Notes

IgG4-related ailment: an research into the clinicopathological range: UK center encounter.
Histopathological alterations of the mamillary bodies are the most conspicuous and the most consistent neuropathological features of several disorders that occur after severe thiamine deficiency, such as Wernicke's encephalopathy and Korsakoff's syndrome. Moreover, they are among the few abnormalities that are visible to the naked eye in these disorders. With a lifetime prevalence of approximately 1.3%, Wernicke's encephalopathy is by far the most frequent cause of damage to the mamillary bodies in humans. Still, there is a persisting uncertainty with regard to the development and the clinical consequences of this damage, because it is virtually impossible to study in isolation. As a rule, it always occurs alongside neuropathology in other subcortical gray matter structures, notably the medial thalamus. Converging evidence from other pathologies and animal experiments is needed to assess the clinical impact of mamillary body damage and to determine which functions can be attributed to these structures in healthy subjects. In this chapter, we describe the history and the current state of knowledge with regard to thiamine deficiency disorders and the contribution of mamillary body damage to their clinical presentations.A major function of the nervous system is to maintain a relatively constant internal environment. The distinction between our external environment (i.e., the environment that we live in and that is subject to major changes, such as temperature, humidity, and food availability) and our internal environment (i.e., the environment formed by the fluids surrounding our bodily tissues and that has a very stable composition) was pointed out in 1878 by Claude Bernard (1814-1878). Later on, it was indicated by Walter Cannon (1871-1945) that the internal environment is not really constant, but rather shows limited variability. Cannon named the mechanism maintaining this limited variability homeostasis. Claude Bernard envisioned that, for optimal health, all physiologic processes in the body needed to maintain homeostasis and should be in perfect harmony with each other. This is illustrated by the fact that, for instance, during the sleep-wake cycle important elements of our physiology such as body temperature, circulating glucose, and cortisol levels show important variations but are in perfect synchrony with each other. These variations are driven by the biologic clock in interaction with hypothalamic target areas, among which is the paraventricular nucleus of the hypothalamus (PVN), a core brain structure that controls the neuroendocrine and autonomic nervous systems and thus is key for integrating central and peripheral information and implementing homeostasis. This chapter focuses on the anatomic connections between the biologic clock and the PVN to modulate homeostasis according to the daily sleep-wake rhythm. Experimental studies have revealed a highly specialized organization of the connections between the clock neurons and neuroendocrine system as well as preautonomic neurons in the PVN. These complex connections ensure a logical coordination between behavioral, endocrine, and metabolic functions that helps the organism maintain homeostasis throughout the day.Deep brain stimulation (DBS) has proven to be safe and effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin, while its application to other neural pathways such as the circuit of Papez is under investigation. In particular, the fornix has gained interest as potential DBS target to decrease rates of cognitive decline, enhance memory, aid visuospatial memorization, and improve verbal recollection. While the exact mechanisms of action of fornix DBS are not completely understood, studies found enhanced hippocampal acetylcholine release, synaptic plasticity, and decreased inflammatory responses in cortex and hippocampus. Nevertheless, it is still premature to conclude that fornix DBS can be used in the treatment of cognitive disorders, and the field needs sound, preclinically tested, and disease-specific a posteriori hypotheses.The study of the placebo effect, or response, is related to the investigation of the psychologic component of different therapeutic rituals. The high rate of placebo responses in Parkinson's disease clinical trials provided the impetus for investigating the underlying mechanisms. Ruling out spontaneous remission and regression to the mean through the appropriate experimental designs, genuine psychologic placebo effects have been identified, in which both patients' expectations of therapeutic benefit and learning processes are involved. Specifically, placebo effects are associated with dopamine release in the striatum and changes in neuronal activity in the subthalamic nucleus, substantia nigra pars reticulata, and motor thalamus in Parkinson's disease, as assessed through positron emission tomography and single-neuron recording during deep brain stimulation, respectively. Conversely, verbal suggestions of clinical worsening or drug dose reduction induce nocebo responses in Parkinson's disease, which have been detected at both behavioral and electrophysiologic level. Important implications and applications emerge from this new knowledge. These include better clinical trial designs, whereby patients' expectations should always be assessed, as well as better drug dosage in order to reduce drug intake.The subthalamic nucleus (STN) is a subcortical, glutamatergic, excitatory, relay nucleus that increases the inhibitory drive of the basal ganglia and suppresses action. It is of central relevance to the neuropsychological construct of inhibition, as well as the pathophysiology of Parkinson's disease (PD). Deep brain stimulation (DBS) of the STN (STN-DBS) is an established surgical treatment for PD that can be complicated by adverse neuropsychiatric side effects, most commonly characterized by impulsivity and mood elevation, although depression, anxiety, apathy, and cognitive changes have also been reported. Notwithstanding these adverse neuropsychiatric effects in PD, STN-DBS may also have a role in the treatment of refractory psychiatric disorders, as more is understood about the physiology of this nucleus and techniques in neuromodulation are refined. In this chapter, we link neuropsychiatric symptoms after STN-DBS for PD to the biological effects of electrode implantation, neurostimulation, and adjustments to dopaminergic medication, in the setting of neurodegeneration affecting cortico-striatal connectivity. We then provide an overview of clinical trials that have employed STN-DBS to treat obsessive-compulsive disorder and discuss future directions for subthalamic neuromodulation in psychiatry.The human subthalamic nucleus (STN) is a small lens shaped iron rich nucleus, which has gained substantial interest as a target for deep brain stimulation surgery for a variety of movement disorders. The internal anatomy of the human STN has not been fully elucidated, and an intensive debate, discussing the level of overlap between putative limbic, associative, and motor zones within the STN is still ongoing. ARN-509 In this chapter, we have summarized anatomical information obtained using different neuroimaging modalities focusing on the anatomy of the STN. Additionally, we have highlighted a number of major challenges faced when using magnetic resonance imaging (MRI) approaches for the visualization of small iron rich deep brain structures such as the STN. In vivo MRI and postmortem microscopy efforts provide valuable complementary information on the internal structure of the STN, although the results are not always fully aligned. Finally, we provide an outlook on future efforts that could contribute to the development of an integrative research approach that will help with the reconciliation of seemingly divergent results across research approaches.The tuberomamillary nucleus (TMN) is located within the posterior part of the hypothalamus. The histamine neurons in it synthesize histamine by means of the key enzyme histidine decarboxylase (HDC) and from the TMN, innervate a large number of brain areas, such as the cerebral cortex, hippocampus, amygdala as well as the thalamus, hypothalamus, and basal ganglia. Brain histamine is reduced to an inactivated form, tele-methylhistamine (t-MeHA), by histamine N-methyltransferase (HMT). In total, there are four types of histamine receptors (H1-4Rs) in the brain, all of which are G-protein coupled. The histaminergic system controls several basal physiological functions, including the sleep-wake cycle, energy and endocrine homeostasis, sensory and motor functions, and cognitive functions such as attention, learning, and memory. Histaminergic dysfunction may contribute to clinical disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, narcolepsy type 1, schizophrenia, Tourette syndrome, and autism spectrum disorder. In the current chapter, we focus on the role of the histaminergic system in these neurological/neuropsychiatric disorders. For each disorder, we first discuss human data, including genetic, postmortem brain, and cerebrospinal fluid studies. Then, we try to interpret the human changes by reviewing related animal studies and end by discussing, if present, recent progress in clinical studies on novel histamine-related therapeutic strategies.Histamine in the brain is produced by a group of tuberomamillary neurons in the posterior hypothalamus and a limited number of mast cells in different parts of the brain. Four G-protein-coupled receptors mediate the effects of histamine. Two of these receptors, H3 and H4 receptors, are high-affinity receptors in the brain and immune system, respectively. The two classic histamine receptors, H1 receptor and H2 receptor, are well known as drug targets for allergy and gastric ulcer, respectively. These receptors have lower affinity for histamine than the more recently discovered H3 and H4 receptors. The H1 and H2 receptors are important postsynaptic receptors in the brain, and they mediate many of the central effects of histamine on, e.g., alertness and wakefulness. H3 receptor is a pre- and postsynaptic receptor, which regulates release of histamine and several other neurotransmitters, including serotonin, GABA, and glutamate. H4 receptor is found in cerebral blood vessels and microglia, but its expression in neurons is not yet well established. Pitolisant, a H3 receptor antagonist, is used to treat narcolepsy and hypersomnia. H1 receptor antagonists have been used to treat insomnia, but its use requires precautions due to potential side effects. H2 receptor antagonists have shown efficacy in treatment of schizophrenia, but they are not in widespread clinical use. H4 receptor ligands may in the future be tested for neuroimmunological disorders and potentially neurodegenerative disorders in which inflammation plays a role, but clinical tests have not yet been initiated.The hypocretins/orexins were discovered in 1998. Within 2 years, this led to the discovery of the cause of human narcolepsy, a 90% loss of hypothalamic neurons containing these peptides. Further work demonstrated that these neurons were not simply linked to waking. Rather these neurons were active during pleasurable behaviors in waking and were silenced by aversive stimulation. This was seen in wild-type mice, rats, cats, and dogs. It was also evident in humans, with increased Hcrt release during pleasurable activities and decreased release, to the levels seen in sleep, during pain. We found that human heroin addicts have, on average, an increase of 54% in the number of detectable Hcrt neurons compared to "control" human brains and that these Hcrt neurons are substantially smaller than those in control brains. We found that in mice, chronic morphine administration induced the same changes in Hcrt neuron number and size. Our studies in the mouse allowed us to determine the specificity, dose response relations, time course of the change in the number of Hcrt neurons, and that the increased number of Hcrt neurons after opiates was not due to neurogenesis.
Read More: https://www.selleckchem.com/products/arn-509.html