Mercury Poisoning: A Case of a Complex Neuropsychiatric Illness

Case Presentation

“Mr. X,” a 42-year-old married taxi driver from Beijing, came to the emergency department with insomnia, a severe and constant burning sensation and pain in the lumbar spine, hip and knee joints, and soles of the feet, and a sense of tremor in his limbs. Treatment with a nonsteroidal anti-inflammatory drug was ineffective. After physical examination, laboratory studies, an X-ray of the affected joints, and MRI of the brain and spine showed no obvious abnormalities, the emergency department referred the patient to a psychiatric hospital with a diagnosis of pain somatoform disorder.

After 2 months of psychopharmacotherapy that included duloxetine (60 mg/day) and mirtazapine (45 mg/day), Mr. X’s lower joint pain had disappeared, but the tremulous sensation in his limbs persisted. He had also started to have dizziness, nausea, ataxia, blurred vision, and further sleep problems—sleeping up to 15 hours a day, falling asleep during conversations or meals, and exhibiting pronounced sleep talking. More remarkably, during supine sleep, his hands and feet were raised up in the air, and he maintained these awkward postures for 1 to 2 hours (Figure 1). Given the complexity of the case, the patient was transferred to a psychiatric teaching hospital, with diagnoses of pain somatoform disorder and sleep disorder, 5 months after the initial presentation.

Mr. X was noted to be a thin, neatly dressed man, ambulating with his wife’s help. Well-oriented and generally cooperative, he was euthymic, with intermittent attention and focus, and his main complaint was his unsteady gait. He was not too concerned about the hypersomnia, the odd behavior during sleep, or the newly reported sensation of having, imbedded in his back, four balls that further divided into smaller ones. His thought process was coherent. Mr. X had no previous personal or family psychiatric history and no history of epilepsy, infectious diseases, or sleep or pain disorders. His relationships were harmonious and his life was free of significant stressors. He smoked occasionally and drank socially; he denied any other substance use. His medical history was positive for chronic psoriasis (for the past 10 years); he had taken daily Chinese herbal decoctions for 3 months from a private clinic before admission 5 months ago.

Findings from physical examination included mild oral mucosal ulcers and swelling of the gums; scattered crusted papules on the head, face, and truncal areas, moderate scaling of the skin in the truncal areas; mild hand tremors and weakness (grade IV, bilaterally); visible atrophy and weakness (grade III, bilaterally) in the lower extremities; weak knee and ankle reflexes (grade 1); poor accuracy in finger-to-nose and heel-to-toe walk tests; unsteady gait; and a positive Romberg test (worse with eyes closed). Touch and temperature sensation tests were normal, as were ECG, chest X-ray, blood count, electrolyte levels, and thyroid, liver, and kidney function tests; hepatitis B and C screens were negative. Routine urine analysis showed a protein level of 1+, at 3.3 g/L. The patient also had mild dyslipidemia and slightly low total serum protein and albumin levels, and his EEG showed increased theta activity and decreased alpha activity. Repeat cranial and lumbar spine MRIs were normal.

Mr. X continued to have narcoleptic attacks and unusual movements, postures, and sleep talking. He even conversed a little with clinicians during these sleep talks, and he recalled such exchanges, as well as various dream content, when he awoke. For example, he recalled having seen a cat taking his money and running off, foxes transforming into clothing, and people in his village scolding him. He reported that he largely believed all these events to be true, which caused concern about a new onset of delirium or psychosis.

The treatment team pursued a new differential diagnosis: mental disorders secondary to intracranial infection, neoplasm, or a substance or toxin; and sleep disorder related to psychomotor seizures. Subsequent investigations were positive for delirium (a score of 23 on the Delirium Rating Scale) (1) and peripheral neuropathy, with electromyography showing a bilateral decrease in peroneal nerve compound motor action potential amplitude. A repeat sleep EEG study was inconclusive because of excessive movement. Enzyme-linked immunosorbent assay tests for routine tumor markers (CA125, CA199, CA153, CEA, and AFP), infectious disease screening for syphilis and HIV antibody, and selective autoantibody testing for neurological paraneoplastic syndrome were all negative.

Based on these results, a toxin-related disorder became the leading option in the differential diagnosis. Recalling that Mr. X took herbal decoctions (a mixture of fresh and dried herbs, with calomel added, boiled and consumed like tea, no fixed formulation) for psoriasis, the treatment team undertook toxicology studies. Inductively coupled plasma-mass spectrometry produced confirmatory results that showed an alarming mercury concentration of 876 mg/kg (normal limit, <0.5 mg/kg) in the herbs he took (2), a serum concentration of 23.2 ng/mL (normal, <2.5 ng/mL), and a urine concentration of 14.8 ng/mL (normal limit, <10 ng/mL) (Beijing specialty laboratory reference range based on Chinese standards; the U.S. Environmental Protection Agency safety benchmark for blood is <5.8 ng/mL [3, 4]). A 24-hour urine analysis showed a 3+ protein level at 6.0 g/L and a high urinary N-acetyl β-D glucosamine (NAG) level at 27.5 U/24 hours.

Mr. X was promptly started on treatment for mercury poisoning at a general hospital, chiefly using the chelator DMPS (2,3-dimercapto-1-propane sulfonate). After three courses, 60 days of mercury chelation, hydration, and enhanced nutritional therapies, Mr. X’s serum mercury level dropped to 3.1 ng/mL, and his urinary level to 3.9 ng/mL. His kidney function improved markedly, his narcoleptic attacks and the bizarre postures and muttering during sleep remitted, his pain lessened, and he could walk and drive and work again. One month after discharge, Mr. X exhibited stable mood, fluent speech, good attention and focus, and clear thought process, and he was free of delusions and perceptual abnormalities. He still had residual proteinuria (a protein level of 1+ at 2.5 g/L and a urinary NAG level of 14.5 U/24 hours).

Discussion

Mercury Poisoning: Background, Definition, Physiopathology, and Treatment

The well-known idiom “mad as a hatter” is a story of mercury poisoning, derived from 18th- and 19th-century hat workers who developed psychosis and dementia after chronic exposure to mercury, which was used to stiffen felt (5). In the 1950s and 1960s, large-scale industrial mercury pollution in Minamata Bay, Japan, caused high mercury levels in fish, the main element of the local diet, resulting in newborns with cerebral palsy, epilepsy, deafness, blindness, linguistic deficits, and mental retardation (6). Today, mercury is the second most common form of heavy metal poisoning in the world (7). Our exposure to mercury is wide ranging, according to its three forms: elemental mercury (e.g., part of fossil fuel emissions, thermometers, fluorescent lights, dental amalgams, and mining and smelting sites); inorganic mercury (e.g., minerals used as medicinal additives such as cinnabar and calomel, teething powder, skin whitening creams, and some disinfectants and preservatives); and organic mercury (e.g., pollution-related methylmercury found in larger, long-lived predator fish high up in the aquatic food chain [8] and thimerosal [49% ethylmercury], used as a preservative in vaccines [7]). U.S. and international efforts to lower mercury exposure are notable on several fronts, including the issuing of public advisories (4), the publication of food guidelines for children and pregnant women to avoid risky fish (8), the establishment of global safety standards (9), the implementation of a scheduled elimination of thimerosal from vaccines (10), the banning of mercury in dental amalgam (10), the monitoring of ecosystems (such as the International Mussel Watch Project, in which trace metals and pollutants are monitored by measuring levels in marine bivalves as sentinel organisms [11]), and the monitoring of fish mercury content if over 1 ppm (e.g., shark [average, 1.327 ppm], swordfish [0.95 ppm], and tuna [0.206 ppm] [8, 10]).

The clinical effects of mercury poisoning are highly dependent on the form of mercury compound involved, the route and duration of exposure, and individual factors. Each form of mercury has both specific and general toxicological effects that overlap in multiple organs: elemental mercury mostly damages the pulmonary, dermatological, and peripheral and central nervous systems; inorganic mercury generally affects the renal and gastrointestinal systems; and organic mercury largely harms the peripheral nervous system and CNS, as it readily crosses the blood-brain barrier (5, 7). Mr. X’s mercury exposure was an inorganic salt (calomel), an additive to his herbal remedy. He had renal and peripheral nervous system symptoms in the early phase, but over time methylation of inorganic mercury by intestinal micro-organisms produces methylmercury, which caused Mr. X’s CNS effects (7). Clinicians need to have a high level of awareness of mercury’s multisystem effects.

Mercury’s neuropsychiatric toxicities largely involve mercuric mercury (Hg²⁺), which is formed through demethylation of methylmercury once it crosses the blood-brain barrier (7, 12). At the cellular level, Hg²⁺ has a high affinity for thiol groups, forming a mercapto group that affects sulfhydryl-containing enzymes and receptors; these in turn cause cell apoptosis, cytoskeleton damage, and an overload of calcium ions and oxygen free radicals in affected areas (13). Neuroanatomically, Hg²⁺ accumulates in the cerebral cortex, cerebellum, basal ganglia, and limbic regions (14). Laboratory and animal studies have shown that Hg²⁺ selectively inhibits synaptic glutamate reuptake, resulting in neurotoxicity (15); causes ion channel, membrane, axonal, and myelin degeneration and growth inhibition; and disrupts neuronal conduction, migration, and cell division. These types of damage correspondingly produce symptoms in cognition, memory, vision, hearing, motor coordination, and muscular control as the disease progresses (13–15). Longitudinal neuropsychological testing also shows significant long-term effects in language, memory, learning, attention, construction, and coordination (16).

Treatment entails first stopping exposure while commencing supportive measures such as hydration, balancing of electrolytes, oxygen therapy, hemodialysis, and blood transfusion. The second step is mercury removal, mainly through chelation, employing DMPS or DMSA (meso-2,3-dimercaptosuccinic acid), and through natural excretion (7, 14).

Neuropsychiatric Problems From Mercury Poisoning: Avoiding Diagnostic Confusion

The significance of neuropsychiatric symptoms of mercury poisoning, such as insomnia, excessive dreaming, fatigue, weakness, memory loss, irritability, and feeling easily overwhelmed, may be easily missed by psychiatrists, as these symptoms can be easily confused with general neurotic or somatization problems (17). Early neurological symptoms are also diverse and nonspecific, typically involving sensory and fine motor disturbances, such as pain and a burning sensation in the limbs, paroxysmal muscle fasciculation, glove-and-stocking paresthesia, and a decrease in sensations (16, 17). Further progression will feature anxiety, depression, excitability, personality changes, delirium, hallucinations, and seizures—a syndrome called “erythrism” (5, 17).

Mr. X’s case was unusual, as his initial presentation to the emergency department showed few classic symptoms of mercury poisoning (17). He was “cleared” and sent to a psychiatric hospital with a diagnosis of psychosomatic disorder. Complicating the picture was the fact that treatment with antidepressants improved Mr. X’s pain. The positive outcome seemed to justify the initial diagnoses, so continuing this course was less likely to be questioned. As the patient’s symptoms progressively changed and worsened—with more neurological findings, severe lethargy, somatic distortions, delusions, delirium, and a host of sleep-related abnormalities—it became imperative to pursue other etiologies. Psychiatrists’ general exposure to cases of mercury poisoning is limited, and therefore awareness tends to be low. Also, Mr. X’s symptoms were diverse and collectively did not correspond clearly to any well-known psychiatric or neurological condition. In particular, the sleep-related abnormalities were distractingly bizarre and were not typically associated with mercury poisoning. This led to misdiagnoses of sleep or epileptic disorders.

Importance of Routine Screening for Alternative Medicine Use

Adding mercury minerals such as cinnabar (mercury sulfide, HgS) and calomel (mercurous chloride, Hg₂Cl₂) to traditional herbal remedies for treatment of psoriasis, eczema, and dermatitis and for detoxification is common in Chinese, Tibetan, and Ayurvedic medicine (18). The Chinese Pharmacopoeia describes mercury as a toxic compound with topical medicinal utility, but not typically ingested as a decoction and not used for long (19). The high mercury content of the ingestible decoction Mr. X was consuming (in the form of Hg₂Cl₂) was an unethical violation to gain effectiveness at the cost of patient safety. In the authors’ review of 69 reported cases of mercury poisoning caused by Chinese herbal medications in China, the vast majority were attributed to inappropriate addition of calomel to treat psoriasis, sexually transmitted diseases, arthritis, and other diseases, causing neurological, hepatic, and renal damage (20, 21). Beyond Asia, some Brazilian herbal folk medicines are known to have a high mercury content (22). Sources of mercury contamination in these herbal medicines may come from all points of production, from polluted growing soil or irrigation to mercury-based fertilizers, pesticides, and preservatives.

Conclusions

Mercury poisoning comes from a wide variety of sources. This case highlights the importance of paying attention to this possibility when encountering unusual somatic and neuropsychiatric presentations. Having knowledge and a high index of awareness and screening for mercury exposure, particularly in herbal medicines, should be incorporated as part of good practice, particularly with Asian and South American patients.