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NeurotoxicantsNeurotoxicants

Dr. Craig JacksonSenior Lecturer in Health Psychology

Faculty of HealthBCU

www.health.bcu.ac.uk/craigjacksonwww.health.bcu.ac.uk/craigjackson

craig.jackson@uce.ac.ukcraig.jackson@uce.ac.uk

NeurotoxinsNeurotoxins

Neurotoxicant syndromes, brought about by substances which adversely Neurotoxicant syndromes, brought about by substances which adversely affect nervous tissueaffect nervous tissue

Constitute one of the ten leading occupational disorders in the United StatesConstitute one of the ten leading occupational disorders in the United States

Neurotoxicant effects constitute the basis for establishing exposure limit Neurotoxicant effects constitute the basis for establishing exposure limit criteria for approximately 40% of agents considered hazardous by the United criteria for approximately 40% of agents considered hazardous by the United States National Institute for Occupational Safety and Health (NIOSH).States National Institute for Occupational Safety and Health (NIOSH).

NeurotoxinsNeurotoxins

Any substance capable of interfering with the normal function of nervous Any substance capable of interfering with the normal function of nervous tissuetissue

Causing irreversible cellular damage Causing irreversible cellular damage

Or resulting in cellular deathOr resulting in cellular death

Neurotoxin will attack selected sites or specific cellular elements of the Neurotoxin will attack selected sites or specific cellular elements of the nervous systemnervous system

Compounds which are non-polar, have Compounds which are non-polar, have greater lipid solubilitygreater lipid solubility, and thus have , and thus have greater access to nervous tissue than highly polar and less lipid-soluble greater access to nervous tissue than highly polar and less lipid-soluble chemicals. chemicals.

NeurotoxinsNeurotoxins

The type and size of cells;The type and size of cells;various neurotransmitter systems affected;various neurotransmitter systems affected;different regions of the brain;different regions of the brain;innate protective detoxifying mechanisms;innate protective detoxifying mechanisms;integrity of cellular membranes and intracellular organelles integrity of cellular membranes and intracellular organelles

all influence neurotoxicant responsesall influence neurotoxicant responses

Neurons (the functional cell unit of the nervous system) have a high Neurons (the functional cell unit of the nervous system) have a high metabolic rate and are at greatest risk for neurotoxicant damage, followed by metabolic rate and are at greatest risk for neurotoxicant damage, followed by oligodendrocytes, astrocytes, microglia and cells of the capillary oligodendrocytes, astrocytes, microglia and cells of the capillary endothelium. endothelium.

Changes in cellular membrane structure impair excitability and impede Changes in cellular membrane structure impair excitability and impede impulse transmission.impulse transmission.

NeurotoxinsNeurotoxins

Toxicant effects:Toxicant effects:

alter protein form;alter protein form;fluid content;fluid content;ionic exchange capability of membranes;ionic exchange capability of membranes;

leading to swelling of neurons, astrocytes and damage to the delicate cells leading to swelling of neurons, astrocytes and damage to the delicate cells lining blood capillarieslining blood capillaries

Disruption of neurotransmitter mechanisms block access to post-synaptic Disruption of neurotransmitter mechanisms block access to post-synaptic receptors, produce false neurotransmitter effects, and alter the synthesis, receptors, produce false neurotransmitter effects, and alter the synthesis, storage, release, re-uptake or enzymatic inactivation of natural storage, release, re-uptake or enzymatic inactivation of natural neurotransmitters.neurotransmitters.

NeurotoxinsNeurotoxins

Clinical manifestations of neurotoxicity are determined by: Clinical manifestations of neurotoxicity are determined by:

• the physical characteristics of the neurotoxicant substance;the physical characteristics of the neurotoxicant substance;

• the dose of exposure to it;the dose of exposure to it;

• the vulnerability of the cellular target;the vulnerability of the cellular target;

• the organism's ability to metabolize and excrete the toxin;the organism's ability to metabolize and excrete the toxin;

• the reparative abilities of the structures and mechanisms affected. the reparative abilities of the structures and mechanisms affected.

METALS:METALS: ArsenicArsenic

SOURCESOURCEPesticides; pigments; antifouling paint; electroplating industry; seafood; Pesticides; pigments; antifouling paint; electroplating industry; seafood; smelters; semiconductors smelters; semiconductors

DIAGNOSISDIAGNOSISAcute: encephalopathyAcute: encephalopathyChronic: peripheral neuropathy Chronic: peripheral neuropathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Axon (c)Axon (c)

METALS:METALS: LeadLead

SOURCESOURCESolder; lead shot; illicit whiskey; insecticides; auto body shop; storage Solder; lead shot; illicit whiskey; insecticides; auto body shop; storage battery manufacturing; foundries, smelters; lead-based paint; lead pipes battery manufacturing; foundries, smelters; lead-based paint; lead pipes

DIAGNOSISDIAGNOSISAcute: encephalopathyAcute: encephalopathyChronic: encephalopathy and peripheral Chronic: encephalopathy and peripheral neuropathy neuropathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYBlood vessels (a)Blood vessels (a)Axon (c)Axon (c)

METALS:METALS: ManganeseManganese

SOURCESOURCEIron, steel industry; welding operations; metal-finishing operations; Iron, steel industry; welding operations; metal-finishing operations; fertilizers; manufacturers of fireworks, matches; manufacturers of dry cell fertilizers; manufacturers of fireworks, matches; manufacturers of dry cell batteries batteries

DIAGNOSISDIAGNOSISAcute: encephalopathyAcute: encephalopathyChronic: parkinsonism Chronic: parkinsonism

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Basal ganglia neurons (c)Basal ganglia neurons (c)

METALS:METALS: MercuryMercury

SOURCESOURCEScientific instruments; electrical equipment; amalgams; electroplating Scientific instruments; electrical equipment; amalgams; electroplating industry; photography; felt making industry; photography; felt making

DIAGNOSISDIAGNOSISAcute: headache, nausea, onset of tremorAcute: headache, nausea, onset of tremorChronic: ataxia, peripheral neuropathy, encephalopathy Chronic: ataxia, peripheral neuropathy, encephalopathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Axon (c)Axon (c)Unknown (c)Unknown (c)

METALS:METALS: TinTin

SOURCESOURCECanning industry; solder; electronic components; polyvinyl plastics; Canning industry; solder; electronic components; polyvinyl plastics; fungicides fungicides

DIAGNOSISDIAGNOSISAcute: memory defects, seizures, disorientationAcute: memory defects, seizures, disorientationChronic: encephalomyelopathy Chronic: encephalomyelopathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYNeurons of the limbic system (a & c)Neurons of the limbic system (a & c)Myelin (c)Myelin (c)

SOLVENTS:SOLVENTS: Carbon DisulphideCarbon Disulphide

SOURCESOURCEManufacturers of viscose rayon; preservatives; textiles; rubber cement; Manufacturers of viscose rayon; preservatives; textiles; rubber cement; varnishes; electroplating industry varnishes; electroplating industry

DIAGNOSISDIAGNOSISAcute: encephalopathyAcute: encephalopathyChronic: peripheral neuropathy, parkinsonismChronic: peripheral neuropathy, parkinsonism

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Axon (c)Axon (c)UnknownUnknown

SOLVENTS:SOLVENTS: n-hexane, methyl butyl ketonen-hexane, methyl butyl ketone

SOURCESOURCEPaints; lacquers; varnishes; metal-cleaning compounds; quick-drying inks; Paints; lacquers; varnishes; metal-cleaning compounds; quick-drying inks; paint removers; glues, adhesives paint removers; glues, adhesives

DIAGNOSISDIAGNOSISAcute: narcosisAcute: narcosisChronic: peripheral neuropathy, unknown (a) Axon (c), Chronic: peripheral neuropathy, unknown (a) Axon (c),

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGY

SOLVENTS:SOLVENTS: PerchloroethylenePerchloroethylene

SOURCESOURCEPaint removers; degreasers; extraction agents; dry cleaning industry; textile Paint removers; degreasers; extraction agents; dry cleaning industry; textile industry industry

DIAGNOSISDIAGNOSISAcute: narcosisAcute: narcosisChronic: peripheral neuropathy, encephalopathyChronic: peripheral neuropathy, encephalopathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Axon (c)Axon (c)UnknownUnknown

SOLVENTS:SOLVENTS: TolueneToluene

SOURCESOURCERubber solvents; cleaning agents; glues; manufacturers of benzene; Rubber solvents; cleaning agents; glues; manufacturers of benzene; gasoline, aviation fuels; paints, paint thinners; lacquers gasoline, aviation fuels; paints, paint thinners; lacquers

DIAGNOSISDIAGNOSISAcute: narcosisAcute: narcosisChronic: ataxia, encephalopathyChronic: ataxia, encephalopathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Cerebellum (c)Cerebellum (c)UnknownUnknown

SOLVENTS:SOLVENTS: TrichloroethyleneTrichloroethylene

SOURCESOURCEDegreasers; painting industry; varnishes; spot removers; process of Degreasers; painting industry; varnishes; spot removers; process of decaffeination; dry cleaning industry; rubber solvents decaffeination; dry cleaning industry; rubber solvents

DIAGNOSISDIAGNOSISAcute: narcosisAcute: narcosisChronic: encephalopathy, cranial neuropathyChronic: encephalopathy, cranial neuropathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYUnknown (a)Unknown (a)Unknown (c)Unknown (c)Axon (c)Axon (c)

INSECTICIDES:INSECTICIDES: OrganophosphatesOrganophosphates

SOURCESOURCEAgricultural industry manufacturing and application Agricultural industry manufacturing and application

DIAGNOSISDIAGNOSISAcute: cholinergic poisoningAcute: cholinergic poisoningChronic: ataxia, paralysis, peripheral neuropathy Chronic: ataxia, paralysis, peripheral neuropathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYAcetylcholinesterase (a)Acetylcholinesterase (a)Long tracts of spinal cord (c)Long tracts of spinal cord (c)Axon (c)Axon (c)

INSECTICIDES:INSECTICIDES: CarbamatesCarbamates

SOURCESOURCEAgricultural industry manufacturing and application flea powders Agricultural industry manufacturing and application flea powders

DIAGNOSISDIAGNOSISAcute: cholinergic poisoning Acute: cholinergic poisoning Chronic: tremor, peripheral neuropathyChronic: tremor, peripheral neuropathy

LOCUS OF PATHOLOGYLOCUS OF PATHOLOGYAcetylcholinesterase (a)Acetylcholinesterase (a)Dopaminergic system (c)Dopaminergic system (c)

DiagnosisDiagnosis

Establishing a diagnosis of a neurotoxicant syndrome and differentiating it Establishing a diagnosis of a neurotoxicant syndrome and differentiating it from neurologic diseases of non-neurotoxicant aetiology requires;from neurologic diseases of non-neurotoxicant aetiology requires;

•understanding of the pathogenesis of the neurological symptoms and understanding of the pathogenesis of the neurological symptoms and observed signs and symptoms; observed signs and symptoms;

•awareness that particular substances are capable of affecting nervous awareness that particular substances are capable of affecting nervous tissue; tissue;

•documentation of exposure; documentation of exposure;

•evidence of presence of neurotoxin and/or metabolites in tissues of an evidence of presence of neurotoxin and/or metabolites in tissues of an affected individual;affected individual;

•delineation of a time relationship between exposure and the appearance of delineation of a time relationship between exposure and the appearance of symptoms with subsequent decrease in symptoms after exposure endssymptoms with subsequent decrease in symptoms after exposure ends

DiagnosisDiagnosis

Proof that a particular substance has reached a toxicant dose level is Proof that a particular substance has reached a toxicant dose level is usually lacking after symptoms appearusually lacking after symptoms appear

Unless environmental monitoring is ongoing, a high index of suspicion is Unless environmental monitoring is ongoing, a high index of suspicion is necessary to recognize cases of neurotoxicologic injurynecessary to recognize cases of neurotoxicologic injury

Identifying symptoms referable to the central and/or the peripheral nervous Identifying symptoms referable to the central and/or the peripheral nervous systems can help the clinician focus on certain substances, which have a systems can help the clinician focus on certain substances, which have a greater predilection for one part or another of the nervous system, as greater predilection for one part or another of the nervous system, as possible culpritspossible culprits

DiagnosisDiagnosis

convulsionsconvulsionsweaknessweaknesstremor/twitchingtremor/twitchinganorexia (weight loss)anorexia (weight loss)equilibrium disturbanceequilibrium disturbancecentral nervous system depressioncentral nervous system depressionnarcosis (a state of stupor or unconsciousness)narcosis (a state of stupor or unconsciousness)visual disturbancevisual disturbancesleep disturbancesleep disturbanceataxia (inability to coordinate voluntary muscle movements)ataxia (inability to coordinate voluntary muscle movements)fatigue and tactile disorders fatigue and tactile disorders

are all commonly reported symptoms following exposure to certain chemicals.are all commonly reported symptoms following exposure to certain chemicals. Constellations of symptoms form syndromes associated with neurotoxicant Constellations of symptoms form syndromes associated with neurotoxicant exposure.exposure.

DiagnosisDiagnosis

Establishing a diagnosis of a neurotoxicant syndrome and differentiating it Establishing a diagnosis of a neurotoxicant syndrome and differentiating it from neurologic diseases of non-neurotoxicant aetiology requires;from neurologic diseases of non-neurotoxicant aetiology requires;

• understanding of the pathogenesis of the neurological symptoms and understanding of the pathogenesis of the neurological symptoms and observed signs and symptoms; observed signs and symptoms;

• awareness that particular substances are capable of affecting nervous awareness that particular substances are capable of affecting nervous tissue; tissue;

• documentation of exposure; documentation of exposure;

• evidence of presence of neurotoxin and/or metabolites in tissues of an evidence of presence of neurotoxin and/or metabolites in tissues of an affected individual;affected individual;

• delineation of a time relationship between exposure and the appearance of delineation of a time relationship between exposure and the appearance of symptoms with subsequent decrease in symptoms after exposure endssymptoms with subsequent decrease in symptoms after exposure ends

Behavioural DisordersBehavioural Disorders

Disorders with predominantly behavioural features ranging from acute Disorders with predominantly behavioural features ranging from acute psychosis, depression and chronic apathy have been described in some psychosis, depression and chronic apathy have been described in some workers. workers.

It is essential to differentiate memory impairment associated with other It is essential to differentiate memory impairment associated with other neurological diseases, such as Alzheimer's disease, arteriosclerosis or neurological diseases, such as Alzheimer's disease, arteriosclerosis or presence of a brain tumor, from the cognitive deficits associated with presence of a brain tumor, from the cognitive deficits associated with toxicant exposure to organic solvents, metals or insecticides. toxicant exposure to organic solvents, metals or insecticides.

Transient disturbances of awareness or epileptic seizures with or without Transient disturbances of awareness or epileptic seizures with or without associated motor involvement must be identified as a primary diagnosis associated motor involvement must be identified as a primary diagnosis separate from similarly appearing disturbances of consciousness related to separate from similarly appearing disturbances of consciousness related to neurotoxicant effects.neurotoxicant effects.

Behavioural DisordersBehavioural Disorders

Subjective and behavioural syndromes;Subjective and behavioural syndromes;HeadacheHeadacheVertigoVertigoFatigueFatiguePersonality changePersonality change

Can all manifest as mild encephalopathy with inebriation, and may indicate Can all manifest as mild encephalopathy with inebriation, and may indicate the presence of exposure to carbon monoxide, carbon dioxide, lead, zinc, the presence of exposure to carbon monoxide, carbon dioxide, lead, zinc, nitrates or mixed organic solvents. nitrates or mixed organic solvents.

Standardized neuropsychological testing is necessary to document Standardized neuropsychological testing is necessary to document elements of cognitive impairment in patients suspected of toxicant elements of cognitive impairment in patients suspected of toxicant encephalopathy, and these must be differentiated from those dementing encephalopathy, and these must be differentiated from those dementing syndromes caused by other pathologies.syndromes caused by other pathologies.

Behavioural DisordersBehavioural Disorders

Specific tests used in the diagnostic batteries of tests must include a broad Specific tests used in the diagnostic batteries of tests must include a broad sampling of cognitive function tests sampling of cognitive function tests

These will generate predictions about the patient's functioning and daily life, These will generate predictions about the patient's functioning and daily life, as well as tests which have been demonstrated previously to be sensitive to as well as tests which have been demonstrated previously to be sensitive to the effects of known neurotoxinsthe effects of known neurotoxins

These standardized batteries must include tests which have been validated These standardized batteries must include tests which have been validated on patients with specific types of brain damage and structural deficits, to on patients with specific types of brain damage and structural deficits, to clearly separate these conditions from neurotoxic effectsclearly separate these conditions from neurotoxic effects

In addition, tests must include internal control measures to detect the In addition, tests must include internal control measures to detect the influence of motivation, hypochondriasis, depression and learning influence of motivation, hypochondriasis, depression and learning difficulties, and must contain language that takes into account cultural as difficulties, and must contain language that takes into account cultural as well as educational background effectswell as educational background effects

Central Nervous System impairmentsCentral Nervous System impairments

Organic affective syndrome (Type I Effect)Organic affective syndrome (Type I Effect)mild mood disorders predominate as the patient's chief complaint, with mild mood disorders predominate as the patient's chief complaint, with features most consistent with those of organic affective disorders of the features most consistent with those of organic affective disorders of the depressive type. depressive type. This syndrome seems to be This syndrome seems to be reversible reversible following cessation of exposure to following cessation of exposure to the offending agent.the offending agent.

Mild chronic toxicant encephalopathyMild chronic toxicant encephalopathyin addition to mood disturbances, central nervous system impairment is in addition to mood disturbances, central nervous system impairment is more prominent. Patients have evidence of memory and psychomotor more prominent. Patients have evidence of memory and psychomotor function disturbance which can be confirmed by neuropsychological testing. function disturbance which can be confirmed by neuropsychological testing. In addition, features of visual spatial impairment and abstract concept In addition, features of visual spatial impairment and abstract concept formation may be seen. Activities of daily living and work performance are formation may be seen. Activities of daily living and work performance are impaired.impaired.

Central Nervous System impairmentsCentral Nervous System impairments

Sustained personality or mood change (Type IIA Effect)Sustained personality or mood change (Type IIA Effect)In mild chronic toxicant encephalopathy, the course is insidious. Features In mild chronic toxicant encephalopathy, the course is insidious. Features may persist after the cessation of exposure and disappear gradually, while may persist after the cessation of exposure and disappear gradually, while in some individuals, in some individuals, persistent functional impairmentpersistent functional impairment may be observed. If may be observed. If exposure continues, the encephalopathy may progress to a more severe exposure continues, the encephalopathy may progress to a more severe stage.stage.

Severe chronic toxicant encephalopathy (Type III Effect)Severe chronic toxicant encephalopathy (Type III Effect) Dementia with global deterioration of memory and other cognitive problems Dementia with global deterioration of memory and other cognitive problems are noted. The clinical effects of toxicant encephalopathy are not specific to are noted. The clinical effects of toxicant encephalopathy are not specific to a given agent. Chronic encephalopathy associated with toluene, lead and a given agent. Chronic encephalopathy associated with toluene, lead and arsenic is not different from that of other toxicant aetiologies. The presence arsenic is not different from that of other toxicant aetiologies. The presence of other associated findings, however (visual disturbances with methyl of other associated findings, however (visual disturbances with methyl alcohol), may help differentiate syndromes according to particular chemical alcohol), may help differentiate syndromes according to particular chemical aetiologies.aetiologies.

Chronic Symptoms DilemmaChronic Symptoms Dilemma

Workers exposed to solvents for long periods of time may exhibit Workers exposed to solvents for long periods of time may exhibit disturbances of central nervous system function which are permanent disturbances of central nervous system function which are permanent

Since an excess of subjective symptoms, including headache, fatigue, Since an excess of subjective symptoms, including headache, fatigue, impaired memory, loss of appetite and diffuse chest pains, have been impaired memory, loss of appetite and diffuse chest pains, have been reported, it is often difficult to confirm this effect in any individual casereported, it is often difficult to confirm this effect in any individual case

Chronic Symptoms DilemmaChronic Symptoms Dilemma

Some epidemiological studies comparing house painters exposed to Some epidemiological studies comparing house painters exposed to solvents with unexposed industrial workers showed that painters had solvents with unexposed industrial workers showed that painters had significantly lower mean scores on psychological tests measuring significantly lower mean scores on psychological tests measuring intellectual capacity and psychomotor coordination than referent controlsintellectual capacity and psychomotor coordination than referent controls

Painters also had significantly lower performances than expected on Painters also had significantly lower performances than expected on memory and reaction time tests memory and reaction time tests

Differences between workers exposed for several years to jet fuel and Differences between workers exposed for several years to jet fuel and unexposed workers, in tests demanding close attention and high sensory unexposed workers, in tests demanding close attention and high sensory motor speed, were also seenmotor speed, were also seen

Impairments in psychological performance and personality changes have Impairments in psychological performance and personality changes have also been reported among car painters. These included visual and verbal also been reported among car painters. These included visual and verbal memory, reduction of emotional reactivity, and poor performance on verbal memory, reduction of emotional reactivity, and poor performance on verbal intelligence tests.intelligence tests.

Multiple Chemical SensitivityMultiple Chemical Sensitivity

Such patients develop a variety of features involving multiple organ systems Such patients develop a variety of features involving multiple organ systems when they are exposed to even low levels of various chemicals found in the when they are exposed to even low levels of various chemicals found in the workplace and the environmentworkplace and the environment

Mood disturbances are characterized by depression, fatigue, irritability and Mood disturbances are characterized by depression, fatigue, irritability and poor concentrationpoor concentration

These symptoms reoccur on exposure to predictable stimuliThese symptoms reoccur on exposure to predictable stimuli

Many of the symptoms of multiple chemical sensitivity are shared by Many of the symptoms of multiple chemical sensitivity are shared by individuals who show only a mild form of mood disturbance, headache, individuals who show only a mild form of mood disturbance, headache, fatigue, irritability and forgetfulness when they are in a building with poor fatigue, irritability and forgetfulness when they are in a building with poor ventilation and with off-gassing of volatile substances from synthetic building ventilation and with off-gassing of volatile substances from synthetic building materials and carpetsmaterials and carpets

The symptoms disappear when they leave these environments.The symptoms disappear when they leave these environments.

Disturbances of Consciousness, Seizure or ComaDisturbances of Consciousness, Seizure or Coma

When the brain is deprived of oxygen (e.g. CO) disturbances of When the brain is deprived of oxygen (e.g. CO) disturbances of consciousness may resultconsciousness may result

Loss of consciousness may be preceded by seizures in workers with Loss of consciousness may be preceded by seizures in workers with exposure to anticholinesterase substances such as organophosphatesexposure to anticholinesterase substances such as organophosphates

Seizures may also occur with lead encephalopathy associated with brain Seizures may also occur with lead encephalopathy associated with brain swellingswelling

Manifestations of acute toxicity following organophosphate poisoning have Manifestations of acute toxicity following organophosphate poisoning have autonomic nervous system manifestations which precede the occurrence of autonomic nervous system manifestations which precede the occurrence of dizziness, headache, blurred vision, myosis, chest pain, increased bronchial dizziness, headache, blurred vision, myosis, chest pain, increased bronchial secretions, and seizuressecretions, and seizures

These parasympathetic effects are explained by the inhibitory action of These parasympathetic effects are explained by the inhibitory action of these toxicant substances on cholinesterase activity.these toxicant substances on cholinesterase activity.

Movement DisordersMovement Disorders

Slowness of movement, increased muscle tone, and postural abnormalities Slowness of movement, increased muscle tone, and postural abnormalities are observed in workers exposed to manganese, carbon monoxide, carbon are observed in workers exposed to manganese, carbon monoxide, carbon disulphide and MPTP. Individuals may appear to have Parkinson's diseasedisulphide and MPTP. Individuals may appear to have Parkinson's disease

Parkinsonism secondary to toxicant exposureParkinsonism secondary to toxicant exposure has features of other nervous has features of other nervous disorders such as chorea and athetosis and usually the cases do not disorders such as chorea and athetosis and usually the cases do not respond well to the drug levodopa. respond well to the drug levodopa.

Dyskinesia (impairment of the power of voluntary motion) can be a common Dyskinesia (impairment of the power of voluntary motion) can be a common symptom of bromomethane poisoningsymptom of bromomethane poisoning

Movement DisordersMovement Disorders

Spasmodic movements of the fingers, face, peribuccal muscles and the Spasmodic movements of the fingers, face, peribuccal muscles and the neck, as well as extremity spasms, may be seenneck, as well as extremity spasms, may be seen

Tremor is common following mercury poisoningTremor is common following mercury poisoning

More obvious tremor associated with ataxia (lack of coordination of More obvious tremor associated with ataxia (lack of coordination of muscular action) is noted in individuals following toluene inhalationmuscular action) is noted in individuals following toluene inhalation

OpsoclonusOpsoclonus is an abnormal eye movement which is jerky in all directions, is an abnormal eye movement which is jerky in all directions, often seen in brain-stem encephalitis, but may also be a feature following often seen in brain-stem encephalitis, but may also be a feature following chlordecone exposurechlordecone exposure

The abnormality consists of irregular bursts of abrupt, involuntary, rapid, The abnormality consists of irregular bursts of abrupt, involuntary, rapid, simultaneous jerking of both eyes in a conjugate manner, possibly simultaneous jerking of both eyes in a conjugate manner, possibly multidirectional in severely affected individualsmultidirectional in severely affected individuals

HeadachesHeadaches

Common complaints of head pain following exposure to various metal Common complaints of head pain following exposure to various metal fumes such as zinc and other solvent vapours may result from;fumes such as zinc and other solvent vapours may result from;•vasodilation (widening of the blood vessels)vasodilation (widening of the blood vessels)•cerebral oedema (swelling)cerebral oedema (swelling)

The experiencing of pain is common to these conditions, as well as carbon The experiencing of pain is common to these conditions, as well as carbon monoxide, hypoxia (low oxygen), or carbon dioxide conditionsmonoxide, hypoxia (low oxygen), or carbon dioxide conditions

““Sick building syndrome” is thought to cause headaches because of excess Sick building syndrome” is thought to cause headaches because of excess carbon dioxide present in a poorly ventilated areacarbon dioxide present in a poorly ventilated area

Peripheral NeuropathyPeripheral Neuropathy

Motor weaknesses may be noted in distal extremities and progress to Motor weaknesses may be noted in distal extremities and progress to unsteady gait and inability to grasp objectsunsteady gait and inability to grasp objects

The distal portions of the extremities are involved to a greater extent, but The distal portions of the extremities are involved to a greater extent, but severe cases may produce proximal muscle weakness or atrophy as wellsevere cases may produce proximal muscle weakness or atrophy as well

Symptoms may sometimes progress for a few weeks even after removal Symptoms may sometimes progress for a few weeks even after removal from exposurefrom exposure

Deterioration of nerve function may persist for several weeks after removal Deterioration of nerve function may persist for several weeks after removal from exposure.from exposure.

Slowing of motor or sensory conduction velocities is generally associated Slowing of motor or sensory conduction velocities is generally associated with demyelination of nerve fibreswith demyelination of nerve fibres

ConclusionConclusion

The differentiation of a neurotoxicant syndrome from a primary neurological The differentiation of a neurotoxicant syndrome from a primary neurological disease poses a challenge to physiciansdisease poses a challenge to physicians

Obtaining a good history, maintaining a high degree of suspicion and Obtaining a good history, maintaining a high degree of suspicion and adequate follow-up of an individual, as well as groups of individuals, is adequate follow-up of an individual, as well as groups of individuals, is necessarynecessary

Early recognition of illness related to toxicant agents in their environment or Early recognition of illness related to toxicant agents in their environment or to a particular occupational exposure is criticalto a particular occupational exposure is critical

Proper diagnosis can lead to early removal of an individual from the hazards Proper diagnosis can lead to early removal of an individual from the hazards of ongoing exposure to a toxicant substanceof ongoing exposure to a toxicant substance

Furthermore, recognition of the earliest affected cases in a particular setting Furthermore, recognition of the earliest affected cases in a particular setting may result in changes that will protect others who have not yet become may result in changes that will protect others who have not yet become affected.affected.