Journal of Neural Transmission最新文献

Botulinum toxin (BT) therapy is the therapy of choice for most forms of dystonia. We want to describe its costs, if all dystonia patients in Germany would have access to optimal BT therapy. For this, we combined the latest data on epidemiology of dystonia and dosing of BT therapy for dystonia. Missing data were generated for this study. Based on official German pharmacy sales prices, optimal treatment for all dystonia patients in Germany with a population of 84.1 million would generate annual drug costs of €155.5 million (cervical dystonia 89.3, tardive dystonia 22.1, generalised dystonia 17.9, blepharospasm 9.3, segmental dystonia 5.9, writer's cramp 5.3, arm dystonia 3.2, oromandibular dystonia 2.3, musician's dystonia 0.3, spasmodic dysphonia 0.1) This is €1.85 annually per capita or 0.3% of the total 2021 drug budget and 42% of the 2021 Parkinson drug budget of German public insurance companies. Actual costs for the health care system are considerably lower, as there are various discounts to consider. Further reductions would be possible. BT therapy's individual costs are high. Its costs for the health care system, however, are marginal. Comparing projected and actual costs, would allow estimating availability and quality of BT therapy of dystonia in Germany.

Spasmodic dysphonia (SD) is now generally considered to be a task-specific focal dystonia. For the first time, we wanted to explore the relationship between SD and dystonia from a combined neurological and phoniatric perspective. For this, we studied 115 patients with non-psychogenic SD by a combined neurological and phoniatric evaluation. Onset of SD was 49.7 ± 19.0 (6-68) years. The female/male ratio was 2. 63% had additional dystonia manifestations (cervical dystonia 35%, arm dystonia 15%, blepharospasm 11%, oromandibular dystonia 11%, writer's cramp 11%, pharyngeal dystonia 10%, generalised dystonia 4%, axial dystonia 2%, spasmodic dyspnoea 2% and segmental dystonia 1%). 71% occurred before, 25% after and 4% together with SD. 17% had a family history of dystonia and 6% a history of exposure to dopamine receptor blocking agents. 41% had mixed SD (SD-M), 31% abductor SD (SD-AB) and 28% adductor SD (SD-AD). SD-M was significantly correlated with additional dystonia manifestations and tremulous SD. No patient showed essential tremor or Parkinsonian syndromes. Two third of SD patients have additional dystonia manifestations and one fifth have a family history of dystonia, considerably more than previously described. In half of all patients, SD starts with non-SD dystonia. Our combined approach revealed a high prevalence of SD-M associated with frequent additional dystonia manifestations including dystonic tremor and a family history of dystonia. Patients presenting with SD should be evaluated for additional dystonia manifestations and dystonia patients should be evaluated for SD. Relevant coexistence of essential tremor and Parkinsonian syndromes cannot be confirmed.

Objectives: It is common for patients with schizophrenia to exhibit symptoms of autism. Both autism spectrum disorders and schizophrenia share similar patterns of empathy deficits. This study purposed to explore the association between autistic features and empathy in Chinese patients with chronic schizophrenia.

Methods: We enrolled 857 patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS), Repeatable Battery for the Assessment of Neuropsychological 7 Status (RBANS), and Interpersonal Reactivity Index (IRI) were employed to assess the participants' clinical symptoms, neurocognition, and empathy, respectively. The severity of autistic symptoms was assessed with the PANSS Autism Severity Scale (PAUSS), with PAUSS scores ≥ 30 were considered to have significant autistic features.

Results: 114 schizophrenia patients (13.3%) had autistic features. Compared to schizophrenia patients without autistic features, those with autistic features had more severe clinical symptoms, and poorer neurocognition and empathic abilities. Female sex and empathic concerns were independently associated with autistic features in patients with chronic schizophrenia.

Conclusions: Our results suggest that autistic features tend to manifest quite commonly among patients with chronic schizophrenia. Empathy deficits are strongly associated with autistic features in patients with chronic schizophrenia, strengthening the view that autistic features may characterize a subgroup of schizophrenia patients.

Monoamine oxidase catalyzes oxidative deamination of monoamine transmitters and plays a critical role in the pathogenesis of neuropsychiatric diseases. Monoamine oxidase is classified into type A and B (MAO-A, MAO-B) according to the substrate specificity and sensitivity to inhibitors. The isoenzymes are different proteins coded by different genes localized on the X-chromosome, but they have identical intron-exon organization, similar protein structure and enzymatic mechanism and are considered to be derived from the same ancestral gene. The isoform-specific transcription organization regulates expression and function of MAO-A in response to cellular signaling pathways and environmental factors. MAO-A shows distinct properties and functions: isoform-specified polymorphisms, localization in catecholamine neurons, expression during early embryonic stage, regulation of brain architecture development and mediation of death and survival of neuronal cells. MAO-A is more flexible to genetic and environmental changes than MAO-B. Defective MAO-A expression impairs embryonic brain development and causes adult abnormal mood and behavior, as shown by human male cases with MAO-A deletion. This paper presents the regulation of brain MAO-A expression epigenetically by interaction between genetic and environmental factors. Association of aberrant MAO-A expression and activity with aggression, asocial behaviors, depressive disorders, and neurodegenerative diseases is discussed. Novel therapeutic strategy for psychiatric diseases by intervention to the regulation of MAO-A expression and activity is proposed.

The exact cause of nigral cell death in Parkinson's disease (PD) is still unknown. However, research on MPTP-induced experimental parkinsonism has significantly advanced our understanding. In this model, it is widely accepted that mitochondrial respiratory failure is the primary mechanism of cell death. Studies have shown that a toxic metabolite of MPTP inhibits Complex I and alpha-ketoglutarate dehydrogenase activities in mitochondria. Since then, many research groups have focused on mitochondrial dysfunction in PD, identifying deficiencies in Complex I or III in PD patients' brains, skeletal muscle, and platelets. There is some debate about the decline in mitochondrial function in peripheral organs. However, since α-synuclein, the main component protein of Lewy bodies, accumulates in peripheral organs, it is reasonable to consider PD a systemic disease. Additionally, mutant mitochondrial DNA with a 4,977 base pair deletion has been found in the brains of PD patients, suggesting that age-related accumulation of deleted mtDNA is accelerated in the striatum and may contribute to the pathophysiology of PD. While the cause of PD remains unknown, mitochondrial dysfunction is undoubtedly a factor in cell death in PD. In addition, the causative gene for familial PD, parkin (now PRKN), and PTEN-induced putative kinase 1 (PINK1), both gene products are also involved in mitochondrial quality control. Moreover, we have successfully isolated and identified CHCHD2, which is involved in the mitochondrial electron transfer system. There is no doubt that mitochondrial dysfunction contributes to cell death in PD.

Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associated with performance on a task aimed at assessing facial emotion recognition. In this study, we explored the association between hypomimia, recognition of facial expressions of basic emotions using the Ekman 60 Faces Test (EF), and brain correlates of both hypomimia and performance on the EF. A total of 94 subjects underwent clinical assessments (neurological and neuropsychological examinations), and 56 of them participated in the neuroimaging study. We found significant correlation between hypomimia, EF Disgust (r = -0.242, p = 0.022) and EF Happiness (r = -0.264, p = 0.012); an independent reduction in Cortical Thickness (Cth) in the postcentral gyrus, insula, middle and superior temporal gyri, supramarginal gyrus, banks of the superior temporal sulcus, bilateral fusiform gyri, entorhinal cortex, parahippocampal gyrus, inferior and superior parietal cortex, and right cuneus and precuneus; and multiple correlations between negative emotions such as EF Disgust or EF Anger and a reduced Cth in fronto-temporo-parietal regions. In conclusion, these results suggest that the association between hypomimia and emotion recognition deficits in individuals with PD might be mediated by shared circuits, supporting the concept that hypomimia is not only the result of the dysfunction of motor circuits, but also of higher cognitive functions.

Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood-brain barrier and the "cytokine storm", appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson's and Alzheimer's disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it's highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the "multiple hit hypothesis". Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate "neuroinflammation" and "inflammation" with regard to the involvement of the blood-brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all.

Anticholinergic (AC) drugs, a medication class that acts by blocking nicotinic and muscarinic acetylcholine receptors, were first utilized for therapeutic purposes in the mid-19th century. Initial applications were as symptomatic therapy for Parkinson disease (PD), a practice continuing to the present. Initially, the AC drugs used were naturally-occurring plant compounds. Synthetic AC drugs were developed in the late 1940s and predominated in neurological therapeutics. Until the advent of pharmaceuticals acting upon striatal dopaminergic motor pathways, AC drugs provided the only effective means for lessening tremors and other clinical problems of the PD patient. However, because dopaminergic compounds are so effective at meeting the needs of the typical PD patient, AC medications are far less utilized by clinicians today. In recent years, there has been only a few investigations of AC drugs as neurological treatments. This review will revisit the clinical landscape of AC pharmacology and application for movement disorders along with recent research in search of improving therapeutics with AC drugs.