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About this book This second edition is a comprehensive study of the viruses that affect the brain and the central nervous system. Show all. Jane et al. Show next xx. Read this book on SpringerLink. Recommended for you. Recently, Wheeler et al. As described so far, CoVs are respiratory viruses that exhibit neurotropic capacities that not only allows them to achieve latency and avoid the immune response of the host, but also have neurological implications that can complicate the disease associated to its infection.

So far, epidemiological reports have allowed to achieve this, but further work in animal models is required to fully comprehend the mechanisms that CoV uses to reach CNS and to achieve more suitable treatments to resolve this viral infection without an exacerbated disease. It is responsible for respiratory illness mainly in newborns, infants and immunocompromised patients, although it can also infect healthy adults, with mild symptoms Edwards et al. Its genome is negative sense and about 13 Kb length, with nine structural proteins codified on it van den Hoogen et al.

Since it is closely related to hRSV, both in its classification and its genome, their diagnosis has been usually mistaken Edwards et al. Currently, there are no effective treatments against this virus, neither vaccines nor specifics treatments, mainly due to the lack of thorough knowledge associated with its immune response and disease pathogenesis Zlateva and Van Ranst, ; Schildgen et al. In humans, there is a handful of reports associated with encephalitis and hMPV-infections. The first approach to this topic was a report described the year in China Peiris et al.

Therein, the authors describe several cases of children with acute respiratory diseases, particularly patients, of which 32 were positive for hMPV RNA detection Peiris et al. Although the scope of this report was not to associate hMPV with any CNS abnormality, they do report five cases of children with a febrile seizure, reaching levels comparable to the ones seen in influenza, the respiratory viruses most prone to induce seizures, as they state Peiris et al.

Following this, the first case in which the presence of hMPV RNA in brain samples of a patient with encephalitis was reported, was the year in Germany Schildgen et al. This report described the case of a month-old boy that was received in a primary care hospital with a high fever and unresponsiveness to stimulus, either verbal or tactile. Previous to its internalization, during the same day he reported seizures and no spontaneous eye movement Schildgen et al.

After 10 days of hospitalization without further improvement, the child was considered to be dead and was extubated. Concomitantly the same year, a case of encephalitis where hMPV RNA was detected in nasal mucus and tracheal aspirates was reported Kaida et al. From this point on, several cases were described where hMPV-infection was related to encephalitis, and in some cases, the detection of genetic material in different CNS samples was detected.

The year , the death of a 6-month-old girl was reported 9 days after her admission to a healthcare unit Hata et al. She exhibited generalized convulsions and was diagnosed with acute encephalopathy the day she was admitted, and 24 h later she fell into a coma. Two years later, Arnold et al. In the first group, composed of patients, 76 samples were hMPV positive, and of those, four patients were reported with seizures. Therein, they also expose data regarding hRSV, showing that of the samples were positive for this virus and only one of the patients was reported with seizures.

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Through statistical analysis, they can confirm that the frequency of hMPV patients with seizures is statistically significant, unlike the one has seen in hRSV. The second group consisted solely of patients hospitalized with high fever or any CNS abnormality, ranging from the age of 6-month-old to 18 years old.

In that group, they reported five patients with hMPV, where seizures were diagnosed in three Arnold et al.

Despite this, they indicate that a normal CSF profile does not necessarily exclude a neurotropic mechanism, as seen for rabies encephalitis, in which only half of the CSF samples are positive for CSF pleocytosis Arnold et al. Likewise, the case reported above by Schildgen et al. Detection of other etiological agents, such as herpes virus and adenovirus, were negative.

More cases in which status epilepticus was reported—a single long-lasting seizure or several seizures in a specific time range- were associated with hMPV. The year , two cases were reported, a month old and a month-old girl, that reported hMPV infection and eventually developed respiratory failure Webster et al. These three cases were discharged without apparent sequelae.

The year , the first reported case of a child with refractory status epilepticus—a non-responsive condition with a worse prognosis than commonly responsive status epilepticus—was described Vehapoglu et al. The 4-month-old boy was received and eventually transported to pediatric ICU. As stated above, treatment with antiepileptic drugs resulted in unresponsiveness.

Viral infections of the enteric nervous system and intestinal dysmotility

Eventually, seizures passed, and 25 days post-admission she was discharged. No evident sequelae were detected, though antiepileptic drugs were maintained for the following 6 months Vehapoglu et al. Most recently, cases of adults with acute encephalitis and hMPV detection have been described. The first report was published the year in Australia, in a year-old man Fok et al. The man was found unconscious after 2 days of respiratory symptoms and immediately hospitalized. No evident sequelae were detected during the following months Fok et al. Remarkably, lesions found in the MRI analysis were similar to the ones described in the previously reported cases Schildgen et al.

Early during that year, Jeannet et al. Then, later that year, the case of a year-old man was reported, although the case dated from 3 years before its publication. The man was admitted with unspecific low backache and fever, MRI was normal, and no unusual symptoms were detected Tan and Wee, Eventually, the patient de-saturated and respiratory failure was diagnosed, with posterior mechanical ventilation. The patient was treated for 1 week with ribavirin unspecific antiviral and eventually respiratory symptoms subdued, although he exhibited reduced cognition and intermittent agitation as sequelae.

He began rehabilitation, but there was not a significant improvement throughout the following 6 months Tan and Wee, However, it has been described that hMPV can persist in the lung of mice after acute infection Alvarez et al. This characteristic could be aiding the virus to eventually reach the CNS, as the latency state is achieved through the infection of neuronal processes that innervate the lungs, as the genetic material of the virus can be detected in them Liu et al.

Moreover, as described by the authors, latent virus can be reactivated upon treatment with immunosuppressive drugs such as steroids. Although there are extensive case reports that indicate neurological manifestations associated to hMPV-infection in humans, further studies are required in mice models to characterize this disease.

Considering that this virus was first described only 17 years ago, there is plenty of work to be done in order to fully comprehend the impact that this virus may be playing in CNS-related pathologies. Respiratory viruses are the leading cause of bronchiolitis and pneumonia throughout the world, affecting varying ranges of ages, but being more aggressive in children, elderly and immunocompromised individuals. Remarkably, extra-pulmonary symptoms have been described in these viruses, highlighting their capacity to cause neurological complications. Febrile seizures, loss of consciousness, convulsion, ataxia, status epilepticus, encephalitis, myelitis, neuritis and MS are among the several extra-pulmonary symptoms that have been described.

Case reports of children, elderly and even adults exhibiting these symptoms have been described throughout the years for all of these viruses, bringing to spotlight the urgency to describe their neuroinvasive capacity. Moreover, the detection of genetic material and even viral proteins in CNS samples, such as CSF or brain, is a recurrent fact described in several case reports. Several ways to achieve CNS have been described, including transneural and hematogenous pathways.

Neurotropic virus

However, the specific mechanisms responsible for dissemination of each of these viruses with neurotropic capacities into the CNS, have not been thoroughly characterized yet. For instance, hRSV has been reported to reach CNS via the hematogenous pathway, although other routes cannot be discarded entirely. IV can reach the brain via the transneural route, mainly by retrograde axonal transport, reaching first vagal and trigeminal nerves.

20 Virus infection

Likewise, CoV has been described to reach the brain via olfactory bulb, spreading from this point onward into the CNS and the periphery. Since hMPV is an emerging virus, no studies have been performed regarding its capacity to reach CNS, so further data for this virus is required. So far, several mice models have been established for every one of these viruses, allowing the acquisition of new data and the development of new insights of their neurotropic capacities and their neurological manifestations. However, further researches are still required, as many aspects of these CNS pathologies remain unknown.

These studies will add new approach edges to a topic that urgently needs to be characterized, as many children may currently be exhibiting these symptoms and are not being treated properly, as the respective viral infection may not be diagnosed.

Volume 2: Neurotropic Retroviruses, DNA Viruses, Immunity and Transmission

All authors listed have made substantial, direct and intellectual contribution to the work and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Afonso, C. Taxonomy of the order Mononegavirales: update Akins, P. H1N1 encephalitis with malignant edema and review of neurologic complications from influenza.

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