Patient #1: “Lewis”

1. Patient #1: “Lewis” • Previously well 11-year-old boy • Sudden onset of strange sensations: • he was moving too fast • he was alternately very tall or shrinking • his left hand was huge • sounds were abnormally loud

2. Patient #1: “Lewis” • During episodes, patient was alert, oriented but frightened • Episodes last approx 20 minutes and occurred approx once per week for 1 month

3. Patient #1: “Lewis” • No hx of seizures, h/a, psych, head trauma, infection, anoxia • No meds, street drugs • FHx: migraine • General, neuro and psych exams all normal • EEG: normal • Attacks aborted by ergotamine and caffeine

4. Patient #2: “Carole” • 17-year-old white female, previously well • Presented with distortion of size and shape of objects seen at a distance. • Associated with fatigue and sore throat. • Episodes occurred q 30 min while awake • PMx and FHx: unremarkable • Meds: none, no hallucinogens

5. Patient #2: “Carole” O/E: • Generalized lymph node enlargement • Spleen palpable 2 cm BCM • Grayish pharyngeal exudate • Neurology exam normal • Ophthalmological exam normal • Psychiatric evaluation normal

6. Patient #2: “Carole” Labs: • Mono-spot positive • Heterophil agglutinin titer: 1:960 • WBC 18 • 30% atypical lymphs (Downey cells) • ESR 12 • Liver enzymes normal • Collagen disease w/u negative EEG: normal

7. Patient #2: “Carole” • Course: Patient treated with IV steroids. Sore throat disappeared immediately, spleen became nonpalpable within a week, lymph nodes returned to normal size. • Visual distortions gradually decreased over time and disappeared spontaneously after 7 months.

8. Alice in Wonderland Syndrome Or Through Neurology Class and What Alyson Found There A. Shaw, PGY-2 CHEO, October 1999

9. Alice in Wonderland Syndrome • Syndrome named for Lewis Carroll’s Alice’s Adventures in Wonderland (1865) • Protagonist, 10 year-old Alice, experiences changes in body size and perception as she travels through Wonderland.

10. Alice in Wonderland Syndrome • First described by Lippman in 1952 • Literary name given by Todd in 1955 Lippman CW. J Nerv Ment Dis. 1952 Todd J. Can med assoc J. 1955

11. Clinical Picture Complex symptoms which are frightening to those affected: • Bizarre perceptual distortions (metamorphopsia) • Micropsia: objects or persons seem too small • Macropsia: objects or persons seem too large • Distorted distance of objects • Objects may appear elongated or swollen • Achromatopsia: disappearance of colour

12. Clinical Picture • Bizarre perceptual distortions (metamorphopsia) con’t: • Palinopsia: preservation of visual images • Optic allesthesia: false orientation of objects in space • Polyopia: one object appearing as two or more • Inverted vision • Illusional symptoms

13. Clinical Picture In addition to metamorphosia, children have been referred for: • Irrelevant or incoherent speech (“Do cats eat bats?”, Jabberwocky, poem parodies) • Talking to themselves (“I give myself very good advice, but I very seldom follow it.”) • Feeling of levitation (running with the red queen)

14. Clinical Picture • Impaired sense of passage of time • Zooming of the environment • Illusional symptoms (seeing wire as snake, rag as a cat, baby as a pig) • Feeling “detached” (“grin without a cat”, “off with her head!”) • Hyperaccusis, tinnitus • Personality changes, crying easily (“pool of tears”)

15. Irrelevant or Incoherent Speech As Alice was falling down the rabbit hole: Down, down, down. There was nothing else to do, so Alice soon began talking again…Dinah, my dear! I wish you were down here with me! [Dinah was the cat] There are no mice in the air, I’m afraid, but you might catch a bat, and that’s very like a mouse, you know. But do cats eat bats, I wonder?” And here Alice began to get rather sleepy, and went on saying to herself, in a dreamy sort of way, “Do cats eat bats? Do cats eat bats?” and sometimes, “Do bats eat cats?” for, you see, as she couldn’t anser either question, it didn’t much matter which way she put it.

16. Alice in Wonderland Syndrome • “I get all tired out from pulling my head down from the ceiling. My head feels like a balloon; my neck stretches and my head goes to the ceiling.” Lippman 1952

17. Alice in Wonderland Syndrome After finishing off the “EAT ME” cake: “Curiouser and curiouser!” cried Alice (she was so much surprised, that for the moment she quite forgot how to speak good English.) “Now I’m opening out like the largest telescope that ever was! Goodbye, feet!” (for when she looked down at her feet, they seemed to be almost out of sight, they were getting so far off)…Just at this moment her head struck against the roof of the hall: in fact she was now rather more than nine feet high…

18. Alice in Wonderland Syndrome “I feel as though my body is growing larger and larger until it seems to occupy the whole room.” Lippman 1952

19. Alice in Wonderland Syndrome

20. Differential Diagnosis • Migraine • Epilepsy • Cerebral lesions • Intoxication with hallucinogenic drugs • Hyperpyrexia • Schizophrenia

21. AWS in Juvenile Migraine • AWS first described as hallucinations pathognomonic of migraine • Seen alone, considered an acephalic migraine equivalent • Acephalic migraines found in 2% of migraineurs referred to pediatric neurology • May also be headache prodrome Shevell M. A guide to migraine equivalents. Contemporary Pediatrics. 1998

22. AWS in Juvenile Migraine • Typically between ages 5 and 12 years • Auras last between 10 to 60 minutes • Not functionally disabling • Between episodes child is well • Usually personal or family hx of migraine

23. More Differential Diagnosis Infectious encephalopathy • Infectious mononucleosis • Coxsackievirus B1 • Varicella

24. EBV Infection • CNS involvment in 1-10% of cases • Neurologic manifestations of EBV: • Meningoencephalitis • Encephalitis • Guillain-Barre syndrome • Mononeuritis • Seizures • Chorea • Acute psychotic reaction Liaw SB. Pediatric Neurology. 1991

25. AWS in EBV Infection • First reported by Copperman SM, Clin Pediatr 1977 • 3 patients ages 9, 17, and 18 years with metamorphopsia present in 6-month period • Dx’ed with infectious mononucleosis based on positive clinical, hematologic, and serologic findings.

26. AWS in EBV infection • None had PMHx or FHx of migraine or sz • None had hallucinogenic drug exposure • EEGs all normal • Distorted perception improved with resolution of underlying mononucleosis • Suggests association with metamorphopsia and infectious mono may not be infrequent

27. AWS in EBV Infection Several other reports since Copperman’s: • Sanguineti G. J Infect Dis. 1983 • Eshel G. Ped Infect Dis J. 1987 • Liaw SB. Pediatr Neurol. 1991 • Cinbis M, Aysun S. Brit J Ophthal. 1992 • Ho CS. Acta Pediatrica Sinica. 1992 • 10 children (3-10 years) with documented EBV

28. AWS and EBV Infection • Metamorphopsia may appear before, during, or after resolution of all clinical symptoms • No neurologic deficits observed • EEG: Normal or parieto-temporal slow wave activity • CT: Normal Lahat E et al. Bevioural Neurology. 1991

29. AWS and Coxsackievirus B1 • Frequent clinical features: Biphasic fever respiratory sx rash Vomiting diarrhea Headache abdo pain • CNS involvement in 15-56% Aseptic meningitis encephalitis Paralysis GBS Transverse myelitis cerebellar ataxia Peripheral neuritis

30. AWS and Coxsackievirus B1 Wang SM, Pediatr Infect Dis J, 1996 • 4-year-old boy with distortion of body form, bizarre behavior, irrelevant speech x 3 days • Fever, cough, abdo pain, watery diarrhea • O/E: mild fever, injected throat, nil else • EEG: normal • Labs: Coxsackie B1 in CSF and rectal swab

31. AWS and Varicella Soriani S, Pediatr Infect Dis J, 1998 • 4 year-old girl c/o parents changing size and walls closing down on her x 2 days • PMX: uncomplicated chicken pox 2 weeks prior • O/E: Normal except crusted varicella lesions • CSF normal • EBV and Coxsackievirus Ab titers negative • EEG: bilateral posterior slowing • Sx persisted x 3 weeks, EEG normal after 2 weeks

32. Other AWS Associations • Takaoka K. Psychopathology. 1999. • 46 year old man with regular consuption of cough syrup containing dl-methylephedrine hydrochloride • Mizuno M, et al. Psychopathology. 1998. • 56 year old man with metamorphosia and distorted perception of time 3 weeks prior to onset of depressive disorder

33. Pathophysiology Not fully determined. Hypotheses: • Vasoconstrictive phase of migraine • In EBV: Encephalitis or encephalopathy localized to the parietal lobe • Variations in symptoms result from different areas of the brain affected • Formed visual hallucinations likely from temporal or occipital lobe dysfunction Golden G. Pediatrics, 1979. Lahat E et al. Behavioural Neurology. 1991.

34. Pathophysiology • Kuo YT, et al. Pediatric Neurology. 1998 • 4 children with Alice in Wonderland Syndrome • No hx of migraine, epilepsy, hallucinogens, or psychosis • Normal CSF, EEG, neurol and ophthal exams • SPECT brain scans during acute stage of AWS • Hypoperfusion of temporal lobe, occipital lobe, and perisylvian area associated with AWS

35. Pathophysiology • Focal inflammation resulting from EBV or other infections causes focal brain parenchymal edema and dysfunction and at the same time decreases the regional cerebral blood flow. Kuo YT, et al. Cerebral Perfusion in Children With Alice in Wonderland Syndrome. Pediatr Neurol 1998;19:105-108.

36. Treatment and Prognosis • Course is self-limited and transitory • Average duration of symptoms: 1 month • Expect complete recovery without neurologic sequelae • No specific therapy during acute episodes • Reassurance and understanding • Treat the underlying condition

37. “The Rushes” • A migraine variant with hallucinations of time in relation to both speech and movement • Named for “Alice” sequel, Through the Looking Glass and What Alice Found There Dooley J, Gordon K, Camfield P. Clinical Pediatrics. 1990.

38. “The Rushes” (con’t) “Alice never could quite make it out, in thinking it over afterwards, how it was that they began: all she remembers is that they were running hand in hand, and the Queen went so fast that it was all she could do to keep up with her: and still the Queen kept crying “Faster! Faster!” but Alice felt she could not go faster, though she had no breath left to say so. The most curious part of the thing was, that the trees and the other things round them never changed their places at all: however fast they went, they never seemed to pass anything.”

39. Conclusions • Awareness of AWS and common infections might prevent incorrect diagnosis and treatment of other conditions associated with AWS such as migraine, epilepsy, or psychiatric condition. • Associated with migraine, the various AWS auras provide a valuable opportunity to learn about the functional organization of the brain.

40. Conclusions Lewis Carroll is a name that should be familiar to pediatricians for his contribution to an increasingly recognized pediatric condition, his genuine devotion to children, and as an illustration of the marriage of arts and medicine.