Impact of COVID-19 on a brain damage unit.

AIM: To report on the impact of COVID-19 on a brain damage unit. METHODS: We reviewed the records of all patients admitted to our brain damage unit. The study included all the significant clinical events from the first positive qualitative real-time reverse-transcriptase-polymerase-chain-reaction assay (April 8th, 2020) for SARS-CoV-2 to the day all patients tested negative (June 8th, 2020). RESULTS: Of the 20 patients (14 men) (age 57.7 ± 14.9; 2-71 months after brain damage; all with a modified Rankin scale score > 4), 16 tested positive for SARS-CoV-2 and remained positive for a mean of 32.3 days (ranging from 26 to 61). One patient died from COVID-19, while 12 patients were asymptomatic and three suffered mild pneumonia without acute respiratory distress syndrome. All patients received prophylactic subcutaneous heparin. Intravenous methylprednisolone was prescribed for three patients with bilateral pneumonia with excellent results. CONCLUSIONS: Most positive cases (93.7%) were not severe. The good outcome was most likely due to the use of prophylactic anticoagulation therapy, the early use of methylprednisolone for pneumonia and the previously reported immunosuppression amid patients with brain damage. This study hopes to encourage further study into brain damage immunity.

[Low-manifest infections in children and adolescents with consequences of perinatal damage of nervous system].

AIM: Study the specter of low-manifest infections (LMI) and their role in children and adolescents with diseases of central nervous system (CNS) against the background of consequences of perinatal damage of nervous system (PDNS). MATERIALS AND METHODS: Infectologic and neurologic examinations were carried out in 42 patients with consequences of PDNS (17 girls and 25 boys, 3 - 15 years). Detection of LMI resulted in etiotropic therapy with evaluation of clinical and laboratory data in dynamics. RESULTS: In 93% (39/42) of patients causative agents of LMI were diagnosed in various combinations and in various biological materials. Among those: Chlamydia spp.--in 71% of patients, Mycoplasma spp.--in 31%, Ureaplasma urealyticum--in 14% (in total the listed microorganisms were diagnosed in 83% of patients); Herpesviridae family viruses--in 75% (HHV-6--in 67%, VEB--in 36%, CMV--in 11%, HSV-1,2--in 11%). Combination of Chlamydia spp. with HHV-6 (R tetr = +0.61) and with VEB (R tet = +0.74) (P < 0.05) was detected. None of the patients had typical signs of encephalitis clinically or based on MRT. MRT signs of gliosis-atrophic changes in the CNS were detected in all the patients. Reduction of a number of psycho-neurologic and neurologic syndromes was noted in all the patients during LMI therapy. CONCLUSION: Most of the patients with consequences of PDNS had low-intensity inflammatory-degenerative process in the CNS determined by LMI, first of all by Chlamydia spp. as well as Mycoplasma spp.

Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis.

OBJECTIVE: The significance of detecting herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of infants with HSV encephalitis after receipt of prolonged therapy with high-dose (60 mg kg(-1) day(-1)) acyclovir is unknown. We report the clinical and laboratory characteristics, neuroimaging studies and outcomes of four neonates with HSV encephalitis who had persistence of CSF HSV DNA, by polymerase chain reaction (PCR) after 15 to 21 days of high-dose acyclovir therapy. STUDY DESIGN: Retrospective chart review. RESULTS: All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death. CONCLUSION: A persistently positive CSF HSV PCR in neonates may be another risk factor for worse neurodevelopmental outcome. Prospective studies are needed to document how often HSV DNA persists in CSF, elucidate whether it represents an initially high CSF viral load, ongoing viral replication or viral resistance, and determine its possible association with neurodevelopmental impairment.

Abnormal social behaviors in young and adult rats neonatally infected with Borna disease virus.

Autism spectrum disorders (ASD) have been the focus of a great deal of research and clinical speculation. This intense interest relates to both the perplexing pathogenesis and devastating consequences of these disorders. One of the obstacles to understanding the pathogenesis of autism and to developing efficient treatment has been the paucity of animal models that could be used for hypotheses-driven mechanistic studies of abnormal brain and behavior development and for the pre-clinical testing novel pharmacological treatments. In this report, we briefly review our animal model of ASD based on neonatal Borna disease virus (BDV) infection and present new data about abnormal social interaction in adult BDV-infected rats. We found that neonatal BDV infection profoundly affected social behaviors in adult rats. Compared to the control rats, both 90- and 180-day-old infected rats spent less time in active social interaction and more time in following their partners. In the intruder-resident test, the BDV-infected resident rats exhibited less aggression towards the intruders and showed more the following-the-intruder behavior. The following-the-partner behavior may be an example of "stereotypic" activity due to BDV-induced abnormal social communication between rats. The previously published results and present findings indicate that neonatal BDV infection significantly altered the normal pattern of social interaction in rats. Co-localization of activated microglia and dying Purkinje cells in BDV-infected rats suggests that the BDV model could be used to study a pathogenic link of Purkinje cell dropout and neuroinflammation to abnormal social behaviors.

Disrupted spatial memory is a consequence of picornavirus infection.

Picornaviruses are a socioeconomically important family of viruses that includes the rhinoviruses and enteroviruses. Many of these viruses, including the "common cold" Coxsackie virus A21, maintain neurovirulent potential and may induce hippocampal injury. The behavioral implications of this injury have not been adequately explored. Using C57BL/6J mice infected with Theiler's murine encephalomyelitis virus, we examined the formation of spatial memories using the Morris water maze test. Virus-infected mice had greater search error compared to sham-infected animals during the location of a hidden platform and were unable to discriminate the location of the training quadrant during the final probe trial. Furthermore, sham-infected mice were place responders whereas virus-infected mice were cue responders, indicating a lack of spatial memory formation in infected animals. Importantly, the degree of memory impairment was correlated to the extent of hippocampal injury. This suggests that picornavirus infection of the human CNS may also result in at least some degree of neurologic deficit. An important implication of such subclinical virus-induced neurologic deficit is that the injury may accumulate over the lifetime of the individual, eventually leading to the manifestation of clinical cognitive or memory deficits.

Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium alpha-luminol (Galavit).

Oxidative stress is involved in many human neuroimmunodegenerative diseases, including human immunodeficiency virus disease/AIDS. The retrovirus ts1, a mutant of Moloney murine leukemia virus, causes oxidative stress and progressive neuro- and immunopathology in mice infected soon after birth. These pathological changes include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell depletion. Astrocytes and thymocytes are directly infected and killed by ts1. Neurons are not infected, but they also die, most likely as an indirect result of local glial infection. Cytopathic effects of ts1 infection in cultured astrocytes are associated with accumulation of the viral envelope precursor protein gPr80env in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress. We have reported (i) that activation of the Nrf2 transcription factor and upregulation of antioxidative defenses occurs in astrocytes infected with ts1 in vitro and (ii) that some ts1-infected astrocytes survive infection by mobilization of these pathways. Here, we show that treatment with a refined monosodium alpha-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2 activation in cultured ts1-infected astrocytes. GVT treatment also inhibits the development of spongiform encephalopathy and gliosis in the central nervous system (CNS) in ts1-infected mice, preserves normal cytoarchitecture in the thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment of infected mice reduces ts1-induced oxidative stress, cell death, and pathogenesis in both the CNS and thymus of treated animals. These studies suggest that oxidative stress mediates ts1-induced neurodegeneration and T-cell loss.

Differential mRNA expression of neurotrophic factors GDNF, BDNF, and NT-3 in experimental herpes simplex virus encephalitis.

Glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) mRNA levels were studied in the course of murine herpes simplex virus encephalitis. Induction of GNDF and NT-3 (both P < 0.05) was found during acute encephalitis. Despite absence of clinical impairment, both neurotrophic factors were overexpressed 2 months (NT-3) and 6 months (GDNF) following infection (both P < 0.05). Neurotrophic factors play an important role in neuronal survival and recovery after acute injury to the central nervous system (CNS) and may represent an additional therapeutic target for treatment of viral encephalitis.

Subacute sclerosing panencephalitis in the differential diagnosis of encephalitis.

The authors describe five cases of subacute sclerosing panencephalitis (SSPE) identified through the California Encephalitis Project that emphasize the importance of considering SSPE in the differential diagnosis of encephalitis, particularly among pediatric patients. SSPE was not suspected in the differential diagnosis of three of the cases until results of measles testing were known. The diagnosis of SSPE is often not considered by clinicians because of its rarity in the United States and the nonspecific clinical manifestations at onset.

Viral teratogenesis: brain developmental damage associated with maturation state at time of infection.

The rat brain continues to mature after birth and is particularly vulnerable to developmental damage following perinatal insult. Borna disease virus (BDV) infection of postnatal day one (PND-1) rat brain causes a non-encephalitic, persistent infection associated with developmental neuroanatomical and behavioral abnormalities. To test the hypothesis that BDV infection during different brain developmental stages yields variable pathological and clinical disease sequelae, rats were examined for BDV-induced neuroanatomical and behavioral abnormalities following inoculation with BDV on PND-15, and the findings were compared to those resulting from inoculation on PND-1. Similar to rats inoculated with BDV on PND-1, PND-15 inoculated rats developed a persistent infection associated with body weight stunting, abnormal salt taste preference and hippocampal neuron degeneration. However, unlike rats infected with BDV on PND-1, PND-15 inoculated rats did not show signs of cerebellar hypoplasia or hyperactivity. Thus, the risk of BDV-induced damage to specific brain regions, and their associated behaviors, appears, in part, dependent upon the brain's developmental stage at time of BDV-infection. These studies provide evidence of the selective vulnerability of specific neuroanatomic regions and behaviors in developing nervous system to virus-induced damage.