Cheng, Ruogu

MOGAD is a rare autoimmune encephalomyelitis that shares similar clinical manifestations with other central nervous system demyelinating diseases. However, they must be distinguished due to their distinct pathogenesis and treatment methods. Currently, the clinical diagnosis of MOGAD primarily relies on patients’ clinical manifestations and imaging features, with biomarker application being relatively limited. Meanwhile, research on MOGAD biomarkers has advanced rapidly, with findings mainly focusing on imaging features, antibody titers, nerve cell markers, cytokines, and inflammatory cell ratios. These biomarkers can distinguish among various autoimmune with similar clinical manifestations and exhibit certain specificity. If these biomarker findings are applied to the clinical diagnosis of MOGAD, they could enhance diagnostic accuracy and support earlier and more accurate diagnosis, while providing a scientific basis for evaluating disease progression and prognosis. We discuss the biomarkers and emerging biomarkers of MOGAD, emphasizing the specific changes and aspects that may be applicable to clinical diagnosis and treatment.

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory and degenerative disease of the central nervous system (CNS). Typically occurring in young and middle-aged individuals, untreated MS can have high rates of disability and recurrence, thereby imposing a significant burden on the patient, their family, and society. Many factors are implicated in the etiology of MS, with the relationship between Epstein-Barr Virus (EBV) infection and the development of MS being the subject of extensive research recently. When the human body experiences a decline in immune function, it may trigger reactivation of EBV, and this reactivation is also believed to increase the risk of onset or relapse of MS. Currently, the phenomenon of cross-reactivity resulting from molecular mimicry following EBV infection (including reactivation status) is theorized as a contributing etiology. EBV-mediated abnormalities in T cells and B cells also play a key role in the development of MS. However, the underlying mechanisms have not been thoroughly understood. Meanwhile, the limited availability of effective treatment options for MS, in particular MS progression, underscores the urgent need for novel therapeutic strategies. Here, we discuss the pathophysiological mechanisms underlying MS, specifically emphasizing the relationship between EBV infection and the disease pathology. Furthermore, we introduced relevant pharmacological targets in order to propose a broader range of therapeutic alternatives for individuals diagnosed with MS.

Noninvasive brain stimulation techniques have emerged as a promising therapeutic option for various central nervous system demyelinating diseases. Demyelinating diseases represent a group of pathological conditions that impact the central or peripheral nervous system. They are characterized by damage to or loss of the myelin sheath surrounding nerve fibers. This damage to myelin sheaths disrupts nerve signal transmission, leading to a wide range of signs and symptoms associated with neurological impairment. Treatment for demyelinating diseases usually aligns with the specific underlying cause. Noninvasive brain stimulation techniques can affect neuronal electrical activity and glial cell function, suggesting a potential option for intervention. In this narrative review, we explore the potential of noninvasive brain stimulation techniques for the treatment of central nervous system demyelinating disorders. Noninvasive brain stimulation techniques, including transcranial magnetic stimulation, transcranial electrical stimulation, transcranial focused ultrasound stimulation, optogenetic stimulation, low-intensity pulsed ultrasound, and transcranial photobiomodulation, have been shown to potentially intervene in the treatment of demyelinating diseases by affecting the electrical activity of nerve cells and glial cell function. In addition, this review summarizes the applications and mechanisms of noninvasive brain stimulation techniques in the treatment of central nervous system demyelinating diseases and how these techniques promote myelin regeneration and improve disease prognosis. This review also summarizes research advances in noninvasive brain stimulation techniques for the treatment of multiple sclerosis, acute disseminated encephalomyelitis, progressive multifocal leukoencephalopathy, and neuromyelitis optical spectrum disorder. Noninvasive brain stimulation techniques can improve disease symptoms by promoting oligodendrocyte proliferation and differentiation, enhancing myelin regeneration, and modulating immune responses. Although noninvasive brain stimulation techniques have shown potential in the treatment of various neurological disorders, their use in treating demyelinating diseases remains challenging. For example, transcranial focused ultrasound stimulation is a relatively new noninvasive brain stimulation technique with the advantages of high spatial resolution and the ability to stimulate deep brain structures, but its safety and efficacy in clinical applications need to be further investigated. Optogenetic stimulation offers highly precise neuromodulation, but its feasibility in clinical practice is limited by technical and ethical constraints. Overall, noninvasive brain stimulation techniques have significant potential in the treatment of central nervous system demyelinating diseases, but further research is needed to optimize stimulation parameters, improve therapeutic efficacy, and gain insight into their mechanism of action. With the continuous development of technology and in-depth clinical trials, noninvasive brain stimulation techniques are expected to become an effective treatment for central nervous system demyelinating diseases and provide new therapeutic options for such patients.

Spinal cord stimulation (SCS), first used for pain relief in 1967, serves as an invasive neuromodulation with the targeted delivery of stimulations and the alertness of neural activities. Based on the gate-controlled theory of pain and multiple research studies, the application of SCS to motor recovery, pain relief, and sensory and cognitive restoration has been shown to be significant. Considering that movement disorders and pain are complications of various diseases, the categories, applications, and technical operation of SCS are coming of age. In terms of its impact on the immune system, SCS alters the trajectory of neurological diseases by modulating local immune responses through immunomodulatory mechanisms that vary depending on the different patterns of SCS. In addition to existing targets, the combinations of SCS and emerging techniques deepen the research at the molecular level, contributing to the exploration of potential targets and novel treatments. However, to secure a place in the future trend of non-invasive and precise treatment, it is necessary to improve SCS in terms of mechanism research, cost reduction, and application to more diseases.