventilated spaces, or excessive skin contact
acute encephalopathy
distal symmetric sensorimotor polyneuropathy (glue-sniffer's neuropathy)
Paresthesias, sensory loss, weakness

19. Lead
Lead is present in paint, batteries, pipes, solder, ammunition, and cables, pottery,
Acute:
syndrome of abdominal colic and intermittent vomiting, accompanied by neurologic symptoms such as headache, tremor, apathy, and lethargy, convulsions, cerebral edema, stupor, or coma

20. Lead Chronic low-level exposure:
impaired intellectual development in children
Peripheral neuropathy
predominantly motor neuropathy with little sensory symptoms
mimics motor neuron diseases such as amyotrophic lateral sclerosis
bilateral wrist drop and foot drop

21. Mercury
exposure to methyl mercury, elemental mer­cury, and inorganic mercuric salts
Mer­cury is used in batteries, fungicides, electronics, and …
a diffuse encephalopathy
euphoria, irritability, anxiety, and emotional lability, confusion and an altered level of consciousness, tremor and cerebellar ataxia
Hearing loss, visual field constriction, hyperreflexia, and Babinski sign

22. Neuropathy:
inorganic mercury
A subacute predominantly motor neuropathy
resembles Guillain-Barre syndrome or amyotrophic lateral sclerosis