Efficacy and Safety of Calculus Bovis Sativus (CBS) for Adult Encephalitis (CBSinEncephalitis)

Based on the records of traditional Chinese medicine, CBS has the functions of purifying the heart, eliminating phlegm, stimulating bile secretion, and soothing the nerves. It has the ability to alleviate fever, coma, delirium, epilepsy, convulsions in youngsters, dental caries, throat swelling, mouth ulcers, carbuncle, and furuncle.

Encephalitis is a neurological condition characterized by widespread or multiple inflammation of brain tissue. The causes of encephalitis are many and can stem from infectious organisms or be induced by autoimmune reactions, the latter being referred to as autoimmune encephalitis (AE). The yearly occurrence rate of encephalitis is 12.6 per 100,000 individuals. Among these cases, approximately 40-50% are caused by infectious factors, whereas 20-30% are attributed to autoimmune encephalitis (AE). The development of viral encephalitis involves the direct invasion of brain tissue by the virus and the immune response of the body to viral antigens. The virus multiplies extensively, leading to the degeneration of neurons, necrosis, the proliferation of glial cells, and the infiltration of inflammatory cells. These severe tissue reactions can result in the formation of demyelinating lesions and damage to blood vessels and the areas surrounding them. Additionally, vascular lesions affect the circulation in the brain and worsen the damage to brain tissue. The development of AE involves several factors, including molecular mimicry, the activation of latent antigen epitopes, the spread of antigen epitopes, and the disruption of the innate immune system caused by persistent pathogen infection.

The mechanisms that are clearer can be summarized as follows: (1) Decrease in the number of receptors on the surface due to cross-linking and internalization: Anti-NMDAR antibodies have the ability to attach to NMDAR on the postsynaptic membrane, resulting in a reduction of NMDAR surface density through cross-linking and internalization. This reduction leads to a decrease in NMDAR-mediated current, which in turn causes learning and memory defects. (2) Protein-protein interaction disruption: Anti-LGI1 antibodies can disrupt the binding between LGI1 and ADAM23 on the presynaptic membrane and ADAM22 on the postsynaptic membrane. This disruption leads to a decrease in the density of anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).

According to the aforementioned background processes, along with the most recent research, there was a decrease in the abundance of gut flora in patients with AE. Transplanting the fecal bacteria of individuals with anti-NMDAR encephalitis into mice's intestines resulted in cognitive impairment in the animals. This indicates that the brain-gut axis may have a significant role in the development of anti-NMDAR encephalitis. From a clinical perspective, patients consume CBS orally in order to achieve its therapeutic benefits. The primary constituents, bilirubin and bile acid, have been documented to possess regulatory effects on the gut microbiota. Thus, we hypothesize that CBS is probable to have neuroprotective and anti-inflammatory impacts on the brain through alterations in the intestinal microbiota and regulation of the brain-gut connection. CBS is expected to decrease the occurrence of symptomatic seizures and enhance the patient's level of consciousness and cognitive abilities.