What is the workup and management of olfactory hallucinations?

Workup and Management of Olfactory Hallucinations

Olfactory hallucinations require neuroimaging to exclude temporal lobe pathology, followed by trial of anticonvulsant therapy if imaging is negative, as these symptoms most commonly represent temporal lobe dysfunction or partial seizure activity.

Initial Clinical Assessment

Key Historical Features to Elicit

• Timing and pattern: Determine if hallucinations are cyclic/episodic versus continuous 1
• Laterality: Distinguish unirhinal (one nostril) versus birhinal (both nostrils) phantosmia, as this fundamentally changes the differential diagnosis 2
• Character of odor: Unpleasant burning smells suggest migraine aura; specific recurring odors may indicate temporal lobe pathology 3
• Associated symptoms: Headache, seizure activity, psychiatric symptoms, or other neurological deficits 1
• Triggers and relieving factors: Can the patient initiate or stop the hallucination with Valsalva, sleep, or nasal water inhalation (suggests cyclic unirhinal phantosmia) 2
• Temporal relationship to other events: Onset after head trauma, viral infection, or concurrent with headaches 1, 3

Red Flag Symptoms Requiring Urgent Workup

• Concurrent neurological deficits (facial pain, visual changes, motor weakness) 1
• Altered consciousness or confusion suggesting encephalitis or status epilepticus 1, 4
• Progressive symptoms over days to weeks 1
• New-onset seizures or myoclonic activity 4, 2

Diagnostic Workup Algorithm

Step 1: Neuroimaging (MANDATORY)

MRI brain with contrast is the initial imaging modality of choice for evaluating olfactory hallucinations, as these symptoms may indicate temporal lobe dysfunction or structural lesions 1.

• MRI protocol should include: T1-weighted, T2-weighted, FLAIR sequences, and contrast-enhanced sequences covering the olfactory pathway (olfactory epithelium, bulbs at cribriform plate, temporal and frontal lobes) 1
• Specific attention to: Hippocampus, amygdala, temporal lobes, and cribriform plate region 4
• CT has no role in evaluating olfactory hallucinations unless assessing for acute trauma or bony anatomy 1

Step 2: Electroencephalography (EEG)

EEG should be performed in all patients with olfactory hallucinations to evaluate for seizure activity, particularly if hallucinations are episodic 5, 2.

• Cyclic unirhinal phantosmia frequently shows ipsilateral sharp waves 2
• Birhinal phantosmia typically shows few EEG changes 2
• Consider prolonged or video EEG monitoring if clinical suspicion for partial seizures is high despite normal routine EEG 4

Step 3: Olfactory Function Testing

Objective olfactory testing is recommended but not required for diagnosis 1.

• Psychophysical testing can characterize degree of olfactory function 1
• Patients with cyclic unirhinal phantosmia typically have normal olfaction 2
• Patients with birhinal phantosmia usually have concurrent hyposmia 2

Step 4: Exclude Sinonasal Pathology

Nasal endoscopy should be performed to exclude inflammatory or obstructive sinonasal disease 1.

• CT maxillofacial is useful only if sinonasal inflammatory disease or structural abnormality is suspected on examination 1
• Most patients with true olfactory hallucinations will have normal nasal examination 5

Management Algorithm

When Imaging Shows Structural Lesion

Immediate neurosurgical or neuro-oncology consultation is required for masses such as glioblastoma multiforme, meningioma, or esthesioneuroblastoma 1, 4.

• Temporal lobe lesions involving hippocampus/amygdala are particularly associated with olfactory hallucinations 4
• Treatment directed at underlying pathology 1, 4

When Imaging and EEG Suggest Seizure Activity

Initiate anticonvulsant therapy as first-line treatment for idiopathic olfactory hallucinations or those associated with epileptiform activity 5, 2.

First-Line: Sodium Valproate

• Dosing: Start at standard anticonvulsant doses (specific dosing not provided in guidelines, use clinical judgment)
• Evidence: Successfully controlled symptoms in case series of idiopathic olfactory hallucination 5
• Monitoring: Follow for symptom resolution and medication side effects 5

Second-Line: Phenytoin

• Use if: Intolerable side effects from valproate or inadequate response 5
• Evidence: Controlled symptoms after valproate discontinuation in reported cases 5

Alternative: GABA-Enhancing Agents

• Rationale: Both cyclic unirhinal and birhinal phantosmia respond to treatments that activate brain GABA activity 2
• Mechanism: Decreased GABA activity in specific brain regions appears responsible for phantosmia 2

When Associated with Migraine

Initiate migraine prophylaxis if olfactory hallucinations occur in temporal relationship to headaches 3.

• Typical presentation: 5-60 minute duration, burning smell, occurs shortly before or simultaneous with headache onset 3
• Phantosmias diminish or disappear with prophylactic headache therapy in majority of patients 3
• Consider olfactory hallucinations as an uncommon but distinctive form of migraine aura 3

When Associated with Psychiatric Disease

Psychiatric consultation and antipsychotic management may be required for olfactory hallucinations in context of schizophrenia 6.

• These patients show specific neuropsychological impairments associated with orbitofrontal cortex dysfunction 6
• Distinguish from neurological causes through comprehensive psychiatric evaluation 1

Common Pitfalls and Caveats

Critical Errors to Avoid

• Never assume olfactory hallucinations are benign or psychiatric without neuroimaging - temporal lobe tumors can present with isolated olfactory hallucinations 4
• Do not confuse olfactory hallucinations with anosmia or dysosmia - these are distinct clinical entities with different etiologies and workups 1
• Recognize that "olfactory hallucinations" described in HSV encephalitis guidelines are not reliable predictors of HSV infection and should not delay broader workup 1
• Avoid stopping anticonvulsant therapy prematurely - symptoms may recur after discontinuation 5

Important Clinical Distinctions

• Cyclic unirhinal phantosmia: Episodic, can be initiated/inhibited by patient maneuvers, frequent EEG changes, normal olfaction 2
• Birhinal phantosmia with associated symptomology: Continuous, cannot be controlled by patient, few EEG changes, concurrent hyposmia 2
• Migraine-associated phantosmia: Brief duration (5-60 minutes), burning smell, temporal relationship to headache, responds to migraine prophylaxis 3

Follow-Up Considerations

• Mean follow-up of 3+ years is appropriate for idiopathic cases on anticonvulsant therapy 5
• Monitor for symptom recurrence if medications are discontinued 5
• Repeat imaging if symptoms change in character or new neurological signs develop 1