Handbook of clinical neurology最新文献

Placebo and nocebo effects are learning phenomena that can be induced not only through direct experience (e.g., classical and operant conditioning) or information (e.g., verbal suggestions), but also through indirect experience via observational learning. Observational learning is not only a powerful method for inducing placebo and nocebo effects; it is also a key mechanism that explains how these effects are formed. This chapter summarizes evidence on the effectiveness of observational learning in inducing placebo and nocebo effects across various symptoms and conditions, including pain. The role of three different types of observational learning - behavioral, symbolic, and verbal modeling - in the induction of these effects is discussed. Furthermore, the chapter reviews the psychological mechanisms, such as expectations, and the neural mechanisms that underlie observationally induced placebo effects. Key factors influencing the effectiveness of observational learning are considered, including the characteristics of both the model (e.g., sex, social status, self-confidence, and accuracy) and the observer (e.g., trait empathy). To provide an overview of the current understanding, the social learning model of placebo effects is introduced. Finally, directions for future research and the clinical implications of studies on observational learning in placebo and nocebo effects are explored.

The specific role of age in the placebo effect has only recently become a focus of systematic studies. Prior to our 2013 review, the literature on placebo effects in children and adolescents was sparse, leaving significant gaps in understanding. Since then, several reviews and meta-analyses have addressed placebo responses in pediatric clinical trials, alongside experimental studies, comparing placebo effects between children, adolescents, and adults. This chapter provides a comprehensive overview of the current knowledge in this domain. Contrary to earlier assumptions, evidence suggests that placebo effects are not systematically larger in children than in adults. Sex differences in placebo responses/effects appear sporadic rather than consistent. Psychological mechanisms underlying the placebo effect, such as expectancy, conditioning, and patient-practitioner interaction, are largely the same in children and adults, though their relative importance may differ across age groups. However, the neurobiologic underpinnings of placebo effects in children remain poorly understood, with existing research providing only preliminary insights. Despite these gaps, the mechanisms of the placebo effect can and should be harnessed to enhance therapeutic outcomes in pediatric clinical practice. Leveraging these mechanisms to maximize placebo responses, while simultaneously minimizing nocebo effects, holds significant potential for improving care in children and adolescents.

The elderly population has been expanding and is expected to continue to do so in the future. This, together with advances in work-up for SNHL, led to an increase in the incidence of VS, with smaller tumor sizes and older ages at the time of diagnosis. One-third of VS exhibit growth, with an average growth rate of 2mm/year. Larger extracanalicular tumors are more likely to grow independent of patient age. Patients with higher baseline SDS fare better, and those managed conservatively have a higher preservation of facial function. Despite extensive research, standardized treatment for VS has yet to be implemented, especially in the elderly population, given the many individual variations. Watchful waiting is a reasonable option for smaller tumors, especially on initial follow-up, providing the highest rates of hearing and facial nerve preservation. An alternative option, which is especially advantageous in high-risk elderly populations, is radiosurgery, providing more than 94% tumor control rate with roughly 57% hearing preservation rate on long-term follow-up. Radiosurgery may be used alone or as an adjunct to microsurgery. Finally, microsurgery remains a feasible option for properly selected elderly patients with reasonable surgical risk, and large Koos grade 4 tumors generally not amenable to radiosurgery.

Vestibular schwannomas (VS) are WHO Grade 1 tumors arising from the vestibule-cochlear nerve and account for 8% of all intracranial neoplasms. In recent years, there has been a dramatic evolution in how the pathology of these tumors is regarded, and there is emerging interest in the role of the tumor microenvironment. In this chapter, we provide a comprehensive description of the pathology and microenvironment of VS, with a particular focus on the interlinked processes of immune cell infiltration and angiogenesis. Improved understanding of the pathophysiology of these tumors has already yielded therapeutic benefits in the form of bevacizumab for NF2-schwannomatosis-associated VS, and the potential role that immunomodulatory agents may play in the management of these patients will become clearer as our appreciation of the tumor microenvironment improves. Given the morbidity associated with current treatment options for VS, it is incumbent upon researchers to advance our understanding of this area so that we may use this information to develop new therapies and improve the care of our patients.

The translabyrinthine approach is one of the most widely used approaches to assess cerebellopontine angle (CPA), particularly for the removal of vestibular schwannomas. It became popularized by William House and William Hitselberger in the 1960s. It has the advantage over other approaches of accessing the CPA at the expense of bone rather than through brain retraction and allows identification of the facial nerve both proximally and distally, thereby assisting nerve preservation during tumor removal. It also provides excellent access for the removal of the intracanalicular portion of tumors. It does, however, require removal of the vestibular apparatus and therefore sacrifices hearing. It may be used in conjunction with other surgical approaches or extended to include removal of the cochlea in order to access the extremities of the CPA or the petrous apex. Indications for the use of the approach and the surgical technique are described including tips to optimize surgical outcome. Complications that might arise following surgery are also discussed.

The development, technique, results, and complications of the retrolabyrinthine/presigmoid approach to the cerebellopontine angle are described. This somewhat overlooked approach allows for potential preservation of hearing and vestibular function and can be applied to the removal of a variety of pathologies in the cerebellopontine angle, including meningiomas, vestibular schwannomas, arachnoid cysts, epidermoid cysts, and other rarer tumors, but is also an option for procedures such as vestibular neurectomy, trigeminal nerve decompression, and auditory brainstem implantation. The addition of contemporary neuromonitoring technology to the approach provides the option for near-real-time monitoring of hearing and facial nerve function during surgery, for overall outcome improvement. The addition of endoscopes to the minimally invasive procedure aids to the surgical field overview, to complete removal of pathology and to preservation of crucial anatomic structures.

Acetylcholine (ACh) is a leading regulatory neurotransmitter in the nervous system, which functions both directly and as modulator of other neurotransmitters. It is found in the central and peripheral nervous system, as well as in the autonomic system-both sympathetic and parasympathetic. In the central nervous system (CNS), ACh functions not only as a neurotransmitter, but also as a modulator of cognitive functions, including long-term and short-term memory, limbic activation, and alertness. No process in the mammalian body can commence without its participation.

Advanced sleep phase (ASP) is seldom brought to medical attention because many individuals easily adapt to their early chronotype, especially if it emerges before the age of 30 and is present in a first-degree relative. In this case, the disorder is considered familial (FASP) and is mostly discovered coincidentally in the presence of other sleep disorders, mainly obstructive sleep apnea syndrome (OSAS). The prevalence of FASP is currently estimated to be between 0.21% and 0.5%. Autosomal dominant mutations in circadian clock genes like PER2, CK1, PER3, CRY2, TIMELESS, and DEC2 have been linked to FASP, some with pleiotropic effects influencing other health aspects like migraine and depression. Early morning awakening is, instead, more common among older individuals, occurring in almost 4% of cases, without considering associated comorbidities. Advanced sleep-wake phase disorder (ASWPD) is characterized by a consistent and distressing anticipation of sleep-wake timing, affecting almost 1% of middle-aged individuals. On average, women have a shorter circadian period than men, making them more susceptible to ASWPD, albeit no significant gender discrepancies have been observed. Age-related alterations in circadian rhythms are exacerbated and compounded by neurodegenerative disorders, impacting the suprachiasmatic nucleus (SCN), sensitivity to light, and light responsiveness in those affected. Conflicting data has surfaced regarding the protective or detrimental effects of ASWPD in studies on aging, mild cognitive impairment (MCI), and diverse dementia conditions.

Non-24-h sleep-wake disorder in blind patients without light perception is an orphan circadian rhythm sleep-wake disorder and is extremely rare in sighted people. Non-24-h sleep-wake disorder is characterized by insomnia and daytime sleepiness alternating with asymptomatic episodes. The frequency of symptomatic periods depends on the daily desynchronization of endogenous circadian pattern of each patient. Diagnosis requires anamnesis, a sleep diary, and actigraphy, if possible; in addition, repeated 24-h measures of circadian markers such as melatonin secretion are also required. Treatment consists of sleep hygiene, behavioral therapy, and melatonin/melatonin agonist administration. Melatonin treatment should start when the circadian rhythm of the patient is in phase with the solar cycle. Efficacy of treatment may be evident after weeks even months from the beginning. There is often a relapse when the medication is stopped.