What are the potential causes of sudden altered sensorium in a patient with ovarian adenocarcinoma and hydrothorax?

Altered Sensorium in Ovarian Adenocarcinoma with Hydrothorax: Differential Diagnosis

In a patient with ovarian adenocarcinoma and hydrothorax presenting with sudden altered sensorium, prioritize evaluation for brain metastases, metabolic derangements (particularly hypercalcemia and hyponatremia), hypoxemia from pleural effusion, and paraneoplastic limbic encephalitis, as these represent the most life-threatening and treatable causes.

Primary Neurological Causes

Brain Metastases

• High-grade serous ovarian carcinoma demonstrates considerable genetic instability and aggressive biological behavior, making CNS metastases a critical consideration 1
• Stage IV disease with pleural effusion indicates advanced metastatic potential, increasing the likelihood of intracranial involvement 1
• Obtain urgent brain imaging (MRI with contrast preferred over CT) to exclude parenchymal metastases, leptomeningeal disease, or hemorrhage into metastatic lesions

Paraneoplastic Encephalitis

• Paraneoplastic limbic encephalitis must be excluded in ovarian cancer patients with cognitive impairment or altered mental status 1
• This represents an immune-mediated process that can occur independently of direct metastatic involvement
• Consider anti-neuronal antibody testing if imaging is negative and metabolic causes are excluded

Metabolic and Systemic Causes

Hypoxemia and Hypercapnia

• Hydrothorax in advanced ovarian cancer produces respiratory symptoms and can lead to significant hypoxemia 1
• Pleural effusion severity directly correlates with gas exchange abnormalities
• Obtain arterial blood gas analysis immediately; consider urgent thoracentesis if respiratory compromise is present

Electrolyte Disturbances

• Hypercalcemia occurs frequently in advanced malignancy and presents with altered mental status, confusion, and lethargy
• Hyponatremia from SIADH (syndrome of inappropriate antidiuretic hormone) is common in malignancy with pleural effusions
• Measure serum calcium, sodium, magnesium, and glucose urgently
• Correct severe abnormalities (calcium >14 mg/dL, sodium <120 mEq/L) emergently with appropriate protocols

Hepatic Encephalopathy

• Peritoneal and omental metastases can cause hepatic dysfunction 1
• Ascites in advanced disease may indicate hepatic involvement
• Check liver function tests, ammonia level, and assess for asterixis

Uremia

• Hydronephrosis from pelvic mass compression or ureteral obstruction can cause acute kidney injury 1
• Measure serum creatinine, BUN, and obtain renal ultrasound if creatinine is elevated

Infection-Related Causes

Sepsis and Meningitis

• Immunosuppression from chemotherapy increases infection risk
• Fever, leukocytosis, or hemodynamic instability warrant blood cultures and consideration of lumbar puncture (after excluding mass lesions)
• Infected pleural effusion (empyema) can cause systemic toxicity and altered mental status

Medication and Treatment-Related Causes

Chemotherapy Toxicity

• Post-chemotherapy cognitive impairment (PCCI) typically presents gradually, but acute neurotoxicity from platinum-based agents or other chemotherapeutics can occur 1
• Review recent chemotherapy administration timing and agents used
• Consider posterior reversible encephalopathy syndrome (PRES) if recent bevacizumab or other anti-angiogenic therapy

Opioid Toxicity

• Pain management in advanced cancer often involves opioids
• Accumulation in renal dysfunction or drug interactions can cause acute delirium
• Check medication list and consider naloxone trial if opioid overdose suspected

Vascular Causes

Cerebrovascular Events

• Hypercoagulability in malignancy increases stroke and venous thrombosis risk
• Obtain brain imaging to exclude ischemic or hemorrhagic stroke
• Consider cerebral venous sinus thrombosis, particularly if headache is present

Critical Diagnostic Algorithm

Immediate evaluation (within 1 hour):

• Vital signs including oxygen saturation
• Fingerstick glucose
• Arterial blood gas if oxygen saturation <92%
• Comprehensive metabolic panel (sodium, calcium, creatinine, liver enzymes)
• Complete blood count
• Brain CT without contrast (emergent if focal neurological signs present)

Urgent evaluation (within 4-6 hours):

• Brain MRI with contrast if CT negative and patient stable
• Chest radiograph to assess pleural effusion size
• Ammonia level if hepatic dysfunction suspected
• Blood cultures if fever or sepsis suspected
• Medication review for neurotoxic agents

Subsequent evaluation (within 24 hours if above negative):

• Lumbar puncture (after excluding mass effect) for CSF analysis including cytology
• Paraneoplastic antibody panel
• EEG if seizure activity suspected
• Thyroid function tests

Common Pitfalls to Avoid

• Do not attribute altered sensorium solely to "cancer-related fatigue" without excluding reversible causes 1
• Do not delay brain imaging in favor of metabolic workup when focal neurological signs are present
• Do not perform lumbar puncture before brain imaging in patients with known metastatic disease due to risk of herniation
• Failing to recognize that hypoxemia from large pleural effusions can cause acute confusion before respiratory distress becomes clinically obvious 1
• Dismissing subtle electrolyte abnormalities (calcium 11-12 mg/dL) that can cause significant neurological symptoms in cancer patients
• Overlooking medication-induced delirium, particularly in elderly patients with renal impairment receiving renally-cleared drugs 1

Prognosis and Management Implications

• Reversible causes (metabolic derangements, infection, medication toxicity) should be aggressively corrected as they significantly impact quality of life 1
• Brain metastases in ovarian cancer may respond to radiation therapy or surgical resection in selected cases
• Paraneoplastic syndromes may improve with treatment of underlying malignancy or immunosuppression
• Large pleural effusions causing hypoxemia require therapeutic thoracentesis or pleurodesis to improve both respiratory function and mental status 1