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Background and aim To describe current diagnostic and therapeutic strategies in organic acidurias (OADs) and to evaluate their impact on the disease course allowing harmonisation. Methods Datasets of 567 OAD patients from the E-IMD registry were analysed. The sample includes patients with methylmalonic (MMA, n  = 164), propionic (PA, n  = 144) and isovaleric aciduria (IVA, n  = 83), and glutaric aciduria type 1 (GA1, n  = 176). Statistical analysis included description and recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. For some analyses, symptomatic patients were divided into those presenting with first symptoms during (i.e. early onset, EO) or after the newborn period (i.e. late onset, LO). Results Patients identified by newborn screening (NBS) had a significantly lower median age of diagnosis (8 days) compared to the LO group (363 days, p  < 0.001], but not compared to the EO group. Of all OAD patients 71 % remained asymptomatic until day 8. Patients with cobalamin-nonresponsive MMA (MMA-Cbl − ) and GA1 identified by NBS were less likely to have movement disorders than those diagnosed by selective screening (MMA-Cbl − : 10 % versus 39 %, p  = 0.002; GA1: 26 % versus 73 %, p  < 0.001). For other OADs, the clinical benefit of NBS was less clear. Reported age-adjusted intake of natural protein and calories was significantly higher in LO patients than in EO patients reflecting different disease severities. Variable drug combinations, ranging from 12 in MMA-Cbl − to two in isovaleric aciduria, were used for maintenance treatment. The effects of specific metabolic treatment strategies on the health outcomes remain unclear because of the strong influences of age at onset (EO versus LO), diagnostic mode (NBS versus selective screening), and the various treatment combinations used. Conclusions NBS is an effective intervention to reduce time until diagnosis especially for LO patients and to prevent irreversible cerebral damage in GA1 and MMA-Cbl − . Huge diversity of therapeutic interventions hampers our understanding of optimal treatment.

Neurocysticercosis is a major cause of seizures worldwide. This double-blind trial of a 10-day course of albendazole included 30 months of follow-up. With the antiparasitic treatment there was some reduction in the number of partial seizures and a significant reduction in the number of seizures with generalization. Fewer seizures with generalization. In the developing world, neurocysticercosis — infection of the central nervous system with Taenia solium larvae — is the single most common cause of acquired epilepsy. 1 In Latin America alone, it is estimated that more than 400,000 persons have neurologic symptoms due to neurocysticercosis. 2 The disease has also become increasingly recognized in industrialized countries, because of immigration from countries where the infection is endemic and improved neuroimaging and serologic means of diagnosis. 3 Recently, neurocysticercosis was found in 10 percent of patients with seizures who presented to an emergency department in Los Angeles and 6 percent of such patients in New . . .

Carbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP. A total of 171 patients with DEACMP were recruited and assigned to the combined therapy group (receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy). Conventional treatments were provided for all patients. The cognition and movement changes in patients were evaluated by the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) before and after the treatment at 1 month, 3 months, and 1 year, respectively. At 1 month, 3 months, and 1 year after the treatment, the MMSE, MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group. There were no significant alterations in blood glucose, blood lipids, or liver and kidney function during the whole treatment session. Some patients experienced loss of appetite, mild headache and minor skin irritations. However, these patients recovered by themselves and needed no additional medications or special treatment. These results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the cognitive and motor functions of patients and is very safe.

The aim of the study was to determine whether the reduction in brain grey matter volume associated with hypertension persisted or was remediated among hypertensive patients newly treated over the course of a year. A total of 41 hypertensive patients were assessed over the course of a 1-year successful anti-hypertensive treatment. Brain areas identified previously in cross-sectional studies differing in volume between hypertensive and normotensive individuals were examined with a semi-automated measurement technique (automated labelling pathway). Volumes of grey matter regions were computed at baseline after a year of treatment and compared with archival data from normotensive individuals. Reductions in regional grey matter volume over the follow-up period were observed despite successful treatment of blood pressure (BP). The comparison group of older, but normotensive, individuals showed no significant changes over a year in the regions tested in the treated hypertensive group. These novel results suggest that essential hypertension is associated with regional grey matter shrinkage, and successful reduction of BP may not completely counter that trend.

Abstract Obstructive sleep apnea is associated with abnormalities in neuropsychologic function, and defects in respiratory control may contribute to pathogenesis. Abnormalities may be reflected in structural brain changes. Twenty-seven male untreated patients with severe sleep apnea without comorbidities, and 24 age-matched control subjects, had T1-weighted brain imaging in a high-resolution magnetic resonance scanner. Twenty-three patients with sleep apnea had repeat imaging after 6 months of continuous positive airways pressure treatment. No areas of gray matter volume change were found in patients using an optimized voxel-based morphometry technique, at p < 0.05 adjusted for multiple comparisons (despite the method being sensitive to changes in gray matter fraction of 0.17 or less in all voxels). Furthermore, no differences were seen in bilateral hippocampal, temporal lobe, or whole brain volumes, assessed by manual tracing of anatomical borders. No longitudinal changes were seen in gray matter density or regional volumes after treatment, but whole brain volume decreased slightly. We have found no gray matter volume deficits nor focal structural changes in severe obstructive sleep apnea. Whole brain volume decreases without focal changes after 6 months of continuous positive airways pressure treatment.

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health.In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters—preferably in vivo—plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.

Pericytes are vascular mural cells embedded in the basement membrane of brain microvessels that, in the CNS, are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. Here the authors examine the key signaling pathways between pericytes and their neighboring cells regulating CNS functions in health and disease. Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles and post-capillary venules. CNS pericytes are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. They integrate, coordinate and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease, including regulation of the blood–brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation and stem cell activity. Here we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes and neurons that control neurovascular functions. We also review the role of pericytes in CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies.

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

Many human brain disorders are associated with characteristic alterations in the structural and functional connectivity of the brain. In this article, we explore how commonalities and differences in connectome alterations can reveal relationships across disorders. We survey recent literature on connectivity changes in neurological and psychiatric disorders in the context of key organizational principles of the human connectome and observe that several disturbances to network properties of the human brain have a common role in a wide range of brain disorders and point towards potentially shared network mechanisms underpinning disorders. We hypothesize that the distinct dimensions along which connectome networks are organized (for example, ‘modularity’ and ‘integration’) provide a general coordinate system that allows description and categorization of relationships between seemingly disparate disorders. We outline a cross-disorder ‘connectome landscape of dysconnectivity’ along these principal dimensions of network organization that may place shared connectome alterations between brain disorders in a common framework.In this Opinion article, Martijn van den Heuvel and Olaf Sporns examine alterations in structural and functional brain connectivity across brain disorders. They propose a common landscape for such alterations that is based on principles of network organization.