What is the most likely diagnosis for a patient with a history of liver transplant, presenting with headaches, visual disturbances, confusion, and episodes of unresponsiveness, with elevated plasma ammonia levels and slight edema of the occipital lobes on CT scan?

Posterior Reversible Encephalopathy Syndrome (PRES) Secondary to Tacrolimus Toxicity

The most likely diagnosis is posterior reversible encephalopathy syndrome (PRES) secondary to tacrolimus neurotoxicity, given the characteristic clinical presentation of headaches, visual disturbances, altered mental status, severe hypertension (170/100), and pathognomonic CT findings of occipital lobe edema in a post-transplant patient on calcineurin inhibitor therapy. 1

Key Diagnostic Features Supporting PRES/Tacrolimus Toxicity

Clinical Presentation

• Neurological symptoms including headaches, visual disturbances, confusion, and episodes of unresponsiveness are classic manifestations of calcineurin inhibitor neurotoxicity 1
• Severe hypertension (170/100 mmHg) is a critical precipitating factor for PRES and commonly occurs with tacrolimus toxicity 1
• Occipital lobe edema on CT is the pathognomonic radiological finding for PRES, representing vasogenic edema in the posterior circulation 1

Why NOT Hepatic Encephalopathy

• Normal ammonia level (60 μmol/L) essentially rules out hepatic encephalopathy as the primary diagnosis 2
• According to the European Association for the Study of the Liver, a normal blood ammonia level has high negative predictive value for hepatic encephalopathy, indicating the patient lacks sufficient hepatic failure and/or portosystemic shunting to justify a working diagnosis of HE 2
• The American Association for the Study of Liver Diseases states that normal ammonia levels in a patient with episodic encephalopathy and liver disease mandate an immediate search for alternative causes of delirium 2
• Elevated transaminases (ALT 155, AST 132) suggest acute liver injury but not the chronic hepatic dysfunction with portosystemic shunting required for HE 3
• Occipital lobe edema is not characteristic of hepatic encephalopathy, which typically shows diffuse cerebral changes on imaging 3

Why NOT Acute Ischemic Stroke

• Bilateral occipital edema rather than focal vascular territory infarction argues against stroke 2
• Absence of acute intracranial hemorrhage on CT makes hemorrhagic stroke unlikely 2
• The episodic and fluctuating nature of symptoms over 2 days is more consistent with metabolic/toxic encephalopathy than acute stroke 3

Why NOT Migraine with Aura

• Persistent altered mental status and confusion far exceed typical migraine symptoms 3
• Episodes of unresponsiveness are not features of migraine with aura 3
• Occipital lobe edema on imaging indicates structural pathology beyond functional migraine 2

Pathophysiology of Tacrolimus-Induced PRES

Mechanism

• Calcineurin inhibitors have direct neurotoxic effects including endothelial dysfunction, disruption of the blood-brain barrier, and vasogenic edema 1
• Hypertension (present in this patient at 170/100) potentiates the neurotoxicity by causing hyperperfusion and breakdown of cerebral autoregulation 1
• Chronic kidney disease (creatinine 2.1, BUN 45) increases tacrolimus levels and reduces clearance, predisposing to toxicity 1

Risk Factors Present

• Post-transplant status (4 months post-liver transplant) 1
• Hypertension (baseline condition, now 170/100) 1
• Chronic kidney disease (creatinine 2.1) 1
• Tacrolimus trough level of 9 may be within therapeutic range but can still cause neurotoxicity in susceptible patients 1

Critical Management Considerations

Immediate Actions

• Reduce or temporarily discontinue tacrolimus while monitoring for rejection 1
• Aggressive blood pressure control to target <140/90 mmHg to prevent progression of vasogenic edema 1
• Avoid medications that increase tacrolimus levels including diltiazem, verapamil, and carvedilol 1
• Avoid NSAIDs as they potentiate calcineurin inhibitor-induced nephrotoxicity 1

Diagnostic Confirmation

• MRI with FLAIR sequences is more sensitive than CT for detecting PRES and should be performed to confirm the diagnosis 3, 2
• EEG can help exclude non-convulsive seizures, which are complications of both PRES and tacrolimus toxicity 3, 1
• Repeat tacrolimus levels to assess for supratherapeutic concentrations 1

Common Pitfalls to Avoid

• Do not assume hepatic encephalopathy based on liver transplant history alone when ammonia is normal 2
• Do not delay tacrolimus adjustment while waiting for MRI confirmation, as PRES can progress to irreversible injury 1
• Recognize that therapeutic tacrolimus levels do not exclude neurotoxicity, as individual susceptibility varies 1
• Pre-transplant hepatic encephalopathy is a risk factor for post-transplant neurological complications, requiring heightened surveillance 1

Prognosis

• PRES is typically reversible with prompt recognition, blood pressure control, and reduction/discontinuation of the offending agent 1
• Failure to recognize and treat PRES can lead to permanent neurological sequelae including seizures and stroke 1