What are the possible causes of recurrent episodes of difficulty with word finding and expressive aphasia in a patient with no significant changes on Magnetic Resonance Imaging (MRI)?

Recurrent Expressive Aphasia with Normal MRI: Differential Diagnosis

The most critical first step is to rule out transient ischemic attacks (TIAs) or seizures, as these represent the most common and treatable causes of recurrent word-finding difficulty with normal structural imaging. 1

Immediate Vascular Assessment

Obtain urgent vascular imaging (CTA or MRA of head and neck) even with normal brain MRI, as TIAs can cause recurrent aphasia without visible infarction on standard sequences. 1 The absence of structural changes on MRI does not exclude:

• Transient ischemic attacks affecting language-dominant hemisphere, which may show no permanent tissue damage but represent high stroke risk 1
• Small vessel disease or hypoperfusion states that may not manifest as visible lesions on routine sequences 2

Seizure Evaluation

Obtain EEG with consideration for prolonged monitoring, as focal seizures (particularly involving temporal or frontal language areas) commonly present as isolated aphasia without motor manifestations. 3 Key features suggesting seizure etiology:

• Stereotyped episodes with abrupt onset and offset 3
• Post-ictal confusion or drowsiness following episodes
• Episodes lasting seconds to minutes rather than hours 3

Migraine-Associated Phenomena

Consider migraine with aura, particularly if episodes are accompanied by headache, visual symptoms, or sensory changes. 2 Basilar migraines can present with isolated language dysfunction and typically show normal neuroimaging 2.

Infectious and Inflammatory Causes

Evaluate for infectious encephalitis (particularly Bartonella henselae if cat exposure) and autoimmune encephalitis, as these can present with recurrent aphasia and initially normal MRI. 3 Critical diagnostic steps:

• Obtain detailed exposure history (cats, ticks, travel) 3
• Check Bartonella henselae serology if lymphadenopathy or cat contact present 3
• Consider autoimmune encephalitis panel (NMDA receptor, LGI1, CASPR2 antibodies)
• Lumbar puncture for CSF analysis if infectious or inflammatory etiology suspected 3

Neurodegenerative Considerations

If episodes are progressive rather than truly recurrent, consider primary progressive aphasia (PPA), which may initially manifest as fluctuating symptoms before becoming persistent. 2, 4 The Alzheimer's Association guidelines distinguish three PPA variants:

• Logopenic variant PPA (most commonly due to Alzheimer's disease): prominent word-finding difficulty with impaired repetition, relatively preserved comprehension 2
• Semantic variant PPA (usually FTLD-TDP43): loss of word meaning, impaired comprehension, fluent but empty speech 2
• Non-fluent/agrammatic variant PPA (usually FTLD-tau): effortful, hesitant speech with agrammatism 2

Advanced imaging with FDG-PET or amyloid PET may be necessary to detect early neurodegenerative changes not visible on structural MRI. 2

Metabolic and Medication-Induced Causes

Review all medications, particularly corticosteroids, as steroid-induced expressive aphasia is a reversible but under-recognized phenomenon. 5 Additional metabolic considerations:

• Hypoglycemia (particularly in diabetics on insulin or sulfonylureas)
• Electrolyte disturbances (hyponatremia, hypercalcemia)
• Thyroid dysfunction
• Hepatic encephalopathy in patients with liver disease 5

Functional Neurological Disorder

Consider functional neurological disorder only after thorough exclusion of organic causes, and diagnosis requires positive clinical signs, not merely negative workup. 1 This should never be a diagnosis of exclusion alone 1.

Recommended Diagnostic Algorithm

1. Immediate: Vascular imaging (CTA/MRA head and neck) to assess for large vessel stenosis or dissection 1
2. Urgent: EEG (consider 24-hour ambulatory monitoring if initial EEG normal) 3
3. If infectious symptoms: Bartonella serology, autoimmune encephalitis panel, consider LP 3
4. If progressive pattern: FDG-PET brain to assess for neurodegenerative patterns not visible on MRI 2
5. Advanced MRI sequences: Diffusion-weighted imaging, perfusion imaging, and susceptibility-weighted imaging may reveal abnormalities not seen on standard sequences 2

Critical Pitfalls to Avoid

• Never attribute recurrent aphasia to "normal aging" or anxiety without comprehensive evaluation 1, 6
• Do not assume normal MRI excludes stroke—TIAs frequently show no imaging changes 1
• Do not delay vascular imaging while pursuing extensive cognitive testing if vascular etiology possible 1
• Always obtain collateral history from family/close contacts, as patients with language disorders often have impaired insight into their deficits 6
• Remember that "word-finding difficulty" may actually represent different phenomena: anomia, paraphasias, circumlocution, or true aphasia—precise characterization guides differential diagnosis 6, 4