What are the causes of altered sensorium in a female patient with a history of trigeminal neuralgia, who has been on carbamazepine (200mg twice daily), lacosamide (50mg), tolvaptan (once daily), and a buprenorphine patch, and has experienced recurrent episodes of hyponatremia, after stopping carbamazepine and receiving normal saline infusion?

Altered Sensorium After Hyponatremia Correction: Osmotic Demyelination Syndrome

The most likely cause of altered sensorium in this patient after normal saline infusion for hyponatremia is osmotic demyelination syndrome (ODS), also known as central pontine myelinolysis, resulting from overly rapid correction of chronic hyponatremia. 1

Primary Mechanism: Overly Rapid Sodium Correction

• Rapid correction of chronic hyponatremia with normal saline can cause osmotic demyelination syndrome, which manifests as altered sensorium, confusion, dysarthria, dysphagia, and in severe cases, quadriparesis or locked-in syndrome 1

• The risk is highest when serum sodium increases by more than 10-12 mEq/L in 24 hours or 18 mEq/L in 48 hours, particularly in patients with chronic hyponatremia from carbamazepine-induced SIADH 1

• Carbamazepine causes dose-related SIADH with signs including headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness 1

Contributing Medication Factors

Carbamazepine Withdrawal Effects

• Abrupt discontinuation of carbamazepine can precipitate confusion and agitation, particularly in elderly patients, due to its relationship to tricyclic compounds and anticholinergic properties 1

• The FDA label specifically warns that carbamazepine has "mild anticholinergic activity" and notes "the possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation" 1

Lacosamide Cardiac Effects

• Lacosamide combined with carbamazepine can cause high-degree atrioventricular blocks and extreme bradycardia, potentially leading to cerebral hypoperfusion and altered mental status 2

• Voltage-dependent sodium channel blockade from both drugs affects cardiac conduction, with documented cases of complete AV block requiring pacemaker placement 2

Buprenorphine Contribution

• Opioid effects from the buprenorphine patch may compound altered sensorium, particularly if renal function is compromised from hyponatremia or if there are drug-drug interactions with other CNS depressants 1

Differential Diagnoses to Exclude

Ongoing Seizure Activity

• Nonconvulsive status epilepticus must be excluded with urgent EEG, as carbamazepine withdrawal can precipitate increased seizure frequency, and altered sensorium may represent subclinical seizure activity 1, 3

• Anti-LGI1 antibody encephalitis presents with nonconvulsive seizures, persistent hyponatremia, and altered sensorium—though rare, this should be considered if standard management fails 3

Recurrent or Worsening Hyponatremia

• Despite initial improvement, hyponatremia may recur if the underlying SIADH from carbamazepine persists or if tolvaptan dosing is inadequate 1

• Check immediate serum sodium, serum osmolality, and urine sodium to assess current electrolyte status 1

Metabolic Encephalopathy

• Hypoglycemia can occur with recurrent hyponatremia and present as altered sensorium 3

• Hepatic encephalopathy is possible if carbamazepine caused hepatotoxicity, though less likely given the clinical timeline 1

Immediate Management Algorithm

Step 1: Assess Sodium Correction Rate

• Obtain immediate serum sodium level and compare to baseline values before saline infusion 1

• Calculate the rate of sodium correction over the past 24-48 hours—if >10-12 mEq/L in 24 hours, ODS is highly likely 1

• If ODS is suspected from overly rapid correction, consider re-lowering sodium with hypotonic fluids or desmopressin under nephrology guidance 1

Step 2: Neurological Evaluation

• Perform urgent EEG to exclude nonconvulsive status epilepticus 3

• Obtain brain MRI with diffusion-weighted imaging to detect osmotic demyelination (appears as hyperintense lesions in pons or extrapontine sites on T2/FLAIR sequences) 1

• Check vital signs including continuous cardiac monitoring for bradycardia or AV block from lacosamide 2

Step 3: Medication Review

• Do not restart carbamazepine given recurrent hyponatremia—consider alternative agents like oxcarbazepine (though it also carries SIADH risk) or lamotrigine for trigeminal neuralgia 4, 5

• Discontinue or reduce lacosamide dose if cardiac conduction abnormalities are present 2

• Reassess buprenorphine necessity and consider dose reduction if contributing to altered mental status 1

Step 4: Supportive Care

• Maintain serum sodium at current level without further rapid changes 1

• Monitor neurological status closely with serial examinations 1

• Ensure adequate cerebral perfusion with blood pressure support if needed 2

Critical Pitfalls to Avoid

• Never correct chronic hyponatremia faster than 6-8 mEq/L in 24 hours—the initial improvement followed by deterioration is the classic pattern of ODS 1

• Do not assume altered sensorium is simply residual hyponatremia without checking current sodium levels and correction rate 1

• Elderly patients and those on diuretics (including tolvaptan) are at higher risk for both SIADH and complications from correction 1

• Recognize that multiple sodium channel blockers (carbamazepine + lacosamide) create additive cardiac and neurological risks 2

• Consider autoimmune encephalitis if standard management fails and seizures persist despite adequate sodium correction 3