What is the cause of facial twitching in a patient with a history of breast cancer, currently on exemestane (aromatase inhibitor) and rivaroxaban (anticoagulant), and how should it be managed?

Facial Twitching in Metastatic Breast Cancer Patient on Exemestane and Rivaroxaban

The facial twitching in this patient is most likely due to brain metastases or metabolic derangements (particularly electrolyte abnormalities from disease progression), and requires urgent neuroimaging and metabolic workup, as neither exemestane nor rivaroxaban are known to cause facial twitching as a direct adverse effect.

Primary Differential Diagnosis

Brain Metastases (Most Likely)

• Progressive metastatic breast cancer with lymphangitis carcinomatosis indicates advanced disease burden, making CNS involvement highly probable 1
• Facial twitching (hemifacial spasm or focal seizures) is a common presenting sign of brain metastases
• Urgent brain MRI with contrast is mandatory to evaluate for parenchymal or leptomeningeal disease

Metabolic Derangements

• Cancer patients with progressive disease frequently develop electrolyte abnormalities that can cause neuromuscular irritability and twitching 1
• Check immediate comprehensive metabolic panel including:
  • Calcium (hypocalcemia or hypercalcemia from bone metastases)
  • Magnesium (hypomagnesemia is common and causes fasciculations)
  • Sodium (hyponatremia from SIADH or other causes)
  • Potassium levels 1

Thromboembolic Complications

• Given history of pulmonary embolism and current anticoagulation, consider cerebral venous sinus thrombosis or arterial stroke despite rivaroxaban 1
• Breast cancer patients have significantly elevated thrombotic risk even on anticoagulation 1
• Brain imaging will evaluate for acute ischemic or hemorrhagic events

Medication Review

Exemestane-Related Considerations

• Exemestane (aromatase inhibitor) is not associated with neurological symptoms such as facial twitching in clinical trials 2, 3, 4
• Most common adverse effects are hot flushes, nausea, and fatigue consistent with estrogen suppression 3, 5
• Exemestane has excellent tolerability profile with rare discontinuation due to adverse events 3

Rivaroxaban-Related Considerations

• Direct oral anticoagulants like rivaroxaban are appropriate for cancer-associated thromboembolism, though LMWH remains preferred first-line 1
• Rivaroxaban does not cause facial twitching as a known adverse effect
• However, must consider intracranial bleeding risk in metastatic cancer patient on anticoagulation 1

Immediate Diagnostic Workup

Neuroimaging (Urgent)

• Brain MRI with and without gadolinium contrast to evaluate for:
  • Parenchymal brain metastases
  • Leptomeningeal carcinomatosis
  • Intracranial hemorrhage (given anticoagulation)
  • Cerebral venous or arterial thrombosis 1

Laboratory Evaluation

• Comprehensive metabolic panel with calcium, magnesium, phosphate 1
• Complete blood count (thrombocytopenia increases bleeding risk on anticoagulation) 1
• Thyroid function tests (patient on levothyroxine; hypothyroidism can cause neuromuscular symptoms)
• Consider parathyroid hormone if calcium abnormal

Additional Considerations

• Electroencephalogram (EEG) if seizure activity suspected based on twitching characteristics
• Neurology consultation for focal neurological examination

Management Algorithm

If Brain Metastases Confirmed

• Immediate oncology and radiation oncology consultation
• Consider corticosteroids (dexamethasone) for cerebral edema
• Evaluate anticoagulation risk-benefit given intracranial disease 1
• Whole brain radiation therapy or stereotactic radiosurgery depending on number and location of lesions

If Metabolic Abnormality Identified

• Correct electrolyte disturbances aggressively 1
• Magnesium supplementation if hypomagnesemia (common in cancer patients)
• Calcium correction if abnormal
• Address underlying cause of metabolic derangement

If Thromboembolic Event

• Therapeutic anticoagulation should continue unless contraindicated by bleeding 1
• LMWH may be superior to rivaroxaban in active malignancy setting 1
• Anticoagulation should continue as long as active malignancy present 1

Critical Pitfalls to Avoid

• Do not attribute new neurological symptoms to medication side effects without excluding structural or metabolic causes in advanced cancer patients 1
• Do not delay neuroimaging—brain metastases require urgent intervention
• Do not discontinue anticoagulation without careful risk-benefit analysis, as cancer patients have 6-fold higher VTE risk 1
• Do not overlook electrolyte abnormalities which are extremely common in progressive cancer with nausea, vomiting, or decreased oral intake 1