1. Occupational Neurotoxicology H.R.Sarreshtahdar, MD Occupational Medicine Specialist

2. General Principles  Dose-Toxicity relationship  Nonfocal or symmetrical sign  Temporal relationship  Multiple neurologic syn. Some recovery is possible after removal of the insulting agent Few toxins present with pathognomonic neurologic syndrome.

3. APPROACH TO PATIENTS 1) Sufficient intense or prolonged exposure to the toxin. 2) An appropriate neurologic syndrome based on knowledge about the putative toxin. 3) Evalution of symptoms and signs over a compatible temporal course. 4) Exclusion of other neurologic disorders that may account for a similar syndrome.

4. Central Nervous System(CNS)  Diffuse toxic encephalopathy Acute Chronic  Selective toxic encephalopathy Cell bodies Ion channels Neurotransmitter system

5. Pripheral Nervous System(PNS)  Polyneuropathy  Myeloneuropathy

6. Neurotoxins

7. Specific Neurotoxins  Metals Lead Arsenic Manganese Mercury  Pesticides Organophosphates  Solvents Carbon disulfide n-Hexane Methanol Trichloroethylene  Plastics Acrylamide  Gases Nitrous oxide Ethylene oxide Methyl bromide

8. Lead  Massive intoxication :  Lead encephalopathy: lead blood levels of 50-70 µ g/dl convulsions, cerebral edema, coma, transtentorial herniation.  Chronic low-level exposure : impaired intellectual development in children.

9. Lead  Classic: bilateral wrist-drop and foot-drop.  The best known clinical syndrome is a predominantly motor neuropathy with little if any sensory symptoms.  Toxicity also may manifest as a generalized proximal & distal weakness and loss of DTR.  lead level > 40 µ g/dl: Asymptomatic & NCV abnormalities:

10. Mercury  Organic mercury :CNS disturbances (tremor, cerebellar ataxia, hearing Loss, visual field constriction, hyperreflexia and Babinski sign)  Inorganic mercury: PNS,Neuropathy = Guillain-Barre syndrome

11. Arsenic  The most common manifestation of neurotoxicity : Peripheral neuropathy. Symmetrical sensorimotor polyneuropathy  Single massive dose: acute polyneuropathy( 1-3 weeks) = Guillain-Barre syn.

12. Manganese  extrapyramidal disorder (idiopathic Parkinson)  Compared to idiopathic Parkinson disease, the extrapyramidal symptoms of manganism are less responsive to dopaminergic therapy.  neurologic deficits often continue to progress for many years after cessation of exposure

13. Carbon Monoxide  0.01-0.02%: headache and mild confusion.  0.1-0.2%: stupor  1% more than 30 minutes can be fatal.  More prolonged or severe hypoxia is accompanied by a varying combination of tremor, chorea, spasticity, dystonia, rigidity, and bradykinesia. encephalopathy, parkinsonism are relatively common.

14. Nitrous Oxide  Myeloneuropathy =Vitamin B 12 deficiency.  Paresthesias in the hands and feet.  Gait ataxia, sensory loss, Romberg sign.  DTR :diminished or lost (peripheral neuropathy)  Serum vitamin B 12 and Schilling test are often normal.  serum homocysteine level may be elevated.

15. Hexacarbons (n-Hexane and Methyl n-Butyl Ketone)  acute encephalopathy euphoria, hallucination, and confusion.  The most well-known syndrome:glue- sniffer'sneuropathy distal symmetric sensorimotor polyneuropathy Early symptoms are paresthesias and sensory loss. Weakness involves distal muscles initially Proximal musculatures are affected in more severe cases.

16. SyndromeNeuroanatomySymptoms and SignsExamples Acute encephalopathy Diffuse; cerebral hemispheres headache, irritability, disorientation, convulsions, amnesia, psychosis, lethargy, stupor and coma Acute exposure to many toxins at sufficient doses Chronic encephalopathy Diffuse; cerebral hemispheres Cognitive and psychiatric dis- turbances Chronic or low-dose exposure to many toxins Parkinsonism Basal ganglia & other extra- pyramidal motor pathways Tremor, rigidity, bradykinesia, gait instability Mn, CO, Methanol Motor neuron disease Spinal cord motor neurons Muscle atrophy, weaknessLead, manganese Myeloneuropathy (myelopathy & polyneuropathy) Spinal cord & peripheral nerves Paresthesias, sensory loss, hyperreflexia, Babinski sign, NO, organophosphates, n-hexane Polyneuropathy Peripheral sensory, motor & autonomic nerve fibers Paresthesias, numbness, weakness, loss of DTR, autonomic failure Many toxins at sufficient doses

17. Focal nerve injuries  Radial nerve  Median nerve - carpal tunnel syn. - entrapment at elbow  Ulnar nerve -cubital nurve syn. -lesion at wrist  TOS