[Holmes tremor as the initial manifestation of EGFR mutated lung cancer]

Lung cancer is the leading cause of cancer-related death worldwide. In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are predictive biomarkers of a high response to tyrosine kinase inhibitors (TKIs). Osimertinib is the TKI of choice due to its efficacy in controlling central nervous system disease. Holmes tremor is a low-frequency, irregular tremor that may occur at rest, posturally, or during action. The lesions causing this syndrome are not confined to a single brain region but involve functionally connected circuits. Its occurrence secondary to brain metastases is rare, and response to osimertinib has not been previously reported. We present the case of a 35-year-old, nonsmoking woman with stage IVB NSCLC harboring an EGFR exon 19 mutation and brain and bone metastases. During the course of her illness, she developed a progressive upper-extremity and head tremor consistent with Holmes tremor. She was treated with dexamethasone and whole-brain radiotherapy. Following initiation of osimertinib, marked clinical improvement was observed within 4 weeks. Ninety days later, a brain MRI demonstrated partial remission of the lesions. Holmes tremor is a heterogeneous clinical entity, and its management typically relies on nonspecific medications with variable efficacy. This case represents, to our knowledge, the first reported instance of Holmes tremor associated with EGFR-mutated NSCLC showing a favorable response to osimertinib.