Transcript Slide 1

‫دکتر سعید تیموری‬
‫متخصص طب کار وبیماریهای شغلی‬
‫مدیریت درمان تامین اجتماعی اصفهان‬
‫درمانگاه قدس عباس اباد‬
INTRUDUCTION
Chemical agents capable of damaging the
(CNS) are ubiquitous in the environment.
 Industrial processes are notorious sources
of the most well known of these
neurotoxins, which contaminate both the
worksite and the surrounding environment.
 The United States Environmental
Protection Agency lists over 65,000
chemicals currently used in the US , adding
2000–3000 new ones each year.

INTRUDUCTION
Despite the presence of selective
permeability barriers metals, gases,
solvents, and other chemicals penetrate
sufficiently to cause deleterious effects.
There are many historical descriptions
of neurotoxicity; for example, lead
poisoning ; homicidal use of arsenic ,
and the Minamata Bay epidemic
(organic mercury) and glue-sniffer's
neuropathy (hexacarbons).
INTRUDUCTION
Neurotoxicity is apparent when intense
high level exposures result in acute
illness.
There is increasing evidence linking
chronic low-level exposures with
neurodegenerative diseases.
GENERAL PRINCIPLES

With few exceptions, pathophysiology
of most neurotoxins is not well
understood

The effects of toxins on the CNS are
more complex than on the peripheral
nervous system.
GENERAL PRINCIPLES
The level and duration of exposure ,
physiologic variables such as the
subject's age influence the clinical
manifestations.
 A well-known example is lead toxicity,
which may lead to an acute confusional
state, chronic mental slowing, or a
peripheral neuropathy.

Neurotoxins
There is evidence that the young are
more susceptible than adults to the
neurotoxic )lead, mercury,
organophosphate insecticides,(
Children absorb a larger dose per unit of
body weight of toxins through the
gastrointestinal and respiratory tracts
than adults(lead)
Nervous Susceptibility Factors
The elderly are more susceptible to
some neurotoxic effects than are young
individuals. Examples sensitivity to
tardive dyskinesia after neuroleptic use
and to neuroleptic malignant
 There is evidence that senescent loss
in neurons causes increased
vulnerability to neurotoxicants.

Neurologic symptoms and signs
Symptoms and deficits depend on which
groups of brain or spinal cord neurons are
affected primarily.
 The most common syndrome is an
encephalopathy from diffuse dysfunction
of cortical or subcortical structures.
 The manifestations are neuropsychiatric
A cute encephalopathy associated with
alteration in the level of consciousness.

Neurologic symptoms and signs
Some toxins cause relatively selective
injury to the vestibular system or the
cerebellum, resulting in dysequilibrium,
vertigo, and gait or limb ataxia.
Basal ganglia involvement may lead to
an extrapyramidal syndrome of
bradykinesia, tremors, and rigidity
. This may resemble idiopathic Parkinson
disease for all practical purposes.
Neurologic symptoms and signs

Peripheral nervous system disorders
lead to sensory disturbances and
weakness, often accompanied by
impairment of the deep tendon reflexe
Neurologic symptoms and signs
The hallmark of most polyneuropathies
is the distal distribution .
 The most common syndrome is
subacute onset of tingling or numbness
experienced in a symmetrical, stockingand-glove distribution.
 Neuropathic pain is present, and is
described variously as burning, deep
aching, or lancinating

Neurologic symptoms and signs
Involvement of the motor nerve fibers
manifests as muscle atrophy and
weakness.
 These deficits appear first in the distalmost muscles ( the intrinsic foot and hand
muscles).
 More severe cases may involve muscles
of the lower legs and forearms, leading to
bilateral foot drop or wrist drop.

GENERAL PRINCIPLES
1. A dose-toxicity relationship exists in the
majority of neurotoxic exposures.

neurologic symptoms appear only after a
cumulative exposure reaches a threshold
level.
GENERAL PRINCIPLES

2.Toxins typically cause a nonfocal;
symmetrical neurologic syndrome.

Significant asymmetry such as
weakness or sensory loss of one limb or
one side of the body, should suggest an
alternative cause.
GENERAL PRINCIPLES
3.There is usually a strong temporal
relationship between exposure and the
onset of symptoms
 Immediate symptoms after acute exposure
are usually attributable to the physiologic
effects of the chemical.
 These symptoms subside quickly with
elimination of the chemical .
GENERAL PRINCIPLES
Delayed or persistent neurologic
deficits
That occur after toxic exposures (for
example, organo-phosphate-related
delayed neuropathy) are generally a
result of pathologic changes in the
nervous system.
 Recovery is still possible, but tends to
be slow and incomplete.

GENERAL PRINCIPLES
4. Nervous system generally has a
limited capability to regenerate, some
recovery is typically possible after
removal of the insulting agent.
 As a corollary, continuing neurologic
deterioration more than a few months
after cessation of exposure to a toxin
generally argues for a direct causative
role of the toxin.

GENERAL PRINCIPLES

. Multiple neurologic syndromes are
possible from a single toxin.
Different neuron and different areas of
the nervous system react differently to
the neurotoxin.
GENERAL PRINCIPLES
The level and duration of exposure ,
physiologic variables such as the
subject's age influence the clinical
manifestations.
 A well-known example is lead toxicity,
which may lead to an acute confusional
state, chronic mental slowing, or a
peripheral neuropathy.

GENERAL PRINCIPLES
6. Few toxins present with a pathognomonic
neurologic syndrome
 Symptoms and signs may be mimicked by many
psychiatric, metabolic, inflammatory, neoplastic,
and degenerative diseases of the nervous system.
 It is important to exclude other neurologic
diseases with appropriate clinical examina
 tion and laboratory investigations.

APPROACH TO PATIENTS
A confident diagnosis of a neurotoxic disorder
can only be made after documentation of all
 (1) a sufficiently intense or prolonged
exposure to the toxin;
 (2) an appropriate neurologic syndrome
based on knowledge about the putative toxin;
 (3) evolution of symptoms and signs over a
compatible temporal course
 (4) exclusion of other neurologic disorders
that may account for a similar syndrome.

IMAGING

The extent and severity of neurologic deficits
are difficult to assess with precision.
Present tools, as (CT) and (MRI), provide only
visualization of macroscopic structural
changes.
While they are invaluable in detecting neoplastic,
inflammatory and infectious disorders of the
nervous system, they are far less helpful in
documenting neurotoxic injuries.
APPROACH TO PATIENTS
A detailed
history of nature,
duration, and intensity of the
exposure is essential in
every evaluation.
APPROACH TO PATIENTS
 What
are the potential toxins?
 What is the mode of exposure?
 How long and how intense are the
exposures?
 Are there other confounding factors
such as alcoholism, psychosocial
issues, and possibility of secondary
gains.
APPROACH TO PATIENTS

Chronic exposures are especially difficult to
assess.

History should be followed by a of the neurologic
complaint

Documentation of the temporal course of the
disease is very important.
APPROACH TO PATIENTS

Symptoms may appear acutely (minutes or
days), subacutely (weeks or months), or
chronically (years).
Fluctuating symptoms may suggest
recurrent exposures or unrelated
superimposed factors.
 Recovery after discontinuation of exposure
helps to implicate the exposure

APPROACH TO PATIENTS

Physical examination of patients with PNS
should include testing of muscle strength,
sensation, and tendon reflexes of all four
extremities.

The longest axons are the most vulnerable,
neurologic deficits are frequently more
severe in the feet than in the hands.
DIAGNOSIS
Prominent sensory impairment in the hands
without signs of neuropathy in the feet is
more likely to be caused by carpal tunnel
syndrome than by a systemic
polyneuropathy.
Most polyneuropathies are accompanied by
absent reflexes of the Achilles tendons
and demonstrable sensory impairment in
the toes.
DIAGNOSIS
. Approximately one-half to two-thirds of
all polyneuropathies remain
undiagnosed .
 Thus, the absence of an alternate
etiology does not necessarily implicate a
toxin.

DIAGNOSIS

Aside from the presence of sufficient
exposure and compatible syndrome, the
diagnosis quite frequently depends on
the documentation of progressive
sensory or motor deficits during
exposure, and recovery of function
months or years after cessation of
exposure.
DIAGNOSIS
The most nonspecific syndrome is a
distal, symmetrical, sensorimotor
polyneuropathy.
 This is indistinguishable from the
neuropathies caused by common
systemic diseases such as
alcoholism, uremia, diabetes mellitus,
and vitamin B12 deficiency.
 Some toxins, such as lead, cause a
neuropathy with prominent weakness.

Symmetric generalized neuropathies

The most common peripheral neuropathy
that results from PNS insults, toxin-induced
injuries, is a symmetric .

These neuropathies probably reflect failure
of axonal transport, with resultant
degeneration distal nerve segments,
predominantly affecting large-diameter
axons.
Symmetric generalized neuropathies
Degeneration subsequently proceeds
proximally toward the nerve cell body,
both in the PNS and in central
projections within the spinal cord distal
axonopathy
 Most distal symmetric axonopathies
have a subacuteonset with gradual
progression.

Symmetric generalized neuropathies

The longest, largest diameter fibers are usually
the most clinically affected, motor and sensory
findings initially appear in the feet, later moving
proximally (length-dependent relationship).

With extreme progression, the vertex of the
head is affected.
Symmetric generalized neuropathies

There is usually an early and symmetric
loss of ankle reflexes; the more
proximal reflexes may be spared until
late in the disease.

In most toxic neuropathies, sensory
symptoms and signs initially
predominate over motor deficits
Symmetric generalized neuropathies
. Muscle wasting may occur in chronic
cases, including loss of hair over the
distal leg,skin ulceration, and loss of
sweating in the feet.
 Because recovery depends on axonal
regrowth, complete recovery is
prolonged and slow

Symmetric generalized
neuropathies

Axonal regenerationoccurs at a rate of, on
average, 2–3 mm/day.

Function is restored in the reverse order to
that lost; proximal muscles recover before
distal muscles, and sensory loss recedes
from proximal to distal levels.
Toxic polyneuropathies
.
 Mostly
sensory or sensorimotor
polyneuropathy (little or no weakness)
Acrylamide
 Carbon disulfide
 Ethylene oxide
 Metals: arsenic, lead, mercury, thallium
 Methyl bromide
 Polychlorinated biphenyls (PCBs)
 Thallium

Toxic polyneuropathies
 Predominantly
motor or
sensorimotor poly neuropathy
with significant weakness
 Hexacarbons: n-hexane, methyl n-butyl
ketone
 Metals: lead, arsenic, mercury
 Organophosphates
Toxic polyneuropathies














"Purely" sensory neuropathy (disabling sensory
loss with no weakness)
Cisplatinum
Pyridoxine abuse Cranial neuropathy
Thallium
Trichloroethylene (trigeminal neuropathy) Prominent autonomic
dysfunction
Acrylamide
n-Hexane (glue-sniffer)
Thallium
Vacor(PNU)
Possible association with neuropathies (mostly anecdotal)
Benzene
Carbon monoxide
Dioxin
Methyl methacrylate
Pyrethrins
Carpal tunnel syndrome
usual presentation acroparesthesias,
numbness, tingling, and burning sensations in
the lateral three fingers
Nocturnal exacerbation of pain

Shaking the hand frequently relieves pain
 palm is usually spared
 Raynaud’s phenomenon may occasionally
be present

Median nerve
CTS most commonly involves the dominant
hand
 bilateral involvement is extremely common
 causes include tuberculous tenosynovitis,
rheumatoid arthritis, osteoarthritis, pregnancy,
hemodialysis, myxedema, acromegaly
 patients with generalized peripheral
neuropathies, such as uremia and diabetes
 Repetitive tasks


CTS should be considered for any
unexplained pain or sensory disturbance

Diagnosis is obvious from the clinical signs
and symptoms.
Confirmatory electrodiagnostic studies
should be obtained in all patients undergoing
surgery.
 The most sensitive physiologic parameter is
sensory and mixed nerve conduction

Treatment
Lead
Acute high-level exposure typically comes
from accidental ingestion, inhalation, or
industrial exposure.
 neurologic symptoms such as headache,
tremor apathy lethargy.
 Massive intoxication can lead to
convulsions, cerebral edema, stupor, or
coma, and eventually to transtentorial
herniation.

Lead
Lead encephalopathy typically appears
in adults at blood levels of 50-70 ftg/d
 Children are more vulnerable than
adults probably because of the
immaturity of the blood-brain barrier


Chronic low-level exposure to lead is
responsible for impaired intellectual
development in children.
Lead

The classic description bilateral wristdrop and foot-drop.

Toxicity also may manifest as a
generalized proximal and distal
weakness and loss of the tendon
reflexes.
Lead

The best known clinical syndrome is a
predominantly motor neuropathy with
little if any sensory symptoms.

It mimics in many ways motor neuron
diseases such as amyotrophic lateral
sclerosis
Lead
In patients with acute encephalopathy,
the radiologic abnormalities reflect focal
areas of edema, and are most
commonly seen in bilateral thalami and
basal ganglia.
 Imaging studies, and autopsy, may
detect intracranial calcification in
patients with chronic lead toxicity.

Arsenic

Peripheral neuropathy is the most
common neurologic manifestation of
toxicity, and may occur after either
acute or chronic exposure
After a single massive dose, an acute
poly neuropathy develops within 1-3 .
weeks
Arsenic

This neuropathy mimics Guillain-Barre
syndrome in many ways, and respiratory
failure may rarely occur.

Occasionally, systemic symptoms may
be accompanied by seizures and
encephalopathy.
Arsenic
Diagnosis of arsenic neuropathy
 EMG and nerve conduction studies
provide evidence of a nonspecific axonal
neuropathy.
Blood arsenic level returns to normal in
about 12 hours, and urine arsenic clears
within 48 to 72 hours after exposure.but
detectable in hair and nail for months
after exposure.
Manganese
The potential risk of organic manganese
in the form of methylcyclopentadienyl
manganese tricarbonyl (MMT), an
additive used in gasolin.
 Compared to idiopathic Parkinson
disease, the extrapyramidal symptoms
of manganism are less responsive to
dopaminergic therapy.
Manganese
Neurologic deficits often continue to
progress for many years after cessation
of exposure.
 Tremor, rigidity, masked facies,
bradykinesias slowly develop.

Heavy metal toxicity.
Arsenic ;Insecticide, Paris green
Sensory
> motor neuropathy, red hands, burning feet,
hyperhidrosis
 Lead
Paint, gas, batteries
Adults:
neuropathy, painful joints; children: cerebral
edema,
encephalopathy, low IQ
 Mercury Industrial, polluted fish
Severe
arm and leg pain, dementia with primarily
motor neuropathy
 Thallium
Insecticide, rat poison
Stocking-glove sensorimotorneuropathy, with
alopecia
THANKS YOUR ATTENTION
“Coasting phenomen’’?
The phenomenon of "coasting," the
continuing deterioration sometimes seen
for up to a few weeks after
discontinuation of toxic exposure.
The delay reflects the time necessary for
the pathophysiologic steps to evolve to
neuronal injury and death.