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Cambridge University Science Magazine
Lewis Carroll’s Alice's Adventures in Wonderland celebrated its 150th anniversary just last year. Ever since Charles Lutwidge Dogson, better known by his pen name Lewis Carroll, published the children's tale in 1865 the story and its crazy characters have served as a powerful source of inspiration for novelists, filmmakers and poets alike.

“Curiouser and curiouser!” cried Alice (she was so much surprised,

that for the moment she quite forgot how to speak good English);

“now I’m opening out like the largest telescope that ever was! Good-bye, feet!”; (for when she looked down at her feet, they seemed to be almost out of sight, they were getting so far off)

While the story is an attempt to escape the audience from reality, some of the issues addressed by Carroll are not so far from particular medical conditions of our world. Just as Alice takes the reader on a journey down to Wonderland, a similar distortion of the world can be created when neural perception in the brain becomes fragmented.

Have you ever considered what a life full of illusion would be like? Imagine your surroundings or even your own body to grow massively out of proportion. What would it feel like to think that you have gone through a series of metamorphic changes similar to those Carroll has Alice experience? Would the misperception in your brain drive you nuts? But this is quite a different Wonderland, a world existing in parallel to the daily lives of some people. Aptly named, Alice in Wonderland Syndrome (AIWS) is a rare neurological phenomenon discovered more than one and a half centuries ago. Affected people experience a dreadfully distorted perception of time, distance, sound and/or size. While the condition is not very well known and relatively poorly studied, it has been well noted that symptoms usually begin to manifest in childhood and mostly affect children.

The term AIWS was first coined by the British psychiatrist Dr John Todd in 1955 and has therefore also been referred to as the Todd Syndrome. AIWS is a rare and transitory condition. Just like how Alice experiences metamorphosis after consuming food in Carroll's story, AIWS patients experience similar distortions visually. Transient symptoms include visual hallucinations and perceptual distortion, where objects and body parts are perceived to be altered in various ways (metamorphopsia), together with enlargement (macropsia) or reduction (micropsia) in size. Interestingly, Carroll himself is reported to have su ered from AIWS associated to severe migraine attacks, which supposedly served as an inspiration for his writing. Carroll's diary reveals that in 1856 he consulted an ophthalmologist about the visual manifestations he experienced regularly.

“Well, I’ll eat it,” said Alice,“and if it makes me grow larger, I can reach the key; and if it makes me grow smaller, I can creep under the door; so either way I’ll get into the garden, and I don’t care which happens!”

Quite contrary to what one would assume, AIWS rarely induces hallucinations. While the imagination can bear quite vivid fruit, individuals can discern that their perception is not in line with reality. Episodes are fairly unpredictable and relatively short. Most common misperceptions happen at night. It is suspected that the syndrome may be triggered by a combination of changes in sensory input, such as the ebbing of noise and light or chemical changes occurring in the brain as we near sleep. Curiously, some people have reported that they are able to control their symptoms by opening or closing their eyes, though the previously described sensations may be accompanied by a lingering of sensory input after the source has been removed. A diagnosis of AIWS requires that affected children report characteristic symptoms while still being “completely normal” in their development and not suffering from conditions like stroke or a brain tumour. Unfortunately, unlike other neurological conditions, AIWS does not reveal itself in MRI or CT scans.

Image: John Tenniel, adapted
Generally speaking, AIWS is not uncommon and likely to be underestimated as a diagnostic entity, since it is symptomatic of other conditions. Several reports suggest a very strong link between migraine auras and AIWS. In fact most people suffering from AIWS experience the neurological condition during auras generated by migraine episodes. A typical migraine attack actually consists of four phases: prodrome, aura, headache and postdrome; although auras may be experienced alone. Medically, auras are de ned as perceptual distortions developing within a short amount

of time, which occur minutes to hours prior to migraine headaches. Although still unclear, auras are thought to be caused by ‘cortical spreading depression’, a process in which excitation of the cerebral cortex (the outer and most complex layer of the brain) is followed by a depression in neuronal activity. It is hypothesised that when this course of overexcitation is followed by a depression passing through the parietal lobe (location: upper, back part of the cortex) it leads to an altered perception just like that experienced in AIWS. is idea is strongly supported by experiments in which electrical stimulation of the posterior parietal cortex has resulted in an altered perception of body size and shape.

In addition to migraine and epilepsy, AIWS is further associated with brain tumors, Epstein- barr-virus infections (a pathogen that causes glandular fever, also known as mono), other infections, hallucinogenic drugs, hyperpyrexia and schizophrenia. As a result, AIWS patients are often misdiagnosed as psychiatric disorders.

“But I don’t want to go among mad people,” Alice remarked.

“Oh, you can’t help that,” said the Cat: “we’re all mad here. I’m mad.You’re mad.”

“How do you know I’m mad?” said Alice. “You must be,” said the Cat,“or you wouldn’t have come here.”

Unfortunately, AIWS has no proven e ective treatment due to the fact that so little is known about its cause and origin. Two theories as to why the syndrome has so little recognition are: 1) children who experience AIWS are too young to describe what they perceive precisely and rather enjoy than dread the altered perception, and 2) adults do not speak up or address medical consultants out of fear of being stigmatised and falsely discriminated against as ‘crazy’. If diagnosed, most therapies consist of first line medication for migraine management or prophylaxis and diet: antidepressant prescription, anticonvulsion prescription, nerve block injections or dietary and lifestyle alterations.

AIWS' symptom of micropsia, which makes objects appear smaller than normal, has also been cited as an in uence for Jonathan Swift`s book Gulliver`s Travels. No matter if it is the catchy name or the possible link to more serious brain diseases, the number of scienti c studies and perceived relationships with creative works have increased apace over the past years. Nevertheless, the AIWS still remains something of a mystery.