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Journal of Neurological Sciences [Turkish] 29:(2)# 31; 393-397, 2012 http://www.jns.dergisi.org/text.php3?id=543 Case Report Acute Encephalopathy Associated With H1N1 Infection: A Case Report Mehmet GENCER, Duygu EKMEKÇİ, Kemal TUTKAVUL, Figen VARLIBAŞ, Hülya TİRELİ Haydarpasa Numune Training and Research Hospital, Department of Neurology, Istanbul, Türkiye Summary We report a 20 year old previously healthy male patient presented with high fever, headache, speech disorder, disorientation, and epileptic seizure. Clinical presentation, cerebrospinal fluid, and magnetic resonance imaging result of the patient were consistent with acute encephalopathy associated with H1N1 infection. Polymerase chain reaction performed on nasopharyngeal swab was positive for pandemic influenza A (H1N1). Following treatment, his neurologic deficit mostly disappeared within 3 days, and MRI scan on the 10th day showed no lesions. Key words: Encephalopathy, H1N1, magnetic resonance imaging, diffusion-weighted image H1N1 İnfeksiyonuna Bağlı Bir Akut Ensefalopati Tablosu : Olgu Sunumu Özet Bu yazıda ateş, baş ağrısı, konuşma güçlüğü, oryantasyon bozukluğu ve epileptik nöbet kliniği ile başvuran ve öncesinde sağlıklı olan 20 yaşında bir erkek olgu sunulmuştur. Klinik bulgular, beyin omurilik sıvı incelemesi ve manyetik rezonans görüntüleme (MRG) bulguları ile hastada H1N1 infeksiyonuna bağlı bir akut ensefalopati tablosu düşünülmüştür. Nazofarenksten alınan materyalin polimeraz zincir reaksiyon ile incelemesi sonucunda hastada influenza A (H1N1) (+) bulunmuştur. Tedavi sonrası 3 gün içinde nörolojik defisit büyük oranda düzelmiş, 10.gün yapılan MRG'de lezyonların kaybolduğu görülmüştür. Anahtar Kelimeler: Ensefalopati, H1N1, manyetik rezonans görüntüleme, difüzyon görüntüleme H1N1 virus usually causes an acute febrile respiratory illness (nonproductive cough, rhinorrhea and sore throat) accompanied by headache and myalgia(7). The incidence of neurologic complication due to H1N1 virus infection is unknown(12). Confirmed cases of influenza virus infection (A and B) have been associated with seizures (febrile and nonfebrile), alteration of mental status, acute inflammatory demyelinating polyneuropathy, acute disseminated encephalomyelitis, transverse myelitis, acute psychosis, frontal lobe syndromes and visual hallucinations. These
INTRODUCTION Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the central nervous system characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord, usually precipitated by a viral infection or vaccination(6). First and second wave activity of the novel influenza A (H1N1) virus was defined as April 1 to July 31 and August 1 and November 30, 2009(3). The 393
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lymphocytes and normal protein level (29,1 mg/dl; range: 15-45 mg/dl ).
complications have been reported sporadically in the literature over the past 60 years(7).
Initial magnetic resonance imaging (MRI) showed significant increased in signal intensity bilaterally at periventricular area, deep white matter, and corpus callosum using T2 and Flair weighted images with diffusion restriction ( Figure 1, Figure 2). The patient did not have contrast MRI scans. Electroencephalogram showed nonspecific bilateral slow wave paroxysms. Polymerase chain reaction performed on nasopharyngeal swab was positive for pandemic influenza A (H1N1) and oseltamivir was started at a dose of 75 mg twice a day. Clinical presentation, CSF and MRI result of the patient were consistent with ADEM. Time-window between the H1N1 infection and ADEM speaks for etiological relation. Following treatment with intravenous high dose metylprednisolone (1 g once daily) for 7 days, his neurologic deficit mostly disappeared within 3 days. MRI scan on the 10th day showed no lesions (Figure 3). Patient was discharged with normal neurologic status after 10 days of medical therapy. Patient was seen again on August 2010 and was symptom free.
CASE PRESENTATION A 20 year old previously healthy male patient was admitted to emergency department on November 2009, with high fever, headache, speech disorder and epileptic seizure. He had been suffering from nausea, cough, and fatigue for the last three days. At the time of the initial evaluation, his body temperature was 37.5°C. He was awake and partially disoriented. His neurologic examination revealed dysarthria, normal cranial nerve function, and gait ataxia. Babinski's sign was negative on both sides. Sensibility and coordination were intact. During clinical follow-up period, he developed generalized tonic seizures which repeated every 15 minutes and last about two minutes. These episodes were followed by a transient periods of confusion. Seizures discontinued after phenitoin infusion. Complete blood count showed mild leukocytosis. Routine biochemistry and sedimentation rate were normal. Cerebrospinal fluid (CSF) contained 4
Figure 1: Coronal FLAIR and axial T2 weighted images of the patient from first admission. MRI showed significant increased in signal intensity bilaterally at periventricular area, deep white matter, and corpus callosum.
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Figure 2: Axial DWI and ADC map of the patient from first admission. DWI and ADC images showed symmetrically diffusion restriction in periventricular area, deep white matter, and corpus callosum.
Figure 3: Axial DWI and FLAIR sequence of the patient at 10th day. MRI scan on the 10th day showed no lesions.
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restriction associated with influenza A infection was reported in children with acute encephalopathy following febrile convulsive status epilepticus, possibly due to excitotoxicity, and also in acute necrotizing encephalopathy, postulated to be secondary to endothelial injury(8). The most prominent findings were encephalopathy and seizure in our case consistent with the literature. A distinctive diffusion restriction in periventricular, subcortical white matter, and corpus callosum on initial MRI was also observed in our case.
DISCUSSION Central nervous system impairment during infections with influenza viruses has been described since the seasonal influenza pandemic of 1918-1920. Neurological complications associated with influenza virus include convulsions, impairment of consciousness, encephalitis and encephalopathy(9). Frequency of neurologic complications with novel influenza A (H1N1) virus infection is unknown. Neuroimaging results in influenzaassociated encephalopathy might be normal, but in severe cases, abnormalities can include diffuse cerebral edema and bilateral thalamic lesions as well as demyelination. EEG might show diffuse abnormalities(2).
Reversible posterior leucoencephalopathy syndrome (RPLS) is a clinical-radiologic syndrome consisting of reversible cortical neurological dysfunction and brainimaging findings showing subcortical oedema involving the posterior circulation, especially the occipital lobes(5). Some of the more common causes include hypertensive encephalopathy, eclampsia, renal failure, immunosuppressant or cytotoxic agents(4). Seizures may also have a major role in the genesis and evolution of RPLS(10). The affected regions are isointense on the diffusion-weighted imaging (DWI) and hyperintense on the apparent diffusion coefficient (ADC) map, (1) indicating vasogenic oedema in RPLS . In our case, distinctive diffusion restriction with hypointensity on ADC map, involving anterior and posterior subcortical white matter regions together with involvement of corpus callosum was observed.
The first instance of neurological complications of H1N1 was reported for 4 children in Dallas on May 2009. 50% of patients described in this report had seizures, and none died or had neurologic sequelae at discharge(2). The second report on neurological complications of H1N1 involved 6 adult patients in Chile on 2009. Grand mal seizures in two patients, delirium in two patients, confusion and decreased level of consciousness in two patients were reported in this study. Four of six patients had normal MRI findings, one had normal computed tomography (CT) finding and in one patient radiological examination could not be performed in this study(9). The most extensive evaluation of neurological complications in children following 2009 H1N1 influenza pandemic was reported by J Extrand et al. They observed neurological complications in 18 of 303 hospitalized patients with H1N1 influenza. Seizures (67%) and encephalopathy (50%) were the most commonly observed neurological complications. Brain MRIs of 7 patients were obtained and were abnormal in 3 of them with cortical and/or subcortical white matter attenuation. However, no MRIs showed diffusion restriction(3). Diffusion
The incidence of neurologic complications from pandemic influenza A (H1N1) has not yet been determined. The pathogenesis of influenza-associated neurologic disease remains unclear(12), and some authors suggest an indirect autoimmune (11) reactivity . Absence of CSF pleocytosis in our case was also consistent with this potential mechanism. We considered the clinical and imaging findings in our case to be consistent with acute disseminated
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encephalomyelitis due to H1N1 virus infection.
REFERENCES
Antiviral treatment should be initiated as soon as possible for any hospitalized patient with neurologic symptoms and suspected seasonal influenza or novel influenza A (H1N1) virus infection. Antiviral medications have been shown to decrease the risk for complications from influenza. However, the effectiveness of antiviral treatment to prevent influenzaassociated encephalopathy sequelae is unknown(2). In our case, a complete improvement was observed after treatment with intravenous high dose metylprednisolone and oseltamivir.
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Correspondence to: Mehmet Gencer E-mail:
[email protected]
Received by: 14 May 2011 Revised by: 11 December 2011 Accepted: 20 January 2012
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