What investigations are indicated for a 53-year-old patient with new-onset vertigo who is taking phenytoin and levetiracetam?

Investigations for New-Onset Vertigo in a Patient on Phenytoin and Levetiracetam

Begin with a comprehensive neurologic examination including HINTS testing (Head Impulse, Nystagmus, Test of Skew), followed by serum phenytoin and levetiracetam levels, and proceed to MRI brain without and with IV contrast if the HINTS examination suggests central vertigo or if performed by a non-expert examiner.

Initial Clinical Assessment

The critical first step is determining whether this represents acute vestibular syndrome (AVS) versus brief positional vertigo. AVS is defined by acute persistent vertigo with nausea/vomiting, gait instability, nystagmus, and head-motion intolerance 1.

HINTS Examination is Key

• If HINTS examination by a specially trained provider is available and shows peripheral vertigo: No imaging is required 1
• If HINTS examination suggests central vertigo OR is performed by non-experts: Proceed to neuroimaging 1
• Critical caveat: When performed by specially trained practitioners, HINTS has 100% sensitivity for detecting posterior circulation infarct versus only 46% for early MRI 1. However, non-expert HINTS testing has shown mixed results 1

Drug-Related Investigations (Priority Given Patient's Medications)

Phenytoin Level - URGENT

Check serum phenytoin concentration immediately. Phenytoin causes dose-dependent vestibular toxicity:

• Phenytoin impairs vestibuloocular reflex parameters even at subthreshold toxic levels 2
• Dizziness is a recognized adverse effect of phenytoin 3
• The patient may be approaching toxic threshold before overt signs appear 2

Levetiracetam Level

Measure serum levetiracetam concentration, particularly because:

• Phenytoin co-administration can decrease levetiracetam levels by 20-30% 4
• Levetiracetam itself causes dizziness in 9% of patients (versus 4% on placebo) 3
• However, levetiracetam does NOT alter phenytoin pharmacokinetics 5

Neuroimaging Algorithm

When Imaging is Indicated:

MRI brain without and with IV contrast is the preferred modality 1:

• Detects acute brain lesions in 11% of patients with acute persistent vertigo and no focal neurologic deficits 1
• Superior soft tissue resolution compared to CT
• Contrast enhancement improves detection of masses, inflammatory, infectious, or demyelinating processes 1

When Imaging May Be Deferred:

• HINTS examination by trained provider shows peripheral vertigo 1
• Detection rate of CNS pathology with normal neurologic exam is <1% 1

Critical Pitfalls to Avoid

1. Do not assume peripheral vertigo based solely on normal neurologic exam: 75-80% of patients with AVS from posterior circulation infarct have NO focal neurologic deficits 1

2. Do not rely on CT head: While rapid, CT misses many posterior circulation infarcts that MRI detects 1

3. Do not overlook drug toxicity: The combination of phenytoin (known vestibular toxin) and levetiracetam (causes dizziness) makes drug-induced vertigo highly plausible 3, 2

4. Age matters for stroke risk: In patients with AVS, cerebrovascular disease prevalence approaches 25% overall and up to 75% in high vascular risk cohorts 1

Practical Algorithm

1. Immediate: Serum phenytoin and levetiracetam levels
2. Bedside: HINTS examination (if trained examiner available)
3. If HINTS suggests central OR examiner not expert-trained: MRI brain without and with IV contrast
4. If phenytoin level elevated: Consider this as primary cause; adjust dosing
5. If all above negative and symptoms persist: Consider temporal bone imaging for peripheral causes (though less likely given medication context)

The 53-year-old age and antiepileptic medication regimen make both drug toxicity and posterior circulation stroke significant concerns that require systematic exclusion 1, 3, 2.