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The Alice in Wonderland Syndrome
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The Alice in Wonderland Syndrome
Edward J. Fine1 University Neurology Service and The Jacobs Neurological Institute, Department of Neurology, University at Buffalo, The State University of New York, Buffalo General Medical Center, Buffalo, NY, USA 1 Corresponding author: Tel.: þ1-716-932-6080, extension 102, Fax: þ1-716-332-4245, e-mail address: [email protected]
Abstract The Alice in Wonderland syndrome is a term applied to altered bizarre perceptions of size and shapes of a patient’s body and illusions of changes in the forms, dimensions, and motions of objects that a patient with this syndrome encounters. These metamorphopsias arise during complex partial seizures, migraine headaches, infections, and intoxications. The illusions and hallucinations resemble the strange phenomena that Alice experienced in Lewis Carroll’s Alice’s Adventures in Wonderland. Charles Lutwidge Dodgson, whose nom de plume was Lewis Carroll, experienced metamorphopsias. He described them in the story that he wrote for Alice Liddell and her two sisters after he spun a tale about a long and strange dream that the fictional Alice had on a warm summer day. The author of this chapter suggests that Dodgson suffered from migraine headaches and used these experiences to weave an amusing tale for Alice Liddell. The chapter also discusses the neurology of mercury poisoning affecting the behavior of Mad Hatter character. The author suggests that the ever-somnolent Dormouse suffered from excessive daytime sleepiness due to obstructive sleep apnea.
Keywords Alice in Wonderland syndrome, Lewis Carroll, Charles L. Dodgson, epilepsy, Epstein– Barr virus, excessive daytime sleepiness, LSD, Lyme disease, metamorphopsias, migraine headache, narcolepsy, palinopsia, sleep apnea
1 INTRODUCTION The British psychiatrist John Todd (1914–1967) first used the memorable term “Alice in Wonderland syndrome” (AIWS) to describe a “singular group of symptoms intimately associated with migraine and epilepsy, although not confined to these Progress in Brain Research, Volume 206, ISSN 0079-6123, http://dx.doi.org/10.1016/B978-0-444-63364-4.00025-9 © 2013 Elsevier B.V. All rights reserved.
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disorders” in 1955 (Todd, 1955). Todd provided medical histories of five adults and an adolescent who had suffered from illusions of alterations of their body images or their external surroundings associated with attacks of migraine headaches or epileptic seizures or a combination of these disorders. Todd’s patients felt they were too small, too tall, or parts of their bodies were changing shape, size, or relationship to the rest of their bodies. Some recalled the feeling of their bodies expanding or contracting in closed spaces or splitting in half. He proposed that these illusions of body image could be the equivalent of more common manifestations of complex partial seizures or migraine headaches. Todd proposed the term AIWS to summarize the wide spectrum of these illusory symptoms. Todd coined the term based upon Lewis Carroll’s book, Alice’s Adventures in Wonderland (Carroll, 1866; Carroll, 2002). The term AIWS has been applied to self-reported somatosensory alterations associated with epilepsy, migraine headaches, intoxications, and infectious diseases after Todd coined the term in 1955. The number of reports in which AWIS appears has grown from single-case histories to a series of histories and outcomes of 10 or more adults or children (Ho et al., 1992; Weidenfeld and Boursiak, 2011). This chapter discusses the history of the syndrome and its etiologies and explains how it is manifested in Carroll’s characters and apparently in Carroll himself. The chapter also summarizes theories about the physiology of this disorder and migraine headache. The author explores controversies and speculations arising from Charles Lutwidge Dodgson’s illnesses that may have been expressed in his writings under the pseudonym of Lewis Carroll.
2 THE ETIOLOGY OF THE ALICE IN WONDERLAND SYNDROME (AIWS) Todd coined the term when he cited Caro W. Lippman’s paper describing two patients who said they experienced a sensation of becoming short and wide during attacks of migraine headache (Lippman, 1952). One patient referred to this sensation as her “Tweedledum or Tweedledee feeling.” That patient recalled the short, barreled-shaped creature depicted in Lewis Carroll’s “Through the Looking Glass and What Alice Found There.” Lippman claimed that he discovered that certain patients suffering from migraine experienced unique “hallucinations” related to their body image and distortions of “the entire body or certain parts of their body.” He prompted these patients by directly asking “Do you have any unusual body sensations just before, during or just after the headache?” Lippman recorded the “hallucinations” of seven patients, some of whom felt that their body had split in half and the remaining half had either shrunk or grown excessively large. Some of Lippmann’s patients were reluctant to explain their odd feelings as they believed they would be considered “crazy.” Case 1 of Lippman’s patients felt she was “about one foot tall” during or before the onset of her headache. This patient confirmed that she was hallucinating when she gazed at her reflection in a mirror and saw that she was her normal height. Lippman’s sixth
2 The Etiology of the Alice in Wonderland Syndrome (AIWS)
patient stated “I get tired from pulling my head down from the ceiling. My head feels like a balloon.” (Lippman, 1952, pp. 345–346). Corbett also noted that patients with migraine headaches and complex illusions were reticent about describing these phenomena until he reassured them. Corbett suggested that children be encouraged to draw what they saw during their episodes of migraine headache and complex visual illusions (Corbett, 1983, pp. 982–984). Lippmann believed that Charles Lutwidge Dodgson (1832–1898), whose nom de plume was Lewis Carroll, suffered from migraine headaches (Lippman, 1952, p. 351). Dodgson was a lecturer in mathematics at Christ Church College, Oxford, England (Fig. 1) (Rolak, 1991). During a rowing trip up the Thames River on July 4, 1862 with Alice Liddell, her two sisters, and his friend the Reverend Robinson Duckworth, Dodgson told a story about a fictional girl named Alice and her dream. Alice Liddell and her two sisters were the daughters of George Liddell, the Dean of Christ Church College. Alice Liddell enjoyed the story so much that she begged Dodgson to write out the story. Dodgson presented Alice with the manuscript, Alice’s Adventures Under Ground, along with his hand drawn illustrations, as a Christmas present in 1862 (Gardener, 1990; Rolak, 1991). The manuscript was published as Alice’s Adventures in Wonderland (Magnusson, 1990, p. 426) (Fig. 2). Lippman made the unsupportable claim that he was the first to describe these migraine equivalents. Hermann Oppenheim (1858–1919), a German-Jewish
FIGURE 1 Charles L. Dodgson, aka Lewis Carroll.
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FIGURE 2 Frontispiece—Alice’s Adventures in Wonderland.
neurologist, had noted in 1913 that one of his patients who suffered from migraine headaches manifested the syndrome. He stated, “Ich habe gesehen in denen an Stelle der echten Hemikranie ein heftiger Schmerz, einer umschreibenen Partie des Rumpfes oder Extremitat sich einstellte der nach einer Dauer von einigen Stunde or einem Tage spontan schwand . . .” (I have seen a case of genuine hemicrania in which there was during an episode of violent migraine an indescribable feeling of detachment of the trunk or extremity after an hour or even a day of spontaneous dizziness—author’s translation) (Oppenheim, 1913, p. 1567).
3 Alice’s Odd Sensations of Body Image and Surroundings
3 ALICE’S ODD SENSATIONS OF BODY IMAGE AND SURROUNDINGS Todd and Lippman drew inferences from Alice’s Adventures in Wonderland to support their thesis that migraine sufferers and persons with epilepsy endure experiences similar to Alice’s. Key passages from Alice’s Adventures in Wonderland support these authors’ claim that their patients experienced changes in body size (metamorphopsia), altered relationships with internal and external space, and odd sensory distortions. Alice dreamed that she followed a white rabbit down a large hole and fell down into a strange world. In that place, she was too large to enter a picturesque garden. She drank the contents of a bottle marked “DRINK ME.” She then began to shrink until she was only 4 inches tall and could enter the garden through a low door. But then, she had forgotten to take the golden key she saw on a glass table that would unlock the door. Despairing that she could not climb up the slippery glass legs of the table, she spied a glass box that was labeled “EAT ME,” which contained cake. After consuming the cake, she felt that her body was expanding like a telescope until her head now 9 feet above the floor struck the roof of the room outside the garden. She was able to reach the key. Alice then began to shrink back to about 2 feet tall (Carroll, 2002, pp. 8–20). Her body size and relation to her surroundings changed rapidly as did Lippman’s and Todd’s patients. Alice again experienced shrinkage of her trunk when she ate a portion of a mushroom that the blue Caterpillar offered her. Her chin suddenly dropped to her feet. A bite from another side of the mushroom made her neck elongate immensely so that a pigeon mistook her for a serpent (Carroll, 2002, pp. 56–63). These odd distortions of body parts, becoming too small or too large, are termed metamorphopsias. The Victorian era neurologist William Gowers (1845–1915) (Fig. 3) reported that patients with seizures experienced feelings of “unreality in what is seen” (Gowers, 1907, p. 21). Objects seemed unreal “as if in a picture” (Gowers, 1907, p. 31). The patient with migraine headaches or seizures arising in the parietal lobe experiences visual hallucinations, perceiving objects as smaller (micropsia) or larger (macropsia) than they actually are (Critchley, 1949). Hachinski and colleagues followed 100 children with migraine headaches of which 16 had visual distortions and hallucinations. The children in their series saw parents or objects upside down and people too small, and one child recalled a horrific hallucination of lying on a railroad track with a train passing over her all associated with headaches (Hachinski et al., 1973). Evans and Rolak described a patient who felt that her body was too big and everything else was too small; in other instances of her migraine attacks, the converse occurred. She was aware that these abnormal feelings were not reality. Her EEG was normal. All of these events were followed by a pounding headache and excessive sensitivity to light and noise, consistent with a diagnosis of complicated migraine (Evans and Rolak, 2004). These case histories mirror the changes in body size visual distortions that the fictional Alice experienced.
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FIGURE 3 William Richard Gowers, FRCP.
4 PHYSIOLOGY OF MIGRAINES MAY EXPLAIN ALICE’S METAMORPHOPSIAS AND CONFUSIONAL STATE Migraine headaches are triggered by stress, red wine and less commonly other alcoholic beverages, nitrate and nitrite-containing foods, aspartame, and smoked foods. Skipping meals can trigger migraines. Once nausea occurs during a migraine headache, the sufferer stops eating or vomits. Hypoglycemia and depletion of potassium that follow intense vomiting increase the intensity of the headache. Evidence for chocolate as a migraine trigger appears tenuous (Silberstein et al., 2008, pp. 180–183). Dodgson referred to his headache as “bilious,” with vomiting so severe as to expel bile. Dodgson avoided alcohol, perhaps because he learned that it triggered attacks of migraine headaches. A spreading wave of depolarization of cells in the cerebral cortex occurs during migraine headaches. Depolarization of the glial cells causes extracellular release of potassium and calcium ions, nitric oxide, and arachidonic acid. Meningeal nociceptor axons are activated by these substances. Nociceptor neurons are part of the trigeminal nerve’s regulation of the brain’s vascular system that becomes activated during a migraine headache. Because of the trigeminal nerve’s connections to the thalamus and thalamic projections onto the sensory cortex, migraine patients feel intense cranial pain during an attack (Charles, 2009; Dalkara et al., 2006).
6 Infections that Induce AIWS
5 CONFUSIONAL STATES ASSOCIATED WITH MIGRAINE OR EPILEPSY Alice’s inability to recite the multiplication tables or a well-known poem to the blue Caterpillar reflects the marked confusion that can occur during a severe migraine headache or after a generalized or partial complex seizure (Golden, 1979; Carroll, 2002, pp. 52–54). However, AIWS is not restricted to persons with migraine headaches or epilepsy.
6 INFECTIONS THAT INDUCE AIWS Viral infections that cause encephalopathy can be associated with the AIWS. H1N1 influenza virus caused an 11-year-old girl to be frightened by hallucinations of her parents talking to her and moving too slowly around her. She was alarmed by the hallucination of a picture zooming in and out. Her real-time polymerase chain reaction test for H1N1 influenza was positive and serology tests for Epstein–Barr virus (EBV) were negative. Her micropsia and macropsia disappeared after Tamiflu antiviral therapy (Augarten and Aderka, 2011). Copperman first described visual hallucinations in two adolescents and a 9 ½year-old boy associated with infectious mononucleosis. One teenage girl saw objects “being more distant than they actually were” and images that were out of focus, shrinking, and enlarging. Her physical examination demonstrated an enlarged spleen and lymph nodes. She had a positive monospot test and an increased heterophile agglutination test confirming the clinical diagnosis of mononucleosis. She made a full recovery after 8 months. The other adolescent girl noted alterations in sizes and shapes for 2 months. She had a positive heterophile agglutination test, spleen enlargement, and increased monocytes in her blood smear (Copperman, 1977). She also made a full recovery. The boy complained of objects seeming to become alternately larger and then smaller than they actually were. He also had swollen lymph nodes, splenic enlargement, increased lymphocytes in his blood smear, and a positive monospot test (Copperman, 1977). Cinbis and Aysun reported that a 7-year-old girl complained of seeing her mother’s head seemed smaller than her body and appeared to her to be colored green for a few minutes. These hallucinations would disappear and then return. Serum tests confirmed the clinical diagnosis of EBV encephalopathy (Cinbis and Aysun, 1991). Coxsackie B1 virus was isolated and identified in the cerebral spinal fluid (CSF) of a 4-year-old boy who had fever, cough, and abdominal pain, but no rash or lymph node enlargement. He complained to his parents that walls were moving in towards him or away from him and that his parents were sometimes too big or too small. He displayed no signs of meningeal irritation; his gait, reflexes, and cranial nerve examinations were normal. The authors entertained the diagnosis of AIWS to account for his visual illusions (Wang et al., 1996). Thus, viral infections can cause visual
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changes (metamorphopsias) similar to those described vividly by Lewis Carroll in Alice’s Adventures in Wonderland. Neuroborreliosis can be associated with AIWS. A 7-year-old boy was evaluated for distorted visual perceptions. He lived in a wooded area where ticks were present. He was frightened by the letters in his storybook becoming smaller and smaller, the book moving away, and he and his father becoming smaller. He had no rashes, fever, headache, or arthralgias. Long-term EEG monitoring did not reveal any changes during these episodes. Laboratory studies revealed increased CSF leukocytes and normal protein and positive serology tests for Lyme disease in serum and CSF. Tests for Bartonella, herpes simplex, enterovirus, cytomegalovirus, and mycoplasma in his CSF were negative. He was treated with intravenous ceftriaxone for 21 days. The micropsia disappeared upon the third day of treatment and never recurred (Binalsheikh et al., 2012). Varicella can cause the AIWS to appear after the onset of the vesicles (Soriani et al., 1998). This 4-year-old girl saw her parents getting smaller and the walls closing in around her. CSF examination was normal, but her EEG contained bilateral posterior slowing activity. She recovered after 3 weeks. Thus, several viruses and the Borrelia spirochete can cause AIWS.
7 INTOXICATIONS THAT CAUSE AIWS Intoxication with drugs that contain chemicals derived from codeine or lysergic acid diethylamide (LSD or “acid”) can induce AIWS in susceptible persons. Takaoka and Takata reported a 46-year-old man who regularly consumed cough medicine and who exhibited metamorphopsias (in this case as distortions of pictures and the television screen), macropsia (as enlarged insects), and feelings of expansion of his own body. His EEG and neurological examination were normal. CT scan of his head revealed only a small “previous” left frontal infarction (Takaoka and Takata, 1999). His visual illusions ended within 1 month after ceasing to consume cough medicine containing dihydrocodeine phosphate and dl-methylephedrine. LSD or “acid” is a potent hallucinogenic agent. Persons who ingest this substance may experience distortions of their vision, false progression of their own body or external objects through space, and reoccurring hallucinations of geometric patterns (Abraham and Aldridge, 1993). Palinopsia, the illusion of persistence of a visual image, after the object has left the field of vision, can follow LSD ingestion. Some persons who have taken LSD repeatedly have described hallucinations that resemble images produced by a stereoscopic camera (Kawasaki and Purvin, 1996). Topiramate, an anticonvulsant often prescribed for prophylactic treatment of migraine headaches, can paradoxically induce AIWS (Ju¨rgens et al., 2011). These authors relate that a 17-year-old girl with migraine headaches felt that her head would grow bigger or shrink from its usual size or that her hands would increase in size and grow heavier when her dose of topiramate was increased to 75 mg/day. Dose reduction to 50 mg/day stopped the attacks and reduced the frequency of her migraine
10 Why Did Lewis Carroll Write About Bizarre Sensory Phenomena?
headaches. Thus, topiramate at a dose toxic for some patients can cause metamorphopsias. Avoidance of topiramate for controlling complicated migraine patients may prevent precipitation of AIWS (Evans, 2006; Ju¨rgens et al., 2011).
8 THE OUTCOME OF AIWS The outcome of AIWS is usually benign, especially for children, except for those patients infected with EBV (Kuo et al., 1998). EBV infections caused AIWS in 3 of 10 children (Ha¨usler et al., 2002). Of the other seven EBV-infected children, one developed a lethal lymphoma and two suffered from long-term effects of encephalitis with seizures. These three children with AIWS were considered to have reactivated EBV. Toxic agents causing migraine can be eliminated or the dose of an offending drug reduced with fortuitous outcomes.
9 THE PHYSIOLOGY OF AIWS Decreased cerebral perfusion has been associated with AIWS. EEG and CT have usually negative in this syndrome. Four patients had metamorphopsias consisting of eyes becoming smaller, seeing blue hues, distorted human faces, and TV pictures seen upside down (Kuo et al., 1998). Nuclear medicine techniques using technetium demonstrated decreased perfusion in frontal lobes, parietal, and temporal lobes and occipital lobes variously in the four patients studied. All scans showed decreased perfusion in the visual tracts and occipital lobes of these patients. These authors noted that these patients’ MRI, CT, and visual evoked potential tests were normal (Kuo et al., 1998). Brumm and colleagues used functional magnetic resonance imaging to demonstrate hypoperfusion in the left and right calcarine gyrus and lingual gyrus in a boy who was having attacks of micropsia when compared with an age-matched normal boy. Another child with micropsia had increased blood flow in left and right inferior parietal cortex compared with an age-matched normal boy. Thus, blood flow alterations may cause micropsia (Brumm et al., 2010). Other authors have postulated that decreased blood flow to the nondominant posterior parietal lobe during a migraine attack may cause metamorphopsias.
10 WHY DID LEWIS CARROLL WRITE ABOUT BIZARRE SENSORY PHENOMENA? Lewis Carroll vividly described Alice’s metamorphopsias because he himself was most likely a migraineur. He experienced the transient visual changes associated with his migraine headaches such as hemianopsia as evidenced by his sketch of a person with the right half of the face, right shoulder, and hand eradicated, characteristic of
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right-sided paracentral negative (ablative) scotoma drawn in 1854–1855 and reproduced in his family journal 1855–62 (Podoll and Robinson, 1999). Dodgson consulted William Bowman in 1856, an eminent oculist (ophthalmologist in modern terms) for advice about his visual disturbances in his right eye. Dodgson’s diaries contain several entries about suffering from “bilious headaches” and ocular distortions as early as 1856, 9 years before he wrote Alice’s Adventures in Wonderland (Podoll and Robinson, 1999). From this information, other authors have concurred that Lewis Carroll used his experiences with complicated migraine when he described Alice’s sense that she was growing or shrinking. In contrast, Blau argued that Lewis Carroll did not experience migraine headaches until after he wrote Alice’s Adventures in Wonderland, based upon Blau reading only entries that were recorded in Dodgson’s diaries between 1885 and 1891 (Blau, 1998; Podoll and Robinson, 1999). Micropsia, macropsia, and teleopsia (objects appearing too far away) elements present in the AIWS are considered migraine variants (Hachinski et al., 1973; Hamed, 2010).
11 THE MATTER OF THE MAD HATTER A Mad Tea-Party is one of the most memorable and bizarre chapters in Alice’s Adventures in Wonderland. The Mad Hatter is a prominent character in this discordant and nonsensical convocation of Alice, the Dormouse, the March Hare, and the Mad Hatter. Charles Dodgson may have modeled the Mad Hatter after Theophilus Carter, an eccentric and often rude furniture dealer in Oxford, England, who always wore a top hat in his emporium (Gardener, 1990, p. 82). Dodgson was acquainted with Carter, as Dodgson taught mathematics at Christ College in Oxford. The Mad Hatter was irritated with Alice and rudely interrupted her repeatedly. His conversation and actions during the tea party were illogical. Alice felt “dreadfully puzzled” by the Mad Hatter’s hostile remarks. They seemed to her “to have no sort of meaning in it, yet it was certainly English” (Gardener, 1990, pp. 84–85). The Mad Hatter called her “stupid” and commanded her not to talk. He also had a tremor that caused him to shake his pocket watch (Gardener, 1990, pp. 91–92). Alice left the tea party abruptly after the Hatter’s diatribes became insufferable (Fig. 4). In the Victorian era, hatters were often considered “mad” (the current term is demented) because they had suffered encephalopathy caused by repeatedly absorbing elemental mercury into their central nervous systems. Victorian era hatters stiffened felt hats with mercury; steaming the hats to fit the wearer’s head caused the mercury to vaporize. In 1938, Neal and Jones examined hatters exposed to mercury vapors and reported behavioral changes, tremors, and exaggerated reflexes (Neal and Jones, 1938). Elemental mercury was absorbed through hatters’ lungs and hands into their blood streams. Mercury leaves the blood easily and localizes in the brain, kidney, and liver (Feldman, 1982). Inhaled mercury vapors accumulate in the cerebral cortex, especially in the parietal and occipital lobes, cerebellar cortex, and brain stem nuclei of monkeys (Berlin et al., 1975). Mercury attaches to and inactivates compounds with sulfhydryl (–SH) groups. Additionally, flavoproteins in mitochondria
12 Why the Dormouse Fell Asleep so Often
FIGURE 4 The Mad Hatter’s tea party—Left to Right: Alice, March Hare, the Dormouse, and the Mad Hatter. From Lewis Carroll, 1866.
are inactivated by mercury and cannot extract and transport electrons to produce ATP from ADP (Feldman, 1982). Thus, these mitochondria are poisoned and their neurons undergo apoptosis (programmed cellular death). Mood changes, depression, irritability, tremor, cerebellar ataxia, and changes in personality occur with chronic exposure to mercury (Feldman, 1982). Thus, Lewis Carroll’s character, the Mad Hatter, manifested many of the signs of chronic mercury toxicity.
12 WHY THE DORMOUSE FELL ASLEEP SO OFTEN The Dormouse fell asleep repeatedly during the tea party. He struggled to remain awake; he was irritable when awakened. He suffered from the effects of excessive daytime sleepiness (EDTS). His cohorts treated him badly. The Mad Hatter pinched him and poured hot tea on his nose to awaken him (Gardener, 1990, pp. 85, 89). Patients who suffer from EDTS often have disturbed sleep. The differential diagnosis of EDTS includes several disorders that disrupt natural sleep: obstructive and central sleep apnea, restless legs syndrome with periodic movements in sleep, narcolepsy with cataplexy or without cataplexy, and rapid eye movement (REM) sleep behavior disorder. Periods of arousals due to central or obstructive apnea interrupt sleep. Hence, these patients whose sleep is disturbed will readily fall asleep at unpropitious times in boring surroundings and after meals. The Dormouse may resemble a person that Lewis Carroll knew who may had sleep apnea or excessive movements in sleep. The story that the Dormouse attempted to tell was inane and devoid of meaning. His performance was bizarre and impaired. Persons with severe EDTS may end up being discharged from employment because of impaired performances, excessive use of sick time, and even deficits of memory and attention (Naegele et al., 1995; Grunstein et al., 1995). Sleep apnea may lead to permanent cognitive decline
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(Canessa and Ferini-Strambi, 2011). Cataplexy is the result of loosing muscular tone with a sudden or unpleasant stimulus and represents the abnormal intrusion of loss of tone in the body that occurs naturally during REM sleep (Guilleminault and Gelb, 1995). The Dormouse was aroused by pinches and hot tea. Although the Dormouse’s somnolence may be attributed to narcolepsy without cataplexy, the absence of cataplexy makes the Dormouse’s EDTS difficult to precisely diagnose (Dauvilliers et al., 2003).
13 CONCLUSIONS The diagnosis of AIWS has gained popularity because this unforgettable term summarizes the bizarre phenomena of visual and somatic alterations associated with migraine headaches, complex partial seizure disorders, viral infections, and intoxications. Neurologists who become aware of the AIWS will converse with these patients more comfortably and encourage AIWS patients to express their experiences without fear of being considered psychotic. Recognition of the vectors of AIWS may prompt treatment of Lyme disease or make a physician aware of toxic levels of topiramate precipitating an AIWS attack. Information compiled in this chapter indicates that the outcome for AIWS is generally favorable. The chapter has also reviewed the possible reasons why Charles Lutwidge Dodgson, aka Lewis Carroll, chose to describe his experiences with migraine headache-induced metamorphopsias to the real-life Alice Liddell. Finally, this chapter cited two examples of classical neurological disorders that Lewis Carroll graphically depicted in Alice’s Adventures in Wonderland, mercury encephalopathy and EDTS. The reader is encouraged to find other neurological disorders in Lewis Carroll’s opus.
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Ju¨rgens, T.P., Ihle, K., Storck, J.-H., May, A., 2011. Alice in Wonderland Syndrome associated with topiramate for migraine prevention. J. Neurol. Neurosurg. Psychiatry 82, 228–229. Kawasaki, A., Purvin, V., 1996. Persistent Palinopsia following ingestion of lysergic acid diethylamide (LSD). Arch. Ophthalmol. 114, 47–50. 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. Pediatr. Neurol. 19, 105–108. Lippman, C.W., 1952. Certain hallucinations peculiar to migraine. J. Nerv. Ment. Dis. 116, 346–351. Magnusson, M., 1990. Chambers Biographical Dictionary. W & R Chambers, Edinburgh, Scotland, pp. xii þ 1604. Naegele, B., et al., 1995. Deficits of cognitive executive function in patients with sleep apnea syndrome. Sleep 18, 43. Neal, P.A., Jones, R.R., 1938. Chronic mercurialism in the hatters’ fur cutting industry. JAMA 110, 337–343. ¨ rzte und Studierende. Verlag Oppenheim, H., 1913. Lehrbuch der Nervenkrankheiten fu¨r A von S. Karger, Band Zwei, Berlin, pp. 790–1926. Podoll, K., Robinson, D., 1999. Lewis Carroll’s migraine experiences. Lancet 353, 1366. Rolak, L.A., 1991. Literary neurological syndromes: Alice in Wonderland. Arch. Neurol. 48, 649–651, History of Neurology. Silberstein, S.D., Lipton, R.B., Dodick, D.W., 2008. Wolff’s Headache and Other Head Pain, eighth ed. Oxford Press, New York, i–xx þ1–844. Soriani, S., Figgioli, R., Scarpa, P., Borgna-Pignatti, C., 1998. Alice in Wonderland Syndrome and Varicella. Pediatr. Infect. Dis. J. 17, 935–936. Takaoka, K., Takata, T., 1999. Alice in Wonderland Syndrome and Lilliputian Hallucinations in a patient with a substance-related disorder. Psychopathology 32, 47–48. Todd, J., 1955. The Syndrome of Alice in Wonderland. Can. Med. Assoc. J. 72, 701–704. Wang, S.-M., Liu, C.-C., Chen, Y.-J., et al., 1996. Alice in Wonderland Syndrome caused by Coxsackievirus B1. Pediatr. Infect. Dis. J. 15, 470–471. Weidenfeld, A., Boursiak, P., 2011. Alice-in-Wonderland syndrome—a case base update and long term outcome of nine children. Child Nerv. Syst. 27, 893–896.
8
The Alice in Wonderland Syndrome
Edward J. Fine1 University Neurology Service and The Jacobs Neurological Institute, Department of Neurology, University at Buffalo, The State University of New York, Buffalo General Medical Center, Buffalo, NY, USA 1 Corresponding author: Tel.: þ1-716-932-6080, extension 102, Fax: þ1-716-332-4245, e-mail address: [email protected]
Abstract The Alice in Wonderland syndrome is a term applied to altered bizarre perceptions of size and shapes of a patient’s body and illusions of changes in the forms, dimensions, and motions of objects that a patient with this syndrome encounters. These metamorphopsias arise during complex partial seizures, migraine headaches, infections, and intoxications. The illusions and hallucinations resemble the strange phenomena that Alice experienced in Lewis Carroll’s Alice’s Adventures in Wonderland. Charles Lutwidge Dodgson, whose nom de plume was Lewis Carroll, experienced metamorphopsias. He described them in the story that he wrote for Alice Liddell and her two sisters after he spun a tale about a long and strange dream that the fictional Alice had on a warm summer day. The author of this chapter suggests that Dodgson suffered from migraine headaches and used these experiences to weave an amusing tale for Alice Liddell. The chapter also discusses the neurology of mercury poisoning affecting the behavior of Mad Hatter character. The author suggests that the ever-somnolent Dormouse suffered from excessive daytime sleepiness due to obstructive sleep apnea.
Keywords Alice in Wonderland syndrome, Lewis Carroll, Charles L. Dodgson, epilepsy, Epstein– Barr virus, excessive daytime sleepiness, LSD, Lyme disease, metamorphopsias, migraine headache, narcolepsy, palinopsia, sleep apnea
1 INTRODUCTION The British psychiatrist John Todd (1914–1967) first used the memorable term “Alice in Wonderland syndrome” (AIWS) to describe a “singular group of symptoms intimately associated with migraine and epilepsy, although not confined to these Progress in Brain Research, Volume 206, ISSN 0079-6123, http://dx.doi.org/10.1016/B978-0-444-63364-4.00025-9 © 2013 Elsevier B.V. All rights reserved.
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disorders” in 1955 (Todd, 1955). Todd provided medical histories of five adults and an adolescent who had suffered from illusions of alterations of their body images or their external surroundings associated with attacks of migraine headaches or epileptic seizures or a combination of these disorders. Todd’s patients felt they were too small, too tall, or parts of their bodies were changing shape, size, or relationship to the rest of their bodies. Some recalled the feeling of their bodies expanding or contracting in closed spaces or splitting in half. He proposed that these illusions of body image could be the equivalent of more common manifestations of complex partial seizures or migraine headaches. Todd proposed the term AIWS to summarize the wide spectrum of these illusory symptoms. Todd coined the term based upon Lewis Carroll’s book, Alice’s Adventures in Wonderland (Carroll, 1866; Carroll, 2002). The term AIWS has been applied to self-reported somatosensory alterations associated with epilepsy, migraine headaches, intoxications, and infectious diseases after Todd coined the term in 1955. The number of reports in which AWIS appears has grown from single-case histories to a series of histories and outcomes of 10 or more adults or children (Ho et al., 1992; Weidenfeld and Boursiak, 2011). This chapter discusses the history of the syndrome and its etiologies and explains how it is manifested in Carroll’s characters and apparently in Carroll himself. The chapter also summarizes theories about the physiology of this disorder and migraine headache. The author explores controversies and speculations arising from Charles Lutwidge Dodgson’s illnesses that may have been expressed in his writings under the pseudonym of Lewis Carroll.
2 THE ETIOLOGY OF THE ALICE IN WONDERLAND SYNDROME (AIWS) Todd coined the term when he cited Caro W. Lippman’s paper describing two patients who said they experienced a sensation of becoming short and wide during attacks of migraine headache (Lippman, 1952). One patient referred to this sensation as her “Tweedledum or Tweedledee feeling.” That patient recalled the short, barreled-shaped creature depicted in Lewis Carroll’s “Through the Looking Glass and What Alice Found There.” Lippman claimed that he discovered that certain patients suffering from migraine experienced unique “hallucinations” related to their body image and distortions of “the entire body or certain parts of their body.” He prompted these patients by directly asking “Do you have any unusual body sensations just before, during or just after the headache?” Lippman recorded the “hallucinations” of seven patients, some of whom felt that their body had split in half and the remaining half had either shrunk or grown excessively large. Some of Lippmann’s patients were reluctant to explain their odd feelings as they believed they would be considered “crazy.” Case 1 of Lippman’s patients felt she was “about one foot tall” during or before the onset of her headache. This patient confirmed that she was hallucinating when she gazed at her reflection in a mirror and saw that she was her normal height. Lippman’s sixth
2 The Etiology of the Alice in Wonderland Syndrome (AIWS)
patient stated “I get tired from pulling my head down from the ceiling. My head feels like a balloon.” (Lippman, 1952, pp. 345–346). Corbett also noted that patients with migraine headaches and complex illusions were reticent about describing these phenomena until he reassured them. Corbett suggested that children be encouraged to draw what they saw during their episodes of migraine headache and complex visual illusions (Corbett, 1983, pp. 982–984). Lippmann believed that Charles Lutwidge Dodgson (1832–1898), whose nom de plume was Lewis Carroll, suffered from migraine headaches (Lippman, 1952, p. 351). Dodgson was a lecturer in mathematics at Christ Church College, Oxford, England (Fig. 1) (Rolak, 1991). During a rowing trip up the Thames River on July 4, 1862 with Alice Liddell, her two sisters, and his friend the Reverend Robinson Duckworth, Dodgson told a story about a fictional girl named Alice and her dream. Alice Liddell and her two sisters were the daughters of George Liddell, the Dean of Christ Church College. Alice Liddell enjoyed the story so much that she begged Dodgson to write out the story. Dodgson presented Alice with the manuscript, Alice’s Adventures Under Ground, along with his hand drawn illustrations, as a Christmas present in 1862 (Gardener, 1990; Rolak, 1991). The manuscript was published as Alice’s Adventures in Wonderland (Magnusson, 1990, p. 426) (Fig. 2). Lippman made the unsupportable claim that he was the first to describe these migraine equivalents. Hermann Oppenheim (1858–1919), a German-Jewish
FIGURE 1 Charles L. Dodgson, aka Lewis Carroll.
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FIGURE 2 Frontispiece—Alice’s Adventures in Wonderland.
neurologist, had noted in 1913 that one of his patients who suffered from migraine headaches manifested the syndrome. He stated, “Ich habe gesehen in denen an Stelle der echten Hemikranie ein heftiger Schmerz, einer umschreibenen Partie des Rumpfes oder Extremitat sich einstellte der nach einer Dauer von einigen Stunde or einem Tage spontan schwand . . .” (I have seen a case of genuine hemicrania in which there was during an episode of violent migraine an indescribable feeling of detachment of the trunk or extremity after an hour or even a day of spontaneous dizziness—author’s translation) (Oppenheim, 1913, p. 1567).
3 Alice’s Odd Sensations of Body Image and Surroundings
3 ALICE’S ODD SENSATIONS OF BODY IMAGE AND SURROUNDINGS Todd and Lippman drew inferences from Alice’s Adventures in Wonderland to support their thesis that migraine sufferers and persons with epilepsy endure experiences similar to Alice’s. Key passages from Alice’s Adventures in Wonderland support these authors’ claim that their patients experienced changes in body size (metamorphopsia), altered relationships with internal and external space, and odd sensory distortions. Alice dreamed that she followed a white rabbit down a large hole and fell down into a strange world. In that place, she was too large to enter a picturesque garden. She drank the contents of a bottle marked “DRINK ME.” She then began to shrink until she was only 4 inches tall and could enter the garden through a low door. But then, she had forgotten to take the golden key she saw on a glass table that would unlock the door. Despairing that she could not climb up the slippery glass legs of the table, she spied a glass box that was labeled “EAT ME,” which contained cake. After consuming the cake, she felt that her body was expanding like a telescope until her head now 9 feet above the floor struck the roof of the room outside the garden. She was able to reach the key. Alice then began to shrink back to about 2 feet tall (Carroll, 2002, pp. 8–20). Her body size and relation to her surroundings changed rapidly as did Lippman’s and Todd’s patients. Alice again experienced shrinkage of her trunk when she ate a portion of a mushroom that the blue Caterpillar offered her. Her chin suddenly dropped to her feet. A bite from another side of the mushroom made her neck elongate immensely so that a pigeon mistook her for a serpent (Carroll, 2002, pp. 56–63). These odd distortions of body parts, becoming too small or too large, are termed metamorphopsias. The Victorian era neurologist William Gowers (1845–1915) (Fig. 3) reported that patients with seizures experienced feelings of “unreality in what is seen” (Gowers, 1907, p. 21). Objects seemed unreal “as if in a picture” (Gowers, 1907, p. 31). The patient with migraine headaches or seizures arising in the parietal lobe experiences visual hallucinations, perceiving objects as smaller (micropsia) or larger (macropsia) than they actually are (Critchley, 1949). Hachinski and colleagues followed 100 children with migraine headaches of which 16 had visual distortions and hallucinations. The children in their series saw parents or objects upside down and people too small, and one child recalled a horrific hallucination of lying on a railroad track with a train passing over her all associated with headaches (Hachinski et al., 1973). Evans and Rolak described a patient who felt that her body was too big and everything else was too small; in other instances of her migraine attacks, the converse occurred. She was aware that these abnormal feelings were not reality. Her EEG was normal. All of these events were followed by a pounding headache and excessive sensitivity to light and noise, consistent with a diagnosis of complicated migraine (Evans and Rolak, 2004). These case histories mirror the changes in body size visual distortions that the fictional Alice experienced.
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FIGURE 3 William Richard Gowers, FRCP.
4 PHYSIOLOGY OF MIGRAINES MAY EXPLAIN ALICE’S METAMORPHOPSIAS AND CONFUSIONAL STATE Migraine headaches are triggered by stress, red wine and less commonly other alcoholic beverages, nitrate and nitrite-containing foods, aspartame, and smoked foods. Skipping meals can trigger migraines. Once nausea occurs during a migraine headache, the sufferer stops eating or vomits. Hypoglycemia and depletion of potassium that follow intense vomiting increase the intensity of the headache. Evidence for chocolate as a migraine trigger appears tenuous (Silberstein et al., 2008, pp. 180–183). Dodgson referred to his headache as “bilious,” with vomiting so severe as to expel bile. Dodgson avoided alcohol, perhaps because he learned that it triggered attacks of migraine headaches. A spreading wave of depolarization of cells in the cerebral cortex occurs during migraine headaches. Depolarization of the glial cells causes extracellular release of potassium and calcium ions, nitric oxide, and arachidonic acid. Meningeal nociceptor axons are activated by these substances. Nociceptor neurons are part of the trigeminal nerve’s regulation of the brain’s vascular system that becomes activated during a migraine headache. Because of the trigeminal nerve’s connections to the thalamus and thalamic projections onto the sensory cortex, migraine patients feel intense cranial pain during an attack (Charles, 2009; Dalkara et al., 2006).
6 Infections that Induce AIWS
5 CONFUSIONAL STATES ASSOCIATED WITH MIGRAINE OR EPILEPSY Alice’s inability to recite the multiplication tables or a well-known poem to the blue Caterpillar reflects the marked confusion that can occur during a severe migraine headache or after a generalized or partial complex seizure (Golden, 1979; Carroll, 2002, pp. 52–54). However, AIWS is not restricted to persons with migraine headaches or epilepsy.
6 INFECTIONS THAT INDUCE AIWS Viral infections that cause encephalopathy can be associated with the AIWS. H1N1 influenza virus caused an 11-year-old girl to be frightened by hallucinations of her parents talking to her and moving too slowly around her. She was alarmed by the hallucination of a picture zooming in and out. Her real-time polymerase chain reaction test for H1N1 influenza was positive and serology tests for Epstein–Barr virus (EBV) were negative. Her micropsia and macropsia disappeared after Tamiflu antiviral therapy (Augarten and Aderka, 2011). Copperman first described visual hallucinations in two adolescents and a 9 ½year-old boy associated with infectious mononucleosis. One teenage girl saw objects “being more distant than they actually were” and images that were out of focus, shrinking, and enlarging. Her physical examination demonstrated an enlarged spleen and lymph nodes. She had a positive monospot test and an increased heterophile agglutination test confirming the clinical diagnosis of mononucleosis. She made a full recovery after 8 months. The other adolescent girl noted alterations in sizes and shapes for 2 months. She had a positive heterophile agglutination test, spleen enlargement, and increased monocytes in her blood smear (Copperman, 1977). She also made a full recovery. The boy complained of objects seeming to become alternately larger and then smaller than they actually were. He also had swollen lymph nodes, splenic enlargement, increased lymphocytes in his blood smear, and a positive monospot test (Copperman, 1977). Cinbis and Aysun reported that a 7-year-old girl complained of seeing her mother’s head seemed smaller than her body and appeared to her to be colored green for a few minutes. These hallucinations would disappear and then return. Serum tests confirmed the clinical diagnosis of EBV encephalopathy (Cinbis and Aysun, 1991). Coxsackie B1 virus was isolated and identified in the cerebral spinal fluid (CSF) of a 4-year-old boy who had fever, cough, and abdominal pain, but no rash or lymph node enlargement. He complained to his parents that walls were moving in towards him or away from him and that his parents were sometimes too big or too small. He displayed no signs of meningeal irritation; his gait, reflexes, and cranial nerve examinations were normal. The authors entertained the diagnosis of AIWS to account for his visual illusions (Wang et al., 1996). Thus, viral infections can cause visual
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changes (metamorphopsias) similar to those described vividly by Lewis Carroll in Alice’s Adventures in Wonderland. Neuroborreliosis can be associated with AIWS. A 7-year-old boy was evaluated for distorted visual perceptions. He lived in a wooded area where ticks were present. He was frightened by the letters in his storybook becoming smaller and smaller, the book moving away, and he and his father becoming smaller. He had no rashes, fever, headache, or arthralgias. Long-term EEG monitoring did not reveal any changes during these episodes. Laboratory studies revealed increased CSF leukocytes and normal protein and positive serology tests for Lyme disease in serum and CSF. Tests for Bartonella, herpes simplex, enterovirus, cytomegalovirus, and mycoplasma in his CSF were negative. He was treated with intravenous ceftriaxone for 21 days. The micropsia disappeared upon the third day of treatment and never recurred (Binalsheikh et al., 2012). Varicella can cause the AIWS to appear after the onset of the vesicles (Soriani et al., 1998). This 4-year-old girl saw her parents getting smaller and the walls closing in around her. CSF examination was normal, but her EEG contained bilateral posterior slowing activity. She recovered after 3 weeks. Thus, several viruses and the Borrelia spirochete can cause AIWS.
7 INTOXICATIONS THAT CAUSE AIWS Intoxication with drugs that contain chemicals derived from codeine or lysergic acid diethylamide (LSD or “acid”) can induce AIWS in susceptible persons. Takaoka and Takata reported a 46-year-old man who regularly consumed cough medicine and who exhibited metamorphopsias (in this case as distortions of pictures and the television screen), macropsia (as enlarged insects), and feelings of expansion of his own body. His EEG and neurological examination were normal. CT scan of his head revealed only a small “previous” left frontal infarction (Takaoka and Takata, 1999). His visual illusions ended within 1 month after ceasing to consume cough medicine containing dihydrocodeine phosphate and dl-methylephedrine. LSD or “acid” is a potent hallucinogenic agent. Persons who ingest this substance may experience distortions of their vision, false progression of their own body or external objects through space, and reoccurring hallucinations of geometric patterns (Abraham and Aldridge, 1993). Palinopsia, the illusion of persistence of a visual image, after the object has left the field of vision, can follow LSD ingestion. Some persons who have taken LSD repeatedly have described hallucinations that resemble images produced by a stereoscopic camera (Kawasaki and Purvin, 1996). Topiramate, an anticonvulsant often prescribed for prophylactic treatment of migraine headaches, can paradoxically induce AIWS (Ju¨rgens et al., 2011). These authors relate that a 17-year-old girl with migraine headaches felt that her head would grow bigger or shrink from its usual size or that her hands would increase in size and grow heavier when her dose of topiramate was increased to 75 mg/day. Dose reduction to 50 mg/day stopped the attacks and reduced the frequency of her migraine
10 Why Did Lewis Carroll Write About Bizarre Sensory Phenomena?
headaches. Thus, topiramate at a dose toxic for some patients can cause metamorphopsias. Avoidance of topiramate for controlling complicated migraine patients may prevent precipitation of AIWS (Evans, 2006; Ju¨rgens et al., 2011).
8 THE OUTCOME OF AIWS The outcome of AIWS is usually benign, especially for children, except for those patients infected with EBV (Kuo et al., 1998). EBV infections caused AIWS in 3 of 10 children (Ha¨usler et al., 2002). Of the other seven EBV-infected children, one developed a lethal lymphoma and two suffered from long-term effects of encephalitis with seizures. These three children with AIWS were considered to have reactivated EBV. Toxic agents causing migraine can be eliminated or the dose of an offending drug reduced with fortuitous outcomes.
9 THE PHYSIOLOGY OF AIWS Decreased cerebral perfusion has been associated with AIWS. EEG and CT have usually negative in this syndrome. Four patients had metamorphopsias consisting of eyes becoming smaller, seeing blue hues, distorted human faces, and TV pictures seen upside down (Kuo et al., 1998). Nuclear medicine techniques using technetium demonstrated decreased perfusion in frontal lobes, parietal, and temporal lobes and occipital lobes variously in the four patients studied. All scans showed decreased perfusion in the visual tracts and occipital lobes of these patients. These authors noted that these patients’ MRI, CT, and visual evoked potential tests were normal (Kuo et al., 1998). Brumm and colleagues used functional magnetic resonance imaging to demonstrate hypoperfusion in the left and right calcarine gyrus and lingual gyrus in a boy who was having attacks of micropsia when compared with an age-matched normal boy. Another child with micropsia had increased blood flow in left and right inferior parietal cortex compared with an age-matched normal boy. Thus, blood flow alterations may cause micropsia (Brumm et al., 2010). Other authors have postulated that decreased blood flow to the nondominant posterior parietal lobe during a migraine attack may cause metamorphopsias.
10 WHY DID LEWIS CARROLL WRITE ABOUT BIZARRE SENSORY PHENOMENA? Lewis Carroll vividly described Alice’s metamorphopsias because he himself was most likely a migraineur. He experienced the transient visual changes associated with his migraine headaches such as hemianopsia as evidenced by his sketch of a person with the right half of the face, right shoulder, and hand eradicated, characteristic of
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right-sided paracentral negative (ablative) scotoma drawn in 1854–1855 and reproduced in his family journal 1855–62 (Podoll and Robinson, 1999). Dodgson consulted William Bowman in 1856, an eminent oculist (ophthalmologist in modern terms) for advice about his visual disturbances in his right eye. Dodgson’s diaries contain several entries about suffering from “bilious headaches” and ocular distortions as early as 1856, 9 years before he wrote Alice’s Adventures in Wonderland (Podoll and Robinson, 1999). From this information, other authors have concurred that Lewis Carroll used his experiences with complicated migraine when he described Alice’s sense that she was growing or shrinking. In contrast, Blau argued that Lewis Carroll did not experience migraine headaches until after he wrote Alice’s Adventures in Wonderland, based upon Blau reading only entries that were recorded in Dodgson’s diaries between 1885 and 1891 (Blau, 1998; Podoll and Robinson, 1999). Micropsia, macropsia, and teleopsia (objects appearing too far away) elements present in the AIWS are considered migraine variants (Hachinski et al., 1973; Hamed, 2010).
11 THE MATTER OF THE MAD HATTER A Mad Tea-Party is one of the most memorable and bizarre chapters in Alice’s Adventures in Wonderland. The Mad Hatter is a prominent character in this discordant and nonsensical convocation of Alice, the Dormouse, the March Hare, and the Mad Hatter. Charles Dodgson may have modeled the Mad Hatter after Theophilus Carter, an eccentric and often rude furniture dealer in Oxford, England, who always wore a top hat in his emporium (Gardener, 1990, p. 82). Dodgson was acquainted with Carter, as Dodgson taught mathematics at Christ College in Oxford. The Mad Hatter was irritated with Alice and rudely interrupted her repeatedly. His conversation and actions during the tea party were illogical. Alice felt “dreadfully puzzled” by the Mad Hatter’s hostile remarks. They seemed to her “to have no sort of meaning in it, yet it was certainly English” (Gardener, 1990, pp. 84–85). The Mad Hatter called her “stupid” and commanded her not to talk. He also had a tremor that caused him to shake his pocket watch (Gardener, 1990, pp. 91–92). Alice left the tea party abruptly after the Hatter’s diatribes became insufferable (Fig. 4). In the Victorian era, hatters were often considered “mad” (the current term is demented) because they had suffered encephalopathy caused by repeatedly absorbing elemental mercury into their central nervous systems. Victorian era hatters stiffened felt hats with mercury; steaming the hats to fit the wearer’s head caused the mercury to vaporize. In 1938, Neal and Jones examined hatters exposed to mercury vapors and reported behavioral changes, tremors, and exaggerated reflexes (Neal and Jones, 1938). Elemental mercury was absorbed through hatters’ lungs and hands into their blood streams. Mercury leaves the blood easily and localizes in the brain, kidney, and liver (Feldman, 1982). Inhaled mercury vapors accumulate in the cerebral cortex, especially in the parietal and occipital lobes, cerebellar cortex, and brain stem nuclei of monkeys (Berlin et al., 1975). Mercury attaches to and inactivates compounds with sulfhydryl (–SH) groups. Additionally, flavoproteins in mitochondria
12 Why the Dormouse Fell Asleep so Often
FIGURE 4 The Mad Hatter’s tea party—Left to Right: Alice, March Hare, the Dormouse, and the Mad Hatter. From Lewis Carroll, 1866.
are inactivated by mercury and cannot extract and transport electrons to produce ATP from ADP (Feldman, 1982). Thus, these mitochondria are poisoned and their neurons undergo apoptosis (programmed cellular death). Mood changes, depression, irritability, tremor, cerebellar ataxia, and changes in personality occur with chronic exposure to mercury (Feldman, 1982). Thus, Lewis Carroll’s character, the Mad Hatter, manifested many of the signs of chronic mercury toxicity.
12 WHY THE DORMOUSE FELL ASLEEP SO OFTEN The Dormouse fell asleep repeatedly during the tea party. He struggled to remain awake; he was irritable when awakened. He suffered from the effects of excessive daytime sleepiness (EDTS). His cohorts treated him badly. The Mad Hatter pinched him and poured hot tea on his nose to awaken him (Gardener, 1990, pp. 85, 89). Patients who suffer from EDTS often have disturbed sleep. The differential diagnosis of EDTS includes several disorders that disrupt natural sleep: obstructive and central sleep apnea, restless legs syndrome with periodic movements in sleep, narcolepsy with cataplexy or without cataplexy, and rapid eye movement (REM) sleep behavior disorder. Periods of arousals due to central or obstructive apnea interrupt sleep. Hence, these patients whose sleep is disturbed will readily fall asleep at unpropitious times in boring surroundings and after meals. The Dormouse may resemble a person that Lewis Carroll knew who may had sleep apnea or excessive movements in sleep. The story that the Dormouse attempted to tell was inane and devoid of meaning. His performance was bizarre and impaired. Persons with severe EDTS may end up being discharged from employment because of impaired performances, excessive use of sick time, and even deficits of memory and attention (Naegele et al., 1995; Grunstein et al., 1995). Sleep apnea may lead to permanent cognitive decline
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(Canessa and Ferini-Strambi, 2011). Cataplexy is the result of loosing muscular tone with a sudden or unpleasant stimulus and represents the abnormal intrusion of loss of tone in the body that occurs naturally during REM sleep (Guilleminault and Gelb, 1995). The Dormouse was aroused by pinches and hot tea. Although the Dormouse’s somnolence may be attributed to narcolepsy without cataplexy, the absence of cataplexy makes the Dormouse’s EDTS difficult to precisely diagnose (Dauvilliers et al., 2003).
13 CONCLUSIONS The diagnosis of AIWS has gained popularity because this unforgettable term summarizes the bizarre phenomena of visual and somatic alterations associated with migraine headaches, complex partial seizure disorders, viral infections, and intoxications. Neurologists who become aware of the AIWS will converse with these patients more comfortably and encourage AIWS patients to express their experiences without fear of being considered psychotic. Recognition of the vectors of AIWS may prompt treatment of Lyme disease or make a physician aware of toxic levels of topiramate precipitating an AIWS attack. Information compiled in this chapter indicates that the outcome for AIWS is generally favorable. The chapter has also reviewed the possible reasons why Charles Lutwidge Dodgson, aka Lewis Carroll, chose to describe his experiences with migraine headache-induced metamorphopsias to the real-life Alice Liddell. Finally, this chapter cited two examples of classical neurological disorders that Lewis Carroll graphically depicted in Alice’s Adventures in Wonderland, mercury encephalopathy and EDTS. The reader is encouraged to find other neurological disorders in Lewis Carroll’s opus.
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