Post on 27-Dec-2015
INTENTIONAL THALLIUM INTENTIONAL THALLIUM POISONING – VERIFICATION POISONING – VERIFICATION
AND TREATMENTAND TREATMENT
Pelclová D (1), Šenholdová Z (1), Lukáš E (1), Urban P (2), Lacina L (3), Vlček K (1), Pelclová D (1), Šenholdová Z (1), Lukáš E (1), Urban P (2), Lacina L (3), Vlček K (1), Fenclová Z (1), Kitzlerová, E (4).Fenclová Z (1), Kitzlerová, E (4).
1. Department of Occupational Medicine, Charles University, Prague 1. Department of Occupational Medicine, Charles University, Prague 2. National Institute of Public Health, Prague2. National Institute of Public Health, Prague
3. Department of Dermatology; 3. Department of Dermatology; 4. Psychiatric Department, 4. Psychiatric Department,
General University Hospital and First Medical faculty, General University Hospital and First Medical faculty, Charles University, Prague, Czech RepublicCharles University, Prague, Czech Republic
THALLIUM
discovered in 1861 by Sir Williams Crooks 1862 by French chemist Claude-Auguste Lamy In Greek, thallos "green twig."
Using spectroscopy, the brightest lines in the spectrum of thallium are green
melting point 300º C (576º F) boiling point 1480º C (2,655º F)
elementary thallium non-toxic monovalent and threevalent salts very toxic LD about 900 mg
THALLIUM
rather uncommon element world production 12 tons/year semiconductors,
photocells, optic glass, thermometers in medicine – Tl201radioactive tracer in heart
scintigraphy to detect myocardial ischaemia occurrence in minerals emissions 1500 tons/year granite, coal
THALLIUM – IN THE PAST
Tl2SO4 has long been used as
rodenticide, insecticide Colorless and tasteless Tl acetate : treatment of veneric diseases, ringworm Depilatory agent Low therapeutic index Banned in the 1970ies in most countries
Toxicokinetics – inorganic salts
absorption by all ways, oral about 90% distribution to all tissues greatest concentration in the intestines, liver,
kidney, heart, brain and muscles excretion by faeces and urine, the proportion 2:1 enterohepatic circulation half-lives 1-30 days
Pathophysiology - 1 Similarities in charge and ionic radius between K+ and Tl+
ions), Tl substitutes for K:
1. blocks energy utilization by Na-K-ATPase channel = (active transport of monovalent ions - K+ across cell membrane)
Thallium disturbs maintaining of a resting potential across the membrane of active cells - Tl has 10-fold greater affinity.
Neuronal, cardiac and skeletal muscle cells 2. blocks energy production from glucose: ADP to ATP by
pyruvate kinase = K requiring enzyme - links anaerobic glycolysis to the Krebs cycle)
inhibition by binding with 50-fold affinity comparing to K.
Pathophysiology - 2
3. damages riboflavin, precursor of FAD forming an insoluble complex and intracellular sequestration of vit. B6
decrease of riboflavin disrupts metabolism by reducing activity of Krebs cycle
4. binds to SH groups and interferes with formation of disulphide bonds in keratin - structural damage to hair, nails
5. causes activation or inhibition of other enzymes (ALA synthetase, B12 metabolism…)
2 Case reports
2 patients, mother and daughter, living in the same household
Very probably intentional poisoning by one member of the family
Oral intake Chronic
Patient Amother
44years old PH: no serious disease OH: super-market manager 1. poisoning November 2004 sudden strong chest pain, following 3
days severe pain with paresthesias in both lower limbs Symptoms disappeared within 3 weeks, following 3 weeks
persisted mild paresthesias and discomfort in the lower limbs
2. poisoning
In March 2005 she developed suddenly a strong muscular pain in the lower limbs. The gait was painful „as on a broken glass“.
within 5 days she became bald. In April – one month stayed at neurology dept. With
suspicion on LI syndrome and posttraumatic stress disorder (anxious, depressive, had work overload and home conflict environment)
EMG, evoked potentials, MRI normal In June improvement, returned to work
3. poisoning
August 2005 Progressive pain in lower limbs with paresthesias Blurred vision – she could differentiate only dark
and light spots in the periphery of the visual field After 3 weeks her condition improved a little Mild pain in the feet and knees persisted several
weeks Vision difficulties persisted Eye fundus : n. opticus atrophy
HospitalizationDept. Occupat. Medicine
Admitted on January 31,2006 5 months after last intoxication 1) attempt to prove the poisoning 2) attempt to improve vision damage – she still could not
read
EMG: mild motor and sensoric damage, EEG borderline
Visual evoked potentials: severe damage with visus BIOLOGICAL HALF-LIFE of thallium broad range of 1-30 days Hoffman RS. Toxicol Rev 2003
Patient B: Historydaughter
22years old woman PH: no serious disease OH: high school,1 year maternity leave FH: mother treated for symptoms of unknown etiology,
father probably psychopathic personality, no treatment, daughter 1 year old, healthy
1 poisoning
In December 2005 suddenly strong pain in lower limbs,
maximum in the stockings distribution, ache in the skin of lower extremities
Anorexia 3rd week symptoms deteriorated, treated with analgesics
(tramadol) 4th week lost all body hair (except eyebrow and eyelashes) She developed blurred vision, weakness of lower limbs,
unable to walk Hospitalized at neurology dept.
Hospitalization at Neurology Dept.
Blood and urine sent to toxicology screening (drugs, metals incl. Cd, Pb, Hg, Se, Zn, Tl,)
5th week: vision damage with maximum in the central area, right and left eye
Shortly also speaking difficulties and feeling of heavy tongue Positive results for thallium in blood and urine
Hospitalization atDept. Occup. Medicine
Admitted on January 26, 2006 7th week of symptoms On admission: On a wheel chair, paraparesis, motor weakness Bald (only eyebrow and lashes left) Could distinguished fingers from 30 cm complained of
strong pain in lower limbs Altered mental status, depressive, anxious Slow speech, low voice
Antidote
Prussian blue - Fe4[Fe(CN)6]3 (ferric hexacyanoferrate), Radiogardase, Heyl CAS 14038-43-8 discovered 1704 by a Berlin color maker Diesbach since the 1960s used to treat Cs and Tl poisonings Binds thallium by ion exchange, adsorption and
mechanical trapping within the crystal structure
Specific treatment
Insoluble, low absorption from the GIT (?) stops enterohepatic circulation of thallium Increases elimination both to faeces and urine Advantage: rare side effects, bluish sweat and
tears Reduces half-life from 8 to 3 days First dose after arrival 6g /12 hours Continued with 12 g/day in 4 doses
Supportive therapy
10% mannitol as cathartic Charcoal (Carbosorb) 2x 25 g/day Analgesics Vit. B12, B6 Topical dermatological treatment supporting hair growth
Thallium concentration in urine µg/l in the daughter Total excretion 8.4 mg in 32 days, further Tl in faeces
Antidotal treatment 22 days
Toxicological analysis in daughter
Thallium found in all biological materials – blood, urine, faeces, hair
Examinations
Neurological (incl. needle EMG, VEP, BAEP, EEG, MRI of the brain)
Ophthalmological (visus, fundus, perimeter) Dermatological Further: ECG, psychiatric, blood biochemical analysis, urinalysis,
kidney functions
January 20052nd month
Unable to walk Severe polyneuropathy Verified by needle EMG sensory, motoric and autonomic Symmetrical Low extremities only
April 20065th month
Able to walk with a walker leg support. Severe motor polyneuropatie. Mild improvement,
esp. Sensitive and autonomic nerves. MRI of the brain: normal finding incl. optic nerves,
tracts, chiasma and visual cortex Atrophy of both optic nerves on the ocular fundus
August 20069th month
Still severe motor polyneuropathy She could walk without support Unstable gait Pathology in EEG, VEP, BAEP Vision of fingers from 0.75 m
EEG, BAEP VEP
Slightly abnormal entrance findings
Control: slow improvement
2nd month: no response due to severe vision damage
5th month: Low peak at right side, no response left side.
9th month: Bilaterally abnormal finding low reproducibility and low VEP, worse left side
FURTHER FINDINGS
ECG – non-specific ST segment and T wave changes during a febrile state with tachycardia
Transthoracic echocardiography – diffuse hypokinesis of the left ventricle, markers normal
Psychiatric examination Neuropsychological testing not possible – visual
problems USG of the abdomen normal Kidney functions normal
Total alopeciadaughter
Reversible Highest value 36.1 μg/g (5th week) Sequential analysis of 1.5 cm hair segments = 6 months Thallium 5.61- 6.24 – 7.41 – 7.81 – 6.67 μg/g hair New hair 6th week of poisoning and 8th day of antidote
treatment– drop to 1.6 μg/g) Daniel J Am Acad Dermatol 2004
Trichological analysis of the acute hair loss of the daughter Normal hair
Light microscopy - The proximal end hair fibre tapered and distorted. Rough surface of the proximal end Amorphous cuticular and cortical cells as a sign of the
pathological keratinisation. (Metter and Vock 1984)
Trichological analysis of the acute hair loss of the daughter
Under transmitted-light microscopy the cortex dark discolorisation and disorganized on the widened club-shaped end.
Gaseous inclusions under the phase contrast microscopy.
Trichological analysis of the new hair of the mother
Hair of the acute loss not available Recent hair – normal finding, smooth surface
of keratinocytes
Thallium in urine (μg/l) Optical Emission Spectrometer - Inductively Coupled Plasma (OES-ICP)
daughter mother normal range
Initial
measurement urine 580.00Jan.15
8.50Jan. 25
0.018-0.021
Thallium in urine (μg/l) voltammetry
daughter mother control subject
before antidote 580 neg. neg.
maximum after antidote/
12 h sample
urine 1170.0 21.0 4.0
end of treatment
12 h sample
urine 2.0 5.4 -
after 6 months urine neg. neg. -
Thallium in blood and faecesOptical Emission Spectrometer - Inductively Coupled Plasma (OES-ICP)
μg/l daughter mother normal range
(OES-ICP)
First
measurement
blood 770.00Jan. 15
0.30Jan. 21
0.049-0.013
mg daughter mother Voltammetry
maximum with antidote
faeces 13 mg/250g 0.25 mg/40g ?
3 days after the end of treatment
faeces 0.1mg/100g 0.05 mg/70g neg.
CONCLUSION - mother
Treatment with Prussian blue produced a higher excretion of thallium in urine
And a measurable amount in faeces In mother the clinical effect was negligible – 1¼ year after last poisoning: EMG: Residual mild axonal sensory neuropathy,
mild improvement after 6 months. Autonomic fibers without damage.
Opthalmologic examination: scotomas of upper and central parts of both visual fields
Visual evoked potentials: prologed latency, lower amplitude
CONCLUSION - daughter
1 year after intoxication EMG examination - Severe damage in motor and
sensory fibers, autonomic normalized already Ophthalmologic examination – mild improvement right eye - scotomas in central and medium
periphery left eye – scotomas in central area
SUMMARY Thallium typically causes damage of
peripheral nerves of lower extremities, vision and hair.
Combination of these symptoms suggests thallium poisoning
Late treatment has low effect Prognosis of hair loss is good Polyneuropathy improves within months till
years Vision damage has the worst prognosis
THANK YOU
3rd victim – dog of the family