Restoring neurological dysfunctions is challenging in patients with the sequels of vertebral and spinal cord lesions. Current guidelines focus on treating the early stage of vertebral and spinal cord lesions, such as tethered cord syndrome, syringomyelia, spinal degenerative diseases, spinal infection, ankylosing spondylitis, myelitis, vertebral and spinal cord vascular malformations, and others, whereas the treatments of the sequels of those lesions have received limited attention. Restoring neurological dysfunctions and damaged structures caused by these lesions could improve patient quality of life. The Chinese Association of Neurorestoratology (Preparatory) and the China Committee of International Association of Neurorestoratology therefore proposed and approved this guideline providing the restorative therapeutic rules and references for physicians to treat patients with neurological dysfunction of sequels from vertebral and spinal cord lesions.

There was much progress in the field of Neurorestoratology in the year of 2022. It included highlighting advances in understanding the pathogenesis of neurological diseases, neurorestorative mechanisms, and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology. There is still controversy about whether amyloid β-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease (AD) pathology. The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found. Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse, limited or failing bidirectional cholinergic upregulation in early cognitive impairment, or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD. Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation, immunomodulation, neurogenesis, neural network or circuitry reconstruction, neuroprotection, nervous structural repair, and neuroplasticity. Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials. However, mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke, spinal cord injury (SCI), and amyotrophic lateral sclerosis in randomized, double-blind, placebo-controlled clinical trials (RDPCTs). Clinical treatments through neurostimulation/neuromodulation and the brain-computer/machine interface yielded positive results in AD, Parkinson's disease, stroke, SCI, cerebral palsy, and other diseases in RDPCTs. Neurorestorative surgery, pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs. Thus, this year, additional guidelines, assessment scales, and standards were set up or revised. These included guidelines of clinical neurorestorative treatments for brain trauma (2022 China version), clinical cell therapy guidelines for neurorestoration (IANR/CANR 2022), SCI or dysfunction quality of life rating scale (SCIDQLRS) (IANR 2022 version). Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases. Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.

The scales evaluating patients' neurological functions and quality of life are the basis of clinical evaluation and/or scientific research of nervous system diseases. Neurological functions of patients with spinal cord injury (SCI) are commonly assessed by using American Spinal Injury Association (ASIA) Impairment Scale or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Generally, the quality of life for SCI patients is evaluated by using several available evaluating scales. International Association of Neurorestoratology (IANR) Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) was designed as one single method to assess various items of quality of life related with SCI, including male sexual function. However, in clinical practice, the ability of returning to society is an important index of quality of life after SCI. Additionally, the female patients' sexual function after SCI that has been neglected in the past should be reconsidered following neurorestorative treatments. Even more, this scale also can be applied to assess the quality of life in patients with spinal cord dysfunction due to diseases or disorders. Thus, the IANR added the ability of returning to society and female patients' sexual function in the current revised version and renamed the scale as Spinal Cord Injury or Dysfunction Quality of Life Rating Scale (SCIDQLRS) (IANR 2022 version). Hopefully, this revised scale is widely used to expand enhanced improvements of quality of life following neurorestorative treatments in patients with SCI or spinal cord dysfunction.

Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage. Promoting standardization of clinical cell therapy procedures is essential for professional associations devoted to cell therapy. The International Association of Neurorestoratology (IANR) and the Chinese Association of Neurorestoratology (CANR; Preparatory) collaborated to release Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017) in 2018. Due to recent advances and achievements in clinical cell therapy worldwide in recent years, IANR and CANR have renewed and updated the guidelines. Except for the requirements of equipment, personnel, and ethics, these revised guidelines include cell type nomenclature, cell quality control, cell types in clinical application, minimal suggested cellular doses, patient-informed consent, indications and contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, the policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility. IANR/CANR recommends that all clinical practitioners follow these cellular therapy guidelines. These guidelines provide references of better cell types, doses, routes, and therapeutic timing windows in different diseases.

Breakthroughs with rapid changes are the themes of the development in Neurorestoratology this year. Given the very difficult circumstances of the persistent COVID-19 pandemic, most of the colleagues in Neurorestoratology have conducted meaningful research and obtained encouraging results, as described in the 2020 Yearbook of Neurorestoratology. Neurorestorative progress during 2021 depicts recent findings on the pathogenesis of neurological diseases, neurorestorative mechanisms and clinical therapeutic achievements. The pathogenesis and risk factors of Alzheimer's disease were parts of the most prominent hot research topics. Yet, it remains controversial whether β-amyloid accumulation and tau protein deposition are the results of, or the reasons for the neurodegenerative processes. Neurogenesis is an important neurorestorative mechanism, however, it is questionable whether neural stem cells are present in the adult humans brain. Thus, neurogenesis may not derive from endogenous neural stem cells in the adult humans. Neurorestorative treatments were important areas of the 2021 research efforts and these therapies are improving the quality of life in patients with neurological diseases. There was major exploration of cell-based therapies for neurological disease and injury. However, unfortunately several multi-center, double-blind or observing-blind, placebo controlled, randomized clinical trials of mesenchymal stromal cells or products of mesenchymal stem cells failed to show positive results in ischemic stroke when employed in the sub-acute or recovery phases as there were no appreciable differences in the quality of life as compared with controls. Excitingly, increased numbers of clinical investigations of brain–computer interface (BCI) were reported that showed benefits for patients with neurological deficits. In pharmaceutical neurorestorative therapies, Aducanumab (Aduhelm) and Sodium Oligomannate are approved respectively by the United States Food and Drug Administration (USFDA) and the China National Medical Products Administration (NMPA) to treat patients with mild-to-moderate Alzheimer's disease. Although, the decisions to approve these drugs are highly contentious in the medical and scientific community because of the contradictory findings or other problems associated with the drug usage. We believe that repeating low-level evidence studies that showed negative results or scanty evidences in randomized control trials is of little significance. However, we strongly recommend conducting multi-center, double-blind, placebo controlled, randomized clinical trials for promising innovative therapeutic methods to facilitate their possible clinical translation.

Brain trauma or traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Along with the conventional therapeutic strategies, neurorestorative treatments for TBI have been developed in recent decades. However, missing standards and guidelines has become a growing issue both in clinical practice and fundamental research. Consequently, the Chinese Association of Neurorestoratology (Preparatory; CANR) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) have reached a consensus to form and approve the Guideline of Clinical Neurorestorative Treatment for Brain Trauma. This guideline addresses the common issues in the evaluation and therapies of TBI patients within the scope of Neurorestoratology, offers recommendations based on state-of-art clinical evidences, and covers cell therapies, neural stimulation therapies, and pharmaceutical therapies. Hopefully, this guideline may provide references to clinical professionals during diagnosis and treatment, maximizing the neurorestorative therapeutic efficacy.

Spinal cord injury (SCI) is catastrophic damage for patients, their family, and society. Researchers and clinicians have been trying to find neurorestorative methods to recover their injured functions and structures. Cell therapy is one of the effective therapeutic strategies for SCI. And it can partially restore their neurological functions, which are once thought as permanent neurological deficits. Currently, cells being used therapeutically in clinic include olfactory ensheathing cells (OECs), mononuclear cells (MNCs), mesenchymal stromal cells (MSCs), Schwann cells, and hematopoietic stem cells, cell products differentiated from embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, and neural stem cells as well as other kinds of cells. Real world data from these cell therapies showed some benefits in some patients with SCI. Due to being affected by many factors, the therapeutic results of some kinds of cells are contradictory and it is hard to compare effects among different types of cells. According to the data of cell therapies, OEC, MNC and MSC transplantation are applied for patients in majority percentage of cases, and OEC transplantation had a higher percentage of benefits. In next step, under the unified standard of cell preparation and quality control as well as the guidelines of clinical cell application, each kind of cells including OECs should be studied using prospective, multicenter, double-blind or observing-blind, placebo-control, randomized studies for SCI patients with different level of injury and chronicity.

Currently, most cellular therapeutic effects for nervous diseases cannot be proven in a multicenter, randomized, double-blind placebo-control clinical trials, except for a few kinds of cells such as olfactory ensheathing cells. These cells show significant improvements in functional recovery and quality of life for patients with chronic ischemic stroke. Also, olfactory neuron transplantation has promising neurorestorative effects on patients with vascular dementia. Human olfactory neuroepithelium can spontaneously and sustainably regenerate or produce new olfactory neurons and glial cell types for decades or a lifetime. The neurorestorative mechanisms of olfactory ensheathing cells are well known; however, little is known about the neurorestorative mechanisms of olfactory neurons. Therefore, I hypothesize that the neurorestorative mechanisms of olfactory neurons after transplantation: (1) can well migrate where they are needed and become local functional neurons, as they need to compensate or replace; (2) must be regulated by some special molecular factors to elongate their axons, modulate or direct synapses to correctly recognize and connect the target cells, and integrate functions. Based on olfactory neuroepithelium cells displaying the special characterization, neurorestorative mechanisms, clinical therapeutic achievements, and hypotheses of effective mechanisms, they (olfactory ensheathing cells and olfactory neurons) may be the most efficient instruments of neurorestoration.