Alice in Wonderland Syndrome: Diagnosis and Management
What is Alice in Wonderland Syndrome?
Alice in Wonderland syndrome (AIWS) is a rare neurological disorder characterized by distortions of visual perception (metamorphopsias), altered body image perception, and disturbed experience of time, along with derealization and depersonalization. 1 The syndrome manifests with specific perceptual distortions including micropsia (objects appearing smaller), macropsia (objects appearing larger), teleopsia (objects appearing farther away), and pelopsia (objects appearing closer than they are). 1
- Approximately 85% of patients present with perceptual distortions in a single sensory modality, and the majority experience only one type of distortion. 2
- AIWS occurs more commonly than traditionally assumed, with up to 30% of adolescents in the general population reporting non-clinical symptoms. 1, 3
- Clinical cases requiring medical attention represent only a small fraction of total AIWS occurrences. 2
Diagnostic Approach
Initial Clinical Assessment
When evaluating suspected AIWS, obtain collateral history from a knowledgeable informant to characterize the acute changes and determine baseline cognitive function. 4
- Document the specific perceptual distortions: visual metamorphopsias (micropsia, macropsia, zoom vision), body schema alterations, time distortions (quick-motion phenomenon, protracted duration), and any associated symptoms like akinetopsia or color distortions. 2
- Assess for focal neurological symptoms including headache, confusion, diplopia, dysarthria, focal weakness, focal numbness, ataxia, dysmetria, and hypertonicity. 5
- Evaluate for symptoms of anxiety, as these commonly accompany AIWS and require specific management. 6
Mandatory Investigations
All clinical cases of AIWS require auxiliary investigations including blood tests, EEG, and brain MRI to identify the underlying etiology. 1
Laboratory Testing
- Complete blood count with differential to evaluate for infection and hematologic abnormalities. 4
- Comprehensive metabolic panel including electrolytes, renal function, liver function, and calcium. 4
- Vitamin B12, copper, and vitamin E levels, particularly in cases with persistent neurological symptoms. 6
- Thyroid function tests to exclude thyroid disorders. 4
- Erythrocyte sedimentation rate and C-reactive protein in patients over 50 years old. 4
Neuroimaging
MRI is the diagnostic modality of choice for evaluating AIWS, as it can identify demyelinating disease, structural lesions, and metabolic abnormalities. 5
- Brain MRI with FLAIR sequences is essential to identify white matter changes characteristic of multiple sclerosis, particularly in young adult females with recurrent episodes. 5
- Combined brain and spine imaging should be considered, as lesions can occur in either location. 5
- CT head is appropriate when MRI is unavailable or contraindicated, though it has lower sensitivity for subtle lesions. 4
Additional Testing Based on Clinical Context
- EEG to evaluate for seizure activity or encephalopathy. 1
- Lumbar puncture when fever is present without clear source, meningeal signs are present, or the patient is immunocompromised, to exclude CNS infection and evaluate for 14-3-3 protein in suspected Creutzfeldt-Jakob disease. 4, 2
- Toxicology screen if substance-related etiology is suspected. 4
Etiologic Classification
Age-Based Differential Diagnosis
The etiology of AIWS varies significantly by age: neurological disorders predominantly affect adults and elderly patients, while encephalitides primarily affect patients aged ≤18 years. 1
In Children and Adolescents (≤18 years)
- Encephalitis (most common cause). 1, 3
- Infectious mononucleosis, H1N1 influenza, Cytomegalovirus encephalitis. 7
- Severe malaria with hyperparasitemia. 7
- Typhoid encephalopathy. 7
In Adults
- Migraine (most common cause in adults). 2, 3
- Multiple sclerosis and other demyelinating diseases, particularly in young adult females with recurrent episodes and focal neurological signs. 5
- Structural brain lesions. 5
- Psychiatric conditions including recurrent depressive disorder. 8
In Elderly Patients
- Creutzfeldt-Jakob disease (Heidenhain variant), which presents with rapid progression, visual symptoms, and cognitive decline. 2
- Cerebrovascular disease. 3
- Neurodegenerative disorders. 3
Critical Red Flags Requiring Urgent Investigation
Rapid cognitive decline, behavioral changes, gait instability, aphasia, or progressive neurological symptoms suggest serious underlying pathology such as Creutzfeldt-Jakob disease and require immediate comprehensive evaluation. 2
- Sudden onset with rapidly progressive symptoms over days to weeks. 2
- Associated paraesthesias, ataxia, or motor deficits. 2
- Cognitive decline, agitation, or emotional lability. 2
- Multiple types of visual distortions (akinetopsia, chloropsia, micropsia, macropsia) occurring simultaneously. 2
Treatment Approach
General Management Principles
Treatment should be directed at the suspected underlying condition, although reassurance that the symptoms themselves are not harmful suffices in approximately 50% of cases. 1, 3
Symptomatic Management
- For anxiety symptoms associated with AIWS, use techniques of redirecting focus and coping strategies. 6
- In cases of speech or communication alterations, implement speech and language therapy with a focus on redirecting techniques. 6
- Ensure proper orientation with clocks, calendars, and familiar objects. 4
- Encourage family presence when possible. 4
- Minimize sensory deprivation or overload with appropriate lighting and reduced excessive noise. 4
Condition-Specific Treatment
For infectious etiologies such as severe malaria, treatment of the underlying infection typically results in complete resolution of AIWS symptoms. 7
- Severe malaria: Quinine for 10 days, with monitoring for seizures during initial treatment. 7
- Encephalitis: Appropriate antimicrobial or antiviral therapy based on identified pathogen. 1
- Migraine-associated AIWS: Standard migraine prophylaxis and acute treatment protocols. 2
- Depression-associated AIWS: Antidepressant therapy, which may normalize metabolic abnormalities in frontal, occipital, and parietal cortices. 8
Pharmacological Considerations
Reserve pharmacological interventions for patients with severe agitation that poses safety risks or prevents essential medical care. 4
- Avoid haloperidol or risperidone for mild-to-moderate symptoms, as they have no demonstrable benefit and may worsen symptoms. 4
- Consider olanzapine, quetiapine, or aripiprazole for symptomatic management when necessary. 4
- Avoid benzodiazepines as first-line agents except in alcohol or sedative withdrawal. 4
Follow-Up and Monitoring
Long-term follow-up should include monitoring of cognitive function and nutritional status, especially in cases with associated vitamin deficiencies. 6
- Reassess patients without an identified etiology periodically, as new diagnostic technologies may reveal previously undetectable conditions. 9
- Monitor for development of additional neurological symptoms that might clarify the diagnosis. 5
- In resource-limited settings where extensive investigation is unaffordable, successful treatment of identified underlying conditions (such as severe malaria) typically coincides with complete regression of AIWS. 7
Common Pitfalls to Avoid
Do not dismiss AIWS as harmless without proper investigation, as it can be the presenting manifestation of serious conditions including Creutzfeldt-Jakob disease, multiple sclerosis, or severe infections. 2
- Overlooking medication side effects as potential causes of perceptual distortions. 4
- Confusing AIWS with schizophrenia spectrum disorders or other primary psychiatric perceptual disorders. 3
- Failing to obtain neuroimaging in patients with focal neurological findings or recurrent episodes. 5
- Using physical restraints as first-line management, which can worsen agitation. 4
- Administering sedatives without addressing the underlying cause. 4
- Assuming benign prognosis without adequate investigation, particularly in elderly patients or those with rapid symptom progression. 2