CASE REPORTS
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Paraneoplastic Isaacs' syndrome: a case series and review of the literature.

OBJECTIVE: Isaacs' syndrome is a rare disease resulting from hyperexcitability of peripheral nerves causing continuous muscle fiber activity characterized by muscle twitching and stiffness at rest and delayed muscle relaxation after voluntary contraction. Our objective was to discuss the relationship of Isaacs' syndrome to paraneoplastic syndromes as reported in the available literature and in 3 patients evaluated at our academic medical center.

METHODS: We review the literature on Isaacs' syndrome and describe 3 patients in whom Isaacs' syndrome heralded underlying malignancy or benign neoplasm, including their presenting symptoms, electrophysiologic findings, and laboratory and pathology results.

RESULTS: In all 3 cases, clinical and electrodiagnostic testing was suggestive of Isaacs' syndrome. Two patients tested positive, and one was negative for voltage-gated potassium channel antibodies. Two of the patients developed malignant tumors, that is, one was diagnosed with metastatic thymoma and one with lymphoplasmacytic lymphoma, ranging from 6 months to 1 year after the diagnosis of Isaacs' syndrome. One patient was diagnosed with a spinal cord hemangioblastoma 5 years after he was diagnosed with Isaacs' syndrome.

CONCLUSIONS: Our case series highlights the association of Isaacs' syndrome with a variety of neoplasms both malignant and benign. Our report also underscores the fact that Isaacs' syndrome may be diagnosed several years before a neoplasm is discovered. In our cases, Isaacs' syndrome overlapped with other neuromuscular disorders, that is, myasthenia gravis in a patient with thymoma and chronic inflammatory demyelinating polyneuropathy in a patient with lymphoplasmacytic lymphoma with paraproteinemia. To our knowledge, this is the first report of an association between Isaacs' syndrome with lymphoplasmacytic lymphoma and a spinal cord hemangioblastoma.

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