International review of neurobiology最新文献

Biomarkers are measurable indicators to assess physiological processes, disease states, or therapy responses. In myasthenia gravis (MG), biomarkers are critical for diagnosis, monitoring, and treatment optimization. Despite advances in MG diagnostics and therapies, predictive biomarkers to personalize treatment remain underdeveloped. Key diagnostic blood biomarkers include antibodies against acetylcholine receptors (AChR) or muscle-specific tyrosine kinase (MuSK), confirming MG diagnosis and guiding treatment decisions. Prognostic markers, such as microRNAs (e.g., miR-150-5p and miR-30e-5p), show promise in predicting disease progression. Pharmacodynamic biomarkers enhance treatment precision, including CD20+ B cell counts for Rituximab and the CYP3A5 gene for Tacrolimus. Emerging research on metabolites, T and B-cell markers, complement factors, and proteomics may help distinguish MG's autoimmune profile. Digital biomarkers, using wearables and sensors, offer innovative patient monitoring. Future efforts integrating multi-omics and big data could revolutionize biomarker discovery, advancing personalized care and improving outcomes for MG patients.

The thymus is a central lymphoid organ responsible for T-cell development and maturation and is crucial in adaptive immunity. This organ creates a specialized environment for thymocyte differentiation and positive/negative selection, ensuring the survival of functional and self-tolerant T cells while eliminating autoreactive clones. This process, which is known as T-cell education, involves interactions between developing T cells and stromal cells, primarily thymic epithelial cells, which present tissue-specific antigens. Proper thymus function remains vital for maintaining immune homeostasis. However, thymic abnormalities have been implicated in Myasthenia Gravis (MG), where the thymus often exhibits lymphofollicular hyperplasia or thymomas, which may trigger an autoimmune response against the acetylcholine receptor at the neuromuscular junction. This leads to impaired neuromuscular transmission and characteristic muscle weakness. Understanding the etiological mechanisms underlying thymic alterations associated with MG is crucial for elucidating immune dysregulation resulting from an abnormal thymus, which may persist even post-therapeutic thymectomy.

The current chapter presents the literature evaluating the effects of classic psychedelic treatments on five substance use disorders: alcohol, tobacco, opioid, stimulant, and cannabis. Most work on psychedelics and substance use disorders was conducted for alcohol use disorder. A range of classic psychedelics (LSD, psilocybin, and ayahuasca) appear to be beneficial for facilitating both reduced drinking and abstinence. Small clinical trials have also shown promising initial results for both tobacco and opioid use disorders. In contrast, no trials have yet been conducted for stimulant and cannabis use disorders. Furthermore, the majority of studies described are naturalistic observational studies or correlational survey data. However, if such observational studies reflect causal therapeutic potential, these studies, combined with clinical trials, suggest potential broad transdiagnostic efficacy of psychedelics across multiple addictive drugs. The transdiagnostic effects of psychedelics are likely due to a combination of biological and psychological factors. Biologically, psychedelics appear to ameliorate deficits in brain areas involved in reward and emotional processing, which may reduce the risk of relapse. Psychologically, the insights gained during a psychedelic experience may reinforce personal motivations for sobriety and support subsequent behavior change. Overall, more work is needed to better characterize the potential benefits and limitations of psychedelic treatment for substance use disorders.

The diagnostic precision of MG, along with the emergence of novel treatments targeting the autoimmune response, has ushered the field into a new era, moving MG management closer to personalized medicine. However, critical gaps remain, including the absence of approved treatments for seronegative MG, limited attention to Lambert-Eaton myasthenic syndrome and congenital myasthenic syndromes, and the need for more precise biomarkers. Current clinical trials primarily rely on outcomes that measure symptoms and/or muscle weakness/fatigability; however, there is a need for biomarkers that better reflect disease activity, enable early diagnosis in seronegative MG, and identify the underlying antibodies in these patients. Predictive biomarkers are also needed to assess the risk of generalization from ocular MG and the likelihood of relapses. Furthermore, despite their efficacy, novel treatments such as complement and FcRn inhibitors are costly and inaccessible in many countries. Future MG research must, therefore, prioritize socioeconomic considerations alongside therapeutic advancements. Also, a better understanding of the fatigue in MG, with differences in men and women, is essential to better design treatment over time.

The diagnostic workup for myasthenia gravis extends beyond the objective evaluation of skeletal muscle fatigue during neurological examinations. It incorporates antibody testing, electrophysiological studies to confirm neuromuscular transmission impairment, and chest imaging to detect thymoma. Positive clinical response to acetylcholinesterase inhibitors may also support diagnosis. Key clinical assessments focus on symptoms of skeletal muscle fatigability, particularly in ocular, bulbar, and limb-girdle muscles. While the ice-pack test is commonly used to assess ptosis, the global availability of acetylcholinesterase inhibitors for testing remains limited. Radioimmunoassay is the most sensitive diagnostic method for MG-specific antibodies, such as AChR and MuSK, followed by cell-based assays that utilize clustered receptors. Enzyme-linked immunosorbent assay (ELISA) is another option, though with reduced specificity. Electrophysiological evaluation begins with repetitive nerve stimulation (RNS) to detect postsynaptic transmission failure, with single-fiber electromyography (SFEMG) employed in cases where RNS results are inconclusive. All patients with MG, regardless of subtype, should undergo chest imaging (CT or MRI) to screen for thymoma. Differential diagnoses to consider include congenital myasthenic syndromes, cranial nerve disorders such as Horner syndrome or third nerve palsy, autoimmune demyelinating polyneuropathy, mitochondrial myopathy, and motor neuron disorders.

Neutral hypnosis offers a valuable state for researchers interested in the nature of consciousness. By minimizing external influences and suggestions, it allows for the investigation of the intrinsic qualities of hypnotic consciousness and its relationship to normal waking states. Studies have shown that neutral hypnosis can result in a significant shift in self-perception. Self-consciousness in neutral hypnosis is often characterized by distortions in the sense of self, fluctuations in self-awareness, and alterations in the experience of agency and body ownership. However, despite these clear effects, the field has largely overlooked the importance of these self-alterations, leading to a notable gap in the literature. In this chapter, we aim to address this gap by examining the existing research on self-consciousness in neutral hypnosis, emphasizing the need for more focused and well-structured studies utilizing the neurophenomenological methodology. Specifically, we propose to apply the neurophysiological three-dimensional model of complex experiential Selfhood, which conceptualizes the self as composed of three dynamically interacting aspects - first-person agency, embodiment, and narrative-reflection - each associated with three distinct sub-networks of the brain's self-referential network. These sub-networks are assessed through EEG operational synchrony analysis, providing a functional measure of their integration. Additionally, we outline several promising avenues for future research, accompanied by testable predictions regarding neurophenomenological alterations in Selfhood as a function of the depth of neutral hypnosis.

Congenital myasthenic syndromes (CMS) result from impaired neuromuscular transmission and are due to genetic mutations in one of several genes involved in the development, function, or maintenance of the neuromuscular junction (NMJ). The clinical presentation, age of onset, and prognosis can vary significantly depending on the underlying genetic defect. Since therapeutic management should be tailored to the specific causative mutation, achieving an accurate diagnosis is essential for optimal patient care. This review summarizes the common diagnostic tests used for CMS and highlights critical features that help differentiate it from other conditions with similar presentations. Key clinical and diagnostic findings are discussed to guide clinicians in identifying potential causative mutations. Finally, we review current treatment options and explore emerging therapies that hold promise for improving patient outcomes.

Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic neuromuscular junction disorder characterised clinically by leg-predominant proximal weakness with spread of weakness distally and cranially with increasing severity as well as reduced reflexes and autonomic symptoms such as a dry mouth. Typical electrophysiological findings include small compound muscle action potentials at rest that augment following short exercise, decrement at low frequency (2-5 Hz) repetitive nerve stimulation, and increment at high frequency (20-50 Hz) repetitive nerve stimulation. Immunologically, antibodies to voltage gated calcium channels are present in the majority of patients. LEMS is associated with small cell lung cancer (SCLC), or rarely other tumours, in approximately 50 % of cases, for which patients should be carefully screened. The synaptic physiology of LEMS demonstrates a reduction in the probability of pre-synaptic acetylcholine vesicle release. This results in a reduced number (reduced quantal content) of miniature endplate potentials such that the post-synaptic summative endplate potential is insufficient to trigger myofiber contraction, manifesting as weakness. The clinical electrophysiological findings reflect normal rate-dependent changes at a neuromuscular junction, in the context of a reduction in quantal release. Treatment of LEMS comprises symptomatic treatments such as 3,4 diaminopyridine (amifampridine), which increases quantal release; immunotherapy; and treatment of underlying malignancy if present. The life expectancy of non-tumour LEMS is normal, although complete remission is uncommon. Progression of SCLC determines prognosis in tumour-associated LEMS, which is nonetheless better than in SCLC without LEMS.