Two cases with infectious etiology responsible for the Syndrome of Alice in Wonderland

Author: Fabiola De Masi
Date: 30/12/2014


Fabiola De Masi

Alice in Wonderland Syndrome


Alice in Wonderland syndrome, first described in 1955, is a manifestation of migraine or seizures. An association with acute infections is also reported, particularly with Epstein Barr virus, varicella, Coxsackie virus B1.
I report a case of an 11-year-old girl who developed Alice in Wonderland syndrome associated with H1N1 influenza and a case of Alice in Wonderland syndrome associated with Lyme disease.

Case Report 1:

In January 2010, an 11-year-old girl presented to the pediatric emergency department with complaints of fever, cough, coryza, and myalgia for 3 days. Concomitantly, she had nighttime audio and visual hallucinations and complained that her parents were talking to her very slowly and moving in slow motion. In addition, she saw a picture zooming in and out, which was very frightening. There were no symptoms of migraine. Her medical history was unremarkable. Treatment with oseltamivir phosphate (Tamiflu) had been started 1 day before her emergency department presentation.
On physical examination, the patient was alert. Her temperature was 36.8°C, heart rate was 107 beats per minute, blood pressure was 92/68 mmHg, and oxygen saturation was 98% on room air. There were no signs of meningeal irritation and no nystagmus; pupils were equal and reactive to light and accommodation; other cranial nerves were intact. Motor and sensory systems as well as the cerebellar function were normal. The rest of the physical examination was normal. Complete blood count reveals hemoglobin of 13.1 g/dL and mild leukopenia (4.67 × 103/μL) with monocytosis (16%). Electrolytes, blood urea nitrogen, creatinine, and liver function tests were within the reference range. Serology for Epstein-Barr virus was negative; real-time polymerase chain reaction for H1N1 was positive. After 2 days, the flu symptoms and her neurological symptoms subsided, and the Tamiflu treatment was discontinued.
The first cases of influenza A (H1N1) virus infection with neurological complications were reported recently in 4 boys. They had a flulike illness associated with seizures or altered mental status, and one of them also experienced visual hallucinations. All of them received antiviral therapy, recovered fully, and had no neurological sequel at the time of discharge.
Our patient experienced micropsia and macropsia, as well as distorted perception of time, movement, and sound, mainly at nighttime as described in AIWS. These symptoms started on the first day of the disease and subsided concomitantly with her flu symptoms, as seen in seasonal flu with associated neurological complications.

Case Report 2:

A healthy 7-year-old boy presented at our clinic after 1 week of distorted visual perception. He initially woke up in the night scared and screaming, saying that “his mind was running fast” and reporting that he heard cheering sounds as if “the room was full of baseball fans.” During these spells he was pale, but manifested no posturing or automatisms. After returning to sleep, he experienced two similar events later the first night. Although he woke up with no complaints in the morning, he came to his father later in the day, looking fatigued and pale. He then vomited once, but manifested no headache. Three nights later, he manifested another event: he woke up from sleep, came downstairs toward his parents, remained standing and stared at them, appearing pale and scared but unable to speak. His parents observed repetitive swallowing and lip-smacking at that time. He did not respond to his name for 1-2 minutes. He demonstrated no rhythmic limb movements during the event. Afterward, he ran upstairs to his room saying “my head is running fast” and “my ears are ringing.” He remained conscious throughout the event. An Emergency Department evaluation produced normal results of an examination, including serum electrolytes and noncontrast cranial computed tomography. The next evening, while reading a storybook, he saw the letters becoming smaller and the book appeared to be a greater distance away. He also felt himself and his father growing smaller. At the time of neurologic evaluation, we confirmed that these episodes were not associated with headache or changes of alertness, and that they had not occurred in the past. No history of fever, skin rash, joint pain, swelling, or tick bites was reported, nor had preceding signs of upper respiratory infection occurred. He was not receiving any medications, and no history of unusual substance ingestion was reported. No personal or family history of migraines or seizures was reported. He lived with his stable, well-educated parents and two healthy sisters, aged 3 and 9 years, in a wooded area on the outskirts of Boston.
The boy’s general physical and neurologic examinations, including mental status, visual fields and ophthalmoscopy, produced normal results. He was admitted to the hospital on day 10 of his illness for a long-term monitoring video electro-encephalogram. During 36 hours of recording, he exhibited three events of distorted perception when he felt himself becoming smaller and the letters of a storybook he was reading becoming smaller and farther away. These events were not associated with electroencephalographic evidence of seizure. Results of a Lyme disease test, performed 6 days into his illness at the insistence of the mother because the family lived in an endemic area, produced positive results.

Image and video hosting by TinyPic

A complete blood count, thyroid function studies, and electrolyte and liver function tests all produced normal results.
An analysis of the patient’s cerebrospinal fluid revealed leukocytes at 22/mm3, erythrocytes at 0/mm3, lymphocytes 76%, monocytes at 20%, neutrophils at 4%, cerebrospinal fluid protein at 23 mg/dL, and cerebrospinal fluid glucose at 63 mg/dL.
Lyme disease Western blot immunoglobulin M on day 10 of illness tested positive in both serum and cerebrospinal fluid. Serum Western blot immunoglobulin M was present in three bands out of three. A Lyme Western blot immunoglobulin G test produced negative results in both serum and cerebrospinal fluid. The patient’s C6 index was greater than 5.0. A Lyme polymerase chain reaction in cerebrospinal fluid produced negative results. Epstein-Barr virus testing was negative. An Epstein- Barr virus-viral capsid antigen and Epstein-Barr virus polymerase chain reaction produced negative results. Herpes simplex virus 1 and 2 polymerase chain reactions in cerebrospinal fluid produced negative results. Polymerase chain reaction testing for Bartonella, enterovirus, cytomegalovirus virus, and mycoplasma, produced negative results. Cranial magnetic resonance imaging with contrast produced normal results. The boy was treated with intravenous ceftriaxone for 21 days, and his signs resolved after 3 days. He received no antimigraine or antiseizure medications. He demonstrated a full recovery within 3 days after admission to the hospital. At no time did he develop a rash. No recurrence of his findings was evident at 12-month follow-up. No follow-up serologic testing was performed.


Patients with the “Alice in Wonderland” syndrome (AWS) experience hallucinations or illusions of expansion, reduction, or distortion of body image.
The name comes from the classic story of Alice's Adventures in Wonderland, written by Lewis Carroll (Charles Lutwidge Dodgson) in 1865. Lippman first described AWS, and subsequently Todd gave the condition its name.
Individuals with true AWS perceive their own body parts changing size. Lanska et al. referred to this as “type A” AWS. Micropsia (objects appear too small), macropsia (objects appear too large), metamorphopsia (objects appear too fat, thin, short, tall, and so on), teleopsia (objects appear further away than they are), and pelopsia (objects appear closer than they are) are extrapersonal visual complaints similar to AWS. Lanska et al. referred to them as “type B.” Lanska et al. categorized “type C” complaints as altered perception of one's body image and externally other people or objects as well. To distinguish self versus extrapersonal illusions, for the purposes of this study we will term types B and C as “Alice in Wonderland”–like syndromes (AWLS). Other authors have also advocated this distinction.
The cause of AWS and AWLS is not known. Various authors however have attributed the condition to migraine, epilepsy, and infection. Lippman's seven patients experienced migraine headaches with altered perception of body image. The migraines occurred before, during, or after the AWS symptoms. Three of Todd's six patients had a family history of migraine and/or epilepsy. Golden's two patients with AWS had repeated headaches and a strong family history of migraines. In addition, Copperman presented three cases with AWS as a presenting symptom of infectious mononucleosis. Similar findings were observed in a boy with Alice in Wonderland syndrome during an episode of micropsia, using functional magnetic resonance imaging. During his episode of micropsia, magnetic resonance imaging demonstrated hypoactivation of the primary and extrastriate regions of visual cortical areas, relative to a control subject.
Lyme disease is well known to affect both the central and peripheral nervous system. Lyme neuroborreliosis in the United Stats is characterized by subacute meningitis, sometimes accompanied by headache, myalgia, malaise, numbness, mild cognitive impairment, or facial nerve palsy. Lyme neuroborreliosis in Europe usually presents with painful radiculitis (Bannwarth’s syndrome or Garin-Bujadoux syndrome). Encephalitic signs in the acute disseminated phase consist of sleep disturbance, difficulty concentration, poor memory, irritability, and emotional labiality.
Other common complaints include difficulty finding words, sleep disturbances, photophobia, auditory hyperacusis, dyslexic-like errors, and mood labiality. Psychiatric manifestations in Lyme neuroborreliosis include visual, vocal, and musical hallucinations. Our patient is unique in that he presented no manifestation of Lyme disease other than metamorphopsia. His diagnosis of neu- roborreliosis was supported by the presence of cerebrospinal fluid pleocytosis and a positive antibody titer against Borrelia burgdorferi in both cerebrospinal fluid and serum. However, because Lyme disease more characteristically presents as acute or chronic psychosis including hallucinations, this case suggests that visual illusions (metamorphopsia) should raise the clinician’s suspicion for neuroborreliosis, even in the absence of systemic manifestations of Lyme disease.

- Alice in wonderland syndrome: presenting and follow-up characteristics 2014


Clinicians should be aware of and consider influenza A (H1N1) in the differential diagnosis of children with flu symptoms and AIWS. On the other hand, the clinician’s awareness of this complication in H1N1 might save the child - in the absence of other neurological deficiencies - from undergoing extensive diagnostic procedures such as lumbar puncture and head computed tomography to rule out other pathological findings of the central nervous system.
Also the signs of Alice in Wonderland syndrome, or of metamorphopsia, should be added to the clinical spectrum of Lyme neuroborreliosis. A high index of suspicion is required to diagnose and treat potentially curable diseases such as neuroborreliosis when they present with unusual signs.

- Lyme Neuroborreliosis Presenting as Alice in Wonderland Syndrome 2012
- Alice in Wonderland Syndrome in H1N1 Influenza Case Report 2011

2015-01-09T10:53:23 - Fabiola De Masi
2015-01-07T14:37:12 - Fabiola De Masi
2015-01-03T23:05:16 - Fabiola De Masi
AddThis Social Bookmark Button