Jürgens TP, Ihle K, Stork JH, May A. "Alice in Wonderland syndrome" associated
with topiramate for migraine prevention. J Neurol Neurosurg Psychiatry. 2011
Various visual and sensory phenomena have been described in migraine with aura. Among those, the 'Alice in Wonderland' syndrome is defined as a distortion of the body image with the patient being aware of its unreal nature. Here, the case of a 17-year-old girl with migraine without aura who developed an 'Alice in Wonderland' syndrome repeatedly on topiramate treatment was presented and potential pathophysiological concepts were discussed.
Evans RW. Reversible palinopsia and the Alice in Wonderland syndrome
associated with topiramate use in migraineurs. Headache. 2006 May;46(5):815-8.
Two patients are reported who developed palinopsia while taking topiramate for migraine prevention which resolved or decreased in frequency or duration on lower doses, but recurred or increased in frequency or duration on higher doses. Both patients had complete resolution of palinopsia when topiramate was discontinued. A third patient is described who developed the "Alice in Wonderland" syndrome about 1 week after starting topiramate for migraine prevention with complete resolution of symptoms about 1 month after stopping. Topiramate use may cause palinopsia and may be associated with the Alice in Wonderland syndrome through an unknown mechanism.
From the past:ReplyDelete
Golden GS. The Alice in Wonderland syndrome in juvenile migraine. Pediatrics.
Two children are reported who had recurrent attacks of impairment of time sense, body image, and visual analysis of the environment. These occurred with a clear state of consciousness and in the absence of any evidence of an encephalitic process, seizures, drug ingestion, or psychiatric illness. Both children had recurrent headaches; one was clearly migrainous. There was a family history of migraine in both cases. These children represent examples of the Alice in Wonderland syndrome in juvenile migraine.
In 1952, the American neurologist Caro W. Lippman (1886–1954) described a very curious transient neurological phenomenon in 7 migraineurs, characterized by the incorrect perception of the body image and perceptual distortions of form, size, movement, color, and speed (ie, metamorphopsia). During these paroxystic episodes the subjects are aware of the illusory nature of their perceptions, which are sometimes accompanied by fear and terror and, especially in the pediatric population, screaming may be part of the clinical picture...ReplyDelete
These rare neurological manifestations were coined "The syndrome of Alice in Wonderland" by the British psychiatrist John Todd (1914–1987) in 1955, because they were very similar to what Charles Lutwidge Dodgson (1832–1898), using the pseudonym Lewis Carroll, described when he wrote "Alice's Adventures in Wonderland" (1865).
Some authors suspected that Dodgson was inspired by his own experience with migraine auras, although there is no reference as to whether he experienced any form of metamophopsia himself. Dodgson was a brilliant mathematician in Oxford who suffered from migrainous auras (many of them without the accompanying headache), which was interpreted as "right paracentral negative scotoma." At around 24 years of age, he consulted an oculist about a problem in his "right eye." Some described him as handsome and asymmetric; a stammerer, he used to write with his right hand but may have been initially left-handed, and a mirror writer. During his childhood a fever left him deaf in one ear. Thus, it is not clear whether all the microsomatognosia or macrosomatognosia or other metamorphopsia used in his classical novel was really the result of illusions secondary to a selective brain lesion or even real migrainous somesthetic auras that inspired him, or whether it was only the fruit of his imagination.
Children and young adults appear to be more susceptible to this syndrome. Thus, we wonder whether there is a degree of immaturity in the brain of subjects with AWS, since the manifestations of the syndrome do not appear to return at a later stage of life, although some individuals may present the illusory crises from childhood through to adult life. AWS may be classified as a migraine variant (or equivalent), as children affected may develop headache (especially migraine with aura) years after presenting the typical illusory episodes in the absence of headache. The AWS associated with migraine was not included among the headache disorders classified in ICHD-3 Beta and apparently no diagnostic criteria were established. After a review of the literature, we understand that the neurological manifestations of the AWS are in the form of short (seconds to few minutes) episodes of hallucination or illusion, affecting mainly individuals with a history of throbbing headache, particularly migraine with aura. Sometimes AWS occurred not only in the son or daughter but also in one of the parents, suggesting some degree of genetic susceptibility. Migraine-associated AWS is a diagnosis of exclusion and the patient should be evaluated with MRI, CSF, and EEG (preferably video-EEG during an illusory episode). Visual evoked potentials may be abnormal.
(continued) Blom enumerated several symptoms found in AWS: (1) derealization (perception that the external world is unreal); (2) depersonalization; (3) somatopsychic duality; (4) perceptual symptoms (illusory changes in the size, distance, or position of stationary objects, ie, metamorphopsias, such as micropsia, macropsia, lilliputianism [seeing people as miniature individuals]) dysmetropsia [distorted perception of the image size], macroproxiopia [visual distortion of the size and distance of the object], microtelepsia [perceiving the object smaller and further away than it is], teleopsia [visual distortion in which the objects appear to be either further away or closer than they actually are], and plagiopsia [objects are perceived as inclined]); (5) illusory feelings of levitation; (6) illusory alterations of time perception; (7) hyperschematia/hyposchematia (contralesional [usually left] expansion or reduction, respectively, of objects); and (8) body schema illusions (micro- or macrosomatognosia [part of the body is experienced as disproportionally small or large, respectively], splitting of the body image). The metamorphopsia may or may not be associated with hallucinations (eg, auditory or visual perceptions of unreal things).ReplyDelete
Visual illusion is a misperception of real external stimuli, affecting axis, distance, size, shape, motion, number of images, extinction, and memory. Podoll and colleagues described AWS as "a variety of self-experienced paroxysmal body schema disturbances (obligatory core symptoms of the AWS) which may co-occur with depersonalization, derealization, visual illusions, and disorders of the time perception, either speeding up or slowing down (facultative symptoms of the AWS)."
AWS was also reported to be caused by epilepsy seizure, acute viral infection (Epstein-Barr virus, varicella, Coxsackie virus B1, H1N1 influenza virus),[84,98–100] encephalitis, Lyme neuroborreliosis,[ psychoactive substance abuse (mescaline, LSD, dextromethorphan, cannabis), hyperpyrexia, and hypnagocic states. Cough syrup (dihydrocodeine phosphate and methylephedrine hydrochloride) use was also reported as a possible cause of AWS. A similar pattern of hallucination and illusion can occur in schizophrenia. During viral infection, pleocytosis may be found and the diagnosis may be regarded as a secondary form of HaNDL, because the illusionary symptoms are the result of a focal brain dysfunction.
Among the 8 children (7–16 years of age) in migraine-associated AWS, 5 were female (63%). In 5 of them the attacks were of <5 minutes duration and in the remaining 3, between 10 and 30 minutes. In a 4-year-old girl the syndrome occurred for 24 hours and was triggered by dextromethorphan as a cough suppressant. In a 15-year-old boy, the illusions appeared after cannabis use.ReplyDelete
Although illusory symptoms may precede the headache episode, they can occur with no clear relationship to it. Of unpredictable onset, the short duration of the attack (usually less than 10 minutes) does not justify its being considered a result of spreading depression (longer-lasting), and it does not display the characteristic progression of a typical migraine aura. It is postulated that the supposed cortical dysfunction in the syndrome may be the result of transient local oligemia or an irritative stimulus in the cerebral cortex.
A retrospective study evaluated 20 children with AWS (infectious cause 9, migraine 8, toxic 2, epilepsy 1). In this series of cases, the symptomatology was as follows: micro-/macropsia (90%), distortions in the forms of objects (85%), displacement of objects (80%), disturbances of body image (40%), acceleration of time (45%), and sensation of unreality (30%). (continued)
(continued) Investigation with MRI is normal. In secondary AWS, brain damage may be encountered involving the parieto-temporal-occipital carrefour, an area associated with spatial processing and body image (particularly the posterior part of the parietal lobe of the nondominant side). Stimulation of the posterior parietal cortex causes autoscopic hallucination (the perception of yourself as an external parallel object, with the delusion that you have a double), a sensation of somatic elongation and illusory disappearance of any of the four limbs, suggesting that this cerebral region is involved during the attacks in AWS.ReplyDelete
In a 56-year-old woman, with a simple partial status epilepticus and continuous metamorphopsia reported as illusions of faces, which were "distorted and swollen, appearing grotesque," a single-photon emission computed tomography (SPECT) study showed an increase in the blood flow in the ventrolateral aspect of the right temporo-occipital junction, corresponding to the middle and inferior occipital, and inferior temporal gyri Interestingly, months earlier, she had presented episodes of flickerings in the left visual field and a zoom sensation of objects, which wasInvestigation with MRI is normal. In secondary AWS, brain damage may be encountered involving the parieto-temporal-occipital carrefour, an area associated with spatial processing and body image (particularly the posterior part of the parietal lobe of the nondominant side). Stimulation of the posterior parietal cortex causes autoscopic hallucination (the perception of yourself as an external parallel object, with the delusion that you have a double), a sensation of somatic elongation and illusory disappearance of any of the four limbs, suggesting that this cerebral region is involved during the attacks in AWS.
In a 56-year-old woman, with a simple partial status epilepticus and continuous metamorphopsia reported as illusions of faces, which were "distorted and swollen, appearing grotesque," a single-photon emission computed tomography (SPECT) study showed an increase in the blood flow in the ventrolateral aspect of the right temporo-occipital junction, corresponding to the middle and inferior occipital, and inferior temporal gyri. Interestingly, months earlier, she had presented episodes of flickerings in the left visual field and a zoom sensation of objects, which was followed by headache in her right occipital region. This indicates that dysfunctions in this cerebral area can not only cause metamorphopsia but may also trigger a headache attack lateralized to the same side.
Since only a limited amount of articles have been published involving a small number of patients with AWS, guidelines to treat these patients are lacking. Three children with recurrent episodes were treated with flunarizine. A patient with abdominal migraine and AWS presented a good prophylactic response after using valproate (1000 mg/day)] Interestingly, topiramate, when used as prophylactic treatment in migraineurs, can also induce AWS attacks. A 17-year-old girl reported that after 4 months of treatment and with a dose of topiramate increased to 75 mg/day, nocturnal distortions of her body image occurred, ie, "her head would grow bigger and the rest of the body would shrink or her hand…would increase in size and become heavier, while the remaining arm would become smaller."
Blom JD. Alice in Wonderland syndrome: A systematic review. Neurol Clin Pract. 2016 Jun;6(3):259-270.ReplyDelete
PURPOSE OF REVIEW:
To summarize the literature on Alice in Wonderland syndrome (AIWS), a disorder characterized by distortions of visual perception, the body schema, and the experience of time.
On the basis of 169 published case descriptions, the etiology of AIWS is divided into 8 main groups, with neurologic disorders affecting mostly adults and elderly patients and encephalitides affecting mostly patients aged ≤18 years. Symptoms of AIWS are also experienced in the general population, with up to 30% of adolescents reporting nonclinical symptoms.
In clinical cases of AIWS, auxiliary investigations (including blood tests, EEG, and brain MRI) are strongly advised. 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 the cases. International classifications such as the DSM and ICD should consider placing the syndrome on their research agenda.
No epidemiologic data on AIWS in the population at large are available. Although it is generally assumed that the syndrome is rare, clinical studies among patients with migraine indicate that the prevalence rate in this group may be around 15%. Moreover, some studies indicate that individual symptoms of AIWS are not rare in the general population. A cross-sectional study of 1,480 adolescents found a lifetime prevalence of micropsia and/or macropsia of 5.6% for males and 6.2% for females. A second cross-sectional study of 3,224 high school students found 6-month prevalence rates of 3.8% for micropsia, 3.9% for macropsia, 2.5% for protracted duration, and 1.3% for the quick-motion phenomenon. A third cross-sectional study 33 of 297 individuals with a median age of 25.7 years found lifetime prevalence rates of 30.3% for teleopsia, 18.5% for dysmorphopsia, 15.1% for macropsia, and 14.1% for micropsia. This study also showed that 38.9% of the affected individuals experienced a single symptom, 33.6% experienced 2, 10.6% experienced 3, and 16.8% experienced 4. 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 join in...
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. One of those groups is “substance-induced,” also known as hallucinogen persisting perception disorder (HPPD), a nosologic construct featured in the DSM-5 and other classifications as a separate diagnostic category that covers perceptual symptoms that arise during (or after the cessation of) the use of illicit substances. The list of conditions associated with AIWS is long and is expected to grow even longer when more cases and case series are published.