Self-Reported Neurological Clinical Manifestations of Metal Toxicity in Metal-on-Metal Hip Arthroplasty

Abstract

Adverse reactions to metal particle debris have been increasingly reported as a complication following large head metal-on-metal (MoM) hip arthroplasty. Elevated metal ion levels are a cause for concern. The aim of this study is to evaluate whether exposure to cobalt is associated with patient characteristics and symptoms of neuropathy, representing nervous system dysfunction. A cross-sectional study was conducted comparing patients with a MoM total hip arthroplasty and patients with a conventional hip arthroplasty. They received three questionnaires, one to assess neurotoxic complaints and two standardised self-administered questionnaires to identify symptoms that are suggestive of peripheral neuropathy. Current and historical data were available for whole blood cobalt levels in all patients. We analysed potential predictive factors for cobalt based on five different cut-off levels (0-2, 2-4, 4-10, 10-20, >20 µg/L). We performed 723 MoM total hip arthroplasties in 643 patients in our clinic. The response rate was 89%. Male-female ratio was 236/280, median age 63.6 years (30-72) with a mean follow-up of 50.6 months (20-86). We also sent the questionnaires to 98 patients in the control group. An increase in the incidence of reported symptoms was not consistent with higher serum cobalt levels. Female gender was the only consistent predictive factor for serum cobalt at different cobalt cut-off levels in the multivariate analysis. The study population did not show an increase in reported symptoms with elevated cobalt levels. Neurotoxic symptoms and whole blood cobalt levels did not show a consistent relationship with different dichotomised levels of cobalt exposure.

Self-Reported Neurotoxic Symptoms in Hip Arthroplasty Patients With Highly Elevated Blood Cobalt: A Case-Control Study

“…The NSC-60, DNS, and DN-10 were previously used to assess the prevalence of systemic cobalt toxicity in Dutch MoM patients. 20,21 Van der Straeten and colleagues 20 noted a significant correlation between increasing blood cobalt levels and frequency of neurotoxic symptoms. The highest prevalence of adverse effects was found in the Co > 20 μg/L group, with female sex and age <50 years acting as confounders.…”

Assessing the Clinical Value of Objective and Patient-Reported Audiovestibular Outcome Measures in the Risk Estimation of Systemic Cobalt Toxicity for Patients With a Metal-on-Metal Hip Implant

“…However, it should be noted that the distribution of blood Co levels in the MoM patient group was strongly right-skewed, resulting in unbalanced comparisons of the lowexposure (n = 44) and high-exposure subgroups (n = 6), which limits the statistical power and may have imposed a type II error. Nevertheless, as mentioned before, the conflicting findings on the dose-response relationship of Co-induced local and systemic toxicity in the available literature (Paustenbach et al 2014;van Lingen et al 2014;Grammatopoulos et al 2017;Ho et al 2017;Lehtovirta et al 2018;Jelsma et al 2020;Leyssens et al 2017Leyssens et al , 2020Leyssens et al , 2021b underline the influence of patientspecific factors in this process (Leyssens et al 2017;Kovochich et al 2019). Hence, blood metal ion measurements should be combined with other clinical investigations and proactive symptom inquiry to appraise a patient's risk for local and/or systemic Co toxicity and assess the need for revision surgery (Chalmers et al 2016;Zywiel et al 2016;Grammatopoulos et al 2017;Kovochich et al 2019;Law et al 2020).…”

“…The past two decades, several case reports and small cohort studies have been published of patients with presumed systemic Co toxicity related to their MoM hip implant. Although the majority of these cases exhibited severely elevated blood Co levels (>20 µg/l), the measured values cover a very wide range (Bradberry et al 2014;Gessner et al 2019;Zywiel et al 2016) and the existing literature displays conflicting evidence on the dose-response relationship between Co exposure and both local and systemic toxicity (Paustenbach et al 2014;van Lingen et al 2014;Grammatopoulos et al 2017;Ho et al 2017;Jelsma et al 2020;Lehtovirta et al 2018;Leyssens et al 2017Leyssens et al , 2020Leyssens et al , 2021b. This implies that patient-specific factors alter the individual susceptibility for and clinical presentation of the condition, which has hampered a widespread establishment of a "threshold Co level" above which toxic effects are likely to arise (Leyssens et al 2017;Kovochich et al 2019).…”

Cytotoxicity of cobalt chloride in brain cell lines - a comparison between astrocytoma and neuroblastoma cells

“…More specifically, neurological symptoms associated with cobaltism include memory loss, cognitive decline, progressive deafness, atrophy of the optical nerve, retinopathy, vertigo, peripheral neuropathy (Catalani et al, 2012), fatigue, depression, and ataxia (Mao et al, 2011). Despite the several medical reports citing neurological symptoms as a result of high Co levels due to MoM implants (Green et al, 2017;Mao et al, 2011;Rizzetti et al, 2009;Tower, 2010), a couple of recent observational studies looking for this association have failed to confirm a relationship between cobaltism and neurological symptoms in MoM patients (Kavanagh et al, 2018;Van Lingen et al, 2014). They reported difficulties with regards to low number of patients with high levels of cobalt in blood (Van Lingen et al, 2014), in addition to deficient case descriptions (Kavanagh et al, 2018).…”

“…Despite the several medical reports citing neurological symptoms as a result of high Co levels due to MoM implants (Green et al, 2017;Mao et al, 2011;Rizzetti et al, 2009;Tower, 2010), a couple of recent observational studies looking for this association have failed to confirm a relationship between cobaltism and neurological symptoms in MoM patients (Kavanagh et al, 2018;Van Lingen et al, 2014). They reported difficulties with regards to low number of patients with high levels of cobalt in blood (Van Lingen et al, 2014), in addition to deficient case descriptions (Kavanagh et al, 2018). Furthermore, in contrast to cardiac signs, neurological symptoms are often downplayed or even go unnoticed as they might be confused with typical signs of ageing.…”