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Letters: Letters to the Editors

Acute Encephalopathy Associated With Influenza C Virus Infection

Takayanagi, Masaru PhD, MD; Umehara, Naoki MD; Watanabe, Hiroshi MD; Kitamura, Taro PhD, MD; Ohtake, Masatoshi PhD, MD; Nishimura, Hidekazu PhD, MD; Matsuzaki, Yoko PhD, MD; Ichiyama, Takashi PhD, MD

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The Pediatric Infectious Disease Journal: June 2009 - Volume 28 - Issue 6 - p 554
doi: 10.1097/INF.0b013e3181a064b2
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To the Editors:

Influenza C virus infection is considered to be milder than the infections caused by influenza viruses A and B; there are no reports of severe complications associated with influenza C virus infections.1 Influenza C virus is distributed worldwide, and the seropositive rate in people aged above 10 years is approximately 100%. However, the clinical diagnosis of type C influenza is complicated by the rarity of specific symptoms and the dearth of facilities equipped with the resources for performing efficient viral isolation. Here we report the first case of acute encephalopathy associated with influenza C virus infection.

The patient (age, 2 years and 4 months) presented with hyperpyrexia. Several hours after the onset of hyperpyrexia, the patient had a generalized convulsion that lasted for approximately 10 minutes, after which the patient exhibited severely disturbed consciousness and symptoms of compensatory shock. His body temperature was 42.0°C.

The pharyngeal and nasal swabs collected on admission tested positive for the influenza C virus but negative for the other viruses. The serum hemagglutination-inhibition titer of antibodies against the isolated virus increased from less than 8-fold at the onset of hyperpyrexia to 128-fold on day 24.

CSF analysis revealed a normal cell count. The cytokine profile on admission revealed markedly elevated serum and CSF concentrations of interleukin (IL)-6 (1527.2 pg/mL and 951.3 pg/mL, respectively) and IL-10 (582.3 pg/mL and 49.3 pg/mL, respectively).

Diffusion-weighted imaging of the brain, performed on day 7, revealed diffuse high-intensity signals over the subcortical white matter. Diffusion-weighted imaging performed on day 24 revealed that the high-intensity signals indicating dendritic forms had disappeared; however, mild diffuse brain atrophy persisted.

Acute encephalopathy with prolonged febrile seizure and late reduced diffusion (AESD) has been suggested to be associated with infection by some viruses (eg, influenza A, influenza B, and human herpes virus type 6).2 AESD is considered the primary form of excitotoxicity-induced acute encephalopathies. The MRI findings obtained in the present case are compatible with those noted in patients with AESD. AESD usually exhibits a biphasic clinical course, with status epilepticus at the onset. However, our patient underwent a monophasic clinical course, and status epilepticus was not noted. This could be attributable to the immediate intensive care that the patient received during the early phase. We considered that the diagnostic criteria for AESD were satisfied in the present case.

The invasion, uncoating, and proliferation mechanisms of the influenza C virus are fundamentally identical to those of the influenza A virus,3 and we can assume that the influenza C encephalopathy is not associated with any unique pathophysiology. A unique feature of our case is the concomitant elevation in the CSF levels of IL-6 and IL-10. The marked elevation in the patient's IL-10, which is not observed in common AESD,4 indicated CNS inflammation.

Masaru Takayanagi, PhD, MD

Naoki Umehara, MD

Hiroshi Watanabe, MD

Taro Kitamura, PhD, MD

Masatoshi Ohtake, PhD, MD

Division of Pediatrics Sendai City Hospital Miyagi, Japan

Hidekazu Nishimura, PhD, MD

Virus Research Center, Clinical Research Division Sendai Medical Center Miyagi, Japan

Yoko Matsuzaki, PhD, MD

Course of Clinical Nursing Yamagata University Faculty of Medicine Yamagata, Japan

Takashi Ichiyama, PhD, MD

Department of Pediatrics Yamaguchi University Graduate School of Medicine Yamaguchi, Japan


1. Matsuzaki Y, Katsushima N, Nagai Y, et al. Clinical features of influenza C virus infection in children. J Infect Dis. 2006;193:1229–1235.
2. Takanashi J, Oba H, Barkovich AJ, et al. Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy. Neurology. 2006;66:1304–1309; commentary 1291.
3. Palese P, Shaw ML. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howly PM, et al, eds. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:1647–1689.
4. Ichiyama T, Suenaga N, Kajimoto M, et al. Serum and CSF levels of cytokines in acute encephalopathy following prolonged febrile seizures. Brain Dev. 2008;30:47–52.
© 2009 Lippincott Williams & Wilkins, Inc.