Alice in Wonderland Syndrome Caused by the 2009 Pandemic H1N1 Influenza A Virus

Abstract

To the Editors: We reported a case of Alice in Wonderland syndrome caused by the 2009 pandemic H1N1 influenza virus, confirmed by elevated antibody titers on a hemagglutinin inhibition assay. The case was a 5-year-old girl. She was previously healthy and had no history of convulsions or headache. She visited her family doctor complaining of a high fever on the second day of sickness in September 2009 and was diagnosed with influenza A infection proved by a rapid test for influenza. She was given oseltamivir for 3 days, and her clinical signs and symptoms disappeared after the initiation of therapy on the seventh day. She complained of micropsia and macropsia. The micropsia and macropsia were subjective complaints, and an examination by our ophthalmologist revealed no abnormality. Neurologic studies including EEG, brain magnetic resonance imaging (3 Tesla) followed by single-photon emission computed tomography showed normal results. There was no recent history of Epstein-Barr virus (EBV), chickenpox, or intestinal viral infection. Laboratory tests on admission revealed a white blood cell count of 9100/μL (44.1% segmented, 6.7% eosinophils, 5.2% monocytes, 43.7% lymphocytes, 0.3% basophils, and no atypical lymphocytes), hemoglobin 14.0 g/dL, and platelet count 319,000/μL. The serum glucose level was 85 mg/dL, aspartate aminotransferase 36 U/L, alanine aminotransferase 17 U/L, sodium 138 mmol/L, potassium 4.6 mmol/L, and chlorine 106 mmol/L. Biochemical markers for a severity of inflammation revealed a normal C-reactive protein (<0.1 mg/dL) with normal levels of lactic dehydrogenase and creatinine kinase. A routine urinalysis showed normal results. Serologic studies revealed EBV-IgM 0.8 (normal: approximately 0.5) and EBV-IgG 0.5 (normal: approximately 0.5), cytomegalovirus-IgM 0.32 (normal: approximately 0.79), and cytomegalovirus-IgG 26.9 (normal: approximately 1.9). Laboratory blood investigations a month after the first visit to the family doctor revealed a hemagglutinin inhibition titer to the 2009 pandemic H1N1 influenza A virus >1:1024. The visual abnormalities disappeared spontaneously within 2 months. Alice in Wonderland syndrome is characterized by visual sensory abnormalities including micropsia and macropsia and they are regarded as a reflection of migraine or psychologic diseases. On the other hand, there have been several reports of this syndrome in cases with viral infections such as EBV,1 varicella,2 or coxsackie B1 virus.3 A case of Alice in Wonderland syndrome associated with H1N1 influenza was reported,4 while we were preparing this manuscript. The neurologic prognosis of Alice in Wonderland syndrome caused by several viral infections is good.2–4 Thus, Alice in Wonderland syndrome is completely different from encephalopathy caused by the 2009 pandemic H1N1 influenza.5 Also, this syndrome seemed to have no relation to neuropsychiatric side effects of neuraminidase inhibitors such as osertamivir or zanamivir. No cases of Alice in Wonderland syndrome attributable to these drugs have been reported in Japan where neuraminidase inhibitors are common medications for seasonal influenza infection. The clear mechanism for a correlation of Alice in Wonderland syndrome to the 2009 pandemic H1N1 influenza remains to be elucidated. Hirohumi Nakaya, MD Takehisa Yamamoto, MD Mika Takano, MD Katsusuke Yamamoto, MD Department of Pediatrics Minoh City Hospital Yasuhiro Hujikawa, MD Division of Pediatrics Hujikawa children's clinic Osaka, Japan Saeko Morikawa, DVM Tetsuo Kase, PhD Department of Virology Osaka Prefectural Institute of Public Health Osaka, Japan Tsunesuke Shimotsuji, MD Department of Pediatrics Minoh City Hospital Osaka, Japan