Clinical and MRI features of neurological complications after influenza A (H1N1) infection in critically ill children

Background

Influenza A (H1N1) can cause severe neurological complications.

Objective

The purpose of this study was to analyze clinical and MRI features of neurological complications after H1N1 infection in critically ill children.

Materials and methods

We retrospectively analyzed clinical and neuroimaging findings in 17 children who were hospitalized in an intensive care unit with severe neurological complications after H1N1 infection in South China between September 2009 and December 2011. All children underwent pre- and post-contrast-enhanced brain MRI. Postmortem studies were performed in two children.

Results

Six children died, five because of acute necrotizing encephalopathy (ANE) and one because of intracranial fungal infection. Eleven recovered; their manifestations of H1N1 were meningitis (3), encephalitis (1) and influenza encephalopathy (7). MRI features of ANE included multiple symmetrical brain lesions demonstrating prolonged T1 and T2 signal in the thalami, internal capsule, lenticular nucleus and pontine tegmentum. Postmortem MRI in two children with acute necrotizing encephalopathy showed diffuse prolonged T1 and T2 signal in the bilateral thalami, brainstem deformation and tonsillar herniation.

Conclusion

Fatal neurological complications in children after H1N1 infection include ANE and opportunistic fungal infection. MRI is essential for identification of neurological complications and for clinical evaluation.     

Acute necrotizing encephalopathy in a child with H1N1 influenza infection

Since the World Health Organization declared a global pandemic of novel influenza A H1N1 in June 2009, there has been a sustained rise in the number of cases of this strain of influenza. Although most cases are mild with complete and uneventful recovery, multiple cases of severe infection with complications including death have been reported. To the best of our knowledge, the majority of fatal outcomes in the United States have been related to pulmonary complications. We report a 12-year-old girl infected with influenza A H1N1 whose clinical course was complicated by rapid progressive neurologic deterioration and striking CT and MRI findings consistent with acute necrotizing encephalopathy (ANE). To our knowledge this has not been reported in the pediatric radiology literature. We hope this case will alert radiologists to this complication and familiarize radiologists with imaging findings that herald ANE.     

Clinical features of hospitalised children with 2009 H1N1 influenza virus infection

Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants.     

2009甲型H1N1流感住院患儿多中心临床研究

目的 了解2009年全国多中心2009甲型H1N1流感住院患儿的临床特征,探讨危重症的高危因素和死亡原因.方法 对2009年秋冬季全国17家医院的810例2009甲型H1N1流感住院患儿的临床表现、实验室检查结果以及治疗和转归进行回顾性总结和分析.结果 810例住院患儿中,男508例,女302例,年龄中位数为43个月,其中＜5岁550例(67.9%),合并基础疾病148例(18.5%).常见的表现及例数为:发热780例(96.3%),流涕294例(36.3%),鼻塞192例(23.7%),咽痛147例(18.1%),咳嗽759例(93.7%),咯痰347例(42.8%),喘息219例(27.0%),呼吸困难163例(20.1%),呕吐130例(16.0%),腹泻66例(8.1%),烦躁79例(9.8%),嗜睡64例(7.9%),惊厥32例(4.0%).常见的实验室异常为:外周血白细胞计数增高或降低377例(46.5%),乳酸脱氢酶增高346例(42.7%),C反应蛋白增高306例(37.8%),天冬氨酸转氨酶增高257例(31.7%),肌酸激酶增高174例(21.5%).586例(72.3%)合并肺炎,49例(6.0%)合并脑炎/脑病,30例(3.7%)合并心肌炎.危重症患儿183例,其基础疾病、外周血白细胞计数增高、中性粒细胞比率增高、淋巴细胞比率降低和C反应蛋白增高的发生率明显高于非危重症患儿.19例死亡,占危重患儿的10.4%,8例死于脑炎/脑病,10例主要死于严重肺炎和急性呼吸窘迫综合征,其中5例同时伴有脑炎/脑病,1例死于继发性真菌性脑膜炎.结论 2009甲型H1N1流感容易引起全身多脏器损害.有基础疾病、外周血白细胞计数增高、中性粒细胞比率增高、淋巴细胞比率降低和C反应蛋白增高可能是发生危重症病例的高危因素.合并严重肺炎和急性呼吸窘迫综合征,以及脑炎/脑病是导致死亡的主要因素.     

不同病情小儿病毒性脑炎神经影像学改变与临床关系

目的　探讨病毒性脑炎(下称病脑)不同病情临床影像学改变与临床的关系。方法　对132例不同病情病脑头颅CT、MRI与临床表现进行分析研究。结果　头颅CT检查122例,异常74例,异常率60.65%。MRI检查16例,异常15例,异常率93.75%。MRI的改变比CT更加明显。病情轻者CT基本正常,但MRI则可有改变。病情中度者以累及灰质为主,表现为灰质肿胀。病情重者同时累及灰、白质。极重度者可伴脑出血。临床疗效好者影像学改变轻,疗效差者影像学改变明显,并发症与后遗症发生率高。结论　病脑患儿头颅CT、MRI检查,尤其MRI对该病的诊断、病情轻重及预后有重要意义。     

Aseptic meningitis in a child due to 2009 pandemic influenza A (H1N1) infection

Neurologic manifestations of seasonal influenza 2009 pandemic influenza A (H1N1) are now known to include encephalitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, transverse myelitis, and acute necrotizing encephalopathy. We report a case of 2009 pandemic influenza A (H1N1) meningitis in a previously healthy six-year-old girl who presented with fever, headache, abdominal pain, and vomiting. The infection was confirmed via nasopharyngeal and throat swabs. She was treated with oseltamivir successfully. To our knowledge, she is the first child diagnosed as pandemic influenza A (H1N1) meningitis.     

Imaging in influenza A encephalitis.

Two cases of influenza A encephalitis seen during an outbreak of influenza types A/England/427/88 (H3N2) and A/Taiwan/1/86 (H1N1) in December 1989 are described. In both children the encephalitis developed within three days of the respiratory symptoms and both became comatose within 48 hours. Virological studies showed that the patients had had a recent influenza A infection. Symmetrical localised hypodense lesions within the thalami and pons were demonstrated in both cases on computed tomography of the brain and striking findings in the pons in one case on magnetic resonance imaging. Influenza A encephalitis is not easy to recognise clinically and serological confirmation can only be made after 10 days. Imaging may provide evidence in the acute stage to support a diagnosis of influenza encephalitis during influenza outbreaks.     

Alice in Wonderland syndrome in H1N1 influenza: case report

The different aspects of the global H1N1 influenza and its complications are currently of great interest. Neurological complications of the disease and its frequency are still unknown. We report a case of an 11-year-old girl who developed Alice in Wonderland syndrome associated with H1N1 influenza. This unique clinical syndrome was previously described in other diseases. The clinician's awareness of the existence of this syndrome in H1N1 influenza might save the child from undergoing extensive diagnostic procedures.     

儿童2009甲型H1N1流感相关神经系统并发症报道

报道儿童2009甲流H1N1流感相关神经系统并发症的临床特征。方法　对深圳市儿童医院2009 - 11 - 04 - 2010 - 01 - 19因2009甲型H1N1流感住院,并发神经系统并发症的21例患儿进行前瞻性调研,对其临床特征及转归进行总结。结果　在150例儿童危重症2009甲型H1N1流感住院患儿中,神经系统并发症的发生率为14.0%（21/150）,其中脑病18例（85.7%）,惊厥2例（9.5%）,脑炎1例（4.7%）。男14例,女7例;年龄中位数为5岁。12例（57%）入住ICU监护,6例（28.5%）接受气管插管及机械通气。17例80.9%）痊愈出院,1例仍在住院,3例（14%）死于脑病。结论　2009甲型H1N1流感相关神经系统并发症发生率高,严重脑病患儿可以导致死亡。随着2009甲型H1N1流感的流行,这一结果应该引起广泛关注。     

��ͯ2009����H1N1���������ϵͳ����֢����

??Objective??To describe the clinical characteristics of neurologic complications associated with 2009 influenza A ??H1N1?? infection in children. Methods??A prospective study of 150 children confirmed 2009 influenza A ??H1N1?? infection in Shenzhen Children Hospital from November 4, 2009, to January 19, 2010 was conducted. The clinical features and outcome of the patients with neurologic complications were analyzed. Results??The incidence rate of neurologic complications associated with 2009 influenza A ??H1N1?? infection was 14% of the hospitalized patients. 18??85.7%?? patients were diagnosed as encephalopathy??2??9.5%?? patients were diagnosed as seizures??1??4.7%?? patient was diagnosed as encephalitis. 14 were male, 7 were female?? the median age was 5 years. 12??57%?? patients were admitted to an ICU, 6??28.5%?? required mechanical ntilation. 17??80.9%?? patients were fully recovered and discharged, three ??14%?? died from severe encephalopathy. Conclusion??The incidence rate of neurologic complications associated with 2009 influenza was high, severe encephalopathy canlead to death. This result should attract a great deal of attention as 2009 influenza A ??H1N1?? pandemic continues.     

Nephrotic Syndrome Following H1N1 Influenza in a 3-Year-Old Boy

Background

The pandemic influenza A/H1N1, spread through the world in 2009, producing a serious epidemic in Italy. Complications are generally limited to patients at the extremes of age (<6 months or >65 years) and those with comorbid medical illness. The most frequent complications of influenza involve the respiratory system.

Case Presentation

A 3-year-old boy with a recent history of upper respiratory tract infection developed a nephrotic syndrome. Together with prednisone, furosemide and albumin bolus, a therapy with oseltamivir was started since the nasopharyngeal swab resulted positive for influenza A/H1N1. Clinical conditions and laboratory findings progressively improved during hospitalization, becoming normal during a 2 month follow up.

Conclusion

The possibility of a renal involvement after influenza A/H1N1 infection should be considered.     

Neurological complications and pandemic influenza A (H1N1) virus infection

Aim: To report on a different clinical course of pandemic influenza A (H1N1) infection among children who were neurologically impaired before the acute onset of the disease, in comparison with children who were neurologically intact. Methods: In a period of 6 months, six children with neurological complications associated with pandemic A (H1N1) infection were identified in a single institution paediatric emergency room. The children suffered from seizures or altered mental status during pandemic A (H1N1) infection. All children underwent extensive clinical and laboratory assessment. Three children were neurologically impaired before the acute onset of the H1N1 infection. The other three were neurologically intact before the acute viral infection. Results: In all six patients, pandemic influenza A (H1N1) viral RNA was detected in nasopharyngeal specimens but none in the cerebrospinal fluid. Five children fully recovered or returned to baseline at discharge. The clinical course of the disease and recovery were different between the children who were neurologically impaired before the acute viral infection and those who were neurologically intact. Conclusions: It is possible that children with various neurological conditions are in a higher risk to develop further neurological complications during pandemic influenza A (H1N1) infection.     

儿童重症和危重症2009甲型H1N1流感临床特征

目的 报道儿童2009甲型H1N1流感重症与危重症的临床特征.方法 对150例经咽拭子实时荧光定量PCR检测确诊为2009甲型H1N1流感重症与危重症患儿的临床资料进行分析.结果 150例患儿中,男103例,女47例,年龄中位数为5岁;≥5岁81例,合并基础疾病21例.常见的表现依次为发热142例(95%),咳嗽133例(89%),呕吐35例(23%),喘息29例(19%),腹痛24例(16%),嗜睡11例(7%),惊厥9例(6%),肌痛9例(6%)和腹泻9例(6%).常见的检验异常为外周血白细胞计数异常60例(40%),C反应蛋白增高49例(33%),乳酸脱氢酶增高4.4例(29%),肌酸激酶增高38例(25%)和天冬氨酸转氨酶增高29例(19%).并发症主要为肺炎97例(65%),脑病18例(12%)和心肌炎7例(5%).使用奥司他韦治疗109例(73%),使用糖皮质激素治疗35例(23%).32例(21%)入住ICU,13例接受气管插管机械通气,14例接受支气管镜检查及冲洗.145例(97%)患儿治愈出院,5例死亡,其中3例死于脑病,1例死于急性呼吸窘迫综合征,1例死于继发性真菌性脑膜炎.结论 重症和危重症2009甲型H1N1流感主要发生在没有基础疾病的年长儿,其表现及检验异常比较广泛.神经系统并发症发生率较高,严重的脑病可引起死亡.早期行支气管镜检查及冲洗有可能减少肺部并发症引起的死亡.     

Herpes encephalitis in children. MRI assessment

The magnetic resonance imaging (MRI) findings in 14 patients with biopsy or polymerase chain reaction proven herpes simplex encephalitis were retrospectively reviewed to evaluate the diagnostic value of MRI in the early diagnosis of herpes simplex encephalitis in children. In addition to the early findings, follow-up MRI scans were obtained in four patients. Typical limbic system involvement was seen in 78 percent of the cases. Contrast-enhanced MRI was found to be superior to routine MRI sequences and computerized tomography (CT) in the early detection of inflammation. Follow-up MR images in four patients demonstrated the volume loss and late petechial hemorrhage in the involved regions. Magnetic resonance imaging is the method of choice in the diagnosis and follow-up of herpes simplex encephalitis.     

Analysis of Fatal Cases of Pandemic Influenza A (H1N1) Virus Infections in Pediatric Patients with Leukemia

Background: Pandemic influenza A/H1N1/2009 virus usually causes mild illness in healthy children. Chronic medical conditions are recognized as increasing the risk for complications of influenza virus infection. Although most studies including children with acute leukemia and H1N1 virus have reported no deaths, some anectodal reports with low patient numbers have reported mortality rates as high as 28.5%. Here, we report patients with leukemia and H1N1 virus and review the literature. Methods: Medical records of all children with leukemia and H1N1 virus in our institution were reviewed for demographic, clinical, and laboratory data. We also carried out a systematic review of the English-language literature. Among the 24 articles found, only patients with leukemia and pandemic H1N1 infections were reviewed by two independent reviewers. Results: Eight of 98 children who received chemotherapy for leukemia were diagnosed with pandemic H1N1 infection. One developed pneumonia and acute respiratory distress syndrome (ARDS) and died. Another one developed hemophagocytic lymphohistiocytosis (HLH) and died due to secondary infection during the 6th week of treatment for HLH. In our study, 2 of 8 patients had a fatal course (25%), compared with an overall mortality of 2.5% in the studies retrieved from PubMed (6/232). Conclusion: Pandemic H1N1 influenza virus caused mortality in patients with ARDS or HLH; an unexpected finding for pandemic H1N1 (2009) influenza virus. Thus, for children with leukemia and infected with H1N1 virus, short- and long-term complications should be kept in mind during evaluation.     

小儿病毒性脑炎(偏瘫型)50例脑电图及影像学改变

本文对５０例病毒笥脑炎（偏瘫型）结合脑电图（ＥＥＧ）、头颅ＣＴ及ＭＲＩ结果分析,资料显示：ＥＥＧ检查５０例,异常４９例,头颅ＣＴ检查４２例,异常２６例,ＭＲＩ检查８例,全部异常。结果表明：ＥＥＧ确是监测脑功能变化及病理变化最敏感的指标,可作为脑内病变转归的客观依据,而ＣＴ、ＭＲＩ等影像学检查对病脑（偏瘫型）的病理解剖形态的显示则是重要的辅助诊断手段。     

Late delirious behavior with 2009 H1N1 influenza: mild autoimmune-mediated encephalitis?

Delirious behavior associated with influenza usually has an onset within a few days after fever and lasts <24 hours. As we encountered several patients with 2009 H1N1 influenza who presented with late-onset and long-standing delirious behavior, we retrospectively evaluated the clinical, radiologic, and laboratory features to elucidate the possible pathophysiology. This information was collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years) with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate drowsiness between the episodes of delirious behavior. Electroencephalography was normal except for 1 patient with high voltage and slow activity bilaterally in the occipital regions. Brain MRI was normal. The outcome was excellent with no neurologic sequel in 4 of the 5 patients. In all 5 patients, autoantibodies against N-methyl-D-aspartate type glutamate receptor were elevated or positive in cerebrospinal fluid or serum; the autoantibody levels normalized in the 3 patients who had follow-up studies. This study indicates that 2009 H1N1 influenza has a tendency to cause late-onset and long-standing delirious behavior, at least in Japanese children. Mild autoimmune-mediated encephalitis should be considered as an underlying cause.     

H1N1 infection in children with haematological and oncological diseases in Norway

Aim: To describe the impact of H1N1 infections in children with haematological and oncological diseases during the 2009 H1N1 pandemics. Methods: A short questionnaire was e‐mailed to all paediatric departments taking care of patients with oncological and chronic haematological diseases, asking for known cases of H1N1 infections in this patient group. Results: Nine children treated for cancer and seven children with haematological diseases were registered. No death occurred, but two patients treated for cancer (acute lymphoblastic leukaemia at diagnosis, acute myeloid leukaemia in chemotherapy‐induced bone marrow aplasia) experienced life‐threatening respiratory complications. Conclusion: In all patients with haematological disease and most cases of oncological diseases, the infections ran a mild course. However, life‐threatening complications occurred in severely immunosuppressed and neutropenic patients. Delay of anticancer treatment is a concern even in mild cases.     

Epstein-Barr virus encephalitis: findings of MRI, MRS, diffusion and perfusion

Epstein-Barr virus is an infection that is known as infectious mononucleosis. Even though the central nervous system is not a primary region of involvement of this disease, neurological complications are reported rarely. In this case report, we evaluated a 15-month-old male who presented to the pediatric neurology clinic due to high fever and a neurologic attack. His serological tests and radiological examinations (magnetic resonance imaging (MRI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI) and MR perfusion) were consistent with Epstein-Barr virus encephalitis, which is a very rare complication of infectious mononucleosis. Additionally, we discuss the MRI, MRS, DWI and MR perfusion findings of our case, which were different from other cases reported in the literature.