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
1. Review neuroanatomy


Vulnerability
Targets of neurotoxicity
2. Clinical approach
3. Case discussion
What makes the nervous system LESS vulnerable?
1.
Blood brain barrier for CNS
What makes the nervous system LESS vulnerable?
2.
Excess neuronal capacity
What makes the Nervous System MORE vulnerable?
1.
High aerobic energy requirements
Most sensitive tissue to loss of oxygen supply
2.
Presence of long, complex cell structures
Axons are most sensitive to damage
Structure of the Neuron
Targets of Neurotoxicity
Damage to:
1. Cell body
neuronopathy
2.
Axon
axonopathy
3.
Myelin
myelinopathy
4.
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