Autoimmune Isaac’s Syndrome With CASPR2 Antibodies Secondary To Mercury Toxicity
Anooshah Ata1, Nadia Khalil2, Neena Viswanathan2, Sanita Raju2, Anthony Bradshaw2, Rebecca Hurst2, Alfred Frontera2
1University of South Florida Morsani College of Medicine, University of South Florida Morsani College of Medicine, 2University of South Florida Morsani College of Medicine
Background:
A 21-year-old man with no significant past medical history presented with one month of acute-onset fasciculations, most pronounced in the bilateral lower extremities with lesser involvement of the upper extremities, abdomen, chest, and face. Additional symptoms included generalized hyperhidrosis, insomnia, low back pain, and painful carpopedal spasms. Neurological exam was notable for continuous fasciculations and myokymia involving the proximal and distal lower extremities and abdominal wall, mild proximal weakness (MRC grade 4/5), and generalized hyperreflexia including bilateral palmomental reflexes. Initial labs revealed an elevated CPK level of 806 and negative UDS. MRI neuroaxis and malignancy screening with CT chest, abdomen, and pelvis were unremarkable. EMG demonstrated widespread fasciculation potentials, doublets, and myokymic discharges with normal motor unit recruitment and morphology. Isaac’s syndrome was clinically suspected, and he was empirically treated with plasmapheresis. Carbamazepine, tizanidine, and gabapentin were started for symptomatic management in addition to glycopyrrolate for his hyperhidrosis. During his hospitalization, a urine mercury level returned elevated at 123 (RR < 20 ug/L) and a serum paraneoplastic panel was positive for CASPR2 antibodies with borderline positive LGI1 and negative VGKC antibody. In retrospect, the patient recalled breaking an old mercury thermometer in his home two months prior to symptom onset. The carpet in his home was removed and chelation therapy with succimer was initiated with gradual reduction in serum and urine mercury levels. Upon follow-up evaluation one month later, his symptoms were markedly improved.
Conclusions:
Isaac’s syndrome resulting from mercury toxicity has rarely been described and is thought to be secondary to triggered autoimmunity. Symptoms typically improve with chelation therapy and supportive management, though plasmapheresis may be required for refractory symptoms. This case highlights the importance of screening for heavy metal toxicity in patients presenting with peripheral nerve hyperexcitability syndromes to prevent delays in diagnosis and treatment.