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Clinical Assessment of Neurotoxicity. Occupational and Environmental Medical Association of Canada 29th Annual Scientific Conference. Chris Martin, MD, MSc, FRCPC [email protected] Director, Institute of Occupational and Environmental Health.

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Clinical assessment of neurotoxicity

Clinical Assessment of Neurotoxicity

Occupational and Environmental Medical Association of Canada

29th Annual Scientific Conference

Chris Martin, MD, MSc, FRCPC

[email protected]

Director, Institute of Occupational and Environmental Health



MedicineMany 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
Overview Medicine

  • Review neuroanatomy

    • Vulnerability

    • Targets of neurotoxicity

  • Clinical approach

  • Case discussion


1 review of neuroanatomy

1. Review of MedicineNeuroanatomy


What makes the nervous system less vulnerable
What makes the nervous system LESS vulnerable? Medicine

  • Blood brain barrier for CNS


What makes the nervous system less vulnerable1
What makes the nervous system LESS vulnerable? Medicine

  • Excess neuronal capacity


What makes the nervous system more vulnerable
What makes the Nervous System MORE vulnerable? Medicine

  • 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
Targets of Neurotoxicity Medicine

Damage to:

  • Cell body

    • neuronopathy

  • Axon

    • axonopathy

  • Myelin

    • myelinopathy

  • Synapse or neuromuscular junction

    • “transmissionopathy”


Neuronopathy
Neuronopathy Medicine

  • Damage is irreversible


Neuronopathy1
Neuronopathy Medicine

  • Damage is irreversible

    Examples:

  • methyl mercury

  • MPTP


Axonopathy
Axonopathy Medicine

  • Damage is reversible in PNS

    irreversible in CNS

  • Sensorimotor neuropathies

  • “Stocking and glove” distribution


Axonopathy1
Axonopathy Medicine

  • Damage is reversible in PNS

    irreversible in CNS

  • Sensorimotor neuropathies

  • “Stocking and glove”distribution

    Examples:

  • carbon disulfide

  • n-hexane

  • acrylamide monomer

  • arsenic

  • trichloroethylene


Myelinopathy
Myelinopathy Medicine

  • lead


Transmissionopathy
MedicineTransmissionopathy”

  • Organophosphate pesticides



What is the typical case before you
What is the typical case before you? Medicine

  • CNS: Chronic encephalopathy

  • PNS: Sensorimotor peripheral neuropathy


History
History Medicine

  • Take a detailed exposure history

    • Strong dose-response relationship


History1
History Medicine

  • Take a detailed exposure history

  • Ask about symptoms of acute intoxication for any body system when actively exposed


History2
History Medicine

  • 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?


History3
History Medicine

  • Obtain detailed information about symptoms

    • Ask for examples of symptom manifestations

    • Functional status, activities of daily living


History4
History Medicine

  • 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


History5
History Medicine

  • 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
Physical Examination Medicine

  • Folstein Mini-Mental Status Exam


Physical examination1
Physical Examination Medicine

  • Folstein Mini-Mental Status Exam

  • Detailed neurological examination

  • Particular attention to nature and distribution of any abnormalities


Investigations
Investigations Medicine

Peripheral Nervous System:

  • Nerve conduction studies / electromyography

  • Quantitative sensory testing

  • Nerve biopsy if n-hexane peripheral neuropathy


Peripheral nervous system
Peripheral Nervous System Medicine

  • 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


Investigations1
Investigations Medicine

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
Central Nervous System Medicine

  • 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
Case Discussion Medicine

  • 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 discussion1
Case Discussion Medicine

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 discussion2
Case Discussion Medicine

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 discussion3
Case Discussion Medicine

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 discussion4
Case Discussion Medicine

Do you think her presentation is due to the exposure?


Case discussion5
Case Discussion Medicine

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 discussion6
Case Discussion Medicine

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


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