Painful Sensory Motor Neuropathy With Albuminocytological Dissociation of the Cerebrospinal Fluid as the Presenting Features of Acute Thallium Poisoning

Dear Editor,

Thallium is a highly toxic, colorless, and tasteless heavy metal.1 Thallium poisoning has a high initial misdiagnosis rate due to its symptoms and signs being nonspecific in the early stage. Here we present a case of thallium poisoning with albuminocytological dissociation of the cerebrospinal fluid (CSF).

A 45-year-old female presented with pain and weakness in the bilateral arms and legs with an 8-day history, which had first appeared within 24 hours after drinking alcoholic beverages with two friends. The pain and weakness were more severe in the distal extremities. She also suffered from dizziness, nausea, vomiting, diarrhea, abdominal pain, bloating, and dyspnea. Her two friends experienced similar symptoms to varying degrees. Magnetic resonance imaging of the brain and spinal cord revealed no abnormalities.

A physical examination revealed that the body temperature was 36.2℃, heartbeat was 106 beats per minute, respiratory rate was 12 breaths per minute, and blood pressure was 126/86 mm Hg. The abdomen was soft with mild tenderness and no rebound tenderness. A neurological examination revealed intact cranial nerves, weakness in the arms and legs (Medical Research Council muscle strength grades of 4/5 and 3/5 in the proximal and distal extremities, respectively), and stocking- and glove-type dysesthesia.

The patient complained of bilateral blurred vision on the day of admission (day 8 since onset). Her best-corrected visual acuities were 20/40 and 20/30 in the right and left eyes, respectively. Horizontal nystagmus was observed. Optical coherence tomography (OCT) revealed that both the retinal nerve fiber layer (RNFL) and ganglion cell layer had normal thicknesses. Visual evoked potentials demonstrated a slightly prolonged P100 (118 and 114 ms on the left and right, respectively). Electrophysiological studies performed on day 8 indicated multiple injuries to the sensory and motor nerves, predominantly in the motor axons (Supplementary Tables 1, 2, 3 in the online-only Data Supplement). Alopecia of the scalp was noted on day 9, sparing her eyebrows, eyelashes, and body hair (Fig. 1A). Heavy-metal poisoning was strongly suspected due to the constellation of gastrointestinal symptoms, alopecia, peripheral neuropathy, and cluster onset. A toxicology test was therefore performed, which revealed blood and urine thallium levels of 0.6 and 8.0 µg/mL, respectively. Thallium poisoning was therefore diagnosed.

Fig. 1
Clinical features of the case. A: Alopecia in a 45-year-old female on day 9 after thallium poisoning. B: Representation of serial changes in the thallium concentration after exposure to thallium and its treatment using Prussian blue. C: Mee’s lines on day 46 after thallium poisoning on the hands (white arrows) and legs (black arrows). White transverse bands corresponding to Mee’s lines in the middle of the nails. D: Symptom progression and outcome during the last follow-up at 500 days after poisoning. CSF, cerebrospinal fluid.

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Lumbar puncture on day 16 revealed elevated protein in the CSF (1,069 mg/L) and a normal white blood cell count (<1×10⁶/L). The thallium concentration in the CSF was 0.0028 µg/mL (Fig. 1B).

Prussian blue (0.7 g, 10 times per day) and 20% mannitol were administered orally. Blood perfusion and continuous venovenous hemodialysis were also performed. The thallium levels in the blood and urine were monitored (Fig. 1B). Vision impairment deteriorated slowly despite these treatments, with best-corrected visual acuities of 20/200 (right eye) and 20/100 (left eye) on day 34. OCT revealed thinning of the RNFL in the bilateral temporal quadrant. White transverse lines consistent with Mee’s line appeared on her nail beds on day 46 and faded within 1 month (Fig. 1C). Sensory disturbance and alopecia were relieved after 2 months. Limb weakness improved considerably after 3 months, and she could independently perform the activities of daily living at the last follow-up on day 500. However, her visual impairment did not improve. The symptoms and signs are listed in Supplementary Table 4 (in the online-only Data Supplement). The development and progression of the symptoms and signs during the 500-day follow-up are shown in Fig. 1D. The police later confirmed that the alcoholic beverage was intentionally poisoned using thallium in an attempted murder.

The selective elevation of the total protein level in the CSF was considered to be albuminocytological dissociation, which is a diagnostic hallmark of Guillain–Barré syndrome.2 Albuminocytological dissociation in the CSF reflected disruption of the blood–CSF barrier at the spinal root level due to nerve inflammation or acute immune responses.3 Autoimmune responses and toxicity-induced neuropathy can also cause albuminocytological dissociation. Albuminocytological dissociation has been reported in cases of acute motor sensory axonal neuropathy related to lithium-effectuated neurotoxicity,4 delayed autonomic neuropathy resulting from ethylene glycol toxicity,5 peripheral neuropathy from vincristine toxicity,6 and poisoning by the heavy metal germanium.7

Thallium impairs the integrity of cell membranes in the peripheral and central nervous systems, and is associated with axonal degeneration.8 In our case we found clear elevation of total protein in the CSF with a normal white blood cell count at day 16 after thallium poisoning. Mildly elevated total protein in the CSF8, 9 has been reported in previous thallium poisoning cases. We assume that this inconsistency could be due to the different intervals between disease onset and CSF analysis.