Acute hemorrhagic leukoencephalopathy associated with influenza A (H1N1) virus

Abstract

Since the declaration of the novel influenza A (H1N1) pandemic by the World Health Organization in June 2009, several neurologic complications have been reported including encephalitis, encephalopathy, seizures, and neuropsychiatric perturbations [1, 2]. Most of the cases concerned children [1] and had a benign course with early and appropriate management. When performed, brain magnetic resonance imaging (MRI) was normal. We report the first case of H1N1 virus related to acute hemorrhagic leukoencephalopathy. A 56-year-old Caucasian woman without past medical history consulted her general practitioner 24 h after the onset of an influenza syndrome. She received imipenem per os 2 g per day for 10 days. On the fifth day, the patient was referred for permanent dyspnea, headache, and 38.5 C fever. No cognitive changes were observed. Pulmonary auscultation found crackles. A chest X-ray showed features of acute respiratory distress syndrome with bilateral infiltrative opacities. At admission, H1N1 was isolated from nasopharyngeal specimens by reverse-transcription polymerase chain reaction (RT-PCR) [3]. The virus could not be isolated by cell culture for sequencing. One hundred fifty milligrams oseltamivir and 40 mg methylprednisolone intravenous per day were administered over 5 days while imipenem was continued. On the sixth day, massive oxygen desaturation occurred despite noninvasive oxygenotherapy. The patient became comatose. She was transferred to the intensive care unit. Mechanical ventilation was then performed after intubation. Brain MRI with T2-, T2*-, and T1-weighted sequences with and without gadolinium infusion showed extensive bilateral hemispheric leukoencephalopathy predominating in the subcortical regions and extending in the right striatum. Several microbleeds were present in the same territories (Fig. 1a–g). MRI angiography was normal. Electroencephalography recorded bilateral slow waves. Cerebrospinal fluid (CSF) was xanthochromic and contained 0.51 g/L protein in a polyclonal pattern with 90 red blood cells and 8 lymphocytes/ mm. PCR was negative for cytomegalovirus, herpes simplex, Epstein–Barr, and H1N1 viruses. Specific antiH1N1 antibody titer determined by hemagglutination inhibition against the A/California/7/2009 strain was 10 in CSF and more than 1,280 in serum. Culture for bacteria and mycosis remained sterile. Neither antinuclear nor onconeural antibodies were noted. On the tenth day, the patient awoke but was deeply confused. The Mini-Mental State Examination (MMSE) score was 19/30 with deficit in time and space orientation and calculation errors. Neurological examination found a left pyramidal syndrome with 4/5 Medical Research Council score on limb muscle testing. Diagnosis of acute partially hemorrhagic leukoencephalopathy linked to the H1N1 virus was reached, and steroid therapy started with methylprednisolone 500 mg daily for 3 days. On the 40th day, muscle strength was normal. The MMSE was 29/30. An extensive neuropsychological expertise showed minor abnormalities with normal memory, verbal comprehension, and executive F. A. Cisse J.-C. Antoine G. Jousserand J.-P. Camdessanche (&) Department of Neurology, University Hospital, 42055 Saint-Etienne Cedex 02, France e-mail: j.philippe.camdessanche@chu-st-etienne.fr