Search

Invasive fungal infections have been increasing in incidence worldwide, primarily due to the growing population of immunosuppressed patients. Fungal central nervous system infections carry a high rate of morbidity and mortality due to difficulty in diagnosis and treatment. This paper provides a review of antifungal agents currently available in the United States, highlighting the pros and cons of each medication in the treatment of CNS infections. Investigational treatment approaches with combination therapy and iron chelation for CNS infections are also discussed. Despite our many advances in modern medicine, we still lack highly effective therapeutic options for treatment of cerebral infections with the angioinvasive fungi Aspergillus and the zygomycetes. [ABSTRACT FROM AUTHOR]

Malignant neoplasms of the central nervous system (CNS) account for about 1.3 % of all tumors and 2.2 % of all cancer-related deaths. CNS tumors consist of heterogeneous group of neoplasms, including different variants of primary brain tumors and metastatic neoplasms. Advanced imaging techniques improved the neuroradiological diagnostic accuracy, although these methods are not specific enough for differentiation of CNS tumors, thus new approaches of patients' diagnosis are critically needed. The best solution for the diagnosis of patients with CNS tumors could be easily available biomarkers, which could be useful for the management of CNS neoplasms. Biomarkers should facilitate the diagnosis, monitor of treatment response and assess the prognosis of patients' survival. Currently, except for rare germ cell tumors, there is a lack of knowledge on biochemical markers for CNS neoplasms. Therefore, in this paper we summarized and referred a number of comprehensive reviews concerning the role of matrix metalloproteinases (MMPs) and their tissue inhibitors in tumor progression, including CNS neoplasms as well as described the general biochemistry of MMPs and their tissue inhibitors. Moreover, we presented the wide variety of previous findings, where authors suggested the significance of selected MMPs and their tissue inhibitors as potential biomarkers of human tumors, including CNS tumors. However, future investigations are needed to be performed before some of these enzymes could finally be used as biomarkers of specific types of CNS neoplasms. [ABSTRACT FROM AUTHOR]

This review first summarizes estimates of the functional response of the central nervous system (CNS) to variations in cosmophysical factors using different psychophysiological indices (electrical activity of the brain, sensorimotor and motor reactions, and higher mental functions such as attention and memory). We analyze the applicability of information technologies to record different physiological parameters. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. This paper reviews the current knowledge derived from positron emission tomography and single photon emission tomography studies quantifying GABA receptor binding in movement disorders of extrapyramidal origin, focusing on essential tremor (ET), Parkinsonism (idiopathic PD and atypical parkinsonian syndromes), dystonia, and Huntington's disease (HD). In ET, there is evidence to suggest a specific disturbance at the level of the GABA receptor and impairment of GABAergic inhibition to be a driving force for the development of rhythmic overactivity in cerebello-thalamo-cortical networks. In dystonia, GABA receptor binding studies have been relevant for unraveling pathophysiological mechanisms causing sensorimotor disinhibition leading to dystonic movements. The role of GABA in idiopathic PD and atypical parkinsonian syndromes is less clear, despite the fact that GABA receptors are expressed on virtually all striatal neurons and that GABA exerts important inhibitory influences upon basal outflow pathways. In HD, reductions of GABA receptor have been reported in the basal ganglia but were found to be less extensive compared with concomitant metabolic reductions. [ABSTRACT FROM AUTHOR]

Plants have been used as a source for food material and natural remedies for the treatment of vast range of diseases. Nature provides us remedies for the treatment of various types of disorders ranging from simple ailments to complicated diseases. Plants are known to possess different pharmacological activities due to the presence of various phytoconstituents. Flavonoids are one of the main active phytoconstituents found in fruits, vegetables, wines, tea and cocoa. Flavonoids exhibit various pharmacological activities such as antioxidant, anti-inflammatory, anti-allergic, antibacterial, oestrogenic, cytotoxic antitumoural, hepatoprotective, antithrombotic and antiviral activity. Diosmetin (3′, 5, 7-trihydroxy-4′-methoxyflavone), the aglycone part of the flavonoid glycosides diosmin occurs naturally in citrus fruit. Although it is found in herbal medicines and plays an important role in the treatment of various ailments, only limited scientific researches have been conducted. The aim of this review is to collect all available scientific literature published on diosmetin and combine it into this paper. This review contains an overview of pharmacological activities, isolation techniques and analytical techniques for diosmetin. Thus, valuable information provided in the present review will help researchers in developing alternative methods for the treatment of diseases from diosmetin. [ABSTRACT FROM AUTHOR]

In the companion paper utilizing a quantitative model of optimal motor coordination (Part I, Rand and Shimansky, in Exp Brain Res 225:55-73, ), we examined coordination between X and Y movement directions (XYC) during reaching movements performed under three prescribed speeds, two movement amplitudes, and two target sizes. The obtained results indicated that the central nervous system (CNS) utilizes a two-phase strategy, where the initial and the final phases correspond to lower and higher precision of information processing, respectively, for controlling goal-directed reach-type movements to optimize the total cost of task performance including the cost of neural computations. The present study investigates how two different well-known concepts used for describing movement performance relate to the concepts of optimal XYC and two-phase control strategy. First, it is examined to what extent XYC is equivalent to movement trajectory straightness. The data analysis results show that the variability, the movement trajectory's deviation from the straight line, increases with an increase in prescribed movement speed. In contrast, the dependence of XYC strength on movement speed is opposite (in total agreement with an assumption of task performance optimality), suggesting that XYC is a feature of much higher level of generality than trajectory straightness. Second, it is tested how well the ballistic and the corrective components described in the traditional concept of two-component model of movement performance match with the initial and the final phase of the two-phase control strategy, respectively. In fast reaching movements, the percentage of trials with secondary corrective submovement was smaller under larger-target shorter-distance conditions. In slower reaching movements, meaningful parsing was impossible due to massive fluctuations in the kinematic profile throughout the movement. Thus, the parsing points determined by the conventional submovement analysis did not consistently reflect separation between the ballistic and error-corrective components. In contrast to the traditional concept of two-component movement performance, the concept of two-phase control strategy is applicable to a wide variety of experimental conditions. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Epileptologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rationale: Women are increasingly prescribed selective serotonin reuptake inhibitors (SSRIs) during pregnancy, with potential implications for neurodevelopment. Whether prenatal SSRI exposure has an effect on neurodevelopment and behavior in the offspring is an important area of investigation. Objectives: The aim of this paper was to review the existing preclinical and clinical literature of prenatal SSRI exposure on serotonin-related behaviors and markers in the offspring. The goal is to determine if there is a signal in the literature that could guide clinical care and/or inform research. Results: Preclinical studies ( n = 4) showed SSRI exposure during development enhanced depression-like behavior. Half of rodent studies examining anxiety-like behavior ( n = 13) noted adverse effects with SSRI exposure. A majority of studies of social behavior ( n = 4) noted a decrease in sociability in SSRI exposed offspring. Human studies ( n = 4) examining anxiety in the offspring showed no adverse effects of prenatal SSRI exposure. The outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy. Conclusions: Preclinical findings in rodents exposed to SSRIs during development point to an increase in depression- and anxiety-like behavior and alteration in social behaviors in the offspring, though both the methods used and the findings were not uniform. These data are not robust enough to discourage use of SSRIs during human pregnancy, particularly given the known adverse effects of maternal mental illness on pregnancy outcomes and infant neurodevelopment. Future research should focus on consistent animal models and prospective human studies with larger samples. [ABSTRACT FROM AUTHOR]

A quantitative model of optimal transport-aperture coordination (TAC) during reach-to-grasp movements has been developed in our previous studies. The utilization of that model for data analysis allowed, for the first time, to examine the phase dependence of the precision demand specified by the CNS for neurocomputational information processing during an ongoing movement. It was shown that the CNS utilizes a two-phase strategy for movement control. That strategy consists of reducing the precision demand for neural computations during the initial phase, which decreases the cost of information processing at the expense of lower extent of control optimality. To successfully grasp the target object, the CNS increases precision demand during the final phase, resulting in higher extent of control optimality. In the present study, we generalized the model of optimal TAC to a model of optimal coordination between X and Y components of point-to-point planar movements (XYC). We investigated whether the CNS uses the two-phase control strategy for controlling those movements, and how the strategy parameters depend on the prescribed movement speed, movement amplitude and the size of the target area. The results indeed revealed a substantial similarity between the CNS's regulation of TAC and XYC. First, the variability of XYC within individual trials was minimal, meaning that execution noise during the movement was insignificant. Second, the inter-trial variability of XYC was considerable during the majority of the movement time, meaning that the precision demand for information processing was lowered, which is characteristic for the initial phase. That variability significantly decreased, indicating higher extent of control optimality, during the shorter final movement phase. The final phase was the longest (shortest) under the most (least) challenging combination of speed and accuracy requirements, fully consistent with the concept of the two-phase control strategy. This paper further discussed the relationship between motor variability and XYC variability. [ABSTRACT FROM AUTHOR]

Presently, there are no effective treatments for several diseases involving the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecular or supramolecular agents to the CNS tissues protected by the blood-brain and blood-arachnoid barriers. A variety of approaches that are being developed for overcoming or bypassing the barriers are based on complex transfer processes. The delivery of biopharmaceuticals and other macromolecules and particulates to the CNS, especially through the leptomeningeal (intrathecal) route, includes a variety of stages, such as leptomeningeal propagation, drainage to the systemic circulation, and penetration into the CNS. The investigation of complex pharmacokinetics that includes convective, as well as diffusional and active transfer processes, greatly benefit from real-time non-invasive in vivo monitoring of the drug transport. Pharmacological positron emission tomography (PET) imaging, which enables such monitoring, plays an increasingly significant role in drug delivery and biopharmacology. PET is a powerful tool for quantitative in vivo tracking of molecules labeled with positron-emitting radionuclides. The high sensitivity, format, and accuracy of the data (similar to those of conventional tissue sampling biodistribution studies) make PET a readily adoptable pharmacological technique. In contrast to the conventional studies, PET also allows for longitudinal nonterminal same-animal studies. The latter may not only improve the data statistics, but also enable preclinical studies (especially in large and/or rare animals) not feasible under the conventional approach. This paper is intended to demonstrate the character of data that can be obtained by PET and to demonstrate how the main patterns of the leptomeningeal route pharmacokinetics can be investigated using this method. Examples of data processing are taken from our recent studies of five model proteins in rats and nonhuman primates. [ABSTRACT FROM AUTHOR]

Background and Objective: Psychotropic drug use is high in nursing homes in Belgium. A practice improvement initiative (including education, professional support and the transition towards person-centred care) achieved significant reductions in psychotropic drug use. The initiative outline was transcribed into a general intervention template, and consequently implemented in five nursing homes (in mixed locations and with a mixed character) in preparation for a future broader roll-out in Belgium. The impact of the intervention on the use of psychotropic drugs in these five nursing homes is reported in this paper. Methods: The general intervention template was fitted into the individual nursing home setting. Education for the nursing home personnel on psychotropic drugs and non-pharmacological alternatives, as well as details for a transition to person-centred care was provided. Psychotropic drug use was recorded using a dynamic cohort study design with cross-sectional observations (November 2016–November 2017). Results: At baseline, participants' (n = 677) mean age was 85.6 years (range 54–109 years), with 72.6% female. Mean medication intake was 8.5 (range 1–22), predominantly central nervous system drugs (Anatomic Therapeutic Chemical classification N, 88.8%). Long-term (> 3 months) psychotropic drug use (62.0%) and concomitant psychotropic drug use (31.5% taking two or more medications) were high. After 12 months, the prevalence of long-term psychotropic drug use decreased significantly (from 62.0 to 52.9%, p < 0.001), likewise the combined use of psychotropic drugs (from 31.5 to 24.0%, p = 0.001). The decrease in the prevalence of antidepressant and hypnosedative use was significant (respectively, from 32.2 to 23.4%, p < 0.001, and from 35.3 to 28.7%, p = 0.006) in contrast to antipsychotic use (from 17.1 to 15.9%, p = 0.522). Conclusions: The stand-alone adaptation of the previously reported initiative using a general template was possible. This intervention resulted in a significant decrease in psychotropic drug use (predominantly hypnosedatives and antidepressants) among nursing home residents after 12 months. [ABSTRACT FROM AUTHOR]

Cytokines are important regulators of brain function under both normal and pathological conditions. Cytokines can be synthesized by resident cells of the central nervous system (CNS) (vascular endothelium, cells of the blood-brain barrier, parenchymal cells of the CNS) or cells in the lumen of blood vessels, as well as introduced with the bloodstream. The ratio between the quantity of cytokines synthesized in the CNS and those entering it from external sources under various conditions remains poorly understood. In this work, we studied the contribution of mRNAs from non-resident cells to the common pool of cytokine (TNFα, IL-1β, IL-6, IL-10, CX3CL1, and TGFβ1) mRNAs in the rat neocortex, hippocampus, dura matter, pia matter, and choroid plexus. We also evaluated the representation of various populations of resident and non-resident immune cells based on the expression of marker genes (Ncf1, Tbx21, Foxp3, RORγc). The removal of blood by transcardial perfusion led to a decrease in the quantity of the TNFα mRNA in the neocortex and hippocampus and of the IL-1β, IL-6, and IL-10 mRNAs in the dura mater. The mRNA levels of other cytokines in studied structures were not affected by perfusion. Our findings suggest that mRNAs present in the blood can make a significant contribution to the mRNA levels of some cytokines in the CNS; therefore, preliminary perfusion of brain tissue is a necessary stage of experimental design for correct estimation of mRNA content in the brain. [ABSTRACT FROM AUTHOR]

Monitoring the quality of clinical trial efficacy outcome data has received increased attention in the past decade, with regulatory guidance encouraging it to be conducted proactively, and remotely. However, the methods utilized to develop and implement risk-based data monitoring (RBDM) programs vary, and there is a dearth of published material to guide these processes in the context of central nervous system (CNS) trials. We reviewed regulatory guidance published within the past 6 years, generic white papers, and studies applying RBDM to data from CNS clinical trials. Methodologic considerations and system requirements necessary to establish an effective, real-time risk-based monitoring platform in CNS trials are presented. Key RBDM terms are defined in the context of CNS trial data, such as "critical data," "risk indicators," "noninformative data," and "mitigation of risk." Additionally, potential benefits of, and challenges associated with implementation of data quality monitoring are highlighted. Application of methodological and system requirement considerations to real-time monitoring of clinical ratings in CNS trials has the potential to minimize risk and enhance the quality of clinical trial data. [ABSTRACT FROM AUTHOR]

Tripeptidyl peptidase I (TPPI) - a lysosomal serine protease - is encoded by the CLN2 gene, mutations that cause late-infantile neuronal ceroid lipofuscinosis (LINCL) connected with profound neuronal loss, severe clinical symptoms and early death at puberty. Developmental studies of TPPI activity levels and distribution have been done in the human and rat central nervous systems (CNS) and visceral organs. Similar studies have not been performed in mouse. In this paper, we follow up on the developmental changes in the enzyme activity and localization pattern in the CNS and visceral organs of mouse over the main periods of life - embryonic, neonate, suckling, infantile, juvenile, adult and aged - using biochemical assays and enzyme histochemistry. In the studied peripheral organs (liver, kidney, spleen, pancreas and lung) TPPI is present at birth but further its pattern is not consistent in different organs over different life periods. TPPI activity starts to be expressed in the brain at the 10th embryonic day but in most neuronal types it appears at the early infantile period, increases during infancy, reaches high activity levels in the juvenile period and is highest in adult and aged animals. Thus, in mice TPPI activity becomes crucial for the neuronal functions later in development (juvenile period) than in humans and does not decrease with aging. These results are essential as a basis for comparison between normal and pathological TPPI patterns in mice. They can be valuable in view of the use of animal models for studying LINCL and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients. [ABSTRACT FROM AUTHOR]

RNA editing is a post-transcriptional process with an important role in gene modification. This editing process involves site-selective deamination of adenosine into inosine in the pre-mRNA, leading to the alteration of translation codons and splicing sites in nuclear transcripts, thereby enabling functionally distinct proteins to arise from a single gene. One important instance is the neuron editing of the ionotropic glutamate receptors (iGluRs). GluRs play a key role in excitatory synaptic transmission and plasticity in the central nervous system (CNS); their channel properties are largely dictated by the subunit composition of the tetrameric receptors. AMPA/kainate channels are assembled from GluA1-4 AMPA or GluK1-5 kainate receptor subunits. In particular, three of the four AMPA and two of the five kainate receptor subunits are subject to RNA editing. The editing positions have been named on the basis of the amino acid substitutions, such as the Q/R site in AMPA GluA2; the Q/R site in GluK1 and GluK2; the R/G site in GluA2, GluA3, and GluA4; and the I/V and Y/C sites in GluK2. These amino acid changes lead to profound alterations of the channel properties. This paper reviews the most relevant data showing the importance of glutamate receptor RNA editing in finely tuning glutamatergic neurotransmission in the normal CNS and following alterations of the editing process in association with disease phenotypes. Overall, these data indicate that a highly regulated process of glutamate receptor editing is of key importance in the proper function of neuronal cells and in their ability to adapt and modulate synaptic function. [ABSTRACT FROM AUTHOR]

The central nervous system uses stereotypical combinations of the three wrist/forearm joint angles to point in a given (2D) direction in space. In this paper, we first confirm and analyze this Donders' law for the wrist as well as the distributions of the joint angles. We find that the quadratic surfaces fitting the experimental wrist configurations during pointing tasks are characterized by a subject-specific Koenderink shape index and by a bias due to the prono-supination angle distribution. We then introduce a simple postural model using only four parameters to explain these characteristics in a pointing task. The model specifies the redundancy of the pointing task by determining the one-dimensional task-equivalent manifold (TEM), parameterized via wrist torsion. For every pointing direction, the torsion is obtained by the concurrent minimization of an extrinsic cost, which guarantees minimal angle rotations (similar to Listing's law for eye movements) and of an intrinsic cost, which penalizes wrist configurations away from comfortable postures. This allows simulating the sequence of wrist orientations to point at eight peripheral targets, from a central one, passing through intermediate points. The simulation first shows that in contrast to eye movements, which can be predicted by only considering the extrinsic cost (i.e., Listing's law), both costs are necessary to account for the wrist/forearm experimental data. Second, fitting the synthetic Donders' law from the simulated task with a quadratic surface yields similar fitting errors compared to experimental data. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) vascular malformations are well-known entities that may cause sudden death from rupture and intracranial hemorrhage. Despite this, relatively few papers deal with these lesions in the forensic literature. Here, we present four cases of sudden, non-traumatic death caused by ruptured CNS vascular malformations. In all four cases, the definitive source of bleeding was not identified grossly, being diagnosed only after relatively extensive histologic examination. When a source of intracranial hemorrhage is not readily identified at autopsy, it is common for forensic pathologists to rule the cause of death in such cases as 'spontaneous intracerebral hemorrhage' or 'spontaneous subarachnoid hemorrhage,' depending on the location of the hemorrhage. Whether or not histologic evaluation is performed in such cases depends on pathologist preference or office policy, and may be influenced by limited available funding for such studies. Because vascular malformations are not always grossly visible at autopsy when accompanied by intracranial hemorrhage, we contend that it is important to thoroughly investigate the underlying cause of such hemorrhage through a meticulous gross examination as well as histologic examination. Such examination will lead to a more accurate assignment of the cause of death, which may have important implications for surviving family members, and will lead to a better understanding of the natural history of these intracranial lesions. A brief discussion of the histologic classification of CNS vascular malformations is provided. [ABSTRACT FROM AUTHOR]

Genetic risk factors play a role in sudden unexpected infant death; either as a cause of death, such as in cases with medium-chain acyl-coenzyme A dehydrogenase deficiency and cardiac arrest due to long QT syndrome, or as predisposing factors for sudden infant death syndrome (SIDS). Most likely genetic predisposition to SIDS represent a polygenic inheritance pattern leading to sudden death when combined with other risk factors, such as a vulnerable developmental stage of the central nervous system and/or the immune system, in addition to environmental risk factors, such as a common cold or prone sleeping position. Genes involved in the regulation of the immune system, cardiac function, the serotonergic network and brain function and development have so far emerged as the most important with respect to SIDS. The purpose of the present paper is to survey current knowledge on SIDS and possible genetic contributions. [ABSTRACT FROM AUTHOR]

Neuroproteomics has become a ‘symbol’ or even a ‘sign’ for neuroscientists in the post-genomic era. During the last several decades, a number of proteomic approaches have been used widely to decipher the complexity of the brain, including the study of embryonic stages of human or non-human animal brain development. The use of proteomic techniques has allowed for great scientific advancements, including the quantitative analysis of proteomic data using 2D-DIGE, ICAT and iTRAQ. In addition, proteomic studies of the brain have expanded into fields such as subproteomics, synaptoproteomics, neural plasma membrane proteomics and even mitochondrial proteomics. The rapid progress that has been made in this field will not only increase the knowledge based on the neuroproteomics of the developing brain but also help to increase the understanding of human neurological diseases. This paper will focus on proteomic studies in the central nervous system and especially those conducted on the development of the brain in order to summarize the advances in this rapidly developing field. [ABSTRACT FROM AUTHOR]

Animal locomotion results from muscle contraction and relaxation cycles that are generated within the central nervous system and then are relayed to the periphery by motoneurons. Thus, motoneuron function is an essential element for understanding control of animal locomotion. This paper presents motoneuron input–output relationships, including impulse adaptation, in the medicinal leech. We found that although frequency-current graphs generated by passing 1-s current pulses in neuron somata were non-linear, peak and steady-state graphs of frequency against membrane potential were linear, with slopes of 5.2 and 2.9 Hz/mV, respectively. Systems analysis of impulse frequency adaptation revealed a static threshold nonlinearity at −43 mV (impulse threshold) and a single time constant ( τ = 88 ms). This simple model accurately predicts motoneuron impulse frequency when tested by intracellular injection of sinusoidal current. We investigated electrical coupling within motoneurons by modeling these as three-compartment structures. This model, combined with the membrane potential–impulse frequency relationship, accurately predicted motoneuron impulse frequency from intracellular records of soma potentials obtained during fictive swimming. A corollary result was that the product of soma-to-neurite and neurite-to-soma coupling coefficients in leech motoneurons is large, 0.85, implying that the soma and neurite are electrically compact. [ABSTRACT FROM AUTHOR]

Type 1 Diabetes Mellitus is one of the most common illnesses found in children under the age of 18 as well as in young adults. Symptoms of this disease, including those with and without severe hypoglycemia, create abnormal blood glucose levels along with abnormal insulin levels. These abnormal chemical levels have been associated with neurocognitive deficits in memory, attention, motor skills, visuospatial abilities and executive functioning. In this paper, available literature on the central nervous system changes associated with the effects of insulin-dependent diabetes on school-aged children and young adults is reviewed. Implications for learning as well as a neurobiological cause of executive function deficits are discussed. [ABSTRACT FROM AUTHOR]

Nk homeobox genes are important regulators of many different developmental processes including muscle, heart, central nervous system and sensory organ development. They are thought to have arisen as part of the ANTP megacluster, which also gave rise to Hox and ParaHox genes, and at least some NK genes remain tightly linked in all animals examined so far. The protostome–deuterostome ancestor probably contained a cluster of nine Nk genes: ( Msx)–( Nk4/ tinman)–( Nk3/ bagpipe)–( Lbx/ ladybird)–( Tlx/ c15)–( Nk7)–( Nk6/ hgtx)–( Nk1/ slouch)–( Nk5/ Hmx). Of these genes, only NKX2.6– NKX3.1, LBX1– TLX1 and LBX2– TLX2 remain tightly linked in humans. However, it is currently unclear whether this is unique to the human genome as we do not know which of these Nk genes are clustered in other vertebrates. This makes it difficult to assess whether the remaining linkages are due to selective pressures or because chance rearrangements have “missed” certain genes. In this paper, we identify all of the paralogs of these ancestrally clustered NK genes in several distinct vertebrates. We demonstrate that tight linkages of Lbx1– Tlx1, Lbx2– Tlx2 and Nkx3.1– Nkx2.6 have been widely maintained in both the ray-finned and lobe-finned fish lineages. Moreover, the recently duplicated Hmx2– Hmx3 genes are also tightly linked. Finally, we show that Lbx1– Tlx1 and Hmx2– Hmx3 are flanked by highly conserved noncoding elements, suggesting that shared regulatory regions may have resulted in evolutionary pressure to maintain these linkages. Consistent with this, these pairs of genes have overlapping expression domains. In contrast, Lbx2– Tlx2 and Nkx3.1– Nkx2.6, which do not seem to be coexpressed, are also not associated with conserved noncoding sequences, suggesting that an alternative mechanism may be responsible for the continued clustering of these genes. [ABSTRACT FROM AUTHOR]

Dendritic spines are small, mushroom-like protrusions from the arbor of a neuron in the central nervous system. Interdependent changes in the morphology, biochemistry, and activity of spines have been associated with learning and memory. Moreover, post-mortem cortices from patients with Alzheimer's or Parkinson's disease exhibit biochemical and physical alterations within their dendritic arbors and a reduction in the number of dendritic spines. For over a decade, experimentalists have observed perforations in postsynaptic densities on dendritic spines after induction of long-term potentiation, a sustained enhancement of response to a brief electrical or chemical stimulus, associated with learning and memory. In more recent work, some suggest that activity-dependent intraspine calcium may regulate the surface area of the spine head, and reorganization of postsynaptic densities on the surface. In this paper, we develop a model of a dendritic spine with the ability to partition its transmission and receptor zones, as well as the entire spine head. Simulations are initially performed with fixed parameters for morphology to study electrical properties and identify parameters that increase efficacy of the synaptic connection. Equations are then introduced to incorporate calcium as a second messenger in regulating continuous changes in morphology. In the model, activity affects compartmental calcium, which regulates spine head morphology. Conversely, spine head morphology affects the level of local activity, whether the spines are modeled with passive membrane properties, or excitable membrane using Hodgkin-Huxley kinetics. Results indicate that merely separating the postsynaptic receptors on the surface of the spine may add to the diversity of circuitry, but does not change the efficacy of the synapse. However, when the surface area of the spine is a dynamic variable, efficacy of the synapse may vary continuously over time. [ABSTRACT FROM AUTHOR]

The purpose of this brief review is to prepare readers who may be unfamiliar with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and the rapidly accumulating changes in the epidemic by providing an introduction to HIV disease and its treatment. The general concepts presented here will facilitate understanding of the papers in this issue on HIV-associated neurocognitive disorders (HAND). Toward that end, we briefly review the biology of HIV and how it causes disease in its human host, its epidemiology, and how antiretroviral treatments are targeted to interfere with the molecular biology that allows the virus to reproduce. Finally, we describe what is known about how HIV injures the nervous system, leading to HAND, and discuss potential strategies for preventing or treating the effects of HIV on the nervous system. [ABSTRACT FROM AUTHOR]

A variety of circulating signals provide essential information to the central nervous system (CNS) regarding nutritional status. The gastrointestinal system produces many such molecules that are now known to have profound effects on feeding behavior and the control of metabolism as a consequence of their ability to regulate the neural circuitry involved in metabolic homeostasis. Although many of these substances have been suggested to directly access such brain centers, their lipophobic characteristics suggest that alternative mechanisms should be considered. In this paper, we consider one such alternative, namely, that a specialized group of CNS structures collectively known as the sensory circumventricular organs (CVOs), which are not protected by the normal blood–brain barrier, may play important roles in such blood to brain communications. Specifically, we review a developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ. Collectively, these observations suggest potentially significant roles for the sensory CVOs in the regulation of energy balance.International Journal of Obesity (2009) 33, S16–S21; doi:10.1038/ijo.2009.11 [ABSTRACT FROM AUTHOR]

Due to the non-stationarity of EEG signals, online training and adaptation are essential to EEG based brain–computer interface (BCI) systems. Self-paced BCIs offer more natural human–machine interaction than synchronous BCIs, but it is a great challenge to train and adapt a self-paced BCI online because the user’s control intention and timing are usually unknown. This paper proposes a novel motor imagery based self-paced BCI paradigm for controlling a simulated robot in a specifically designed environment which is able to provide user’s control intention and timing during online experiments, so that online training and adaptation of the motor imagery based self-paced BCI can be effectively investigated. We demonstrate the usefulness of the proposed paradigm with an extended Kalman filter based method to adapt the BCI classifier parameters, with experimental results of online self-paced BCI training with four subjects. [ABSTRACT FROM AUTHOR]

Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m(2) of MTX (4 h infusion on day 1) and 1.5-2 g/m(2)/day of IFO (3 h infusion on days 3-5). The study included 20 patients with a median age of 65 years (range, 30-83) and CNS relapse of a malignant lymphoma. Seventeen patients had been pretreated with up to two chemotherapy regimens. The objective response rate was 90% with 12 complete or unconfirmed complete (CR and CRu) and six partial remissions. All patients had at least stabilization of their neurological symptoms. Myelosuppression was the most common toxicity. The median follow-up time was 14.9 months. The median time to neurological progression was 8.9 months. Twelve patients received subsequent therapy, including high-dose chemotherapy with autologous stem cell transplantation in five cases. The median overall survival was not reached. Systemic chemotherapy with HDMTX/IFO is a feasible and promising treatment modality for CNS relapse of a malignant lymphoma. [ABSTRACT FROM AUTHOR]

Study design:Experts opinions consensus.Objective:To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI).Background and Rationale:The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function.Methods:Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function.Results:Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function.Conclusion:This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.Spinal Cord (2009) 47, 36–43; doi:10.1038/sc.2008.121; published online 28 October 2008 [ABSTRACT FROM AUTHOR]

The goal of this paper was to determine if trunk antagonist activation is associated with impaired neuromuscular performance. To test this theory, we used two methods to impair neuromuscular control: strenuous exertions and fatigue. Force variability (standard deviation of force signal) was assessed for graded isometric trunk exertions (10, 20, 40, 60, 80% of max) in flexion and extension, and at the start and end of a trunk extensor fatiguing trial. Normalized EMG signals for five trunk muscle pairs ( RA rectus abdominis, EO external oblique, IO internal oblique, TE thoracic erector spinae, and LE lumbar erector spinae) were collected for each graded exertion, and at the start and end of a trunk extensor fatiguing trial. Force variability increased for more strenuous exertions in both flexion ( P < 0.001) and extension ( P < 0.001), and after extensor fatigue ( P < 0.012). In the flexion direction, both antagonist muscles (TE and LE) increased activation for more strenuous exertions ( P < 0.001). In the extension direction, all antagonist muscles except RA increased activation for more strenuous exertions ( P < 0.05) and following fatigue ( P < 0.01). These data demonstrate a strong relationship between force variability and antagonistic muscle activation, irrespective of where this variability comes from. Such antagonistic co-activation increases trunk stiffness with the possible objective of limiting kinematic disturbances due to greater force variability. [ABSTRACT FROM AUTHOR]

Abstract Objective  Cavernous malformations (CMs) are vascular malformations affecting any part of the central nervous system. CMs in the pediatric age group are known to be different from those of adults both in origin and clinical characteristics. In this paper, we report our experience in managing CMs in pediatric patients. Materials and methods  Between January 1994 and December 2006, 33 patients younger than 20 years of age with intracranial CMs were treated with microsurgery or radiosurgery. We retrospectively reviewed the presentation and treatment of these 33 patients (18 boys and 15 girls; average age 11.6 years). Results  The most common symptom at presentation was seizure (19 children, 57.6%). The most common type of CM, classified on the basis of magnetic resonance imaging, was type II (18, 54.5%). The supratentorial compartment was the most frequent location (27, 71.8%), and only six CMs (18.2%) were observed in the infratentorial compartment. Microsurgery was performed on 25 patients (75.8%), and radiosurgery was performed on eight patients (24.2%). The overall post-treatment results were positive. Only two children (6.1%) had persistent presurgical neurological signs, although the treatment ameliorated them. No progression of the preoperative neurological signs or onset of new neurological deficits was seen in any of the patients. In our patient group, the microsurgical removal of CMs resulted in the prevention of recurrent hemorrhage and the control of seizure disorders in all cases. Conclusions  Our results suggest that pediatric patients with symptomatic CMs should be treated surgically because of the risk of recurrent hemorrhaging and the general benefits of CM removal. [ABSTRACT FROM AUTHOR]

Abstract Introduction  Intramedullary cavernous angiomas (ImCA) of the spinal cord are very uncommon malformations especially in the pediatric population where only ten cases have yet been reported within the available literature. Case report  In this paper, the authors report the case of a 12-year-old girl presenting with a T11 level hematomyelia because of a cavernous angioma. Microsurgical excision was performed with good clinical outcome and no magnetic resonance imaging evidence of residual cavernoma 30 months later. Discussion  Despite the small number of cases reported in children, this one contributes to the literature identifying special features of presentation and management of ImCA for pediatric patients. Because a higher risk of recurrent bleeding has been demonstrated for ImCA, with dramatic clinical consequences, microsurgical removal remains the only definitive treatment. [ABSTRACT FROM AUTHOR]

Abstract  Drugs based on 5-phenyl-2,4 diamino pyrimidine and 6-phenyl-1,2,4 triazine derivatives are well known for their effects on the central nervous system. The study presented here provides detailed crystal structures of two pyrimidine derivatives which have neuroprotective properties in models of both grey and white matter ischemia. Recently published studies suggest that the compounds lamotrigine (a triazine derivative), and the two pyrimidines BW1003C87 (I) and sipatrigine (II) mediate their primary in vivo mode of action by inhibiting voltage-gated Na channels. The X-ray crystal structures will contribute valuable data for applications involving binding and modelling studies of the biological actions of these drugs. Graphical Abstract   X-ray crystallographic structures of neuroprotective pyrimidine derivatives: (I) the mesylate salt of BW1003C87 and (II) sipatrigine base Rex A. Palmer*, Brian S. Potter, Michael J. Leach and Babur Z. Chowdhry Surface representations, [20] are a useful tool with respect to considerations employed for the purposes of drug design. Shown here are the neuroprotective drug molecules (a) BW1003C87 and (b) Sipatrigine Base (BW619C89) derived from their solid state structures reported in this paper. The molecules are viewed edge on to ring B with the two adjacent Cl atoms uppermost on the left. [ABSTRACT FROM AUTHOR]

Rare monogenic dementias have repeatedly exposed novel pathways guiding to details of the molecular pathogenesis behind this complex clinical phenotype. In this paper, we have studied polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), an early onset dementia with bone fractures caused by mutations in TYROBP (DAP12) and TREM2 genes, which encode important signaling molecules in human dendritic cells (DCs). To identify the pathways and biological processes associated with DAP12/TREM2-mediated signaling, we performed genome wide transcript analysis of in vitro differentiated DCs of PLOSL patients representing functional knockouts of either DAP12 or TREM2. Both DAP12- and TREM2-deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences compared to control cells due to defects in the actin filaments. Not unexpectedly, transcript profiles of the patient DCs showed differential expression of genes involved in immune response. Importantly, significantly diverging transcript levels were also evident for genes earlier associated with other disorders of the central nervous system (CNS) and genes involved in the remodeling of bone, linking these two immunological genes with critical tissue phenotypes of patients. The data underline the functional diversity of the molecules of the innate immune system and implies their significant contribution also in demyelinating CNS disorders, including those resulting in dementia. [ABSTRACT FROM AUTHOR]

Task-oriented, repetitive and intensive arm training can enhance arm rehabilitation in patients with paralyzed upper extremities due to lesions of the central nervous system. There is evidence that the training duration is a key factor for the therapy progress. Robot-supported therapy can improve the rehabilitation allowing more intensive training. This paper presents the kinematics, the control and the therapy modes of the arm therapy robot ARMin. It is a haptic display with semi-exoskeleton kinematics with four active and two passive degrees of freedom. Equipped with position, force and torque sensors the device can deliver patient-cooperative arm therapy taking into account the activity of the patient and supporting him/her only as much as needed. The haptic display is combined with an audiovisual display that is used to present the movement and the movement task to the patient. It is assumed that the patient-cooperative therapy approach combined with a multimodal display can increase the patient's motivation and activity and, therefore, the therapeutic progress. [ABSTRACT FROM AUTHOR]

Disseminated herpes simplex virus type 1 (HSV-1) infection during pregnancy is poorly described even though it is associated with high maternal and fetal morbidity and neonatal mortality in humans. In a previous paper using mice as a model, the authors demonstrated that HSV-1 is transmitted hematogenously from mother to offspring, the virus colonizing the central nervous system and provoking high mortality. In the present study, viral DNA levels in latently infected mothers were investigated during pregnancy and after delivery in mice. Samples from different organs were obtained before gestation (latency), three times during pregnancy (17, 4.5, and 1 day before delivery), and four times after delivery (1 day, 1 week, 1 and 2 months). A dramatic decrease in viral DNA concentration was observed during pregnancy, especially in the nervous system, with postnatal recovery to latent levels. All the brain regions studied showed similar trends. The viral copy numbers detected in mothers at delivery +1 day were independent of viral inoculum size. The spread of the virus to the above organs was examined immunohistochemically and, in general, more intense viral staining was observed after delivery in each. Because immunoglobulin levels can be modified by infections during pregnancy, the authors examined the levels of specific HSV-1 antibodies. Variation in HSV-1 DNA concentration was found to be associated with changes in the full spectrum of immunoglobulins (but especially immunoglobulin M [IgM]) over pregnancy, whereas at delivery -1 day a significant inverse relationship between immunoglobulins and HSV-1 DNA was observed. IgGs provided protection during the postnatal phase. [ABSTRACT FROM AUTHOR]

The present paper introduces an original biofeedback system for improving human balance control, whose underlying principle consists in providing additional sensory information related to foot sole pressure distribution to the user through a tongue-placed tactile output device. To assess the effect of this biofeedback system on postural control during quiet standing, ten young healthy adults were asked to stand as immobile as possible with their eyes closed in two conditions of No-biofeedback and Biofeedback. Centre of foot pressure (CoP) displacements were recorded using a force platform. Results showed reduced CoP displacements in the Biofeedback relative to the No-biofeedback condition. The present findings evidenced the ability of the central nervous system to efficiently integrate an artificial plantar-based, tongue-placed tactile biofeedback for controlling control posture during quiet standing. [ABSTRACT FROM AUTHOR]

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.Spinal Cord (2007) 45, 222–231. doi:10.1038/sj.sc.3102009; published online 19 December 2006 [ABSTRACT FROM AUTHOR]

The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.Spinal Cord (2007) 45, 190–205. doi:10.1038/sj.sc.3102007; published online 19 December 2006 [ABSTRACT FROM AUTHOR]

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.Spinal Cord (2007) 45, 206–221. doi:10.1038/sj.sc.3102008; published online 19 December 2006 [ABSTRACT FROM AUTHOR]

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community.Spinal Cord (2007) 45, 232–242. doi:10.1038/sj.sc.3102010; published online 19 December 2006 [ABSTRACT FROM AUTHOR]

Amyloid peptides (Aβ) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Aβ regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Aβ peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds Aβ(1-40) favouring its β-sheet conformation both in vitro and in vivo and hence the formation of β-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that Aβ peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Customizing the parameter values of brain interface (BI) systems by a human expert has the advantage of being fast and computationally efficient. However, as the number of users and EEG channels grows, this process becomes increasingly time consuming and exhausting. Manual customization also introduces inaccuracies in the estimation of the parameter values. In this paper, the performance of a self-paced BI system whose design parameter values were automatically user customized using a genetic algorithm (GA) is studied. The GA automatically estimates the shapes of movement-related potentials (MRPs), whose features are then extracted to drive the BI. Offline analysis of the data of eight subjects revealed that automatic user customization improved the true positive (TP) rate of the system by an average of 6.68% over that whose customization was carried out by a human expert, i.e., by visually inspecting the MRP templates. On average, the best improvement in the TP rate (an average of 9.82%) was achieved for four individuals with spinal cord injury. In this case, the visual estimation of the parameter values of the MRP templates was very difficult because of the highly noisy nature of the EEG signals. For four able-bodied subjects, for which the MRP templates were less noisy, the automatic user customization led to an average improvement of 3.58% in the TP rate. The results also show that the inter-subject variability of the TP rate is also reduced compared to the case when user customization is carried out by a human expert. These findings provide some primary evidence that automatic user customization leads to beneficial results in the design of a self-paced BI for individuals with spinal cord injury. [ABSTRACT FROM AUTHOR]

Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia with central nervous system hypomyelination (CACH) syndrome, is an autosomal recessive transmitted leukoencephalopathy related to mutations in each of the 5 genes ( EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), essential for protein synthesis. VWM is characterised by ataxia, spasticity, variable optic atrophy and intermittent episodes of acute regression of clinical and neurological status. Another key step in diagnosis, besides clinical picture and gene sequencing, is magnetic resonance imaging (MRI), which typically shows a progressive rarefaction of the brain white matter, and its replacement by cerebrospinal fluid (CSF). In the present paper we summarise the up-to-date knowledge about VWM and include the full list of known mutations. [ABSTRACT FROM AUTHOR]

Tremor is a clinical feature characterized by oscillations of a part of the body. The detection and study of tremor is an important step in investigations seeking to explain underlying control strategies of the central nervous system under natural (or physiological) and pathological conditions. It is well established that tremorous activity is composed of deterministic and stochastic components. For this reason, the use of digital signal processing techniques (DSP) which take into account the nonlinearity and nonstationarity of such signals may bring new information into the signal analysis which is often obscured by traditional linear techniques (e.g. Fourier analysis). In this context, this paper introduces the application of the empirical mode decomposition (EMD) and Hilbert spectrum (HS), which are relatively new DSP techniques for the analysis of nonlinear and nonstationary time-series, for the study of tremor. Our results, obtained from the analysis of experimental signals collected from 31 patients with different neurological conditions, showed that the EMD could automatically decompose acquired signals into basic components, called intrinsic mode functions (IMFs), representing tremorous and voluntary activity. The identification of a physical meaning for IMFs in the context of tremor analysis suggests an alternative and new way of detecting tremorous activity. These results may be relevant for those applications requiring automatic detection of tremor. Furthermore, the energy of IMFs was visualized as a function of time and frequency by means of the HS. This analysis showed that the variation of energy of tremorous and voluntary activity could be distinguished and characterized on the HS. Such results may be relevant for those applications aiming to identify neurological disorders. In general, both the HS and EMD demonstrated to be very useful to perform objective analysis of any kind of tremor and can therefore be potentially used to perform functional assessment. [ABSTRACT FROM AUTHOR]

Recent experiments on frogs and rats, have led to the hypothesis that sensory-motor systems are organized into a finite number of linearly combinable modules; each module generates a motor command that drives the system to a predefined equilibrium. Surprisingly, in spite of the infiniteness of different movements that can be realized, there seems to be only a handful of these modules. The structure can be thought of as a vocabulary of "elementary control actions". Admissible controls, which in principle belong to an infinite dimensional space, are reduced to the linear vector space spanned by these elementary controls. In the present paper we address some theoretical questions that arise naturally once a similar structure is applied to the control of nonlinear kinematic chains. First of all, we show how to choose the modules so that the system does not loose its capability of generating a "complete" set of movements. Secondly, we realize a "complete" vocabulary with a minimal number of elementary control actions. Subsequently, we show how to modify the control scheme so as to compensate for parametric changes in the system to be controlled. Remarkably, we construct a set of modules with the property of being invariant with respect to the parameters that model the growth of an individual. Robustness against uncertainties is also considered showing how to optimally choose the modules equilibria so as to compensate for errors affecting the system. Finally, the motion primitive paradigm is extended to locomotion and a related formalization of internal (proprioceptive) and external (exteroceptive) variables is given. [ABSTRACT FROM AUTHOR]

This paper describes a neuro-musculo-skeletal model of the human lower body which has been developed with the aim of studying the effects of spinal cord injury on locomotor abilities. The model represents spinal neural control modules corresponding to central pattern generators, muscle spindle based reflex pathways, golgi tendon organ based pathways and cutaneous reflex pathways, which are coupled to the lower body musculo-skeletal dynamics. As compared to other neuro-musculo-skeletal models which aim to provide a description of the possible mechanisms involved in the production of locomotion, the goal of the model here is to understand the role of the known spinal pathways in locomotion. Thus, while other models focus primarily on functionality at the overall system level, the model here emphasizes functional and topological correspondance with the biological system at the level of the subcomponents representing spinal pathways. Such a model is more suitable for the detailed investigation of clinical questions related to spinal control of locomotion. The model is used here to perform preliminary experiments addressing the following issues: (1) the significance of spinal reflex modalities for walking and (2) the relative criticality of the various reflex modalities. The results of these experiments shed new light on the possible role of the reflex modalities in the regulation of stance and walking speed. The results also demonstrate the use of the model for the generation of hypothesis which could guide clinical experimentation. In the future, such a model may have applications in clinical diagnosis, as it can be used to identify the internal state of the system which provides the closest behavioral fit to a patient’s pathological condition. [ABSTRACT FROM AUTHOR]

Principal components analysis (PCA) has not been very much in vogue within the field of movement coordination even though it is useful to reduce data dimensionality and to reveal underlying data structures. Traditionally, studies of coordination between two joints have predominantly made use of relative phase analyses. This has resulted in the identification of principal constraints that govern the Central Nervous System’s organization and the control of coordination patterns. However, relative phase analyses on pairwise joints have some drawbacks because they are not optimal for revealing convergent patterns among multijoint coordination modes and for unraveling generic control strategies. In this paper, we present a method to analyze multijoint coordination based on the properties of PC, more specifically the eigenvalues and eigenvectors of the covariance matrix. The comparison between relative phase analysis and PCA shows that both provide similar and consistent results, underscoring the latter technique’s sensitivity to the study of coordination performance. In addition, it provides a method for automatic pattern detection as well as an index of performance for each joint within the context of the global coordination pattern. Finally, the merit of the PCA technique within the context of central pattern generators (CPG) will be discussed. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) is a debilitating immunopathy that afflicts approximately 5,000 patients annually in the United States, a number that represents roughly half of the incidence of spinal cord injuries (J. M., Meythaler, 1997). Of these 5,000 new cases per year, 4-15% will die, 20% will possess deficits in ambulation or require ventilator assistance more than one year later, and more than two-thirds will have persistent fatigue (J. M., Meythaler, 1997; Hughes et al., 2003). These figures suggest that GBS is currently a legitimate cause of long-term disability.Many secondary complications may follow GBS that include dysautonomia, deep vein thrombosis, anemia, immobilization, and pain and sensory involvement (J. M., Meythaler, 1997; J. M. Meythaler, M. J. De Vivo, and W. C. Braswell, 1997). These medical complications have not been studied systematically, and the psychosocial complication of pain following GBS has certainly been overlooked in the literature. The present paper utilized a limited sample of 18 patients (N= 18) with persistent motor deficits at least one year after onset of GBS. We examined their pain and perceived quality of life as part of an ongoing federally funded study which will ultimately attempt to determine if 4-aminopyridine (4-AP) significantly improves motor function in patients with residual weakness from GBS. Findings suggest that while most persons do not rate themselves as depressed one year after GBS onset, 22% of respondents did exceed the cutoff for clinical depression on the CES-D. Age and gender do not appear to be related to any component of pain in GBS; however, self-ratings of physical and mental health do appear to be significantly related to pain experience. The nature of this relationship was not determined, and merits further investigation in future studies. [ABSTRACT FROM AUTHOR]

This paper seeks to consider the validity and utility of two related terms in spinal and other injuries: complex regional pain syndrome (CRPS) and chronic pain syndrome (CPS). It is argued that the words chronic regional pain syndrome convey neither understanding of the condition nor of its mechanism. They simply redefine the clinical problem, but fail to establish specific diagnostic features or consistent primary pathogenesis. CRPS is best construed as a reaction to injury, or to excessive, often iatrogenic, immobilization after injury; but it is not an independent disease. The diagnosis of CPS groups together ill-defined symptoms under a convenient, but medically untestable and therefore inept label. Patients, lawyers, and support groups commonly deny psychogenesis, with the sadly mistaken notion that this implies a bogus or spurious cause.Spinal Cord (2005) 43, 263-268. doi:10.1038/sj.sc.3101709 Published online 4 January 2005 [ABSTRACT FROM AUTHOR]