What is the differential diagnosis for a 17-year-old patient with anorexia nervosa, currently on day 8 of refeeding, with prophylactic thiamine supplementation, presenting with acute onset headache and left lower extremity weakness, despite a normal neuro exam, and elevated transaminases (liver enzymes) due to refeeding syndrome?

Differential Diagnosis for Acute Headache and Left Lower Extremity Weakness on Day 8 of Refeeding

The most critical diagnosis to consider is Wernicke's encephalopathy from thiamine deficiency, despite prophylactic supplementation, followed by cerebrovascular accident (stroke), refeeding-related electrolyte disturbances causing neurological dysfunction, and less likely but possible intracranial hemorrhage or venous sinus thrombosis.

Primary Differential Considerations

1. Wernicke's Encephalopathy (Most Critical)

Even with prophylactic thiamine, this patient may have inadequate thiamine stores or dosing, particularly given the acute neurological presentation. 1

• Thiamine deficiency can precipitate acute encephalopathy, confusion, and focal neurological deficits including weakness when carbohydrates are introduced during refeeding 1
• The classic triad (confusion, ataxia, ophthalmoplegia) is present in only 10-16% of cases; focal weakness and headache can be presenting features 1
• Prophylactic oral thiamine may be insufficient in severely malnourished anorexia nervosa patients who require 200-300 mg IV daily 1, 2
• The acute onset on day 8 of refeeding aligns with the typical 4-day window when refeeding complications manifest 1

2. Cerebrovascular Accident (Stroke)

Acute focal neurological deficit (left lower extremity weakness) with headache in a refeeding patient raises immediate concern for ischemic or hemorrhagic stroke. 1, 3

• Severe electrolyte disturbances from refeeding syndrome can precipitate cardiac arrhythmias leading to embolic stroke 1, 3
• Hypophosphatemia-induced cardiac arrhythmias occur in up to 20% of severe refeeding cases and can cause sudden cardiac death or embolic events 1
• Pre-existing cardiac muscle atrophy from chronic malnutrition increases arrhythmia risk 3
• Dehydration and electrolyte shifts can increase thrombotic risk 1

3. Severe Hypophosphatemia with Neurological Manifestations

Rapid drops in plasma phosphate from refeeding can provoke acute neurological symptoms including confusion, weakness, and seizures. 1

• Hypophosphatemia is the most frequent and clinically significant electrolyte disturbance in refeeding syndrome 1
• Neurological manifestations include delirium, confusion, seizures, and focal weakness from phosphate-depleted cellular energy failure 1
• The transaminase elevation suggests hepatic involvement, which commonly accompanies severe refeeding syndrome 1
• Muscle weakness and rhabdomyolysis can occur with severe hypophosphatemia 1

4. Cerebral Venous Sinus Thrombosis

Fluid retention and hypercoagulability during refeeding create risk for venous thrombosis. 1

• Acute water and sodium retention occurs as anabolic metabolism resumes during refeeding 1
• Headache with focal neurological deficit is classic for venous sinus thrombosis
• Dehydration from chronic malnutrition followed by rapid fluid shifts increases thrombotic risk 1

5. Intracranial Hemorrhage

Less likely but must be excluded given acute focal deficit with headache.

• Electrolyte disturbances and potential coagulopathy from malnutrition could contribute 1
• Thiamine deficiency itself can rarely cause hemorrhagic complications

Immediate Diagnostic Workup Required

Urgent Imaging

• Emergent non-contrast head CT to exclude hemorrhage, followed by MRI brain with diffusion-weighted imaging if CT negative (standard stroke protocol)
• MRI is more sensitive for Wernicke's encephalopathy (shows symmetric T2 hyperintensities in thalami, mammillary bodies, periaqueductal gray) 1

Critical Laboratory Assessment

• Immediate electrolytes including phosphate, potassium, magnesium, calcium - measure 2-3 times daily when refeeding complications suspected 1
• Thiamine level (though treatment should not await results) 1
• Complete metabolic panel including glucose 1
• Lactate level (elevated in thiamine deficiency) 1, 4
• Cardiac monitoring for arrhythmias 1, 3

Additional Studies

• ECG to assess for QTc prolongation and arrhythmias 3
• Coagulation studies if hemorrhage suspected 1

Immediate Management Protocol

1. Thiamine Administration (Do Not Wait for Imaging)

Administer thiamine 500 mg IV three times daily immediately, before any additional glucose or nutrition. 1, 2

• Never delay thiamine in suspected Wernicke's encephalopathy - irreversible neurological damage or death can occur 1, 2
• Standard prophylactic dosing (200-300 mg daily) may be insufficient in acute deficiency 1
• Continue high-dose thiamine for minimum 3 days, then 200-300 mg IV daily 1
• Administer full B-complex vitamins IV simultaneously 1

2. Aggressive Electrolyte Correction

Immediately supplement phosphate 0.3-0.6 mmol/kg/day IV, potassium 2-4 mmol/kg/day, and magnesium 0.2 mmol/kg/day IV. 1

• Restrict energy supply to 5-10 kcal/kg/day for 48 hours before gradually increasing 1
• Monitor electrolytes every 6-8 hours until stable 1
• Correct severe deficiencies before resuming full refeeding 1

3. Cardiovascular Monitoring

Continuous cardiac telemetry to detect arrhythmias that could cause embolic stroke. 1, 3

• Monitor for QTc prolongation, which is common in anorexia nervosa and worsens with electrolyte disturbances 3
• Volume status and fluid balance monitoring 1

4. Neurological Consultation

• Urgent neurology evaluation for stroke workup if imaging shows acute pathology
• Consider EEG if seizure activity suspected 1

Critical Pitfalls to Avoid

• Never assume prophylactic thiamine dosing is adequate - acute deficiency can occur despite supplementation, particularly with oral dosing in malabsorption 1, 2
• Do not continue aggressive refeeding in the setting of acute neurological symptoms - temporarily reduce to 5-10 kcal/kg/day 1
• Do not correct electrolytes alone without simultaneous feeding, as this provides false security without correcting massive intracellular deficits 1
• Never administer glucose or carbohydrates before thiamine in suspected deficiency - this precipitates acute Wernicke's encephalopathy 1, 2
• Do not dismiss focal neurological findings as "functional" in anorexia nervosa patients - organic pathology must be excluded 3

Risk Stratification Context

This patient meets multiple very high-risk criteria for severe refeeding complications: 1, 3, 2

• Chronic anorexia nervosa with severe malnutrition
• Day 8 of refeeding (within the critical first 72-hour to 5-day window) 1
• Already manifesting refeeding syndrome (transaminase elevation) 1
• Acute neurological deterioration during refeeding 1

The combination of headache with focal weakness in this context represents a medical emergency requiring immediate intervention before definitive diagnosis, as both Wernicke's encephalopathy and stroke are time-sensitive, potentially fatal conditions. 1, 3, 2