Episodic neurological channelopathies

Inherited episodic neurological disorders are often due to mutations in ion channels or their interacting proteins, termed channelopathies. There are a wide variety of such disorders, from those causing paralysis, to extreme pain, to ataxia. A common theme in these is alteration of action potential properties or synaptic transmission and a resulting increased propensity of the resulting tissue to enter into or stay in an altered excitability state. Manifestations of these disorders are triggered by an array of precipitants, all of which stress the particular affected tissue in some way and aid in propelling its activity into an aberrant state. Study of these disorders has aided in the understanding of disease risk factors and elucidated the cause of clinically related sporadic disorders. The findings from study of these disorders will aid in the diagnosis and efficient targeted treatment of affected patients.     

Mental disorders and an acidic glycan-from the perspective of polysialic acid (PSA/polySia) and the synthesizing enzyme,ST8SIA2

Mental disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder, are challenging to manage, worldwide. Understanding the molecular mechanisms underlying these disorders is essential and required. Studies investigating such molecular mechanisms are well performed and important findings are accumulating apace. Based on the fact that these disorders are due in part to the accumulation of genetic and environmental risk factors, consideration of multi-molecular and/or multi-system dependent phenomena might be important. Acidic glycans are an attractive family of molecules for understanding these disorders, because impairment of the fine-tuned glycan system affects a large number of molecules that are deeply involved in normal brain function. One of the candidates of this important family of glycan epitopes in the brain is polysialic acid (PSA/polySia). PSA is a well-known molecule because of its role as an oncodevelopmental antigen and is also widely used as a marker of adult neurogenesis. Recently, several reports have suggested that PSA and PSA-related genes are associated with multiple mental disorders. The relationships among PSA, PSA-related genes, and mental disorders are reviewed here.     

Clinical approach to the diagnosis of acid-base disorders.

An ability to rapidly and effectively diagnose and treat acid-base disorders is essential to the management of seriously ill patients. In this paper an approach to the diagnosis of pure and mixed acid-base disorders is presented that is based upon an understanding of the bicarbonate buffer system and a knowledge of the well defined and predictable compensatory responses that occur in association with each of the primary acid-base disorders. With this approach a number of acid-base problems are presented and solved.     

Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders

Peroxisomal disorders are an important group of neurometabolic diseases. The clinical presentation is varied in terms of age of onset, severity, and different neurological symptoms. The clinical course spans from death in infancy, rapid functional decline, slow decline on long-term followup, to apparent stable course. Leukoencephalopathy and developmental anomalies are characteristic findings on cerebral MR imaging. From a diagnostic point of view the disorders can be clinically subdivided into four broad categories: (1) the Zellweger spectrum disorders and the peroxisomal ?-oxidation disorders, (2) the rhizomelic chondrodysplasia punctata spectrum disorders, (3) the X-linked adrenoleukodystrophy/adrenomyeloneuropathy complex and (4) the remaining disorders. This article discusses the role of MRI findings in the clinical approach of peroxisomal disorders with neurological disease. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of peroxisomes in Health and Disease.     

Angststörungen in der Schwangerschaft und nach der Geburt:

Anxiety disorders are widespread. In contrast to affective disorders, they are characterized by a high persistence and a low remission rate. A considerable number of women suffer from anxiety disorders not only prior to conception but also throughout the transition into parenthood. The detection of anxiety disorders is complicated by the overlap of somatic and anxiety symptoms. Additionally, certain anxiety syndromes are specifically exacerbated during pregnancy. We present the diagnostic criteria of the most important anxiety disorders and highlight the symptoms that make an adequate diagnosis during pregnancy difficult. We outline the natural course and delineate options for referral and intervention.     

Subtypes of Ataques de Nervios: The Influence of Coexisting Psychiatric Diagnosis

The current study assesses the relationship between presenting symptomatology of the self-labeled Hispanic popular diagnosis of ataques de nervios and the specific co-morbid psychiatric diagnoses. Hispanic subjects seeking treatment at an anxiety disorders clinic (n = 156) were assessed with a specially designed self-report instrument for both traditional ataque de nervios and panic symptoms, and with structured or semi-structured psychiatric interviews for Axis-I disorders. This report focuses on 102 subjects with ataque de nervios who also met criteria for panic disorder, other anxiety disorders, or an affective disorder. Distinct ataque symptom patterns correlated with co-existing panic disorder, affective disorders, or other anxiety disorders. Individuals with both ataque and panic disorder reported the most asphyxia, fear of dying, and increased fear during their ataques. People with ataques who also met criteria for affective disorder reported the most anger, screaming, becoming aggressive, and breaking things during ataques. Ataque positive subjects with other anxiety disorders were less salient for both panic-like and emotional-anger symptoms. The findings suggest that (a) ataque de nervios is a popular label referring to several distinct patterns of loss of emotional control, (b) the type of loss of emotional control is influenced by the associated psychiatric disorder, and (c) ataque symptom patterns may be a useful clinical marker for detecting psychiatric disorders. Further study is needed to examine the relationship between ataque de nervios and psychiatric disorders, as well as the relationship to cultural, demographic, environmental, and personality factors.     

Cardiac conduction disorders in six infants with "near-miss" sudden infant deaths.

Cardiac conduction disorders caused sudden serious illnesses in six infants that might have been fatal if diagnosis and treatment had been delayed. These cases provide circumstantial evidence to support a link between cardiac conduction disorders and some sudden infant deaths. A further potential long-term effect of these disorders is illustrated in one child in whom psychomotor retardation seemed to develop after an episode of cerebral hypoxia that was probably by an arrhythmia associated with the Wolff-Parkinson-White syndrome. Cardiac conduction disorders may be detected by routine neonatal ECG screening, and it may therefore be appropriate to start prophylactic antiarrhythmic treatment in certain children before clinical signs develop.     

Mitochondrial DNA-related Disorders

Mitochondrial diseases are a group of disorders due to a mitochondrial respiratory chain deficiency. They may depend on mitochondrial genome (mtDNA-related disorders) as well as on a nuclear genome defect (nDNA-related disorders). mtDNA-related disorders encompass an increasing number of clinical pictures associated with more than 250 different provisional or confirmed pathogenic changes in mtDNA. Although some clinical syndromes are nosologically defined, most of the cases present with polymorphous phenotypes ranging from pure myopathy to multi-system involvement. Complexity of mitochondrial genetics is in part responsible for the extreme clinical intra- and inter-familial heterogeneity of this group of diseases. In this review, we briefly report an updated classification and overview the main clinical pictures of this class of diseases.     

Minireview on Achillea millefolium Linn

Yarrow (Achillea millefolium L.) is an important medicinal plant with different pharmaceutical uses. A. millefolium has been used for centuries to treat various diseases including malaria, hepatitis and jaundice. A. millefolium is commonly prescribed to treat liver disorders. It is also used as an anti-inflammatory agent and is a hepatoprotective herb. A. millefolium is considered safe for supplemental use. It has antihepatotoxic effects also. It is prescribed as an astringent agent. It is prescribed in hemorrhoids, headache, bleeding disorders, bruises, cough, influenza, pneumonia, kidney stones, high blood pressure, menstrual disorders, fever, rheumatoid arthritis, gout, osteoarthritis, hemorrhagic disorders, chicken pox, cystitis, diabetes mellitus, indigestion, dyspepsia, eczema, psoriasis and boils.     

Prevalencia de los trastornos de ansiedad en las personas mayores de 65 años: una revisión sistemática

Anxiety is an emotional problem that causes discomfort and suffering to those that suffer from it. Anxiety disorders can affect the functioning in different facets of a person's life. Studies on the prevalence of anxiety disorders in people over 65 years show variable results, ranging between 0.1% and 17.2%. Most of these studies include samples of the general population, in which the population of people over 65 years is under-represented. These studies evaluate older people with the same diagnostic tools used to assess anxiety disorders in people under 65 years, and collect data from people between 65 and 75 years old, leaving out people aged 75 and over. A systematic review of the prevalence studies of anxiety disorders in elderly people is presented. It is concluded that when representative samples of people over 65 years are used and evaluated with suitable tools, the prevalence rate of these disorders in the elderly is much higher than previously thought, reaching an annual prevalence rate of 20.8%.     

Human Borna disease virus-infection and its therapy in affective disorders

Patients with affective disorders show an enhanced prevalence of Borna disease virus (BDV)-infection. Furthermore, BDV causes latent infection preferably in limbic central nervous structures and is suggested to be causally related to subtypes of affective disorders, especially with melancholic clinical features or bipolarity. Such a possible link was highlighted by the first report of amantadine showing an antidepressive and an antiviral efficacy against BDV in a patient with a bipolar disorder. This article summarizes clinical studies which followed this first report on the use of amantadine in BDV-infected patients with an affective disorder. A special focus is given on an open clinical study in patients with depression (n = 25), a study in remitted patients with affective disorders (n = 16), and the effect of amantadine on severe hypomanic or moderately manic patients with a bipolar disorder in an on-off-on study. In these studies amantadine reduced clinical symptoms paralleled by a reduction of BDV-infection in depressive patients, it also reduced all three BDV-parameters (BDV-Ab, -AG, and -CICs) in remitted patients, and it even reduced severe hypomania and moderate mania in bipolar patients. These data suggest the existence of an etiopathogenetic link between BDV and subtypes of affective disorders.     

Personality disorders in the elderly: diagnostic aspects

This article describes the usefulness of the DSM personality disorders. In conclusion the presence of personality disorders during a lifetime is not always an enduring pattern of (the same) conduct disorders. Despite this, the DSM describes a static course of mainly interpersonal behaviour. Next to this, the utility of the DSM-Axis-II assessment and general personality assessment in relation to older adults will be discussed. In general these instruments are not very suitable for the assessment of the disposition and gravity of personality disorders in the elderly. It is proposed to develop specific profiles with regard to personality disorders in the elderly by applying the Delphi-technique on existing personality assessment. A Delphi panel of experts in the field of personality pathology in older adults can be asked to mention a certain personality disorder and describe this on a certain personality selfreport list, like the shortened version of the TCI.     

Language cannot be reduced to biology: Perspectives from neuro-developmental disorders affecting language learning

The study of language knowledge guided by a purely biological perspective prioritizes the study of syntax. The essential process of syntax is recursion — the ability to generate an infinite array of expressions from a limited set of elements. Researchers working within the biological perspective argue that this ability is possible only because of an innately specified genetic makeup that is specific to human beings. Such a view of language knowledge may be fully justified in discussions on biolinguistics, and in evolutionary biology. However, it is grossly inadequate in understanding language-learning problems, particularly those experienced by children with neurodevelopmental disorders such as developmental dyslexia, Williams syndrome, specific language impairment and autism spectrum disorders. Specifically, syntax-centered definitions of language knowledge completely ignore certain crucial aspects of language learning and use, namely, that language is embedded in a social context; that the role of envrironmental triggering as a learning mechanism is grossly underestimated; that a considerable extent of visuo-spatial information accompanies speech in day-to-day communication; that the developmental process itself lies at the heart of knowledge acquisition; and that there is a tremendous variation in the orthographic systems associated with different languages. All these (socio-cultural) factors can influence the rate and quality of spoken and written language acquisition resulting in much variation in phenotypes associated with disorders known to have a genetic component. Delineation of such phenotypic variability requires inputs from varied disciplines such as neurobiology, neuropsychology, linguistics and communication disorders. In this paper, I discuss published research that questions cognitive modularity and emphasises the role of the environment for understanding linguistic capabilities of children with neuro-developmental disorders. The discussion pertains to two specific disorders, developmental dyslexia and Williams syndrome.     

Drug resistance in brain diseases and the role of drug efflux transporters

Resistance to drug treatment is an important hurdle in the therapy of many brain disorders, including brain cancer, epilepsy, schizophrenia, depression and infection of the brain with HIV. Consequently, there is a pressing need to develop new and more effective treatment strategies. Mechanisms of resistance that operate in cancer and infectious diseases might also be relevant in drug-resistant brain disorders. In particular, drug efflux transporters that are expressed at the blood-brain barrier limit the ability of many drugs to access the brain. There is increasing evidence that drug efflux transporters have an important role in drug-resistant brain disorders, and this information should allow more efficacious treatment strategies to be developed.     

EFFECTS OF HEALTH DISORDERS AND POOR NUTRITIONAL STATUS ON GUSTATORY FUNCTION

Gustatory function is not static within an individual. Taste sensitivity and preferences are modified by numerous, well-documented external factors (e. g. smoking) as well as less widely recognized physiologic or internal idiosyncratic attributes such as salivary composition and genetic make-up. In addition, no single gustatory attribute adequately characterizes an individual's taste world. Measures of threshold sensitivity, suprathreshold sensitivity and preference may vary independently necessitating the assessment of each to derive a reliable assessment of an individual's gustatory status. Measures of taste preference, however, appear to hold the greatest predictive power for dietary behavior. Gustatory disorders may be manifest in the following forms: hypergeusia, hypogeusia, dysgeusia, ageusia, food aversions and food cravings. Each of these disorders is defined and, to the extent that information is available, the prevalence, etiology and clinical significance of each is discussed. Following this, a general scheme is presented along with numerous examples for evaluating the potential impact health or nutritional disorders may have on gustatory function. Finally, implications of health and nutritional disorders for applied sensory research are briefly considered.     

Neuropathological Aspects of Mitochondrial DNA Disease

Mitochondrial DNA disorders are an important cause of neurological disease, yet despite our awareness of the importance of these conditions, relatively little is known about the neuropathology of these disorders and even less about the mechanisms involved in neuronal dysfunction and death. In this review we detail important features from neuropathological studies available and highlight deficiencies that are currently limiting our understanding of mitochondrial DNA disease. We also discuss possible future approaches that might resolve some of these outstanding issues. Further study of these disorders is critical because mitochondria play a central role in neuronal survival and it is likely that an understanding of the mechanisms involved in neuronal dysfunction and cell death in mitochondrial DNA disease may have implications for other neurodegenerative diseases.     

Mood and anxiety disorders in women with PCOS

Women with polycystic ovary syndrome have gynecologic, reproductive and metabolic co-morbidities that span their entire lifespan. More recently a higher risk of mood and anxiety disorders has been reported in women with PCOS. Women with PCOS have higher depression scores and a higher risk of depression independent of BMI. Although clinical features of hyperandrogenism affect health related quality of life, the association between hirsutism, acne, body image and depression is currently unclear. Similarly there is limited data on the association between variables such as biochemical hyperandrogenism or infertility and depression. Women with PCOS are also at risk for symptoms of generalized anxiety disorder. There is insufficient data examining the risk of other anxiety disorders such as social phobia, obsessive compulsive disorders and panic disorder. In a number of patients some of these disorders coexist increasing the health burden. These data underscore the need to screen all women with PCOS for mood and anxiety disorders and adequately treat women who are diagnosed with these conditions.     

PET imaging of the basal ganglia

The present chapter reviews PET imaging in basal ganglia disorders; Parkinson's disease is used as a model of these disorders because the neurochemical pathobiology of this disease is well known and great advances in the imaging area have been achieved. Other basal ganglia disorders including Tourette's syndrome, dystonia, Huntington's chorea and Wilson's disease are also dealt with. With PET and SPECT techniques, the whole integrative dopaminergic network of neurons can be studied, which plays an important role in differential diagnostics. Furthermore, pharmacological effects of medication can be visualized and the role of stereotaxic neurosurgery can be evaluated. Finally, functional imaging gives clues about the prognosis and rehabilitation aspects of the basal ganglia disorders.     

The status of psychodynamic psychotherapy as an empirically supported treatment for common mental disorders – an umbrella review based on updated criteria

To assess the current status of psychodynamic therapy (PDT) as an empirically supported treatment (EST), we carried out a pre-registered systematic umbrella review addressing the evidence for PDT in common mental disorders in adults, based on an updated model for ESTs. Following this model, we focused on meta-analyses of randomized controlled trials (RCTs) published in the past two years to assess efficacy. In addition, we reviewed the evidence on effectiveness, cost-effectiveness and mechanisms of change. Meta-analyses were evaluated by at least two raters using the proposed updated criteria, i.e. effect sizes, risk of bias, inconsistency, indirectness, imprecision, publication bias, treatment fidelity, and their quality as well as that of primary studies. To assess the quality of evidence we applied the GRADE system. A systematic search identified recent meta-analyses on the efficacy of PDT in depressive, anxiety, personality and somatic symptom disorders. High quality evidence in depressive and somatic symptom disorders and moderate quality evidence in anxiety and personality disorders showed that PDT is superior to (inactive and active) control conditions in reducing target symptoms with clinically meaningful effect sizes. Moderate quality evidence suggests that PDT is as efficacious as other active therapies in these disorders. The benefits of PDT outweigh its costs and harms. Furthermore, evidence was found for long-term effects, improving functioning, effectiveness, cost-effectiveness and mechanisms of change in the aforementioned disorders. Some limitations in specific research areas exist, such as risk of bias and imprecision, which are, however, comparable to those of other evidence-based psychotherapies. Thus, according to the updated EST model, PDT proved to be an empirically-supported treatment for common mental disorders. Of the three options for recommendation provided by the updated model (i.e., “very strong”, “strong” or “weak”), the new EST criteria suggest that a strong recommendation for treating the aforementioned mental disorders with PDT is the most appropriate option. In conclusion, PDT represents an evidence-based psychotherapy. This is clinically important since no single therapeutic approach fits all psychiatric patients, as shown by the limited success rates across all evidence-based treatments.     

Eye disorders in neurofibromatosis (NF1)

Neurofibromatosis type 1 (NF 1) is an autosomal dominant disorder with high index of spontaneous mutations and extremely varied and impredictible clinical manifestations. The aim of this work was to give an account of eye disorders in NF1. 132 patients of age 0-16 years with NF1 were followed up for 15 years. They were checked repeatedly for ophthalmologic disorders. Frequent eye disorders were: Lisch nodules (Iris hamartomas, IH) 78%, hyperthelorism 19.7%, bulbomotoric disorders 15.9%, disorders of the optic disc 16.7% and optic gliomas (18.9%). The highest incidence of eye disorders by NF1 patients showed Lisch nodules (IH). Its ease of clinical recognition and if present with other diagnostic signs (for instance café au lait patches) could be deemed as reliable diagnostic criterion of NF1 in childhood.