Abstract
Silver toxicity is a rare condition. The most notable feature is a grey-blue discoloration of the skin, argyria, although harmful effects on the liver and kidney may be seen in severe cases. Neurological symptoms are an unusual consequence of silver toxicity. So far no effective treatment has been described for this metal overdose. We report the case of a 75-year-old man who had a history of self-medication with colloidal silver and presented with myoclonic seizures.
Case
A 75-year-old male, former electronic engineer, was admitted to hospital with fever, a chest infection and myoclonic seizures. He had a four-year history of a gradually progressive neurodegenerative disorder characterized by asymmetrical parkinsonism and myoclonic jerks initially affecting the left upper limb. There had been some progression of the akinetic-rigid symptoms to the right side and he had developed some alien limb phenomena in the left arm accompanied by a prominent grasp reflex. On the basis of these clinical findings, a diagnosis of corticobasal degeneration had been made. Although he had been treated with a combination of dopamine agonists and levodopa, there had been little clinical response. In the 12 months prior to this admission, he had increasing difficulty swallowing and was hospitalized on several occasions with probable aspiration pneumonia. Other significant past medical history included ischaemic heart disease, mild asthma and non-insulin-dependent diabetes mellitus. His medications at presentation included co-beneldopa (levadopa and benserazide), ropirinole, simvastatin, aspirin and ramipril.
At admission to hospital, signs of a highly asymmetric (predominantly left sided) akinetic-rigid syndrome were confirmed. In addition, frequent and sustained myoclonic jerky movements of the left upper limb were noted. There were signs of a right-sided lower respiratory tract infection but examination of the cardiovascular and gastrointestinal systems were essentially unremarkable. An inconsistent failure of ocular pursuit movements was noted later in the course of his admission and apart from his dysphagia, no other cranial nerve abnormalities were apparent. There was no pyramidal weakness and there was no discoloration of the patient's skin. The sclerae and mucosae were normal in appearance.
A series of analytical investigations were performed. The majority were within reference ranges except for the serum selenium of 0.58 μmol/L (reference range: 0.89–1.65). A chest X-ray confirmed that there was patchy air space and peribronchial shadowing in the right mid and upper zones consistent with infective change. The results of computed tomography of the head showed generalized brain volume loss and mild periventricular chronic ischaemic changes. Magnetic resonance imaging of the brain showed changes consistent with moderate global cerebral atrophy, with more pronounced widening of parietal sulci. Signal changes were noted in the pons and the posterior deep white matter, consistent with small vessel ischaemic disease.
During his inpatient stay, myoclonic seizures were observed repeatedly by the hospital staff taking care of him. Further questioning of his wife on his use of alternative medicine practices revealed that he had irregularly ingested several spoons of colloidal silver up to four times a day for the last four years. The patient was convinced that the colloidal silver had ‘antibiotic’ properties and he employed this treatment ‘whenever he felt a cold coming on’. He prepared the silver solution himself by an electrolytic process, placing bars of silver in water and running an electronic current through it to suspend the silver in solution. The silver concentration in a preparation of the fluid found at his home was 477 μmol/L (51.4 mg/L). One week after admission, the concentration of silver in serum was 628.3 nmol/L (67.7 μg/L) (reference range <2.8 nmol/L). After five weeks of hospitalization, excretion of silver in urine was 10.6 nmol/24 h (reference range <7.42 nmol/L).
After two months of hospital treatment, his aspiration pneumonia had been successfully treated with antibiotics and his myoclonus controlled with clonazepam. He was discharged to a nursing home. He was advised to discontinue ingesting the silver fluid preparation.
The patient was followed up 10 months later. The serum silver concentration remained high at 111.4 nmol/L (12.01 μg/L) (reference range <2.8 nmol/L). The serum selenium concentration was 0.66 μmol/L (reference range: 0.89–1.65).
Discussion
This patient presented as an emergency with an aspiration pneumonia and worsening neurological sequelae of what was thought to be corticobasal degeneration. The discovery of possible silver toxicity was unexpected, as the patient had no signs suggestive of argyria, or any typical systemic indications of acute intoxication, e.g. anorexia, weakness, loss of weight, anaemia or respiratory depression. The sequence of symptoms, i.e. the onset of neurological abnormalities following the commencement of colloidal silver ingestion, suggests a causal relationship, although it remains possible that the association was coincidental. The chronic presentation was confirmed by raised silver and persistently low selenium concentrations in the blood.
Presentation with non-specific neurological symptoms has been reported before in cases of silver toxicity. Mirsattari et al. 1 described a patient with colloidal silver-induced status epilepticus and who developed paralysis, coma and myoclonic jerks. He died approximately nine months after commencing daily self-medication and five months after onset of symptoms. Silver deposition in the grey matter of his cerebellum, and in blood and CSF, was revealed when specimens were analysed by high-resolution inductively coupled plasma mass spectrometry. Convulsive seizures were described in a patient with schizophrenia, who had used silver antismoking pills for 40 years. 2 In another case, a patient using drops for tongue ulcers developed argyria and manic-depressive psychosis. At autopsy, silver deposits were demonstrated in many parts of her central nervous system (CNS), principally the choroid plexus, basal ganglia, hypothalamus, substantia nigra and cerebellum. 3 People presenting with argyria due to chronic industrial exposure to silver have complained of headaches, tiredness and anxiety. 4
Although silver toxicity is uncommon, 5 it has been shown in animal studies 6 and in humans 7 that silver ions can penetrate the blood–brain barrier. However, it has not been proven that accumulation of silver ions is directly toxic to the CNS. 8 Almost 30 years ago experimental studies on animals clearly demonstrated the deposition of silver in the neurons of the globus pallidus, brainstem, spinal cord, basal ganglia, cerebellum (deep nuclei) and trigeminal nerve in rats. 9 On the basis of their experimental results, these authors hypothesized that patients with chronic silver exposure and argyria, who present with loss of coordination, cerebellar ataxia, convulsions and electroencephalograph changes, would have silver sulphide deposition throughout the brain. 9 However, a link between neurological presentation and pathological structural changes in the CNS has not been verified.
To our knowledge, this is the first report of corticobasal degeneration and myoclonic seizures associated with high levels of silver in serum. Our case differs from a previous report of myoclonic seizures in association with silver ingestion, 1 where the patient had used a homemade colloidal silver for four months. Our patient developed a slowly progressive neurodegenerative disorder over a period of four years, the onset of his symptoms following the commencement of his self-medication with a colloidal silver preparation.
Another novel feature of this case is the low serum selenium concentration. Silver inhibits the activity of the selenoprotein glutathione peroxidise in the liver tissue as shown in in vitro studies by binding selenium and thus inducing selenium deficiency. 10 Moreover, it has been reported in experimental tests that selenium reduces the cytostatic effect of silver and delays the silver-induced liver necrosis triggered by glutathione peroxidase inhibition. 11,12 Selenium antagonizes silver ions and causes accumulation of silver in nanocrystals in the brain tissue 12–14 that would suggest its potential as an antidote for silver intoxication. Finally, silver ions are believed to be toxic until they are bound to functional groups and finally deposited in silver-sulphur/silver-selenium compounds. 14
It should be noted that selenium deficiency-related seizures have been described in children 15 and that antioxidant depletion in the elderly may be associated with cognitive impairment. 16
The hypotheses based on results from experimental studies could explain the low level of selenium in our patient. Low serum selenium is seen in the presence of infection, but in this patient the selenium concentration remained low after recovery from the infection. It suggests that selenium ions were deposited as silver selenide compounds in tissues. Raised silver concentration long after the patient abstained from colloidal silver preparation indicates the constant release of these ions from the tissue pools.
The current knowledge on the clinical aspect of silver neurotoxicity is still incomplete. The rarity of diagnosed silver neurotoxicity merits detailed clinical investigation in patients who have ingested silver salts.
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