What is the most likely diagnosis for a patient presenting with right chest pain, who initially was able to engage in conversation but then developed a change in mental status, word finding difficulty, confusion, and persistent vomiting, with initial negative troponin (cardiac enzyme) and electrocardiogram (EKG) results?

Most Likely Diagnosis: Acute Stroke with Possible Cardioembolic Source

The most likely diagnosis is an acute ischemic stroke, given the rapid progression from normal conversation to word-finding difficulty, confusion, and altered mental status, despite negative initial cardiac workup. The right chest pain may represent a red herring or a concurrent but unrelated symptom, though life-threatening cardiopulmonary causes must still be excluded urgently.

Critical Immediate Actions Required

This patient requires emergent neuroimaging (non-contrast head CT or MRI) within minutes of presentation to evaluate for acute stroke, as the combination of acute mental status changes with focal neurological deficits (word-finding difficulty) represents a neurological emergency. 1

• The ACR Appropriateness Criteria emphasizes that acute mental status changes with focal neurological signs mandate immediate brain imaging to exclude intracranial hemorrhage or acute ischemic stroke 1
• Time is critical: if stroke is confirmed and within the therapeutic window, thrombolytic therapy or mechanical thrombectomy may be life-saving
• The negative troponin and ECG make acute coronary syndrome less likely as the primary cause of the neurological symptoms 1

Differential Diagnosis Framework

Primary Consideration: Acute Stroke

• Word-finding difficulty (aphasia) and confusion represent focal neurological deficits highly suggestive of stroke, particularly involving the left hemisphere language centers 1
• Altered mental status can be an accompanying feature of stroke, especially with larger infarcts or posterior circulation involvement 1
• The rapid progression from normal conversation to confusion over minutes to hours is classic for acute cerebrovascular events
• Persistent vomiting may indicate posterior circulation stroke affecting the brainstem or cerebellar structures 1

Secondary Considerations Requiring Exclusion

Pulmonary Embolism (PE):

• PE can present with chest pain, altered mental status, and even psychopathological symptoms that mimic psychiatric emergencies 2
• PE is frequently misdiagnosed in elderly patients presenting with significantly altered mental status 2
• The combination of chest pain with neurological symptoms and negative initial cardiac workup should raise suspicion for PE 3
• PE can cause elevated troponin and ECG changes mimicking ACS in 36% of cases, though initial troponin was negative here 3
• If stroke imaging is negative or shows findings inconsistent with the clinical picture, immediately measure D-dimer and consider CT pulmonary angiography 4

Aortic Dissection:

• Can present with chest pain and neurological deficits if dissection extends to involve cerebral vessels 1
• Persistent vomiting and altered mental status can occur with aortic dissection 4
• The ACR guidelines note that aortic dissection may be suggested from chest radiograph but requires CT angiography for definitive diagnosis 1

Cardiac Source of Embolism:

• Atrial fibrillation, endocarditis, or cardiac thrombus could cause both chest discomfort and embolic stroke
• The initial negative ECG does not exclude paroxysmal arrhythmias 1
• Continuous cardiac monitoring beyond 24 hours is recommended for patients at increased risk for cardiac arrhythmias 1

Critical Diagnostic Algorithm

Step 1: Immediate Neurological Assessment (0-10 minutes)

• Perform focused neurological examination documenting specific deficits (aphasia type, motor weakness, sensory changes, cranial nerve findings)
• Obtain non-contrast head CT immediately to exclude hemorrhage and identify early ischemic changes 1
• If CT is negative but clinical suspicion remains high, proceed urgently to MRI with diffusion-weighted imaging (DWI), which is more sensitive for acute ischemia 1

Step 2: Concurrent Cardiopulmonary Evaluation

• Repeat troponin at 6-12 hours from symptom onset, as initial negative troponin does not exclude evolving myocardial injury 1
• Obtain chest X-ray to evaluate for alternative causes including pneumonia, pneumothorax, widened mediastinum, or heart failure 1, 5
• If neuroimaging is negative or inconclusive, measure D-dimer and strongly consider CT pulmonary angiography to exclude PE 4, 3
• Consider CT angiography of chest if aortic dissection remains in differential 1

Step 3: Risk Stratification for Stroke Etiology

• Obtain echocardiography (transthoracic, possibly transesophageal) to identify cardiac source of embolism 1
• Continuous cardiac monitoring to detect paroxysmal atrial fibrillation 1
• Vascular imaging (CT angiography or MR angiography) of head and neck vessels to identify large vessel occlusion or stenosis

Common Pitfalls to Avoid

Do not assume negative troponin and ECG exclude all cardiac causes:

• Rare cases of acute coronary syndrome can present with negative troponin even on repeated testing 6
• Cardiac arrhythmias causing embolic stroke may not be captured on initial ECG 1
• PE frequently presents with chest pain and negative initial cardiac workup 3

Do not delay neuroimaging while pursuing cardiac workup:

• The window for thrombolytic therapy in acute stroke is narrow (typically 4.5 hours from symptom onset)
• Mechanical thrombectomy may be effective up to 24 hours in selected patients
• Every minute of delay in stroke treatment results in loss of 1.9 million neurons (general medical knowledge)

Do not dismiss the chest pain as unrelated without thorough evaluation:

• The combination of chest pain with neurological symptoms may indicate PE, aortic dissection, or cardioembolic stroke 2, 4, 3
• Physical examination contributes minimally to diagnosing these conditions unless shock or specific findings are present 7

Do not misattribute neurological symptoms to psychiatric causes:

• PE can manifest with psychopathological symptoms including confusion and altered mental status that mimic psychiatric emergencies 2
• Initial misdiagnosis results in inappropriate referral and significant delays in life-saving treatment 2

Disposition and Management

Immediate admission to stroke unit or intensive care unit with continuous neurological and cardiac monitoring is mandatory 1

• If acute ischemic stroke is confirmed and patient is within therapeutic window, initiate appropriate reperfusion therapy per stroke protocols
• If PE is diagnosed, initiate anticoagulation immediately unless contraindicated 3
• If aortic dissection is identified, urgent cardiothoracic surgical consultation is required 4
• The persistent vomiting requires management to prevent aspiration and may indicate increased intracranial pressure or posterior circulation involvement 1