Rare disease: Alice in Wonderland Syndrome

"It was much pleasanter at home, when one wasn't always growing larger and smaller, and being ordered about by mice and rabbits."- Alice from Alice in Wonderland by Lewis Caroll.

Alice in Wonderland Syndrome, or AIWS for short, is a fascinating condition that affects the way a person perceives the world around them. Named after Lewis Carroll's famous character, Alice, who experiences some strange changes in size and perspective, AIWS can cause a person to feel as though they are growing or shrinking, or that objects around them are changing in size or shape. 

In 1955, John Todd who was an English psychiatrist (1914−1987) described AIWS as self-experienced paroxysmal body image illusions involving distortions of the size, mass, or shape of the patient's own body or its position in space. This phenomenon often occurred with depersonalisation and derealisation. For e.g. an AIWS case study of a 30 years old patient with long term headache episodes stated that objects appeared larger than they actually were and his fingers appeared to be smaller than they actually were. 

These distortions can be compared to something called "Lilliputian hallucinations," which are named after a place in a famous book called "Gulliver's Travels." In the book, Lilliput is a tiny island with very small people. So, just like how everything in Lilliput is smaller than usual, in this condition, people might see things as smaller than they actually are or in strange and unusual ways.

AIWS is a rare disease. As a 2019 case report article investigated, no more than 180 “clinical” cases of AIWS have been described (i.e., cases in need of medical attention).

In 65% of cases, AIWS occurred in children under 18 years of age. The male/female ratio seems to vary with the age: while in younger age male are predominantly affected with 2.69-fold risk of having AIWS (in a sample aged 5 to 14 years) while females were significantly more prevalent (56.7%) among senior students (16–18 years). There are no large-scale epidemiological studies available due to a lack of concrete diagnostic criteria. 

Over the past 60 years, AIWS symptoms have come to include 42 visual symptoms and 16 nonvisual symptoms. Commonly, these symptoms constitute distortions of sensory perception rather than hallucinations or illusions.

A study performed by Liu et al interviewed 48 patients (average age 8.1 years) diagnosed with AIWS. Common visual symptoms are listed below with their prevalence in brackets:

• Micropsia (~69%): a condition in which visual objects are perceived to be smaller than they are objectively sized

• Teleopsia (50%): a disorder in which objects appear much farther away than they are

• Macropsia (25%): a condition in which visual objects are perceived to be larger than they are objectively sized

• Metamorphopsia (15%): a syndrome in which the shape of objects appears distorted

• Pelopsia (10%): a disorder in which objects appear nearer than they actually are

The duration of symptoms of AIWS tends to be short, mostly on the order of minutes to days; however, symptoms may also persist for years or even be lifelong.

AIWS is not enlisted in the International Classification of Headache Disorders (ICHD) 3 beta, even if it seems strictly related to migraine which in fact is the first cause of AIWS in adults (27.6%) and the second in children (26.8%)

Valenca et al proposed following criteria for migrane-related AIWS diagnostics:

• One or more episodes of self-experienced body schema illusion or metamorphopsia

• Duration < 30 min

• Accompanied by headache or a history of migraine

• Cerebrospinal fluid (CSF), and electroencephalogram (EEG) all normal (visual evoked potentials may be abnormal)

In clinical cases of AIWS, auxiliary investigations (including blood tests, EEG, and brain Magnetic resonance imaging [MRI] are strongly advised.

Although the causes of AIWS are not studied fully, some of the causes may be:

• Typical migraine

• Temporal lobe epilepsy

• Brain tumours

• Psychoactive drugs

• Epstein-Barr virus infections (glandular fever)

In about 20% of cases there is no known cause. Family history may be one of the cause as well. In a retrospective study of 48 children with AIWS revealed a family history of migraine in 46%; 5 parents (33%) of affected patients had also experienced AWS symptoms.

Encephalitis among youths and neurologic disorders in elderly patients were mainly described conditions in the context of AIWS.

Treatment should be directed at the suspected underlying condition, although reassurance that the symptoms themselves are not harmful seems to suffice in about 50% of cases. 

The treatment plan can consist of migraine prophylaxis and migraine diet (e.g. low tyramine diet). However, it is important to note that chronic cases of AIWS do exist. A person suffering from the disorder chronically may have distortions and hallucinations several times during the day, and the manifestations may take some time to subside.

Rare conditions such as AIWS are inadequately investigated, which may impose critical challenges in providing accurate medical care as healthcare providers may not have enough insights regarding the epidemiology and pathophysiology of these disease.

Awareness and support need to be raised for those affected by rare diseases such as AIWS so that they can receive the medical attention, resources, and care they need to live healthy and fulfilling lives.

Medical Writer II & Medical Devices Lead