Who is Alice?

The well-known childhood classic by Lewis Carroll, ‘Alice in Wonderland’, has a not so well-known disease named after it. Alice in Wonderland syndrome (AIWS) is a disorder that The well-known childhood classic by Lewis Carroll, ‘Alice in Wonderland’, has a not so well-known disease named after it. Alice in Wonderland syndrome (AIWS) is a disorder that affects one’s perception of their body size in relation to their environment, causing a condition known as micropsia. It is similar to Alice’s experience when she gulped from the bottle labelled “DRINK ME” that made her shrink and when she ate the scrumptious cake in a glass box labelled “EAT ME” and grew large. The disease is very rare and often misdiagnosed, especially due to the absence of a univocally accepted diagnostic criteria. 
Though underlying medical conditions of patients vary, a majority of the population have bThough underlying medical conditions of patients vary, a majority of the population have been recorded to have suffered from migraine (Mastria, Mancini, Viganò, & Di Piero, 2016). Uncannily, Carroll experienced frequent migraines that he described in his diary as ‘bilious headaches’ and wrote of facing visual disturbances that made him see moving fortifications. This is like how Alice’s fall into the rabbit hole was described: “Either the well was very deep, or she fell very slowly, for she had plenty of time as she went down to look about her and to wonder what was going to happen next”.  Could this be enough evidence to assume that Alice’s adventure to Wonderland was indeed Carroll’s life?

The “DRINK ME” bottle and “EAT ME” cake ingredients

Alice found no information in the bottle nor the glass box, except for direct instructions to eat it and drink it. Hence, she could not determine the reason for her shrinking and growing. Similarly, AIWS is a rare disorder with very little clinical research to elucidate it. There are no large scale epidemiological studies conducted and the estimated percentage of patients worldwide is assumed to be only around 10%, while the causes are thought to be varied. Commonly, headaches, epileptic cases, infectious diseases such as Epstein-Barr virus, brain and psychiatric conditions, cerebrovascular diseases and drugs are reported as etiologies (Moawad, 2016). Studies show evidence for cerebral damages in AIWS patients. When a blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) brain scan was performed on a 12-year old boy with Streptococcus infection – onset AIWS, activation of the visual cortical areas was lower during a micropsia episode (figure 1) (Brumm et al., 2010). Another study among children between 3 and 10 with AIWS observed reduced blood flow in the temporal-occipital lobe and perisylvian area (Kuo, Chiu, Shen, Ho, & Wu, 1998). A study that assessed the brain areas responsible for perception of body size concluded that the illusion of waist shrinking is mediated by higher-order somatosensory areas in the parietal cortex (Ehrsson, Kito, Sadato, Passingham, & Naito, 2005). Hence, could the drink and the cake that caused Alice to shrink or grow possibly be sensory effects caused by neural networks that followed unique signalling pathways in response to a stimulus?

The endless tea party

The mad tea party in Wonderland had a large table, but the Dormouse, Hatter and March hare were all crammed up in a corner and complained that there wasn’t enough room for Alice. The research on AIWS is much the same. Time is as large as the table but just a few AIWS patients at the table, ready to be studied, with much of the research on AIWS coming from high-income countries such as North America and Europe. Since the studies have small sample sizes, the results are prone to ambiguity and false positives (Moawad, 2016). Therefore, more invites should be sent out for the tea party! Organising global research efforts to study AIWS can help form concrete theories regarding the pathogenesis and epidemiology of the disorder, thereby facilitating the formation of a univocally accepted diagnostic criteria. Data from observational studies and an accepted diagnostic criterion will minimise misdiagnosis while catalysing translational research to discover novel therapeutics that can help Alices worldwide to finally leave Wonderland. 

While we commemorate ‘Rare diseases Day’ on the 28^th of February, let us remember to support research on rare diseases such as AIWS because extensive studies determining the genetics and molecular patterns of such diseases will pave the way for the discovery of novel treatments, bringing hope to those suffering in silence. While it is true that rare diseases affect only a very small fraction of the global population and that drug discovery costs exceed the potential return on investment, it is an important factor in the physical and emotional burden on people with rare diseases and their loved ones. Should people and children with rare diseases be denied the good quality of life that most of us take for granted? Should access to medication be the right of some and not all? The ethnic dilemma continues.

The medical landscape has changed considerably in the last two decades. Gene therapy and molecular medicine along with interdisciplinary collaborations between biologists and engineers have made discovery research more efficient. We can now sequence the human genome and even single cells in any tissue. The advent of such high throughput techniques coupled with advancements in technology and the power of big data should enable simultaneous research of rare diseases because it allows easy comparability of data and extrapolation of information to benefit more than one demography. It is even possible that robust research conducted to better understand these rare diseases can help identify treatment mechanisms for the more prevalent disease conditions. For example, by the enhanced understanding of the rare disease cystic fibrosis, it was found that the mutant gene present in the rare condition also accounts for male infertility and alcohol-induced pancreatitis. Hence, developing promising treatments for rare diseases could be repurposed to alleviate the severity of common diseases. 

Author: Esther Swamidason

References

• Brumm, K., Walenski, M., Haist, F., Robbins, S. L., Granet, D. B., & Love, T. (2010). Functional magnetic resonance imaging of a child with Alice in Wonderland syndrome during an episode of micropsia. Journal of American Association for Pediatric Ophthalmology and Strabismus, 14(4), 317–322. https://doi.org/10.1016/j.jaapos.2010.03.007
• Ehrsson, H. H., Kito, T., Sadato, N., Passingham, R. E., & Naito, E. (2005). Neural Substrate of Body Size: Illusory Feeling of Shrinking of the Waist. PLoS Biology, 3(12), e412. https://doi.org/10.1371/journal.pbio.0030412
• Kuo, Y.-T., Chiu, N.-C., Shen, E.-Y., Ho, C.-S., & Wu, M.-C. (1998). Cerebral perfusion in children with Alice in Wonderland syndrome. Pediatric Neurology, 19(2), 105–108. https://doi.org/10.1016/s0887-8994(98)00037-x
• Mastria, G., Mancini, V., Viganò, A., & Di Piero, V. (2016). Alice in Wonderland Syndrome: A Clinical and Pathophysiological Review. BioMed Research International, 2016, 1–10. https://doi.org/10.1155/2016/8243145
• Moawad, H. (2016, August 10). Alice in Wonderland Syndrome. Retrieved February 19, 2022, from Neurology live website: https://www.neurologylive.com/view/alice-wonderland-syndrome

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