Fatal encephalitis associated with novel influenza A (H1N1) virus infection in a child

A 4-year-old girl presented with fever, coughing, and vomiting; followed by unconsciousness. Magnetic resonance imaging showed hyperintense changes in the thalami bilaterally, brain stem, cerebellum, and subcortical cortex. Novel influenza A (H1N1) virus was identified by polymerase chain reaction in patient's nasopharyngeal swab specimen. We reported a rare case of clinically severe, novel influenza A-associated encephalitis. Novel influenza A should be considered in the differential diagnosis in patients with seizures and mental status changes, especially during an influenza outbreak.     

Acute disseminated encephalomyelitis associated with influenza A H1N1 infection

Acute disseminated encephalomyelitis is an immune-mediated inflammatory disorder of the central nervous system, characterized by demyelination. Acute disseminated encephalomyelitis predominantly involves the white matter of the brain and spinal cord, and often follows upper respiratory tract infection. We describe a case of acute disseminated encephalomyelitis associated with the influenza A (H1N1) virus. The H1N1 virus usually causes febrile respiratory signs, e.g., fever, cough, and sore throat. Although these signs exhibit a self-limited course, the frequencies of severe complications and death are increasing. To date, only a few reports of acute disseminated encephalomyelitis secondary to the H1N1 virus have been published.     

Acute myelopathy associated with H1N1 virus infection

The swine-origin influenza A (H1N1) virus caused a pandemic infection in June 2009. The incidence of neurological complications due to H1N1 virus infection is unknown. Two cases of cervical acute myelopathy associated with H1N1 virus infection are reported. Both patients (male 29 years and female 24 years) suffered moderate to severe sensory and motor symptoms, but recovered completely within a few weeks. Acute myelopathy is a rare complication of H1N1 infection, but appears to be of similar course and prognosis as myelopathy associated with conventional viral infection.     

Acute necrotizing encephalopathy of childhood associated with influenza type B virus infection in a 3-year-old girl

Acute necrotizing encephalopathy of childhood represents a novel entity of acute encephalophathy, predominantly affecting infants and young children living in Taiwan and Japan. It manifests with symptoms of coma, convulsions, and hyperpyrexia after 2 to 4 days of respiratory tract infections in previously healthy children. The hallmark of acute necrotizing encephalopathy of childhood consists of multifocal and symmetric brain lesions affecting the bilateral thalami, brainstem tegmentum, cerebral periventricular white matter, or cerebellar medulla. The etiology and pathogenesis of this kind of acute encephalopathy remain unknown, and there is no specific therapy or prevention. The prognosis is usually poor, and less than 10% of patients recover completely. We report a 3-year-old previously healthy girl presenting with acute necrotizing encephalopathy of childhood associated with influenza type B virus infection, which resulted in severe neurologic sequelae. We also review the current knowledge of the clinical, neuroimaging, and pathologic aspects of acute necrotizing encephalopathy of childhood.     

Muscle biopsy features in critical ill patients with 2009 influenza A (H1N1) virus infection

Higher serum creatine kinase (CK) levels in critically ill patients with a confirmed 2009 influenza A (H1N1) infection suggests a possible relationship between the H1N1 virus and muscle tissue. However, there have been no reports with an emphasis on muscle biopsies for patients infected with the H1N1 virus. The objective of this study was to investigate the histological characteristics of the muscle biopsies from critically ill patients with confirmed 2009 H1N1 infections. A series of ten patients with confirmed 2009 H1N1 infection, who presented increased serum CK levels, was analyzed. Histological study found small histochemical alterations in muscles fibers (mainly in NADH, SDH, COX, myophosphorylase, adenylate deaminase and PAS stains), and no histological changes were compatible with inflammatory myopathy. Although our critically ill patients had elevated CK levels, they exhibited few histological/histochemical abnormalities in their muscle biopsy samples; however, those alterations could be consistent with metabolic dysfunction associated with influenza H1N1 infection.     

Unusual posterior reversible encephalopathy syndrome in a case of influenza A/H1N1 infection

Central nervous system involvement is an uncommon though potentially a severe complication during influenza infection; the pathogenic mechanisms of the neurological syndromes described in humans are largely unknown. We describe a case of a 51-year-old man who presented with fever and behavioral changes but no focal neurological deficits. The next day, the condition rapidly evolved into a severe neurological syndrome with recurrent focal motor seizures with secondary generalization. At the brain MRI, FLAIR disclosed a slight area of increased signal in the left mesial frontal cortex extending to the frontopolar area and insula. At DWI, a mild hyperintensity was evident in the mesial-frontopolar cortex, with normal ADC values. MR perfusion was indicative of severe hypoperfusion. Fungal, bacterial and viral cultures in CSF, blood and urine were negative. The nasopharyngeal swab PCR was positive for the H1N1-influenza A virus. The patient was thus treated and by day five the neurological examination results had returned to normal. A follow-up MRI, performed two weeks later, only revealed a residual slight hyperintensity in the left medial frontal cortex. The onset of a rapidly evolving encephalopathy syndrome, its close association with a MRI brain pattern of acute vasogenic edema and favorable outcome support a diagnosis of PRES during influenza A infection. However, the topographic characteristics of the cerebral lesion seem to define a PRES with an atypical pattern.     

Acute necrotizing encephalopathy associated with enterovirus infection

Acute necrotizing encephalopathy is a rare, clinically distinct entity of acute encephalopathy triggered by acute febrile diseases, mostly viral infections. It is postulated to arise from uncontrolled cytokine release during a febrile illness, and is most often seen in East Asia. We describe a rare Saudi patient of acute necrotizing encephalopathy attributable to enterovirus in a 4 years and 6 months old girl. A work-up revealed elevations in serum and cerebrospinal fluid interleukin-6 and tumor necrosis factor-α. The outcome on intravenous pulse methylprednisolone was good. This case is the first, to the best of our knowledge, of acute necrotizing encephalopathy reported from Saudi Arabia with a good outcome despite severe magnetic resonance imaging findings and delay in the steroid treatment.     

Influenza-associated encephalopathy with elevated antibody titers to pandemic (H1N1) 2009 influenza

Pandemic H1N1 influenza (pH1N1) has been associated with encephalopathy, but the role of adaptive immunity in disease pathogenesis remains unclear. A child presented with seizures 5 days after onset of respiratory symptoms with pH1N1, with no detectable virus in cerebrospinal fluid. The authors compared her serum cytokines and pH1N1 antibody titers to those of 22 children with pH1N1, seasonal influenza, or other respiratory viral infections. They also compared her cerebrospinal fluid biomarkers to those of 20 children with confirmed or probable central nervous system infection or viral infection without central nervous system involvement. Her serum antibody titers were several-fold higher, and levels of proinflammatory cytokines in cerebrospinal fluid and serum were lower than those of controls. Antibody titers in cerebrospinal fluid were undetectable. The delayed onset of neurologic manifestations, normal cytokine levels in serum and cerebrospinal fluid, markedly elevated hemagglutinating and neutralizing antibody titers, and absence of virus and antibodies in cerebrospinal fluid raise the possibility of a post-infectious autoimmune-mediated process.     

Acute hemorrhagic leukoencephalopathy associated with influenza A (H1N1) virus

Journal of Neurology -     

Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection

Acute encephalitis, encephalopathy, and seizures are known rare neurologic sequelae of respiratory tract infection with seasonal influenza A and B virus, but the neurological complications of the pandemic 2009 swine influenza A (H1N1) virus, particularly in adults, are ill-defined. We document two young adults suffering from H1N1-associated acute respiratory distress syndrome and renal failure who developed cerebral edema. The patients acutely developed a transtentorial brain herniation syndrome including a unilateral third nerve palsy (dilated and unresponsive pupils), elevated intracranial pressure, coma, and radiological evidence of diffuse cerebral edema. In both patients, neurological deterioration occurred in the context of hyponatremia and a systemic inflammatory state. These patients illustrate that severe neurologic complications, including malignant cerebral edema, can occur in adults infected with H1N1 virus, and illustrate the need for close neurological monitoring of potential neurological morbidities in future pandemics.     

Serum D-dimer changes and prognostic implication in 2009 novel influenza A(H1N1)

Background

The patients with Influenza A (H1N1) have a higher mortality compared with suffering from seasonal influenza. However, many clinical characteristics are still not clear. In the course of clinical treatment on H1N1, we found there were some apparent abnormal clinical indexes being detected at the preliminary diagnosis for severely ill patients, especially the obvious increasing of D-dimer. D-dimer may be associated with the prognosis of Influenza A (H1N1).

Methods

Patients' clinical data (age, gender, body mass index, primary diseases, etc.) and the preliminary diagnostic clinical indexes including blood creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactic dehydrogenase (LDH), T cell subsets, blood gas analysis, D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT) and plasma fibrinogen (FG) were retrospectively analyzed.

Results

Compared with the non-respiratory failure group, the cases in respiratory failure group, especially in death sub-group have lower lymphocytes, higher LDH and D-dimer, as well as decreasing oxygenation index during the preliminary diagnosis(P < 0.05). The disease severity (Apche II scores) was independently associated with preliminary oxygenation index and LDH (R² = 0.511, p < 0.01). The correlation analysis shows that there is a negative correlation between the D-dimer and oxygenation index (r = − 0.510, P < 0.01) in the preliminary diagnosis. Meanwhile, there is also a negative correlation between preliminary diagnostic D-dimer and the lowest oxygenation index after admission (r = − 0.573, P < 0.01).

Conclusions

The peripheral blood lymphocytes (including CD3, CD4 and CD8), LDH, oxygenation index and D-dimer detected in the preliminary diagnosis are important indexes that may affect the disease progress and prognosis of H1N1 patients. The significantly increased D-dimer and corresponding hyoxemia indicate the probability of formation of pulmonary microthrombus. Thus, it may be necessary to consider the anticoagulant therapy.     

EEG findings in a case of acute necrotizing encephalopathy of childhood associated with influenza A virus infection

We reported here a case of symptomatic partial epilepsy following acute necrotizing encephalopathy of childhood associated with influenza A virus infection. This 2-year-old boy underwent repeated EEG recordings, which at the acute stage was dominated by diffuse 1-2 Hz slow waves. The background activity was 5 Hz theta waves on the 49th day. Paroxysmal activities appeared after the 89th day of illness. On the 231st day, EEG showed spike-and-waves on the left and right frontal areas. Interestingly, paroxysmal activities preceded the onset of epileptic seizures by 7 months, and spike-and-waves by 2 months. After 10 months, he had generalized seizures with fever, and partial seizures on awakening without fever. Interictal EEG showed spike-and-waves on the bilateral frontal areas, and diffuse polyspikes and slow waves were occasionally seen. Though the background activity improved, his consciousness level did not recover probably because the thalamus, basal ganglia, brainstem were damaged more severely than the cerebral cortex.     

Acute necrotizing encephalopathy associated with human herpesvirus-6 infection

An extremely rare case of acute necrotizing encephalopathy caused by human herpesvirus-6 variant type B infection is reported. The patient, a 14-month-old previously healthy female, presented with high fever and generalized tonic convulsion followed by rapid deterioration of consciousness. On the second day of the illness, the protein level of the cerebrospinal fluid increased without pleocytosis. On the third day, magnetic resonance images demonstrated symmetric, abnormal signal intensity lesions in the bilateral thalamus, cerebellum, and brainstem. On the fourth day, characteristic maculopapular rash of exanthema subitum appeared on the trunk. Human herpesvirus-6 deoxyribonucleic acid was detected by the polymerase chain reaction in the serum, and immunoglobulin G and immunoglobulin M of serum human herpesvirus-6 were positive. On the twelfth day of illness, the patient died as a result of severe brain damage. Acute necrotizing encephalopathy should be included in the differential diagnosis when examining infants and young children with fulminating consciousness disturbance and intractable convulsion. In addition, as a causative virus, human herpesvirus-6 has to be considered at the pre-eruptive stage of exanthema subitum. Magnetic resonance images are useful because they reveal the characteristic distribution of lesions specific to acute necrotizing encephalopathy.     

Productive infection in the murine central nervous system with avian influenza virus A (H5N1) after intranasal inoculation

The H5N1 type of influenza A virus isolated from human patients in 1997 has a characteristic hemagglutinin and was considered to be directly transmitted from birds. Although neuropathogenicity of this virus was not demonstrated in human autopsy cases, some experimental studies using mice have disclosed that this virus infects the central nervous system (CNS) after intranasal inoculation. In this study we focused on the topographical localization of virus-infected cells in the murine CNS after intranasal inoculation. We immunohistochemically examined virus-infected cells in mouse tissues using a rabbit antiserum recognizing the nucleoprotein of influenza A virus. The virus-infected cells appeared initially in the respiratory tract. Thereafter, the virus antigen-positive cells appeared in the olfactory system and the cranial nerve nuclei innervating the facial region. This suggests that this virus is principally transmitted from the nasal cavity to CNS through the cranial nerves. Neurons were frequently infected and glial and ependymal cells were also infected. Transneuronal transmission of the virus might play the important role of viral spread within the CNS.     

Acute disseminated encephalomyelitis associated with Influenza A H1N1 infection

Previous studies had not suggested acute disseminated encephalomyelitis (ADEM) during Influenza A H1N1 infection. We report the case of patient who had predominant neurological complication following Influenza A H1N1 infection. The patient, who showed clinical and MRI evidence of ADEM, had significant recovery, which in part, may be related to early treatment. The patient demonstrated that the prognosis of Influenza A H1N1-associated ADEM may not be poor.