By Marcello Cherchi, MD PhD
For patients
Heavy metals (such as arsenic, cadmium, lead, mercury and thallium) are found naturally in the environment in very small amounts. If they are concentrated and consumed by humans, they can cause damage to various body parts, including the brain and nerves. Poisoning by some heavy metals can cause problems with hearing and equilibrium, and your doctor may check for this. Confirmation of heavy metal poisoning, and treatment of this problem, is usually done by a medical toxicologist.
For clinicians
Toxicity to humans from heavy metals is largely the consequence of industrial activity that results in accidental environmental contamination and subsequent human exposure through air, water and food. Less commonly, heavy metal exposure results from intentional poisoning (such as arsenic or thallium). There is no uniformly accepted definition of heavy metals, but the most medically relevant elements are usually cited as arsenic, cadmium, lead, mercury and thallium. Otoneurological effects of heavy metal toxicity are non-specific (with the possible exception of impaired vertical optokinetic nystagmus in mercury toxicity), so these diagnoses are more likely to be suspected from the history and laboratory tests (such as serum markers). If heavy metal toxicity is suspected, a medical toxicology consultation is appropriate.
Definitions
Toxicity to humans from heavy metals is largely the consequence of industrial activity that results in accidental environmental contamination (Tchounwou et al. 2012) and subsequent human exposure through air, water and food (Balali-Mood et al. 2021). Less commonly, heavy metal exposure results from intentional poisoning (such as arsenic or thallium).
There is no uniformly accepted definition of heavy metals. The most medically relevant elements are usually cited as arsenic, cadmium, lead, mercury and thallium.
Arsenic
Clinicians occasionally encounter cases of intentional arsenic poisoning. The mechanisms of injury from arsenic toxicity are thought to include damage of capillary endothelium, thiol binding, uncoupling of oxidative phosphorylation (interfering with ATP synthesis) and disruption of neurotransmitter homeostasis (Balali-Mood et al. 2021).
Reported otoneurological symptoms of arsenic toxicity can include bilateral sensorineural hearing loss, tinnitus, and disequilibrium (Suo et al. 2024). Reported ocular motor findings in arsenic toxicity include up beat nystagmus on upward gaze (Nakamagoe et al. 2013; Nakamagoe et al. 2006).
Other clues to the diagnosis of arsenic toxicity include pancytopenia, dermatological abnormalities, hepatic and renal failure (Balali-Mood et al. 2021).
Cadmium
On 12/15/22 Consumer Reports published an article (https://www.consumerreports.org/health/food-safety/lead-and-cadmium-in-dark-chocolate-a8480295550/, last accessed on 9/14/24) documenting the presence of cadmium in several brands of chocolate. In response to that article patients began asking us about the relationship between cadmium and disequilibrium.
The mechanisms of injury in cadmium toxicity are thought to include DNA damage (and thus genomic instability), generation of radical oxygen species and thence oxidative stress (Balali-Mood et al. 2021).
As of this writing there are very few studies on the question of otoneurological consequences of cadmium toxicity. Most of the data are from animal studies. The few human studies are inconclusive.
Other clues to the diagnosis of cadmium toxicity include bone degeneration, pulmonary injury and hepato-renal dysfunction (Balali-Mood et al. 2021).
Animal studies on cadmium
The data on the relationship between cadmium and vestibular function comes mostly from animal studies. Most of these are in vitro studies that describe the effects of cadmium on calcium and potassium channel currents in vestibular neurons. A few of these are in vivo studies that report on vestibular function in live animals.
One study reported that in vestibular neurons in mice, in various calcium channel sub-types (L‑, N‑, P‑, Q‑), barium currents were mostly blocked by nifedipine, and the residual current was blocked by cadmium (Desmadryl et al. 1997).
One study of type II vestibular hair cells in guinea pigs identified a cadmium-sensitive inward-flowing calcium current (Rennie and Ashmore 1991).
One study in guinea pigs reported that in type II vestibular hair cells from the saccule, acetylcholine-gated large conductance potassium channels were inhibited by cadmium (Kong et al. 2007). A study of vestibular nerve afferents in rats identified a similar blocking effect of cadmium on voltage-sensitive potassium currents (Ramakrishna and Sadeghi 2020).
One study of lead and cadmium exposure in mice reported that lead caused a decline in vestibular function, whereas cadmium did not (Klimpel et al. 2017).
Human studies on cadmium
There are very few studies in humans, and their results are difficult to interpret as they do not separate the effects of cadmium and lead.
One study of balance in humans reported an inverse relationship between (1) performance on the Romberg test of standing balance on firm and compliant support surfaces, and (2) blood concentrations of lead and cadmium (Min et al. 2012). Note that this study did not separate the levels of cadmium and lead, so it could not ascertain whether any apparent effects were due to one element or the other.
A human study of balance in children reported no relationship to prenatal exposure of cadmium and lead (Taylor et al. 2015).
Lead
Lead toxicity in the pediatric population usually comes to medical attention due to cognitive/behavioral abnormalities and developmental delay.
In adults, lead toxicity more commonly results from acute or acute-on-chronic chemical exposure, including sniffing volatile substances that include compounds such as tetraethyl lead (Cairney et al. 2002).
The mechanisms of injury from lead toxicity are thought to include an increase in inflammatory cytokines (IL-1β, TNF-α, IL-6), increased serum endothelin-1, nitric oxide and eosinophil peroxidase, inactivation of δ-aminolevulinic acid dehydratase and ferrochelatase (interfering with heme biosynthesis), and reduced levels of glutathione, superoxide dismutase, catalase and glutathione peroxidase (Balali-Mood et al. 2021).
From the otoneurological perspective, there are reports of lead exposure manifesting with “nystagmus,” but the available literature from human cases is unfortunately not more descriptive than this (Cairney et al. 2004). Animal studies report impaired post-rotatory nystagmus (Mameli et al. 2001).
Other clues to the diagnosis of lead toxicity include cognitive problems, cardio-pulmonary dysfunction, hepatic dysfunction and anemia (Balali-Mood et al. 2021).
Mercury
Much of the early literature on mercury toxicity arose from studying the consequences of the massive industrial accident in Minamata Bay, Japan, where a chemical factory released methylmercury wastewater into the ocean from the 1930s to the 1960s, and this organic mercury contaminated fish that entered the food chain consumed by humans.
The mechanisms of injury from mercury toxicity are thought to include thiol binding, enzyme inhibition, production of radical oxygen species, reduction of aquaporin mRNA, inhibition of glutathione peroxidase, and increased expression of c-Fos (Balali-Mood et al. 2021).
From the otoneurological perspective, mercury poisoning can manifest with spontaneous and positional nystagmus, and impaired horizontal and vertical optokinetic nystagmus (Mizukoshi et al. 1975; Mizukoshi et al. 1989; Mizukoshi et al. 2002).
Additional clues to the diagnosis of mercury toxicity include other neurological damage, hepato-renal dysfunction, gastrointestinal ulceration, and teratogenicity (Balali-Mood et al. 2021).
Thallium
Thallium poisoning sometimes occurs through consumption of food grown in contaminated soil. Clinicians also occasionally encounter cases of intentional thallium poisoning.
The mechanisms of injury in thallium toxicity are thought o include disruption of sulphhydryl groups on mitochondrial membranes thereby interfering with sodium-potassium ATP-ase (Misra et al. 2003).
There is very little literature on otoneurological effects of thallium. Existing reports only comment on the symptom of “vertigo” (Jimenez et al. 2023) and the presence of “nystagmus” (Misra et al. 2003) without further characterization.
Other clues to the diagnosis of thallium toxicity may include diffuse weakness, painful acral paresthesias, optic neuritis and other cranial nerve dysfunction, choreoathetosis and alopecia. Initially, cases of thallium toxicity are sometimes misdiagnosed as Guillain-Barre syndrome (Cvjetko et al. 2010; Misra et al. 2003).
Final comments
The otoneurological findings in heavy metal toxicity are non-specific (with the possible exception of impaired vertical optokinetic nystagmus in mercury toxicity), so these diagnoses are more likely to be suspected from the history and laboratory tests (such as serum markers). If heavy metal toxicity is suspected, a medical toxicology consultation is appropriate.
References
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