NeuroToxicology 27 (2006) 291–295

Brief communication

Central nervous system effects in acute thallium poisoning
Yu-Tai Tsai a, Chin-Chang Huang a,*, Hung-Chou Kuo a, Hsuan-Min Wang a,
Wu-Shiun Shen b, Tung-Sheng Shih c, Nai-Shin Chu a
a

Department of Neurology, Chang Gung Memorial Hospital and University, 199 Tung-Hwa North Road, Taipei, Taiwan
b
Department of Clinical Pathology, Chang Gung Memorial Hospital, Taipei, Taiwan
c
Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, Taipei, Taiwan
Received 4 March 2005; accepted 31 October 2005
Available online 5 December 2005

Abstract
We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two
patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage,
followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests
revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity,
proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients.
Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological
studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions.
We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a
severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum
might resolve.
# 2005 Elsevier Inc. All rights reserved.
Keywords: Thallium poisoning; Neurotoxic disease; MRI; Neuropsychology; Toxicology

1. Introduction
Thallium, discovered by William Crookes in 1861, is a wellknown heavy metal toxic to humans and animals. Thallium salts
have been used for the treatment of many diseases, including
tuberculosis, gonorrhea, syphilis, and fungal infections on the
scalp. In addition, thallium has been used as a depilatory agent,
and has had many victims, particularly among children, due to
ingestion (Galvan-Arzate and Santamaria, 1998; Prick, 1979;
Van Kesteren, 1994). An outbreak of thallotoxicosis was reported
in California in 1932, and was attributed to use of a rodenticide
for the control of a ground squirrel infestation (Munch et al.,
1933). Recently, thallium has been utilized in the manufacturing
of optical lenses, semiconductors, scintillation counters, low
temperature thermometers, green-colored fire works, imitation
jewelry, and chemical catalysts. The therapeutic use of these salts
has been abandoned, but the hazards of an accidental ingestion of

* Corresponding author. Tel.: +886 3 3281200x8418; fax: +886 3 3287226.
E-mail address: cch0537@adm.cgmh.org.tw (C.-C. Huang).
0161-813X/$ – see front matter # 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.neuro.2005.10.009

thallium-containing rodenticides, or its use in homicidal or
suicidal ingestion, occur occasionally (Bank et al., 1972;
Cavanagh et al., 1974; Mathews and Anzarut, 1968; Moore
et al., 1993; Papp et al., 1969; Reed et al., 1963; Smith and
Doherty, 1964).
The clinical manifestations of acute thallium poisoning,
consisting of the characteristic dermatological findings of
alopecia, hyperkeratosis, and Mees’ lines in nails, have been
well described (Galvan-Arzate and Santamaria, 1998; Prick,
1979; Tromme et al., 1998). The neurological symptoms
include dysesthesia, painful neuropathy, muscle weakness,
cranial nerve palsies, ataxia, tremor, convulsion, coma, and
death (Dumitru and Kalantri, 1990; Prick, 1979; Van Kesteren,
1994; Yokoyama et al., 1990). The term ‘‘encephalopathia
thallica’’ implies a variety of conditions, from non-specific
giddiness, lack of drive, and memory impairment, to a decline
in intelligence and irreversible dementia (Prick, 1979).
Neuropathological studies of the brain are limited and reveal
edematous changes and vascular engorgement in the cerebral
hemispheres, and chromatolytic changes in the motor cortex,
globus pallidus, substantia nigra, and brainstem nuclei (Davis

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et al., 1981; Kennedy and Cavanagh, 1976; Prick, 1979; Tanaka
et al., 1978). Neuroimaging studies of the brain are likewise
rare (Insley et al., 1986). Recently, we encountered two patients
with thallium intoxication who developed confusion in the
acute stage, followed by cognitive impairment. Herein, we
report the central nervous system (CNS) manifestations,
neuropsychological studies, and brain magnetic resonance
image (MRI) findings of acute thallium intoxication.
2. Case report
2.1. Patient 1
On March 15, 2002, a 48-year-old woman developed nausea,
vomiting, loss of taste, and perioral numbness a few hours after
drinking approximately 750 mL of bottled water and eating
breakfast. Generalized myalgia was experienced in the afternoon, and progressed to severe painful dysesthesia in the soles
of the feet on the following day.
On examination, she had excruciating bilateral leg and foot
pain that was aggravated from touching the lower extremities.
She could not tolerate extensive neurological examinations due
to severe allodynia. Her vital signs were normal, and her family
and past histories were unremarkable. She was confused and
disoriented to time, place, and person; she had incoherent speech,
lacked attention, delusion, and reported visual hallucinations.
Deep tendon hyper-reflexia was observed in all upper and lower
extremities while plantar reflexes were normal. Dry mouth,
decreased salivation, and aphthous ulcers were also noted.
Laboratory examinations showed normal hemograms,
serum glucose, renal function, and electrolytes, with aspartate
aminotransferase (AST): 21 U/L, alkaline phosphatase: 38 U/
L, and a slightly increased level of alanine aminotransferase
(ALT): 85 U/L (ref.: 0–36 U/L). The initial electroencephalography (EEG) showed diffuse theta waves indicating a mild
diffuse cortical dysfunction. Brainstem auditory evoked
potentials (BAEP) and visual evoked potentials (VEP) studies
were normal.
One week later, erythematous skin rashes appeared on the
face, cheek, and perioral areas, and they became acneiform or
pustular eruptions. Visual hallucination, confusion, and
disorientation to time, place, and person were still present.
In addition, there was a multi-directional gazing nystagmus.
The secretion of both saliva and tears was reduced. She also had
diarrhea, and tachycardia (100–130 beats/min). Urine retention
was noted, and her urodynamic examinations revealed detrusor
hyporeflexia and a low urinary flow rate. Initial brain MRI
images were performed on April 3, 2002, which showed
hypointense lesions in T1 weighted images (T1WI), hyperintense lesions in T2 weighted images (T2WI), and fluidattenuated inversion recovery in the corpus striatum (Fig. 1).
Three weeks later, a loss of scalp hair started.
2.2. Therapy
The patient was treated with intravenous infusion for forced
diuresis since intoxication was suspected to have occurred.

Activated charcoal was also started and Prussian blue 1 g daily
in four divided dosages was available until 3 weeks later while
a definite diagnosis was made from the toxic level of urinary
thallium. The hair loss continued for 1 month until a nearly
total loss of scalp hair occurred. Hair loss was also noted in the
lateral aspect of the eyebrows, but the eyelash, axillary hair,
and pubic hair were relatively preserved. At the same time,
muscle weakness and hyporeflexia of the lower limbs
developed. One month after intoxication, scaling on the soles
of her feet was found and persisted for 1 month. In addition, a
prolonged (10 h) hemoperfusion was performed twice to more
rapidly enhance thallium elimination. Prussian blue 1 g every
8 h was continued until June 10, when urinary thallium
elimination decreased to 65.6 mg/day. The repeated brain MRI
on April 30 showed that the lesions had resolved. Two months
later, the follow-up EEG was also normal. The Mees’ lines
appeared 3 months later. The Mini-Mental State Examination
(MMSE) was performed 2 months later, and yielded 17 (total
score 30) in this patient. Neuropsychological studies
performed by a Chinese version of the neuropsychological
test battery which has been commonly used in the Taiwanese
population (Kuo et al., 2005a; Lin et al., 2003) and also
showed impairments in digital span (backward), memory
registration, memory recall, memory recognition, verbal
fluency, judgment of line orientation, and proverb reasoning.
However, the comprehension, repetition, naming of language,
construction, and calculation were normal. Six months later,
the MMSE showed an improvement with a score of 28 in this
patient. In addition, her neuropsychological status improved
but memory registration, memory recall, memory recognition,
and verbal fluency remained abnormal. However, agitation,
aggression, anxiety, a depression, sleep disturbance, and
emotional liability were found by a test of the Neuropsychiatric Inventory (NPI) (Cummings et al., 1994). The patient was
treated each day with gabapentin 1600 mg and amitriptylline
75 mg daily for relief of neuralgia during the 1-year follow-up
period.
2.3. Toxicology survey
The heavy metal survey of the urine, using inductively
coupled plasma mass spectrometry (ICPMS) (Perkin-Elmer
SCIEX ELAN model 5000), showed a high concentration of
thallium, with 14,520 mg/L (ref.: 0–10 mg/L) on March 20, while
the levels of mercury, lead, cadmium, arsenic, manganese,
nickel, zinc, copper, bismuth, tellurium, and stibium were unremarkable. The blood thallium level was 2056 mg/L on March 20.
In the food samples, there was neither thallium or arsenic,
nor other toxic heavy metals. However, in the bottled water, a
very high concentration of thallium (3124 mg/L) was noted.
The thallium concentrations of water from other places such as
tap water, and drinking water from the same building were
normal. Serial 24-h urinary concentrations of thallium
gradually decreased from 1177.9 mg/day on May 3, to
65.6 mg/day on June 10. The blood thallium levels were
also decreased from 455 ng/g on April 16, to 4.7 ng/g on
June 20.

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293

Fig. 1. Initial brain MRI showing increased signal intensity lesions (arrows) in the corpus striatum on T2W (A) and FLAIR (B), 2 weeks after thallium intoxication
and a follow-up brain MRI 6 weeks later showing that the lesions had resolved (C) as compared with the previous lesions (D).

2.4. Patient 2
A 52-year-old man (husband of patient 1) developed an
acute onset of perioral numbness, a decrease of taste sensation,
nausea, and poor appetite a few hours after drinking of the same
bottled water (about 500 mL) and finishing his breakfast on
March 15, 2002. Aching pain in both distal lower limbs was
experienced at night. On the following day, paresthesia and
dysesthesia were noted in the distal lower extremities. During
the examination, the vital signs were stationary and his
consciousness was clear except for disorientation to time and
lack of attention. In addition, dry mouth and generalized hyperreflexia were found. Biochemistries revealed an increased total
bilirubin level: 1.8 mg/dL (ref.: 0.0–1.3 mg/dL), ALT: 80 U/L
(ref.: 0–36 U/L), but normal renal, and thyroid functions. The
EEG, BEAP, and VEP were normal. Erythematous skin rashes
appeared on the face, cheek, and perioral regions 1 week later.
In the second week, the skin rashes transformed to acneiform or
pustular eruptions. Alopecia started in the third week,
particularly the scalp hair, and lateral aspect of the eyebrows.
Furthermore, tachycardia, urinary retention, and diarrhea were

also observed. Bilateral distal leg muscle weakness developed
in the second week along with scaling of the soles of the feet.
The initial brain MRI studies on April 3 were normal. The score
of MMSE was 19. Neuropsychological tests revealed impairments in digital span (backward), memory registration,
memory recall, memory recognition, verbal fluency, and
similarity. The Mees’ lines were noted at the end of the
second month. However, 6 months later, the MMSE score was
improved to 29. In addition, the neuropsychological studies
also improved except verbal fluency. In the 1-year follow-up
period, he still had anxiety, depression, memory impairment,
and emotional liability.
2.5. Therapy
In the acute stage, he was treated with an intravenous
infusion of normal saline for forced diuresis and activated
charcoal. In addition, gabapentin and amitriptylline were also
given for relief of painful extremities. After a definite diagnosis
3 weeks later, a therapy of Prussian blue 250 mg every 6 h was
available and started. The Prussian blue was increased to 1 g

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every 8 h and continued in the following 2 months after the
daily urinary concentration was decreased to 38.7 mg/day on
June 10. In addition, two courses of prolonged hemoperfusion
were also performed.
2.6. Toxicology survey
The heavy metal survey of the urine revealed 11,326 mg/L of
thallium and the blood thallium level was 950 mg/L on March
20. Serial 24-h urinary concentrations of thallium gradually
decreased from 977.4 mg/day on May 3, to 38.7 mg/day on June
10. The blood thallium levels were also decreased from 306 ng/
g on April 16, to 1.9 ng/g on June 20.
3. Discussion
We present the sequential changes in the clinical features
and neurological manifestations of two patients with acute
thallium intoxication. The prominent CNS symptoms were
confusion, incoherent speech, delusion, and visual hallucination in the acute stage, and anxiety, depressive mood, lack of
attention, memory impairment, and emotional liability in the
chronic stage. Initial neuropsychological test revealed impairments in digital span, memory registration, memory recall and
memory recognition, reasoning for similarity, proverb reasoning, and verbal fluency 2 months later. The follow-up
neuropsychological test 6 months later showed a prominent
improvement except memory registration, memory recall, and
memory recognition in patient 1 and verbal fluency in both
patients.
The couple developed severe pain in both feet, erythematous
skin rashes, peripheral neuropathy and alopecia. The clinical
manifestations strongly indicated arsenic or thallium intoxication. The heavy metal survey with ICPMS 2 weeks later
confirmed thallium poisoning from the bottled water, which
eventually proved to be deliberately tainted. In the peripheral
nervous system, a primarily distal axonopathy involving both
large and small myelinated fibers and even unmyelinated fibers,
particularly in the lower extremities, has been reported
elsewhere compatible with the previous studies (Dumitru
and Kalantri, 1990; Kennedy and Cavanagh, 1976; Kuo et al.,
2005b; Yokoyama et al., 1990).
Thallium intoxication may induce CNS and peripheral
pathology (Prick, 1979; Van Kesteren, 1994). Prominent
effects include central neuropathies, ataxia, tremor, and
mental disturbances (Munch et al., 1933). Mental disturbances include poor attention, anxiety, depression, altered
consciousness, hallucination, and paranoid syndromes (Prick,
1979; Tanaka et al., 1978; Van Kesteren, 1994). Interestingly,
our patients developed hyper-reflexia initially, and 2 weeks
later, the tendon reflexes changed to hypo-reflexia. The data
indicated that the upper motor neuron lesions might have been
present since the acute stage. Initially, patient 1 had
incoherent speech, confusion, delusion, and hallucination,
correlated with diffuse slow waves on the EEG, as compared
with patient 2. Patient 1 also ingested a relatively higher
amount of thallium (about 2.4 g) than patient 2 (about 1.5 g).

In addition, urinalysis confirmed a higher urine thallium
concentration in patient 1 as compared with that of patient 2
(14.5 mg/L versus 11.3 mg/L). The data indicated that a
higher thallium exposure might induce a more prominent
CNS symptomatology.
Both patients had mental impairments with neurotic-like
symptoms and a depressive mood in the 1-year follow-up
period. Serial neuropsychological tests also confirmed a
disturbance including reversed digital span, memory registration, memory recall, memory recognition, and verbal fluency.
The data indicated a selective involvement of the temporal lobe
and its related restructures. In previous reports, mental
disturbances and symptomatic epilepsy may present, particularly in patients with lesions in the temporal lobes (Prick, 1979).
To our knowledge, neuroimaging studies have rarely been done
(Insley et al., 1986). Normal brain CT or MRI scans have been
reported in patients with cognitive impairments and frequent
aggressive outbursts after thallium poisoning (Insley et al.,
1986; McMillan et al., 1997). Initial brain MRI studies of
patient 1 also revealed lesions in the corpus striatum. This
lesion was no longer noted in the follow-up MRI. From the
above data, the neuropsychological findings were not
compatible with the brain MRI abnormalities. However, the
neuropsychological impairments persisted longer than the
lesions in the brain MRI. The brain MRI lesions presented only
in one patient. Although it is difficult to make a definitive
conclusion, brain MRI studies may reveal acute effects due to
severe thallium poisoning. In addition, although the underlying
pathology is unknown, previous pathological studies have
shown alterations in the cortical and corpus striatum neurons,
with central chromatolysis, and edematous changes in the
subcortical white matter (Kennedy and Cavanagh, 1976; Prick,
1979; Tanaka et al., 1978). In our patient 1, the hypointense
lesion in T1-weighted images and the hyperintense lesion in
T2-weighted images might indicate an edematous change or
demyelination.
The cellular mechanisms of thallium toxicity include the
substitution of potassium in Na–K-ATPase, as well as a high
affinity for the sulfhydril or thiol group of mitochondrial
membranes (Prick, 1979). Therefore, thallium inhibits many
enzyme reactions and protein production. However, the
mechanisms of differential involvement in the corpus striatum
and asymmetrical lesions in brain MRI were unclear. In human
and experimental studies, the highest thallium concentrations
were found in the corpus striatum, thalamus, and hypothalamus
(Davis et al., 1981; Insley et al., 1986). It was also noted that
thallium accumulated more rapidly in the hypothalamus and
corpus striatum than in other brain regions (Brown et al., 1985;
Rios et al., 1989). However, further investigations on the
pathogenesis of differential and asymmetrical involvements are
warranted.
Acknowledgements
This study was supported in part by a grant from the National
Science Council (NCS 92-2314-B-182A-117) of Taiwan. We
also express our thanks to YC Hsieh for her assistance.

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