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Clinical Assessment of Neurotoxicity. Occupational and Environmental Medical Association of Canada 29th Annual Scientific Conference. Chris Martin, MD, MSc, FRCPC cmartin@hsc.wvu.edu Director, Institute of Occupational and Environmental Health.
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Clinical Assessment of Neurotoxicity Occupational and Environmental Medical Association of Canada 29th Annual Scientific Conference Chris Martin, MD, MSc, FRCPC cmartin@hsc.wvu.edu Director, Institute of Occupational and Environmental Health
These are among the most challenging cases in Occupational Medicine
“Many complain of their Memory, few of their Judgment”. - Benjamin Franklin “Tout le monde se plaint de sa mémoire, et personne ne se plaint de son jugement”. - François de la Rochefoucauld
Overview • Review neuroanatomy • Vulnerability • Targets of neurotoxicity • Clinical approach • Case discussion
What makes the nervous system LESS vulnerable? • Blood brain barrier for CNS
What makes the nervous system LESS vulnerable? • Excess neuronal capacity
What makes the Nervous System MORE vulnerable? • High aerobic energy requirements • Most sensitive tissue to loss of oxygen supply • Presence of long, complex cell structures • Axons are most sensitive to damage
Targets of Neurotoxicity Damage to: • Cell body • neuronopathy • Axon • axonopathy • Myelin • myelinopathy • Synapse or neuromuscular junction • “transmissionopathy”
Neuronopathy • Damage is irreversible
Neuronopathy • Damage is irreversible Examples: • methyl mercury • MPTP
Axonopathy • Damage is reversible in PNS irreversible in CNS • Sensorimotor neuropathies • “Stocking and glove” distribution
Axonopathy • Damage is reversible in PNS irreversible in CNS • Sensorimotor neuropathies • “Stocking and glove”distribution Examples: • carbon disulfide • n-hexane • acrylamide monomer • arsenic • trichloroethylene
Myelinopathy • lead
“Transmissionopathy” • Organophosphate pesticides
What is the typical case before you? • CNS: Chronic encephalopathy • PNS: Sensorimotor peripheral neuropathy
History • Take a detailed exposure history • Strong dose-response relationship
History • Take a detailed exposure history • Ask about symptoms of acute intoxication for any body system when actively exposed
History • Take a detailed exposure history • Ask about symptoms of acute intoxication for any body system when actively exposed Example: For solvents, dermatitis? Headache? Nausea? Felt drunk? Syncope?
History • Obtain detailed information about symptoms • Ask for examples of symptom manifestations • Functional status, activities of daily living
History • Obtain detailed information about symptoms • Determine chronology of symptoms in relation to exposure • Symptoms occur at the time of or shortly after exposure • Course of symptoms after cessation of exposure important
History • Obtain detailed information about symptoms • Determine chronology of symptoms in relation to exposure • Complete medical history to ascertain other possible causes • Alcohol, cardiovascular disease, psychiatric disease, family history
Physical Examination • Folstein Mini-Mental Status Exam
Physical Examination • Folstein Mini-Mental Status Exam • Detailed neurological examination • Particular attention to nature and distribution of any abnormalities
Investigations Peripheral Nervous System: • Nerve conduction studies / electromyography • Quantitative sensory testing • Nerve biopsy if n-hexane peripheral neuropathy
Peripheral Nervous System • Key points in formulating diagnosis: • Most toxic neuropathies are symmetric with greater distal involvement • Recovery following cessation of exposure • In general, for about 25-40% of peripheral neuropathies, diagnosis is unknown
Investigations Central Nervous System: • Imaging studies usually normal unless very advanced disease • Other investigations (lumbar puncture, EEG, labs) to rule out other causes • Most sensitive investigation is neuropsychiatric testing • Testing is user dependent • Report should provide numerical scores on test • Read the entire report • Include investigations for effects of exposure on other systems (Example LFT’s for solvents)
Central Nervous System • Key points in formulating diagnosis: • Most toxic CNS disorders are diffuse without focal pathology • Onset when exposed • Stable following cessation of exposure for chronic solvent encephalopathy1 • Must rule out other causes • May need longitudinal information • Consider the impact of a diagnosis of “brain damage” from “chemical poisoning” 1. van Valen E, Wekking E, van der Laan G, Sprangers M, van Dijk F. The course of chronic solvent induced encephalopathy: A systematic review. Neurotoxicology. 2009 Nov;30(6):1172-86.
Case Discussion • 39-year old female clerk at prison facility • Exposed to sewer gases as well as agents applied to unclog commodes • At 1:30 PM upper airway irritation, headache, nausea with vomiting • Left work at 2:50 PM
Case Discussion 3 days later: • difficulty with concentration, poor memory, photophobia, difficulty speaking, reduced smell and taste, difficulty writing • Very poor level of functioning since exposure • Presents to ER one week after exposure
Case Discussion Physical exam: • Mental status - poor recall, serial 7’s, good judgement, general knowledge • Performs tasks after approximately 3 second delay • Reduced olfaction, otherwise cranial nerves intact • Photophobia
Case Discussion Physical exam: • Difficulty with alternating movements, finger-nose, tandem gait • Romberg’s sign negative • Power, tone, reflexes, sensation intact • Aphasia: rhythmic quality, selective omission of articles
Case Discussion Do you think her presentation is due to the exposure?
Case Discussion Do you think her presentation is due to the exposure? • Not a high level exposure, not likely to have been exposed to compatible neurotoxic agent
Case Discussion Do you think her presentation is due to the exposure? • Not a high level exposure, not likely to have been exposed to compatible neurotoxic agent • Delay in symptoms