H1N1 Encephalitis with Malignant Edema and Review of Neurologic Complications from Influenza

Background  

Influenza virus infection of the respiratory tract is associated with a range of neurologic complications. The emergence of 2009 pandemic influenza A (H1N1) virus has been linked to neurological complications, including encephalopathy and encephalitis.     

Heightened neurologic complications in children with pandemic H1N1 influenza

The 2009 pandemic influenza A (H1N1) has been recognized to cause neurological complications including seizures and encephalopathy. We identified 18 children with 2009 H1N1 influenza and neurological complications from first and second wave activity, and compared characteristics to seasonal influenza. Seizures, encephalopathy, and status epilepticus were common presentations. Focal neurological symptoms persisted in 22% of patients at discharge. Compared to seasonal influenza, patients with pandemic 2009 influenza were more likely to have encephalopathy, focal neurological findings, aphasia, and abnormal electroencephalographic findings. In addition, we noted a trend toward heightened neurological complications following second wave influenza activity. ANN NEUROL 2010     

Complex partial status epilepticus associated with adult H1N1 infection

In the wake of the worldwide H1N1 pandemic, there has been evidence that the H1N1 influenza virus is associated with neurological complications. This is the first report describing status epilepticus in an adult patient with H1N1 virus infection, to our knowledge. This patient had no prior history of epilepsy and presented with complex partial status epilepticus. This was further illustrated on electroencephalographs and MRI brain changes that corresponded with the patient’s clinical state and which subsequently resolved on follow-up. Although uncommon, H1N1 infections may result in central nervous system complications in adults and it is crucial to treat such patients with urgency.     

Guillain-Barré syndrome associated with the D222E variant of the 2009 pandemic influenza A (H1N1) virus: case report and review of the literature

Guillain-Barré syndrome (GBS) is an acute immune-mediated disorder of the peripheral nervous system and a triggering infectious event is often reported in the weeks before the disease onset. Influenza viruses have been associated with Guillain-Barré syndrome (GBS), both after infection and, in rare cases, after vaccination. However, GBS has rarely reported to be a neurological complication of the recent pandemic influenza A(H1N1) 2009 virus infections. Here we describe the case of a young man, who developed acute severe motor inflammatory demyelinating polyradiculoneuropathy during influenza A(H1N1)2009 infection. Peculiar features are the findings of a mutated haemagglutinin gene (D222E variant), which has never previously been associated with neurological involvement, and the almost simultaneous appearance of respiratory infectious and immune-mediated neurological symptoms. Moreover we review the clinical presentation, laboratory findings and outcome of influenza-related GBS.     

Swine flu (H1N1) infection among patients with neurologic disorders. A review of published evidence

Although the 2009 Swine flu (H1N1) pandemic has apparently been abolished, there are still lessons to be learnt. We reviewed the clinical and pathological manifestations of CNS involvement of influenza A virus infection. Neurologic disorders were most commonly seen as underlying medical conditions in swine flu, and neurological complications of the H1N1 vaccination. The major point with regard to the H1N1 pandemic is a mild disease with high contagiosity, which can have severe outcomes in those with underlying diseases including neurological ones.     

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.     

Neurologic complications of 2009 influenza-a H1N1 infection in children

Little is known about the neurologic complications of the 2009 Influenza-A H1N1 epidemic in children. We present a retrospective analysis of children evaluated at a tertiary children's hospital who tested positive for H1N1 with neurologic complications. A total of 164 children tested positive for H1N1. Thirty-one of these patients (19%) were evaluated and discharged from the emergency department. Thirty-nine (24%) were treated in the intensive care unit, the remaining 94 (57%) were treated in medical in-patient units. Six subjects died (3.7%). Neurologic complications identified included headache, encephalitis, polyneuropathy, seizures, and malignant hyperthermia. The rate of neurologic complications in this cohort of patients who tested positive for H1N1 was 19%. The incidence of serious neurologic complications was 3%, with another 3% of patients who experienced rapid clinical deterioration and subsequently died. Our observation of neurologic complications associated with 2009 influenza-A H1N1 epidemic suggests the need for clinical vigilance during future influenza epidemics.     

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.     

Neurologic and Muscular Complications of the 2009 Influenza A (H1N1) Pandemic

In the spring of 2009 a new triple-reassortant of influenza A (H1N1) virus appeared in Mexico and rapidly spread around the world, becoming a pandemic that primarily infected children and uncommonly older adults. Accompanying the pandemic were associated neurologic and muscular syndromes that affected primarily children and included febrile seizures, encephalopathy/encephalitis with or without seizures, delirium, focal neurologic syndromes, Guillain-Barré syndrome, myositis, and myocarditis. Neither the frequency nor the severity of these syndromes appears different from those recognized during periods of infections of previous influenza A viruses. I review the clinical, laboratory, neuroimaging, and pathologic characteristics of the associated syndromes appearing in the first wave of the pandemic, compare them to similar cases occurring in previous years, and explore several theories of pathogenesis.     

Acute necrotizing encephalopathy during novel influenza A (H1N1) virus infection

A novel swine‐origin influenza A (H1N1) virus was recently identified in Mexico. Some cases of infection with neurological complications have been reported to date. We report a case of acute necrotizing encephalopathy associated with the novel H1N1 virus in a 2‐year‐old European girl who suddenly developed fever, seizures, and altered mental status. Brain and spinal cord magnetic resonance imaging showed bilateral symmetrical lesions of the insulae, thalami, geniculate bodies, and pons tegmentum suggestive of an acute necrotizing encephalopathy. An involvement of meninges and spinal cord was observed configuring an acute necrotizing meningoencephalomyelitis. ANN NEUROL 2010;68:111–114     

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.     

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.     

Miller Fisher syndrome in a toddler with influenza A (pH1N1) infection

A 17-month-old previously healthy child presented with a 2-day history of inability to fully open his eyes and slight gait ataxia. In the month preceding admission, he had had low grade, intermittent fevers, followed by a nonproductive cough and sneezing. During hospital admission he lost deep tendon reflexes and was unable to walk. Lumbar puncture revealed abnormally high protein, and a nasopharyngeal specimen was positive for influenza A (pH1N1). He received intravenous immunoglobulin and oseltamivir with clinical improvement. Although it is difficult to ascertain whether pH1N1 or another microorganism was responsible for this toddler's neurologic syndrome, this is the first reported case of Miller Fisher syndrome associated with pH1N1. During pandemics, one may expect to see an increased incidence of uncommon neurologic complications of influenza.     

Safety of influenza and H1N1 vaccinations in patients with myasthenia gravis, and patient compliance

Myasthenia gravis (MG) exacerbations may be triggered by infections.In the winter of 2009/2010, the Israeli Ministry of Health recommended that each individual with a chronic condition be vaccinated against both the seasonal influenza and the H1N1 virus. We examined vaccination practices in 74 MG patients. Only 38 patients (51.4%) received the seasonal influenza vaccine, and 24 (32.4%) received the H1N1 vaccine. No exacerbation of MG was found, and therefore seasonal influenza and H1N1 vaccines seem to be safe in MG.     

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology,Diagnosis, and Management

Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.     

Cortical vision loss as a prominent feature of H1N1 encephalopathy

A 20-year-old woman infected with the 2009 H1N1 strain of influenza A developed bilateral visual loss. Brain MRI showed restricted diffusion of the parietal and occipital lobes, and her spinal fluid did not contain inflammatory cells. This report describes an unusual case of H1N1 influenza A virus infection primarily affecting the posterior visual pathways.     

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.     

Myelopathy following influenza vaccination in inflammatory CNS disorder treated with chronic immunosuppression

We report a patient who developed a transverse myelitis with Brown-Séquard syndrome following a prophylactic influenza vaccination, despite being chronically immunosuppressed for a steroid-responsive optic neuropathy. Although influenza vaccination is recommended in patients receiving chronic immunosuppression, its use may on occasion be associated with neurological complications previously reported in immunocompetent individuals.