Mercury poisoning manifesting as concurrent parkinsonism and Morvan’s syndrome: A dual neurotoxic-autoimmune phenomenon

Dear Sir, A 55-year-old hypertensive man with a 1-year history of resting tremors and slowness of movements in the right upper and lower limbs, progressing to severe disability. Over 2 months, he developed insomnia, unprovoked anger outbursts, paranoia, and visual hallucinations, which evolved to full-blown confusion and delirium 10 days before admission. Additionally, he experienced autonomic dysfunction, including urinary hesitancy, dribbling, incomplete evacuation with preserved bladder sensations, and constipation, along with significant weight loss. His medical history included childhood poliomyelitis with residual left leg paralysis and a 2-year history of persistent dry cough treated with native Ayurvedic and Siddha medications [Supplementary Table 1]. On examination, he had confusion, fluctuating systolic blood pressure (90–170 mmHg) and heart rate (60–130 bpm), masked facies, decreased blink rate, and cogwheel rigidity (right > left). He exhibited a high-amplitude 4–5 Hz resting tremor in the right upper and lower limbs, alongside myokymia in the thighs, arms, and abdominal wall [Video 1]. His hemogram, liver, and thyroid function tests were normal. Laboratory findings revealed hyponatremia (124 mEq/L), elevated creatinine kinase (580 U/L), and raised Cerebro Spinal Fluid (CSF) protein (64 mg/dL) with lymphocytic pleocytosis (10 cells/mm³). Post-treatment serum sodium was 138 mEq/L (normal range: 135–145 mEq/L). Heavy metal screening showed elevated mercury levels in blood (10.19 µg/L) and urine (171.6 µg/L). Nerve conduction studies revealed no response in the left peroneal nerve, likely due to post-polio paralysis, while electromyography demonstrated myokymic and neuromyotonic discharges [Figures 1 and 2]. Magnetic resonance imaging of the brain was normal, and electroencephalogram showed diffuse theta-delta slowing. Computed tomography of the thorax and abdomen were normal. Notably, the autoimmune panel, including voltage-gated potassium channel (VGKC) complex antibodies (LGI-1 and CASPR2), was negative. This suggests that the autoimmune pathophysiology in this case may involve alternative or yet unidentified autoantibodies, which aligns with reports of seronegative Morvan’s syndrome (MS). The paraneoplastic panel was negative [Supplementary Table 2]. While the clinical presentation strongly supported Parkinsonism, advanced imaging such as Dopamine Transporter (DaT) scan or F-Dopa Positron Emission Tomography (PET) was not performed due to resource constraints. Future cases may benefit from these modalities to confirm dopaminergic neuron loss. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_xta09iok"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Figure 1: EMG showing myokymic discharges and occasional neuromyotonic dischargesFigure 2: EMG showing myokymic dischargesWe treated the patient with Intravenous Methylprednisolone (1 g/day for 5 days), followed by plasma exchange, resulting in significant improvement in insomnia, neuropsychiatric symptoms, and myokymia. Residual extrapyramidal features partially responded to levodopa–carbidopa 125 mg, half a tablet three times daily. MS is a rare autoimmune disorder associated with VGKC antibodies, characterized by neuropsychiatric symptoms, insomnia, peripheral nerve hyperexcitability, autonomic dysfunction, and hallucinations.[1] This case is unique, as MS presented with an initial and predominant extrapyramidal syndrome, a rare feature in MS that, if present, is mild.[2] The patient’s symptoms were likely driven by mercury toxicity, which can induce direct neurotoxicity manifesting as Parkinson’s disease-like features, as well as provoke autoimmune mechanisms potentially triggering MS. Mercury induces autoimmunity through proinflammatory cytokine expression, abnormal lymphocyte proliferation, and a loss of self-tolerance.[3] Higher doses cause direct neurotoxicity by the ionic form binding to electrophilic groups of target cells,[4] while subtoxic levels may modulate immune responses, potentially leading to autoimmune syndromes like MS. The patient’s improvement with immunosuppressive therapy further supports an autoimmune etiology. Peripheral nerve hyperexcitability syndromes have also been linked to mercury-containing Ayurvedic and Siddha medications.[5] Mercury is implicated in neurodegenerative disorders, as it causes dopamine neuron loss, altered gene expression in dopamine signaling, oxidative stress, excitotoxicity, and mitochondrial dysfunction in the substantia nigra, resulting in Parkinsonian features.[5] To our knowledge, this is the first reported case of concurrent mercury-induced Parkinsonism and autoimmune-mediated MS in the same patient, highlighting mercury’s dual role in neurotoxicity and autoimmunity. Acknowledgement None. Author contribution A. Research project Conception: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Organization: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Execution: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran B. Statistical analysis Design: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Execution: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Review and Critique: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran C. Manuscript preparation Writing of the first draft: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Review and Critique: Pushkar Pazhani, Jayaram Saibaba, Rajeswari Aghoram, Ramkumar Sugumaran Ethical compliance statement The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.