Lithium salts have been used in the prophylaxis and treatment of depression and bipolar
disorder for more than 50 years. The narrow therapeutic range of lithium, together with
other well-characterised adverse effects, has limited its use. Patients receiving lithium for
bipolar disorders may experience acute or chronic toxicity after starting treatment. Acute
toxicity commonly presents as neurotoxicity, nephrogenic diabetic insipidus, or thyroid
dysfunction. Among the neurotoxic side-effects, nystagmus, ataxia, tremor, fasciculation,
clonus, seizure, and even coma have been well described in the literature.1,2
manifestation of lithium toxicity.
In this case report, we describe an uncommon but reversible neurological
A 49-year-old man who had bipolar affective disorder was receiving treatment with lithium,
trifluoperazine and trihexyphenidyl (Artane; Synco, Hong Kong) as therapy for more than
10 years. He was taking sustained-release lithium 400 mg in the morning and 600 mg at
night and there had been no recent change in his drug regimen. Apart from the psychiatric
illness, he also had cardiomyopathy, for which he was receiving long-term treatment with
aspirin, acertil, carvedilol, furosemide, and aldactone. He was noted to have decreased
cognitive function in the recent few months, associated with muscle weakness and
(E4V4M5). Haemodynamically, he was stable with a blood pressure of 110/60 mm Hg and
pulse rate of 70 beats per minute and in sinus rhythm. His body temperature was minimally
raised (37.9°C). The initial serum lithium level was 3.2 mmol/L (therapeutic range, 0.5-1.0
mmol/L). He was therefore managed as acute lithium toxicity with saline diuresis and
achieved a good response.
On admission he was confused, with a Glasgow Coma Scale score (GCS) of 13/15
was performed after brain computed tomography (CT) to rule out central nervous system
(CNS) infection. Brain CT revealed tiny hypodense foci in the right basal ganglion and
lumbar puncture showed no evidence of CNS infection. The cerebrospinal fluid (CSF)
revealed a white cell count of <0.001 x 109 /L, Gram smear was negative, protein level was
0.35 g/L (reference range, 0.15-0.45 g/L), and the glucose level was 5 mmol/L (paired serum
level, 7.4 mmol/L). Electroencephalography was suggestive of a metabolic encephalopathy.
In view of his decreased cognitive function and body temperature, lumbar puncture
to 5/15 (E1V1M3). Neurological examination revealed generalised hypotonia of all the
four limbs, together with bilateral up-going plantar reflexes. He was intubated for airway
protection and a repeat brain CT showed no change. Just before his clinical deterioration,
the serum lithium level had been 1.6 (down from 3.2) mmol/L.
Four days after hospital admission, his GCS suddenly decreased from 13/15 (E4V4M5)
Continuous veno-venous haemofiltration (CVVH) was initiated for suspected lithium-
related toxicity. The CVVH was performed with the polysulfone filter (Ultraflux AV600S;
The patient was transferred to the Intensive Care Unit (ICU) for further management.
A rare neurological complication due to lithium
Bipolar disorder; Giant axonal
neuropathy; Lithium compounds;
Lithium/poisoning; Peripheral nervous
Hong Kong Med J 2012;18:343-5
B6, Intensive Care Unit, Queen
Elizabeth Hospital, Jordan, Hong Kong
CH Chan, FHKCA, FHKAM (Anaesthesiology)
AKH Leung, FHKCA, FHKAM (Anaesthesiology)
YF Cheung, MRCP, FHKAM (Medicine)
PYC Chan, MB, ChB, MRCP
KW Au Yeung, FHKCA, FHKAM (Anaesthesiology)
KY Lai, MRCP, FHKAM (Medicine)
Correspondence to: Dr CH Chan
Anne KH Leung
Phillip YC Chan
KW Au Yeung
Lithium salts have been used in treatment of depression and bipolar disorder for more than
50 years. Neurotoxic side-effects such as nystagmus, ataxia, tremor, fasciculation, clonus,
seizure and even coma have been well described in the literature. We present a case of
generalised peripheral neuropathy following lithium intoxication. It is a rare presentation
with delayed onset and characterised by a rapid downhill course. Diagnosis was confirmed by
nerve conduction tests, which showed axonal neuropathy. Despite the profound neurological
effects of this toxicity, it is readily reversible with supportive care and the prognosis is good.
Fresenius, Germany), at a blood flow of 150 to 180
mL/min, and ultra-filtration rate of 2 L/h, with
bicarbonate-based replacement fluid (HEMOSOL
BO, Hospal, Italy). Low-molecular-weight heparin
was given as anticoagulation.
decreased to 0.8 mmol/L and the treatment was
stopped. He remained comatose with GCS of 6/15
(E1V1M4) 24 hours after ICU admission. Neurological
generalised hypotonia, quadriplegia, and areflexia
except for bilateral up-going plantar reflexes. No
other cranial nerve involvement was demonstrated.
No muscle relaxant had been administered in the
ICU, but during CVVH he was sedated for 8 hours
with morphine and midazolam.
After 8 hours of CVVH, the serum lithium had
long tract signs, magnetic resonance imaging
was performed, but showed no abnormal signal
intensity over the brainstem in restricted diffusion or
contrast enhancement films. Nerve conduction tests
confirmed the presence of axonal neuropathy, with
a generalised decrease in compound motor action
potentials and relatively normal conduction velocity
but absent F waves in all four limbs. There was no
evidence of demyelinating neuropathy and hence a
nerve biopsy was not performed.
In view of cranial nerve involvement and
excluded. Urine and serum examination for heavy
metal (mercury, lead, copper) levels, porphyria,
pseudocholinesterase levels, and immune markers
were all negative. Cerebrospinal fluid was also
negative for anti-GQ1b.
Other metabolic causes of neuropathy were
with supportive therapy. By day 3, he had developed
nephrogenic diabetes insipidus; his serum sodium
increased from 149 to 160 mmol/L. Fluid replacement
therapy was instituted and the sodium level gradually
normalised over the next 4 days to 144 mmol/L.
The patient was closely monitored in the ICU
improve; he was able to follow commands, gradually
resumed spontaneous movement and power in all
By day 3 in the ICU, the patient had started to
four limbs, and the next day he was successfully
extubated. After 5 days in the ICU, he made a rapid
neurological recovery with return of eye movements
and gag reflex. Bulbar function returned to normal
and he was able to eat without choking.
general ward, having regained limb power (grade 4/5,
with normal reflexes) and never had a demonstrable
sensory deficit. His serum sodium level returned to
the normal range. He continued to make a speedy
recovery and was discharged to a convalescent
hospital 10 days after discharge from the ICU. Later, he
was discharged home, but walked with a quadripod
whilst receiving psychiatric rehabilitation for 4
months. Finally he was able to walk independently
without a quadripod.
After 8 days in the ICU he returned to the
Neurotoxicity related to acute lithium poisoning
is well recognised. However, frank peripheral
neuropathy is a rare presentation, about which there
are limited case reports.3-11
the presenting features included critical illness
polyneuropathy, Guillain-Barré syndrome and its
variants, hypernatraemia, heavy metals poisoning,
pesticide poisoning, and abnormal porphyrin
metabolism. All these differential diagnoses were
excluded by a carefully taken history and special
In our patient, the differential diagnosis of
studies, tests for pseudocholinesterase, and immune
markers were all negative. The polyneuropathy of
critical illness seldom involves cranial nerves and
the rapidly reversible neurological recovery made
this differential diagnosis unlikely. Guillain-Barré
syndrome and its variants were also excluded by the
lumbar puncture findings, the negative anti-GQ1b
level in the CSF and the absence of demyelinating
neuropathy on nerve
Hypernatraemia secondary to diabetes insipidus
was also unlikely as it occurred at a time the patient’s
GCS was improving very significantly (day 3 in the
ICU). Acute lithium intoxication with peripheral
neuropathy therefore appeared to be the most likely
Thus, the urinary heavy metal screen, porphyrin
of case reports,4,6-9 but shared certain presenting
features and physical findings encountered in our
patient. One feature was a delayed presentation of
CNS symptoms, which usually occurred 3 to 5 days
after the acute intoxication. All the reports described
hypotonia of all four limbs with depressed reflexes.
Our case presented a similar picture with an acute
deterioration on day 4, which was associated with
a decrease in GCS, together with generalised
A literature search yielded a very limited number
#??Lithium?poisoning??# Download full-text
hypotonia of all four limbs. The diagnosis was
confirmed by nerve conduction tests that showed
axonal neuropathy. Finally, all the reports described
a good prognosis with clinical recovery upon
discontinuation of lithium.
neuropathy with lithium toxicity is far from clear.
Acute axonal dysfunction seems to be the hallmark,
which may be attributed to intracellular accumulation
of lithium and interference with propagation of the
The biological mechanism of peripheral
discrepancy between the serum lithium level and
lithium concentrations in the brain,14 consistent with
intracellular accumulation and much lower serum
lithium levels. Worsening of neurological symptoms
has also been well-documented even when the serum
lithium levels were within the therapeutic range.15
It has been postulated that there could be a
uncommon in lithium toxicity,16 it carries a good
prognosis; clinical recovery occurs within weeks
acute axonal neuropathy is
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Acute generalized polyneuropathy accompanying lithium
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neuropathy due to lithium intoxication. Ann Neurol
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due to lithium intoxication. J Neurol Neurosurg Psychiatry
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and clinical problems of lithium prophylaxis. Br J Psychiatry
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to months after discontinuation of the drug. In our
patient, clinical deterioration occurred on day 4
when the serum lithium level had nearly returned to
the therapeutic range. The patient started to improve
7 days after stopping the medication and following
one session of CVVH to further normalise the serum
lithium level. He was discharged to convalescence 21
days after hospitalisation.
We present a case of generalised peripheral
neuropathy following lithium intoxication, which is a
rare presentation characterised by a delayed but rapid
downhill course. As in our patient, such neurological
deterioration usually occurs 3 to 5 days after the acute
intoxication, and is associated with hypotonia of all
four limbs and areflexia. Diagnosis was confirmed by
nerve conduction tests showing axonal neuropathy.
Despite the profound neurological involvement,
it is readily reversible with supportive care and the
prognosis is good.