Mercury Poisoning: A Case of a Complex Neuropsychiatric Illness

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).

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.

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.