Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature

Balamuthia mandrillaris is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of Balamuthia GAE is difficult because symptoms are non-specific. Here, we report a case of Balamuthia amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a Mycobacterium abscessus infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed B. mandrillaris, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post COVID condition. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevent SARS-CoV-2 entry in the brain thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Brain entry of SARS-CoV-2 through endothelial cells is prevented by melatonin through allosteric binding to human angiotensin-converting enzyme 2 (ACE2), which interferes with the cell entry receptor function of ACE2 for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.

Disrupting Neurons and Glial Cells Oneness in the Brain—The Possible Causal Role of Herpes Simplex Virus Type 1 (HSV-1) in Alzheimer’s Disease

Current data strongly suggest herpes simplex virus type 1 (HSV-1) infection in the brain as a contributing factor to Alzheimer’s disease (AD). The consequences of HSV-1 brain infection are multilateral, not only are neurons and glial cells damaged, but modifications also occur in their environment, preventing the transmission of signals and fulfillment of homeostatic and immune functions, which can greatly contribute to the development of disease. In this review, we discuss the pathological alterations in the central nervous system (CNS) cells that occur, following HSV-1 infection. We describe the changes in neurons, astrocytes, microglia, and oligodendrocytes related to the production of inflammatory factors, transition of glial cells into a reactive state, oxidative damage, Aβ secretion, tau hyperphosphorylation, apoptosis, and autophagy. Further, HSV-1 infection can affect processes observed during brain aging, and advanced age favors HSV-1 reactivation as well as the entry of the virus into the brain. The host activates pattern recognition receptors (PRRs) for an effective antiviral response during HSV-1 brain infection, which primarily engages type I interferons (IFNs). Future studies regarding the influence of innate immune deficits on AD development, as well as supporting the neuroprotective properties of glial cells, would reveal valuable information on how to harness cytotoxic inflammatory milieu to counter AD initiation and progression.

Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy

Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2−/− mice using CRISPR/Cas9-mediated genome editing. Rnaset2−/− mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8+ effector memory T cells and inflammatory monocytes into the grey and white matter. Single nuclei RNA sequencing reveals homeostatic dysfunctions in glial cells and neurons and provide important insights into the mechanisms of hippocampal-accentuated brain atrophy and cognitive impairment. The Rnaset2−/− mice may allow the study of CNS damage associated with RNaseT2 deficiency and may be used for the investigation of potential therapies.

Prevotella brain abscess in a healthy patient with a patent foramen ovale: Case report

Background: Brain abscesses are relatively rare life-threatening infectious lesions often concomitant with a direct spillover of inflammation in the head or neck, hematogenous infections, and immunocompromised conditions. They rarely occur in adults without such predisposing factors. Prevotella is a well-known dental pathogen that very rarely causes brain abscesses. Case Description: We report such an abscess in a 51-year-old man who was innately healthy and had no oral lesions. A comprehensive computed tomography examination of the chest, abdomen, and pelvis, was inconclusive but a transesophageal echocardiogram bubble study revealed a mild patent foramen ovale (PFO) that matched Grade 1 criteria. We deduced that the right-left shunt due to the PFO could have contributed to the brain infection and treated the patient successfully via surgical abscess aspiration and antibiotics. Conclusion: In case of a brain abscess occurring in healthy adults, it is essential to investigate the source of infection and the existence of an arterio-venous shunt, such as PFO.

Disseminated Mycobacterium avium Complex Infection Causing Multiple Skull Defects in an Immunocompetent Patient: A Case Report

Mycobacterium avium complex (MAC) infection mainly causes pulmonary disease. However, in 20% to 30% of cases, it also induces various extrapulmonary diseases. Disseminated MAC infection occasionally occurs in immunocompromised patients but very rarely in immunocompetent patients. An 80-year-old immunocompetent woman presented with multiple chronic wounds on the scalp that had not improved despite prolonged treatment. A scalp abscess caused by disseminated MAC infection 4 years ago had gone through repeated cycles of improvement and aggravation despite continued use of anti-mycobacterial agents and active wound care. Enhanced brain computed tomography and magnetic resonance imaging revealed multiple skull defects and abscesses invading the dura mater. Under general anesthesia, the infected scalp skin and bone were sufficiently removed, and the bone and soft tissue defects were repaired with cranioplasty using a titanium mesh plate and local flap. As exemplified in this case, multiple chronic wounds unresponsive to treatment need to be screened for MAC infection. As chronic MAC infection in the scalp can cause skull destruction and brain infection, it needs to be treated aggressively at an early stage to prevent serious morbidity and mortality. Effective MAC infection management involves adequate medication, regular follow-up imaging, and active surgical procedure.

Can Propolis Be a Useful Adjuvant in Brain and Neurological Disorders and Injuries? A Systematic Scoping Review of the Latest Experimental Evidence

Propolis has been used therapeutically for centuries. In recent years, research has demonstrated its efficacy as a potential raw material for pharmaceuticals and nutraceuticals. The aim of the present scoping review is to examine the latest experimental evidence regarding the potential use of propolis in protecting the brain and treating neurological disorders and injuries. A systematic scoping review methodology was implemented. Identification of the research themes and knowledge gap was performed. After applying the exclusion criteria, a total of 66 research publications were identified and retrieved from Scopus, Web of Science, Pubmed, and Google Scholar. Several key themes where propolis is potentially useful were subsequently identified, namely detoxification, neuroinflammation, ischemia/ischemia-reperfusion injury/traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and epilepsy models, depression, cytotoxicity, cognitive improvement, regenerative medicine, brain infection, and adverse effects. In conclusion, propolis is shown to have protective and therapeutic benefits in alleviating symptoms of brain and neurological disorders and injuries, demonstrated by various in vitro studies, animal models, and human clinical trials. Further clinical research into this area is needed.

Japanese Encephalitis with Global Aphasia- A Case Report

Introduction: Japanese Encephalitis (JE) is a brain infection caused by the Japanese Virus of Encephalitis (JEV).JE is also known as Mosquito-Borne Encephalitis, Summer Encephalitis and Brain Fever etc. Global aphasia is caused by a number of factors, one of which is JE. Presentation of Case: A 15 years old male child was brought to Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha, Maharashtra, India on date 22/08/2019 with complaints of fever since 7 days with 2 episodes of seizures with loss of consciousness for approximately 20 hours and the patient was unable to speak after becoming conscious. On examination, the patient had a fever, was lethargic and appeared depressed, unable to speak, and experienced pain when moving his hands. The patient had a complete blood count, which revealed that his haemoglobin percent, total red blood count, were all low, while his RDW and granulocytes were high. RBCs are predominantly normocytic Normochromic RBCs with mild anisopoikilocytosis, with a few microcytic RBCs, pencil cells, and tear drop cells visible on a peripheral smear as well as platelets were adequate, and no Hemiparasite was found. CSF analysis, CT scan of the brain, an MRI of the brain, and a blood test for P. Falciparum were all performed for diagnostic purposes. The patient was diagnosed as Japanese Encephalitis with Global Aphasia after comprehensive examinations. He was treated Tab. Cefexime, Tab. Levetiracetam, Tab. Phenytoin, Tab. Paracetamol, and Tab. Emset, as well as nursing care was provided based on his needs. Conclusion: Patient showed spontaneous recovery.

Canine bocavirus-2 infection and its possible association with encephalopathy in domestic dogs

Canine bocaviruses (CBoVs) have been recognized as pathogens associated with intestinal diseases. Hematogenous spreading caused by CBoV has been documented and may potentiate the virus entry across the blood-brain barrier to initiate a brain infection. This study focused attention on CBoV detection in cases of encepahlopathy and attempted to determine its viral localization. A total of 107 dog brains that histologically exhibited encephalopathy (ED) were investigated for the presence of CBoVs using polymerase chain reaction (PCR). Thirty-three histologically normal brain samples from dogs were used as a control group (CD). CBoV-2 was detected in 15 ED dogs (14.02%) but not in CD dogs (p = 0.02), while no CBoV-1 and -3 were detected. Among the CBoV-2 positive dogs, brain histological changes were characterized by nonsuppurative encephalitis, with inclusion body-like materials in some brains. In situ hybridization (ISH) and transmission electron microscopy (TEM) confirmed the presence of CBoV-2 viral particles in glial cells, supporting neurotropism of this virus. ISH signals were also detected in the intestines, lymphoid organs, and the heart, suggesting both enteral and parenteral infections of this virus. Whole genome characterization and evolutionary analysis revealed genetic diversity of CBoV-2 sequences and it was varying among the different countries where the virus was detected. This study points to a possible association of CBoV-2 with encephalopathy in dogs. It also highlights the genetic diversity and cellular tropism of this virus.