TOXIC/METABOLIC DISORDERS
RITE REVIEW
Toxin 1
• A 44-yo man presented with a 5 year history
of numbness, tingling pain in his extremities
and pain in the epigastrium
Toxin 1
• A 44-yo man presented with a 5 year history
of numbness, tingling pain in his extremities
and pain in the epigastrium. He has worked
for many years in a battery-recycling unit. On
exam, he is slightly weak in the radial
distribution bilaterally and he has a bluish
discoloration to his gums.
LEAD
• Nonspecific
•
- Neuropathy (axonal, sensory and motor)
•
- Abdominal pain
• Specific
•
- Bluish discoloration of the gums
•
- Microcytic anemia with basophilic stippling
•
- Increased coproporphyrin levels
•
- Radial motor nerves particularly affected
LEAD
Microcytic anemia, Basophilic Stippling
LEAD
Thickened Metaphyseal Lines (Lead Accumulation)
Toxin 2
• Based on a true story…..
• A Chinese man presents with 1-2 weeks of
headache, abdominal pain, vertigo, lethargy,
constipation, and numbness and tingling of the
extremities. He has noticed some double vision
and lack of visual acuity in the past few days. He
has also noticed that his hair is beginning to come
out quite easily. He notes that he recently
requested a divorce from his wife and moved out,
but she requested that he move back in to help
care for the children last month, which he did.
Toxin 2
• Thallium levels are “off the charts.”
• Investigators learned subsequently that the
patient’s wife had ordered four bottles of
thallium from Bristol Myers Squib in the two
months before her husband’s hospitalization.
Thallium
• Nonspecific
– GI Symptoms
– Small fiber neuropathy
– Cranial nerve and autonomic involvement
– Alopecia [was a depilatory]
• Specific
– Acts at Na+/K+ ATPase system
Thallium
• Sources
– “The poisoner’s poison,” “inheritance powder”
– Used to be used as a depilatory
– Used to be used as a rodenticide, now banned bcs of
accidental deaths.
– Foreign Cases
– Occupational Exposures (electronics, lenses, semiconductors,
alloys, gamma radiation detection equipment, imitation jewelry, artist's paints,
low temperature thermometers, and green fireworks.)
• Murderpedia.org (case of Tianle Li, 2011)
Thallium
• What is the antidote?
Thallium
• What is the antidote?
– PRUSSIAN BLUE
Toxin 3
• A 35-year-old man comes into clinic 3 months of
insidious onset of numbness and tingling in his
toes and fingertips, progressing slowly in the
ensuing weeks to involve the feet and hands. For
the past 2-3 weeks, he has had burning pain and
has noted weakness in gripping tools. Further
questioning reveals the patient has been a
carpenter since completing high school 17 years
ago. For the last 10 years, he has lived in a rural,
wooded area in a home he built.
• On exam, skin has brown patches of
hyperpigmentation, with scattered overlying pale
spots in and around the axillae, groin, nipples,
and neck. The palms and soles show multiple
hyperkeratotic corn-like elevations 4 to 10 mm in
diameter. Three irregularly shaped, sharply
demarcated, erythematous, scaly plaques,
measuring 2 to 3 cm, are noted on the patient’s
torso. The remainder of the physical examination
is normal.
Arsenic
• Nonspecific
– Rash and GI upset
– Found in hair, bone, fingernails
• Specific
– Reacts with sulfhydryl groups of proteins to mess up
oxidative metabolism of neuron
– Acute neuropathy
• Source
– Semiconductors, treated woods,
pesticides/herbicides/insecticides
– Another “inheritance powder”
Toxin 4
• A 46 yo male CEO comes to clinic with diffuse
pain. He feels like he is becoming gradually
weaker and is feeling like his walk is becoming
somewhat clumsier. He is also feeling more
panicky, has difficulty sleeping, and was
recently diagnosed with a new anxiety
disorder. He has had several months of
abdominal pain and nausea with a 16 pound
unintentional weight loss in the past 3
months.
Toxin 4
• When you ask about general health practices,
he says he is very health-conscious, eating fish
at every meal for the past year or so.
METHYL MERCURY
• Nonspecific:
•
- Hallucinations, dementia, personality change
•
- Ataxia
•
- Choreathetosis
•
- Distal paresthesias
•
- Absorbed through the skin and GI tract
• Specific:
•
- Cerebellar granular cell neuron degeneration
•
- Depletes cellular selenium (essential micronutrient)
•
- Constricted visual fields
•
- Tx: penicillamine or dimercaptosuccinic acid.
Toxin 5
• A 30-year-old male welder presented with a
two-year history of gait disturbance. A
neurological assessment revealed features of
parkinsonism which included hypophonia,
hypomimia, mild bradykinesia and rigidity
with no resting tremor, a reduction in arm
swing.
Toxin 5
Manganese
•
•
•
•
•
•
Patients with biliary atresia are at risk
Prolonged parenteral nutrition is a risk
Can see in liver disease (hepatically cleared)
Parkinsonism
Dystonia
T1 weighted hyperintensity
in the globus pallidus
Toxin 6
Toxin 6
Toxin 6
• Nonspecific:
– Headache, vomiting
– Parkinsonism
• Specific
– CNS demyelination days to weeks after
exposure
– A cherry-red color in the tissues, including the brain
– Necrosis of the bilateral globus pallidus
– Treatment is high flow hyperbaric oxygen
– Binds to hemoglobin with an affinity 100-200 times that of oxygen
• Source
– Weird Al’s parents died from this
– Furnace
Carbon Monoxide
• Nonspecific:
– Headache, vomiting
– Parkinsonism
• Specific
– CNS demyelination days to weeks after
exposure
– A cherry-red color in the tissues, including the brain
– Necrosis of the bilateral globus pallidus
– Treatment is high flow hyperbaric oxygen
– Binds to hemoglobin with an affinity 100-200 times that of oxygen
• Source
– Weird Al’s parents died from this
– Furnace, car with plugged up exhaust pipe
Toxin 7
• A 22-year-old man presented after waking the previous day
with numbness below his knees. His symptoms progressed
over a few days to paraesthesia in the fingers, and difficulty
with walking and performing fine tasks with his hands
• On exam
–
–
–
–
Flaccid tone with distal>proximal weakness
Broad-based gait
Positive Romberg.
Sensation to light touch and pinprick was reduced below the
knees, vibration sense was absent below the anterior superior
iliac spines and joint position sense absent below the ankles.
• CBC, CMP, TSH, B12 nl.
Toxin 7 – Case Continued
• Thought to be AIDP, treated with IVIG
• He admitted to using ‘whippits’ increasingly
over the six weeks before presentation, now
up to 120 g (15 whippits) per day.
• Although B12 was normal, methylmalonic
acid levels were markedly raised at
29 653 nmol/L (<280).
• Treated with IM vitamin B12.
• His sensory symptoms and strength
gradually improved over the next
six months, though he still requires a stick to
walk.
Nitrous Oxide
• Nonspecific
– Paresthesias in the limbs
• Specific
– Dorsal columns and corticospinal tracts affected (subacute
combined degeneration picture)
– “Reverse Lhermitte’s Sign”
– Oxidizes the cobalt moiety of methylcobalamin
– Interferes with transformation of homocysteine to methionine
– Schilling test (normal – B12 absorption). B12 and/or MMA may
be abnormal or normal.
• Source
– Whippits
A Whippets Case
Toxin 8
• Seven people present to a local ED in Washington state
with numbness and tingling in their mouths and
extremities. Five of them had nausea, 4 had vomiting,
3 had diarrhea, 3 were having trouble walking and felt
clumsy, 2 had whole body weakness, one was short of
breath. There were 4 males and 3 females, aged 19 to
67 years.
• The most affected was a 62 year old female who
developed dysarthria and a floating sensation in
addition to nausea and vomiting. She was transported
by emergency medical services after she became
ataxic, fell and could not stand up.
Toxin 8 continued
• Her exam revealed pronounced dysarthria and
diminished gag reflex in addition to her
subjective dyspnea, oral paresthesia, and
sensation of her throat closing up. Due to
concerns of impending airway compromise,
the patient was emergently intubated, placed
on a ventilator, and transferred to the
intensive care unit (ICU).
Saxitoxin
• Paralytic shellfish poisoning
• Coastal United States.
• Produced by certain dinoflagellates and
concentrated in the flesh of filter feeding
mollusks, including clams, oysters,
Saxitoxin
• Blockade of voltage-gated fast sodium channels,
inhibiting signal propagation in neural tissue.
• Symptoms – onset within 1-2 hours, recovery
with in 24-48 hours
– paresthesias of the mouth, face, and lips
– feelings of floating; tingling of the extremities
– Rapidly progressive weakness and paralysis
– GI sx in many victims
– HTN is commonly seen
• Dx - clinical, but can be confirmed by
measurement of saxitoxin levels either in the
shellfish meat or the patient’s urine or serum.
• Tx - No antidote. Supportive care.
Saxitoxin
• Commonly called “red tide,” but can
occur with other color changes in water
(green, brown, or yellow). Clear water
can have toxic levels, leading to the
recommendation that such events be
called “harmful algal blooms” instead of
“red tides.”
• Three orders of magnitude more toxic
than sodium cyanide (Lethal Dose 50:
saxitoxin 10mcg/kg, cyanide 10mg/kg).
• DDx: tetrodotoxin, ciquatoxin, and
brevetoxin (location makes less likely),
Vibrio (food poisoning), chemical and
nerve agents.
• Keys to this case: story, time course,
location
Saxitoxin Coastal USA
Toxin 9
• Minnesota, 2014
• A 30 yo man and his sister presented to the ED. Thirty
minutes after eating dinner, the man experienced perioral
and tongue numbness, numbness and weakness in his
extremities, extreme fatigue, and dyspnea. He also
complained that "my teeth can't feel themselves." Despite
self-induced vomiting, his symptoms did not resolve, after
which he went to the ED. His sister had similar symptoms.
• When asked what he ate, the patient stated that he had
purchased dried fish described as globefish from a street
vendor in New York City and transported the fish to
Minnesota himself.
• Another case far away….
Toxin 9 continued
• Singapore, 2013
• A previously well 35-year-old Japanese lady with no significant past
medical history presented to the ED with giddiness and weakness of
the left upper limb and both lower limbs. She complained of
numbness and tingling sensation around the mouth areas. She had
no GI symptoms. The symptoms occurred an hour after eating at a
local Japanese restaurant.
• VSS. She was conscious and alert throughout her consult and
admission. On examination, she had decreased power over the left
upper limb and both lower limbs. She was unable to get up from
the bed to walk.
• What is the toxin?
Tetrodotoxin
• Tetraodontidae is a family of primarily marine and estuarine
fish in the order Tetraodontiformes. The family includes many
familiar species, which are variously called pufferfish, puffers,
balloonfish, blowfish, bubblefish, globefish, swellfish, toadfish,
toadies, honey toads, sugar toads, and sea squab
UNPUFFED
PUFFED
Tetrodotoxin
• Fugu = pufferfish
• Found in Asia, banned or regulated in many
countries
• Heat stable and water soluble (cooking or
drying doesn’t kill it)
• Sx within 30 minutes to 6 hours of ingestion,
with recovery usually in 24 hours
• Blockage of the sodium channels (heart,
skeletal muscles, CNS, PNS). Stimulates
chemoreceptor trigger zone in the medulla
oblongata resulting in depression of the
respiratory and vasomotor centres.
Tetrodotoxin
•
Sx:
–
–
–
–
–
Headache, diaphoresis, nausea, vomiting, malaise
Paresthesias
Dysarthria, dysphagia
Weakness
More severe: hypotension, cardiac arrhythmias, paralysis,
and cranial nerve dysfunction may develop.
– Death results from respiratory failure and cardiovascular
collapse and in severe cases can occur as early as 17 minutes
after ingestion
•
•
•
Dx: medical history and toxidrome. Can get
tetrodotoxin levels from food if history is ambiguous.
Mass spec if food unavailable
Tx: symptomatic and supportive. Some use vomiting,
gastric lavage, activated charcoal. Observe or 24-48
hours.
(Other tx ideas have been sodium bicarbonate,
cysteine, cholinesterase inhibitors, naloxone, and
steroids. In animal studies, monoclonal antibodies and
4-aminopyridine have shown promising potential).
Toxins 8, 9, & 10
• Paralysis without sensory loss
Toxins 8 & 9
•
•
•
•
Paralysis without sensory loss
Reversibly binds to membrane
voltage gated sodium channels
Indo-Pacific Ocean
Source?
•
•
•
•
Paralysis without sensory loss
Reversibly binds to membrane
voltage gated sodium channels
New England and the West Coast
Source?
Toxins 8 & 9
•
•
•
•
Paralysis without sensory symptoms
Reversibly binds to membrane
voltage gated sodium channels
Indo-Pacific Ocean
Source?
•
•
•
•
Paralysis without sensory
symptoms
Reversibly binds to membrane
voltage gated sodium channels
New England and the West Coast
Source?
Toxins 8 & 9
•
•
Paralysis without sensory symptoms
Reversibly binds to membrane
voltage gated sodium channels
• Indo-Pacific Ocean
• Source: TETRODOTOXIN
• Pufferfish, porcupinefish, ocean
sunfish, triggerfish
•
•
•
•
•
Paralysis without sensory
symptoms
Reversibly binds to membrane
voltage gated sodium channels
New England and the West Coast
Source: SAXITOXIN
Mussels, clams, oysters, scallops
Toxins 10
•
•
•
Paralysis without sensory symptoms
Presynaptic neuromuscular block
Impaired excitation-secretion coupling due to reduced
calcium availability
Toxins 10
•
•
•
Paralysis without sensory symptoms
Presynaptic neuromuscular block
Impaired excitation-secretion coupling due to reduced
calcium availability
Toxin 10
•
•
•
Paralysis without sensory symptoms
Presynaptic neuromuscular block
Impaired excitation-secretion coupling due to reduced
calcium availability
TICK PARALYSIS
Holocylotoxin
Toxin 11
•
Nonspecific
•
Sensory neuropathy
•
Specific
•
Opens voltage gated Na channels in peripheral nerves at
nodes of Ranvier causing spontaneous depolarization
•
Paradoxical sensory disturbances (hot feels cold and cold
feels hot.)
•
Source ?
Toxin 11
•
Nonspecific
•
Sensory neuropathy
•
Specific
•
Opens voltage gated Na channels in peripheral nerves at
nodes of Ranvier causing spontaneous depolarization
•
Paradoxical sensory disturbances (hot feels cold and cold
feels hot.)
•
Source ?
Toxin 11
Nonspecific
- Sensory neuropathy
Specific
- Opens voltage gated Na channels in peripheral nerves at nodes of Ranvier
causing spontaneous depolarization
- Paradoxical sensory disturbances (hot feels cold and cold feels hot.)
Source:
Reef fish like grouper, barracuda, red snapper, parrot fish, tiger fish
Produced by marine micro-organisms and passed up the food chain
CIGUATERA
Toxin 12
Nonspecific
- Sweaty, HTN, tachycardia
Specific
- Acute release of acetylcholine from
synaptic terminals
Source or toxin?
Toxin 12
Nonspecific
- Sweaty, HTN, tachycardia
Specific
- Acute release of acetylcholine from
synaptic terminals
Source or toxin?
Toxin 12
Nonspecific
- Sweaty, HTN, tachycardia
Specific
- Acute release of acetylcholine from
synaptic terminals
BLACK WIDOW SPIDER bite
Latrotoxin
Toxin 14
•
•
•
•
•
•
•
•
Cleaves SNARE proteins SNAP 25 or VAMP
Fixed, dilated pupils and dry mouth
Double vision, droopy eyelids, dysphagia
Inhibition of release of acetylcholine from presynaptic
terminals
Descending paralysis
A constipated, hypotonic infant with unreactive pupils
Incremental response on high frequency repetitive
stimulation
Toxin can be found in the stool.
Toxin 14
•
•
•
•
•
•
•
•
Cleaves SNARE proteins SNAP 25 or VAMP
Fixed, dilated pupils and dry mouth
Double vision, droopy eyelids, dysphagia
Inhibition of release of acetylcholine from presynaptic
terminals
Descending paralysis
A constipated, hypotonic infant with unreactive pupils
Incremental response on high frequency repetitive
stimulation
Toxin can be found in the stool.
BOTULISM
Botulism
Botulism
Toxin 13
Toxin 13
•
•
•
•
•
Targets synaptobrevins in the presynaptic nerve
terminals in the brainstem and spinal cord. Impairs
release of inhibitory neurotransmitters.
Pupils are spared
Trismus, facial rigidity, opisthotonos
Children born at home to unimmunized mothers
from an infected umbilical stump.
Rusty nails
Toxin 13
•
•
•
•
•
Targets synaptobrevins in the presynaptic nerve
terminals in the brainstem and spinal cord. Impairs
release of inhibitory neurotransmitters.
Pupils are spared
Trismus, facial rigidity, opisthotonos
Children born at home to unimmunized mothers from
an infected umbilical stump.
Rusty nails
TETANUS
Toxin 13
•
•
•
•
•
Targets synaptobrevins in the presynaptic nerve
terminals in the brainstem and spinal cord. Impairs
release of inhibitory neurotransmitters.
Pupils are spared
Trismus, facial rigidity, opisthotonos
Children born at home to unimmunized mothers from
an infected umbilical stump.
Rusty nails
TETANUS
Toxin 15
•
•
•
•
•
•
•
Pinpoint pupils that do not dilate with any stimulus
Hypersecretion (salivation, sweating) and fascics
Unconsciousness and respiratory depression
Inhibition of acetylcholinesterase
Delayed axonal motor neuropathy with ataxia and
spasticity
Treat with atropine
Nerve gases (i.e. Sarin), and pesticides
Toxin 15
•
•
•
•
•
•
•
Pinpoint pupils that do not dilate with any stimulus
Hypersecretion (salivation, sweating) and fascics
Unconsciousness and respiratory depression
Inhibition of acetylcholinesterase
Delayed axonal motor neuropathy with ataxia and
spasticity
Treat with atropine
Nerve gases (i.e. Sarin), and pesticides
ORGANOPHOSPHATES
Toxin 16
Nonspecific:
Parkinsonism
Specific:
Potent inhibitor of mitochondrial complex I
Selective loss of substantia nigra compacta neurons
Toxin 16
Nonspecific:
Parkinsonism
Specific:
Potent inhibitor of mitochondrial complex I
Selective loss of substantia nigra compacta neurons
ROTENONE
Toxin 17
Acute onset neuropathy [like arsenic]
Nerve biopsy: Paranodal giant axonal enlargements or
“balloons.”
Toxin 17
Acute onset neuropathy [like arsenic]
Nerve biopsy: Paranodal giant axonal enlargements or
“balloons.”
Toxin 17
Acute onset neuropathy [like arsenic]
Nerve biopsy: Paranodal giant axonal enlargements or
“balloons.”
n-HEXANE (hexacarbon)
Toxin 18
•
•
•
Cerebral edema and petechial hemorrhages
Birefringent calcium oxalate crystal deposition in
tissues
•
Oxalic acid crystals in the urine
Treat with ethanol, dialysis, correction of
acidosis, and correction of hypocalcemia.
Toxin 18
•
•
•
Cerebral edema and petechial hemorrhages
Birefringent calcium oxalate crystal deposition
in tissues
•
Oxalic acid crystals in the urine
Treat with ethanol, dialysis, correction of
acidosis, and correction of hypocalcemia.
ETHYLENE GLYCOL
Toxin 19
•
•
•
•
•
White matter abnormalities
Subcortical dementia and paranoid psychosis
Cerebellar ataxia
Hypointense lesions in thalamus and/or
basal ganglia
Glue sniffers
Toxin 19
White matter abnormalities
Subcortical dementia and paranoid psychosis
Cerebellar ataxia
Hypointense lesions in thalamus and/or
basal ganglia
Glue sniffers (but not n-Hexane
based glue sniffers)
TOLUENE
Toxin 20
Toxin 20
•
•
•
•
Hemorrhagic lesions in the putamen
Impaired vision from destruction of retinal ganglion cells
Metabolized to formaldehyde and then to
formic acid, which is the true toxin
Treat with bicarbonate and ethanol
Toxin 20
•
•
•
•
Hemorrhagic lesions in the putamen
Impaired vision from destruction of retinal ganglion cells
Metabolized to formaldehyde and then to
formic acid, which is the true toxin
Treat with bicarbonate and ethanol
•
METHANOL
Toxin 21
•
•
•
•
•
Blocks reuptake of norepinephrine
Raises dopamine levels in the nucleus accumbens
May cause opsoclonus
Withdrawal causes dysphoria, agitation, craving
sweets
Preferred treatment of withdrawal is a
dopaminergic drug
Toxin 21
•
•
•
•
•
Blocks reuptake of norepinephrine
Raises dopamine levels in the nucleus accumbens
May cause opsoclonus
Withdrawal causes dysphoria, agitation, craving
sweets
Preferred treatment of withdrawal is a
dopaminergic drug
Toxin 21
•
•
•
•
•
Blocks reuptake of norepinephrine
Raises dopamine levels in the nucleus accumbens
May cause opsoclonus
Withdrawal causes dysphoria, agitation, craving
sweets
Treat withdrawal with a dopaminergic drug
COCAINE
Toxin 22
-
Prescription drug that causes ragged red fibers
Myalgias, weakness, elevated CK levels
Reverse transcriptase
inhibitor that depletes
mitochondrial DNA
Toxin 22
-
Prescription drug that causes ragged red fibers
Myalgias, weakness, elevated CK levels
Reverse transcriptase
inhibitor that depletes
mitochondrial DNA
ZIDOVUDINE (AZT)
Toxin 23
•
•
•
•
•
Peripheral neuropathy
Occasionally affects proximal muscles
first, mimicking a myopathy
Can also cause psychosis, chorea,
Parkinsonism, and catatonia
Causes headache and nausea when it’s working
Blocks the conversion of acetaldehyde to
acetic acid
Toxin 23
•
•
•
•
•
Peripheral neuropathy
Occasionally affects proximal muscles
first, mimicking a myopathy
Can also cause psychosis, chorea,
Parkinsonism, and catatonia
Causes headache and nausea when it’s working
Blocks the conversion of acetaldehyde to
acetic acid
DISULFIRAM (Antabuse)
Toxin 24
- Toxic optic neuropathy
- Symmetric insidious visual loss
- Yellow-green dyschromotopsia is the
earliest symptom
Toxin 24
- Toxic optic neuropathy
- Symmetric insidious visual loss
- Yellow-green dyschromotopsia is the
earliest symptom
- Used to treat TB and mycobacterial infections
Toxin 24
- Toxic optic neuropathy
- Symmetric insidious visual loss
- Yellow-green dyschromotopsia is the
earliest symptom
- Used to treat TB and mycobacterial infections
ETHAMBUTOL
Toxin 25
•
•
•
First, small fiber sensory loss with autonomic dysfunction
Later, distal symmetric weakness
Impaired function of microtubules involved
in axonal transport
Toxin 25
•
•
•
First, small fiber sensory loss with autonomic dysfunction
Later, distal symmetric weakness
Impaired function of microtubules involved
in axonal transport
VINCRISTINE toxicity
Toxin 26
•
•
•
•
•
•
Neuropathy
EMG: Myopathic units and fibrillations
Muscle biopsy: vacuolar myopathy
Inhibits microtubular polymerization by
interacting with tubulin
Used to treat gout and Familial Mediterranean
Fever
Used in the U.S. since 19th century, but wasn’t FDA
approved until 2009
Toxin 26
•
•
•
•
•
•
Neuropathy
EMG: Myopathic units and fibrillations
Muscle biopsy: vacuolar myopathy
Inhibits microtubular polymerization by
interacting with tubulin
Used to treat gout and Familial Mediterranean Fever
Used in the U.S. since 19th century, but wasn’t FDA
approved until 2009
COLCHICINE toxicity
Toxin 27
-
Chemo agent that causes leukoencephalopathy
Lesions are frequently periventricular
Toxin 27
-
Chemo agent that causes leukoencephalopathy
Lesions are frequently periventricular
METHOTREXATE
Toxin 28
•
•
•
•
Toxicity comes from inhibition of mevalonic
acid, a precursor of Coenzyme Q10
Necrotizing myopathy
Myalgias much more common than true myopathy
Toxic action potentiated by use of clofibrate,
gemfibrozil, or cyclosporine
Toxin 28
•
•
•
•
Toxicity comes from inhibition of mevalonic
acid, a precursor of Coenzyme Q10
Necrotizing myopathy
Myalgias much more common than true myopathy
Toxic action potentiated by use of clofibrate,
gemfibrozil, or cyclosporine
STATINS
Toxin 29
-
-
Calcineurin inhibitor: causes neuro and
nephrotoxicity
Cortical blindness
Tremor
Encephalopathy and seizure
Kidney toxicity →wasting of magnesium
→ Lowers seizure threshold
Toxin 29
-
-
Calcineurin inhibitor: causes neuro and
nephrotoxicity
Cortical blindness
Tremor
Encephalopathy and seizure
Kidney toxicity →wasting of magnesium
→ Lowers seizure threshold
CYCLOSPORINE
Toxin 30
•
•
•
•
•
Common cause of tardive dyskinesia
Acute dystonic reaction, usually in younger
patients within 48 hours of administration
Treat with anticholinergic like benztropine
Neuroleptic malignant syndrome
Used to treat gastroparesis
Toxin 30
Common cause of tardive dyskinesia
Acute dystonic reaction, usually in younger patients
within 48 hours of administration
- treat with anticholinergic like benztropine
Neuroleptic malignant syndrome
Used to treat gastroparesis
METOCLOPRAMIDE
Toxin 31
•
•
•
Used to treat pain
Can cause seizures or myoclonus
Mixed with selegiline leads to central excitatory
syndrome with HTN, tremor, MS Δ’s
Toxin 31
•
•
•
Used to treat pain
Can cause seizures or myoclonus
Mixed with selegiline leads to central excitatory
syndrome with HTN, tremor, MS Δ’s
MEPERIDINE
Toxin 32
•
•
•
•
•
Induces myopathy in patients with mitochondrial disorders
(MELAS) or CPT2 deficiency
Hepatotoxicity [especially if POLG or <2 years old]
Side effects include alopecia, obesity, and tremor
Neural tube defects
Used to treat epilepsy, bipolar disorder, and migraines
Toxin 32
•
•
•
•
•
Induces myopathy in patients with mitochondrial
disorders (MELAS) or CPT2 deficiency
Hepatotoxicity [especially if POLG or <2 years old]
Side effects include alopecia, obesity, and tremor
Neural tube defects
Used to treat epilepsy, bipolar disorder, and
migraines
VALPROIC ACID toxicity
Toxin 33
•
•
•
•
•
Very common medication that causes myopathy
CK is usually normal
Treatment of other myopathies.
Buffalo hump, moon facies.
Osteoporosis, psychosis, weight gain, etc.
Toxin 33
•
•
•
•
•
Very common medication that causes myopathy
CK is usually normal
Treatment of other myopathies.
Buffalo hump, moon facies.
Osteoporosis, psychosis, weight gain, etc.
CORTICOSTEROID toxicity
Toxin 34
•
•
•
•
Primary site of damage is dorsal root ganglion
Can also affect large myelinated sensory axons
Disruption of fast axonal transport
Ovarian, and small cell lung cancer, specifically
Toxin 34
•
•
•
•
Primary site of damage is dorsal root ganglion
Can also affect large myelinated sensory axons
Disruption of fast axonal transport
Ovarian, and small cell lung cancer, specifically
CISPLATIN toxicity
Toxin 35
•
•
•
Headaches, increased ICP
Abducens palsy
High concentrations in the livers of polar
bears, seals, and walruses, and huskies.
Toxin 35
•
•
•
Headaches, increased ICP
Abducens palsy
High concentrations in the livers of polar
bears, seals, and walruses, and huskies.
VITAMIN A
Condensing it down
• Neuropathy
–
–
–
–
–
–
–
–
Lead
Thallium
Arsenic
Ciguatera
Disulfiram/Antabuse
Vincristine
Colchicine
Cisplatin
• Mees lines
– Arsenic
– Thallium
SECTION 2:
DEFICIENCIES [5]
Deficiency 1
•
•
•
•
Hemorrhagic necrosis in mammillary bodies
Confusion, extraocular defects, ataxia
An amnestic disorder with abnormalities
limited to memory and learning
Precipitated by carbohydrate or glucose loading
Deficiency 1
•
•
•
•
Hemorrhagic necrosis in mammillary bodies
Confusion, extraocular defects, ataxia
An amnestic disorder with abnormalities
limited to memory and learning
Precipitated by carbohydrate or glucose loading
THIAMINE (Vitamin B1)
deficiency
Deficiency 2
•
•
•
•
•
•
Spinocerebellar degeneration mimics Friedreich's
ataxia
Dystrophic axons in the posterior columns
Celiac disease or fat malabsorption are risks
May be caused by a mutation of the gene that encodes
alpha-tocopheral transport protein
Bassen-Kornzweig disease (abetalipoproteinemia)
causes this deficiency, and causes neuropathy and
retinopathy.
Cognitive disorders, ataxia
Deficiency 2
•
•
•
•
•
•
Spinocerebellar degeneration mimics Friedreich's
ataxia
Dystrophic axons in the posterior columns
Celiac disease or fat malabsorption are risks
May be caused by a mutation of the gene that encodes
alpha-tocopheral transport protein
Bassen-Kornzweig disease (abetalipoproteinemia)
causes this deficiency, and causes neuropathy and
retinopathy.
Cognitive disorders, ataxia
•
VITAMIN E deficiency
Deficiency 3
•
•
•
•
•
Corticospinal tract dysfunction
Dorsal column dysfunction
Pancytopenia
Excess zinc ingestion is a risk
Gastric bypass surgery is a risk
Deficiency 3
•
•
•
•
•
Corticospinal tract dysfunction
Dorsal column dysfunction
Pancytopenia
Excess zinc ingestion is a risk
Gastric bypass surgery is a risk
COPPER deficiency
Deficiency 4
•
•
•
•
Autosomal recessive deficiency can cause
neonatal onset seizures
Vitamin supplementation prevents seizures
Diminished activity of glutamic acid decarboxylase
Neuropathy from too much OR not enough of this
vitamin
Deficiency 4
•
•
•
•
Autosomal recessive deficiency can cause
neonatal onset seizures
Vitamin supplementation prevents seizures
Diminished activity of glutamic acid decarboxylase
Neuropathy from too much OR not enough of this
vitamin
PYRIDOXINE (Vitamin B6) deficiency
Deficiency 5
•
•
•
•
•
•
Dorsal column and corticospinal tract dysfunction
Dementia, psychosis, and neuropathy
Upper motor neuron signs AND distal hyporeflexia
High MCV anemia
Elevated homocysteine and methylmalonic acid
Risk factors: gastric bypass, pernicious
anemia, H2 blockers
Deficiency 5
•
•
•
•
•
•
Dorsal column and corticospinal tract
dysfunction
Dementia, psychosis, and neuropathy
Upper motor neuron signs AND distal hyporeflexia
High MCV anemia
Elevated homocysteine and methylmalonic acid
Risk factors: gastric bypass, pernicious
anemia, H2 blockers
COBALAMIN (Vitamin B12)
Presynaptic Neuromuscular Block (3)
Presynaptic Neuromuscular Block
• Holocylotoxin – Tick Paralysis
• Tetanus
• Botulism
Paralysis without Sensory Symptoms
(3-5)
Paralysis without Sensory Loss
•
•
•
•
Tetrodotoxin
Saxitoxin
Holocylotoxin
(Tetanus and Botulism)
Excess Acetylcholine (2)
Excess Acetylcholine
• Latrotoxin – Black Widow
• Organophosphates
Subacute Combined Degeneration (4)
Subacute Combined Degeneration
•
•
•
•
B12
Vitamin E
Copper
Nitrous Oxide - Whippits
Myopathy (5+1 mimic)
Myopathy (5+1 mimic)
•
•
•
•
•
Colchicine
Statins
Valproic Acid (in pts with mitochondrial disorder)
Corticosteroids
Zidovudine
• (Disulfuram can seem like a myopathy, causing
proximal neuropathy)
Putamenal Hemorrhage
Putamenal Hemorrhage
Putamanal Hemorrhage
• Methanol
Hemorrhagic Necrosis in Mamillary
Bodies
Hemorrhagic Necrosis in Mamillary
Bodies
• B1 Deficiency – Wernicke’s
Damages DRG (dorsal root ganglion)
Damages DRG (dorsal root ganglion)
• Cisplatin
Hair Loss
Hair Loss
• Thallium
Paradoxical Sensory Disturbances
Paradoxical Sensory Disturbances
• Ciguatoxin
Necrosis of the Globus Pallidus
• CARBON MONOXIDE POISONING!!!!
Necrosis of the Globus Pallidus
• THE END