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Try out PMC Labs and tell us what you think. Learn More. To summarize the literature on Alice in Wonderland syndrome AIWSa disorder characterized by distortions of visual perception, the body schema, and the experience of time. First described inAlice in Wonderland syndrome AIWS is a perceptual disorder characterized by distortions of visual perception metamorphopsiasthe body schema, and the experience of time.

After 60 years of relative obscurity, AIWS has begun to receive scientific attention. This renewed interest is in part because of the current possibility to explore the brain's networks responsible for mediating its symptoms with the aid of functional imaging techniques. This article presents an overview of the literature on AIWS published over the past 60 years and summarizes its implications for clinical practice and research. All cross-references were checked systematically. The search terms yielded hits in PubMed. Of these, 59 articles had AIWS as their main subject.

Via cross-references an additional 11 articles were found, yielding a total of 70 articles. A total of patients were described, 20 from one case series 7 and 48 from another case series. Because one patient was described twice, 910 the total of original case descriptions was Patient sex was mentioned for patients; Age was mentioned in patients; mean age was Table 1 presents an overview of the many disorders, intoxications, and other conditions that have been described in the context of AIWS.

Among youths, the most frequently described condition was encephalitis Among the group of adults and elderly patients, neurologic disorders were most frequently described The course and outcome were described in patients. In 54 patients One patient received electroconvulsive treatment 11 and another patient received repetitive transcranial magnetic stimulation 2 ; both treatments were successful. The remaining patients received no treatment or it was unspecified. Full remission was obtained in In chronic conditions such as epilepsy and migraine, full remission was obtained only rarely.

Conditions in which Alice in Wonderland syndrome has been described in the literature, with the s of case descriptions per age group. Incidentally, Todd was well aware that he was not the first to describe those individual symptoms. Many of them had appeared before in the literature on hysteria, 13 on general neurology, 14— 17 and on soldiers with occipital wounds after World Wars I and II.

Lippman 21 was also the first to suggest that the bodily changes experienced by Alice might well be inspired by body schema illusions Lewis Carroll had experienced himself. Carroll pseudonym of the British mathematician Charles Lutwidge Dodgson, — had migraines, and his diaries indicate that his attacks were sometimes preceded by aural phenomena. And Todd, by adopting the name, chose a memorable moniker for a group of symptoms hitherto described in isolation of each other.

Over the past 60 years, AIWS symptoms have come to include 42 visual symptoms table 2 and 16 somesthetic and other nonvisual symptoms table 3. What these symptoms have in common with each other is that they constitute distortions of sensory perception rather than hallucinations or illusions.

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Illusions do have a source in the outside world, albeit one that is often fleetingly misperceived or misinterpreted. Thus music may be heard in the drone of passing traffic and a curtain moving in the wind may be mistaken for an intruder. Like illusions, distortions are based on sensory impressions, but they feature highly specific changes in highly specific aspects of the sensory input picture.

For example, all straight lines may be perceived as wavy dysmorphopsiaall vertical lines as slanted plagiopsiaall stationary objects as moving kinetopsiaor all eyes as unnaturally big prosopometamorphopsia.

Strikingly, micropsia and macropsia have been described most frequently in the literature in Visual distortions metamorphopsias that may be experienced in the context of Alice in Wonderland syndrome.

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Somesthetic and other nonvisual distortions that may be experienced in the context of Alice in Wonderland syndrome. The duration of symptoms of AIWS tends to be short, mostly on the order of minutes to days 26 ; however, symptoms may also persist for years 2 or even be lifelong. In the historical literature this phenomenon has been explained as a of cerebral asthenopia 2829 i. No epidemiologic data on AIWS in the population at large are available. A second cross-sectional study of 3, high school students 32 found 6-month prevalence rates of 3. A third cross-sectional study 33 of individuals with a median age of This study also showed that This buildup might indicate a common underlying etiologic process responsible for the mediation of all 4 symptoms or a stochastic process in which the presence of one symptom lowers the threshold for another one to in.

The symptoms of AIWS are attributed to functional and structural aberrations of the perceptual system.

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Area V4 of the extrastriate visual cortex, for example, responds selectively to color, whereas area V5 responds to movement. Both areas also respond to shape and depth, but bilateral loss of function of V4 in achromatopsia the inability to see color and bilateral loss of V5 in akinetopsia the inability to see motion.

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The inability to visually perceive vertical lines plagiopsia or lines under a different angle is attributed to loss of function of orientation columns that are grouped together throughout the horizontal layers of visual cortex. Similarly, various neuron populations have been identified as being responsible for mediating different types of metamorphopsia, and for other metamorphopsias educated guesses have been made.

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An example of the latter situation can be found in complex types of prosopometamorphopsia, in which human faces may be perceived consistently as animal faces, 27 and even in an apparently straightforward symptom such as micropsia, which was found to be associated with a consistent pattern of occipital hypoactivation and parietal hyperactivation in an fMRI study. In these cases, parts of the network located around the parieto-temporo-occipital junction are responsible, 37 although here too a mismatch between higher-order components of the network as a whole may be at play, as in ischemia of distal parts of the anterior cerebral arteries that supply parts of the perceptual network responsible for integrating composite sensory data for awareness of the body schema.

The conditions responsible for mediating the symptoms of AIWS are legion. Table 1 presents those described so far in the literature, classified into 8 main groups. The list of conditions associated with AIWS is long and is expected to grow even longer when more cases and case series are published. Cases with a suspected central origin should prompt auxiliary investigations including blood tests, EEG, and brain MRI scan, even though the chances of finding any demonstrable lesions are generally considered to be low.

The differential diagnosis of AIWS and its individual symptoms is complex, as it involves at least 3 levels of conceptualization. First, the symptoms need to be distinguished from other positive disorders of perception such as hallucinations and illusions, with which they may be easily confused. Second, their most likely cause needs to be established. As table 1 indicates, many diagnoses are possible. Therefore, third, whether the diagnosed condition may be responsible for mediating the symptoms must be established. Because metamorphopsias and other distortions are also experienced by individuals in the general population, situations may arise in which the disorder diagnosed is not causally connected with the symptoms at hand or in which a therapeutic intervention turns out to be the actual cause.

Most nonclinical and clinical cases of AIWS are considered benign, in the sense that full remission of the symptoms can often be obtained, sometimes spontaneously and in other cases after proper treatment. However, in clinical cases with an underlying chronic condition such as migraine and epilepsysymptoms tend to recur in concordance with active phases of the disease, and in cases of encephalitis the prognosis may also vary. As a consequence, the need to treat requires careful assessment, proper knowledge of the natural course of the various underlying conditions that are possible, and a careful explanation to the patient of what to expect from which therapeutics under which circumstances.

In many cases reassurance will suffice. Whenever treatment is considered useful and necessary, it needs to be aimed at the suspected underlying condition. In clinical practice this mostly involves the prescription of antiepileptics, migraine prophylaxes, antiviral agents, or antibiotics.

The literature indicates that antipsychotics are rarely prescribed 7 and that in most cases their effectiveness is considered marginal. Moreover, when distortions are experienced as comorbid symptoms in patients with psychosis, it is important to take into the possibility that they can sometimes be induced or aggravated by antipsychotics because of their potential to lower the threshold for epileptic activity as has been described for risperidone.

The of case descriptions of AIWS is small, especially considering the fact that the syndrome appears to be seriously underdiagnosed and that individual symptoms may be systematically neglected. This may be at least partly because international diagnostic classifications have so far refrained from including the syndrome. The operational definition of AIWS and its diagnostic criteria are in need of further development.

More specifically, the question remains whether distortions in the olfactory, gustatory, auditory, sexual, coenesthetic, kinesthetic, proprioceptive, algesic, vestibular, and thermic modalities should be added to the list of possible symptoms of AIWS. Other limitations are the lack of systematic epidemiologic data and our limited insight into the many etiologic and pathophysiologic mechanisms possible in this context.

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Functional imaging techniques such as SPECT and fMRI have the potential to aid in localizing the network structures involved in mediating the symptoms of AIWS; however, so far, only 5 case reports have been published, 2— 6 probably because patients with longer-lasting distortions are hard to find and contrast als in individual patients may be weak. Sinceno more than case descriptions of AIWS have been published. Although reassurance seems to suffice in roughly half of the clinical cases, the suspicion of a central origin of the symptoms should prompt auxiliary investigations in the form of blood tests, EEG, and brain MRI.

Although firm evidence to justify these auxiliary investigations is lacking, I recommend them on clinical grounds because of the spectrum of known etiologies and the prospect of improved outcome in a substantial of cases after adequate treatment. Treatment, if necessary, needs to be directed at the suspected underlying cause. Regarding research, much larger patient sample sizes are needed to allow for sufficient statistical power of empirical studies of AIWS and its individual symptoms. In addition, epidemiologic surveys in the population at large are needed to establish sound prevalence data.

As an alternative or an adjuvant strategy, one might consider creating an international database for cases of AIWS, with special attention paid to phenomenological characteristics, diagnostic findings including substance abusenatural course, and treatment. For such a database to be effective, all new cases of AIWS should be subjected to a systematic assessment, including proper history-taking, neurologic and other physical examinations, and auxiliary investigations.

In chronic cases, functional imaging techniques may be helpful in establishing specific neurobiological correlates of individual symptoms although there are often various practical obstacles to be overcome. Last but not least, our insight into the nature of AIWS might be enhanced by network analyses of the mutual relationships of individual symptoms as well as their relationships with the perceptual networks underlying them. In the meantime, however, it is possible to carry out a careful diagnostic procedure to help this partly hidden group of patients obtain a proper diagnosis and, if possible, adequate reassurance and, if necessary, appropriate treatment.

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AIWS is characterized by perceptual distortions rather than hallucinations or illusions and therefore needs to be distinguished from schizophrenia spectrum and other psychotic disorders. When symptoms of AIWS are transient and not associated with any other pathology, reassurance that the symptoms themselves are not harmful may suffice. Based on the large spectrum of known etiologies and the prospect of improved outcome, I recommend auxiliary investigations to address symptom reoccurrence causing major distress or dysfunction, with or without other pathology.

Supplemental data at Neurology. Full disclosure form information provided by the author is available with the full text of this article at Neurology. National Center for Biotechnology InformationU. Journal List Neurol Clin Pract v. Neurol Clin Pract. Author information Article notes Copyright and information Disclaimer.

Corresponding author. Correspondence to: : ln. Funding information and disclosures are provided at the end of the article.

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The Article Processing Charge was paid by the author. Received Oct 11; Accepted Jan The work cannot be changed in any way or used commercially. This article has been cited by other articles in PMC. Abstract Purpose of review: To summarize the literature on Alice in Wonderland syndrome AIWSa disorder characterized by distortions of visual perception, the body schema, and the experience of time. Open in a separate window.

Figure 1. Alice experiences total-body macrosomatognosia. Illustration by John Tenniel Figure 2. A Alice experiences partial macrosomatognosia, and B Alice experiences total-body microsomatognosia. Illustrations by John Tenniel Table 1. Phenomenology Over the past 60 years, AIWS symptoms have come to include 42 visual symptoms table 2 and 16 somesthetic and other nonvisual symptoms table 3.

Table 2. Table 3. Pathophysiology The symptoms of AIWS are attributed to functional and structural aberrations of the perceptual system. Treatment and prognosis Most nonclinical and clinical cases of AIWS are considered benign, in the sense that full remission of the symptoms can often be obtained, sometimes spontaneously and in other cases after proper treatment. Limitations The of case descriptions of AIWS is small, especially considering the fact that the syndrome appears to be seriously underdiagnosed and that individual symptoms may be systematically neglected.

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Take-home points AIWS is characterized by perceptual distortions rather than hallucinations or illusions and therefore needs to be distinguished from schizophrenia spectrum and other psychotic disorders When symptoms of AIWS are transient and not associated with any other pathology, reassurance that the symptoms themselves are not harmful may suffice Based on the large spectrum of known etiologies and the prospect of improved outcome, I recommend auxiliary investigations to address symptom reoccurrence causing major distress or dysfunction, with or without other pathology In clinical cases, treatment needs to be directed at underlying conditions.

Footnotes Supplemental data at Neurology. Carroll L. Alice's Adventures in Wonderland. London: MacMillan and Co. Treatment of Alice in Wonderland syndrome and verbal auditory hallucinations using repetitive transcranial magnetic stimulation. A case report with fMRI findings. Psychopathology ; 44 — Clin Nucl Med ; 38 — Cerebral perfusion in children with Alice in Wonderland syndrome.

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