An Enigmatic Case of Acute Mercury Poisoning: Clinical, Immunological Findings and Platelet Function

Abstract

Severe mercury intoxication is very rare in developed countries, but still occurs as the result of volatile substance abuse, suicide attempts, occupational hazards, or endemic food ingestion as reported in the cases of public health disasters in Iraq and in Minamata Bay, Japan. Here, we describe the dramatic physical and cognitive decline of a 23-year-old patient caused by a severe methyl mercury (MeHg) intoxication of unknown origin. We show serial magnetic resonance imaging (MRI) of the patient's brain, as well as ex vivo analyses of blood and cerebrospinal fluid including multicolor flow cytometric measurements, functional assays of hemostaseologic efficacy, and evaluation of regulatory effector molecules. Together with the clinical history, our findings show the progressive neuronal degeneration accompanying the deterioration of the patient. Moreover, the ex vivo analyses display alterations of thrombocyte function and coagulation, as well as an immunological milieu facilitating autoimmunity. Despite the successful reduction of the MeHg concentration in the patient's blood with erythrocyte apheresis and chelator therapy, his condition did not improve and led to a persistent vegetative state. This case illustrates the neurotoxicity of MeHg following severe intoxication for the first time by serial MRI. Data on immune-cell and thrombocyte function as well as on coagulation in mercury poisoning reveal potential implications for anticoagulation and immunomodulatory treatment.

Keywords: brain edema; hemostasis; mercury intoxication; neurotoxicity; vegetative state.

Figure 1

Imaging and (neuro)immunological findings in a young patient with acute mercury intoxication of unknown etiology. (A) Serial magnetic resonance imaging of the brain at indicated time points demonstrating progressive cortical and subcortical atrophy and diffusion restriction, especially in the temporal lobes. (B) Results of lumbar puncture at indicated time points. Left panel: Total numbers of cerebrospinal fluid (CSF)-derived cells (red) and protein (blue) levels are depicted. Dotted lines indicate the mean ± SD of 25 control patients with somatoform disorders. Right panel: CSF-derived cells were stained for flow cytometric analysis using fluorochrome-conjugated monoclonal antibodies. Following acquisition, CD3⁺CD56⁻ T cells were further subdivided into CD4⁺ (blue) and CD8⁺ (red) and analyzed for the expression of the activation marker HLA-DR.

Figure 2

Immune-cell function in acute mercury poisoning. Ex vivo analyses of peripheral blood mononuclear cells of the patient were performed in comparison to respective healthy controls (Ctrl; N = 4, mean ± SD). [(A)—left] The frequencies of CD4⁺CD3⁺HLA-G⁺ and CD4⁺CD3⁺Foxp3⁺ regulatory T (T_reg)-cell subsets were determined by flow cytometric analysis. [(A)—right] Furthermore, expressions of FoxP3⁺Helios⁺ and FoxP3⁺CD39⁺ on CD4⁺CD25⁺CD127^low T_reg cells were assessed. (B) Levels of CD40, CD80, CD83, CD86, CD87, and MHC-II on CD1c⁺CD11c⁺CD11b⁺CD19⁻ dendritic cells are shown (right). FI, fluorescence intensity.

Figure 3

Blood count and hemostaseologic response in acute mercury poisoning of unknown origin. (A) Red blood cells (RBC), hemoglobin (Hb), and hematocrit (HCT) of the patient are shown in comparison to a respective healthy control (Ctrl). (B) The patient’s endogenous thrombin potential (ETP) level was determined in relation to Ctrl. (C) Flow cytometric analysis of agonist [adenosine diphosphate (ADP)- and collagen]-induced binding of soluble fibrinogen to platelets from patient vs. Ctrl. (D) Flow cytometric analysis of agonist (ADP and collagen)-induced binding of soluble fibrinogen to control platelets in presence of high 2,3-dimercapto-1-propanesulfonate (DMPS) doses. AU, arbitrary units.