[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 3 : Tardive dyskinesia]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 3 : Spätdyskinesien.

The treatment of schizophrenic psychoses with antipsychotic drugs (AP) is often associated with an increased risk of delayed occurrence of antipsychotic-associated movement disorders. Persistence and chronicity of such symptoms are very frequent. The risk of developing tardive dyskinesia (TD) is associated with the pharmacological effect profile of a particular AP, with treatment duration and age. This systematic review article summarizes the current study situation on prevalence, risk factors, prevention and treatment options and instruments for early prediction of TD in schizophrenic psychoses. The current data situation on treatment strategies for TD is very heterogeneous. For the treatment of TD there is preliminary evidence for reduction or discontinuation of the AP, switching to clozapine, administration of benzodiazepines (clonazepam) and treatment with vesicular monoamine transporter (VMAT2) inhibitors, ginkgo biloba, amantadine or vitamin E. Although TD can be precisely diagnosed it cannot always be effectively treated. Early detection and early treatment of TD can have a favorable influence on the prognosis and the clinical outcome.

[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 1 : Dystonia, akathisia und parkinsonism]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 1 : Dystonien, Akathisie und Parkinsonismus.

Acute antipsychotic-induced movement disorders (AIMD) are clinically relevant since they are frequently associated with high subjective distress, and since over the long-term they can negatively impact treatment adherence of patients with schizophrenic psychoses. This review article summarizes the relevant studies on the prevalence, risk factors, prevention and treatment options and instruments for early prediction of acute AIMD in schizophrenic psychoses. The current evidence and treatment recommendations are divided into three main areas: acute dystonia, akathisia, and parkinsonism. For the treatment of acute dystonia trihexyphenidyl and biperiden have shown their efficacy. Considering pharmacological treatment of akathisia, there is some preliminary evidence for medication with lipophilic beta-receptor blockers (propranolol and pindolol), clonidine, benzodiazepines, mianserin, mirtazapine und trazodone. The treatment options for drug-induced parkinsonism include reduction or switching from one antipsychotic to another with a lower affinity for dopamine D2 receptors, amantadine or in the regular administration of anticholinergic drugs. In conclusion, acute AIMD is easily to recognize but is not always effectively and durably treated. Early recognition and treatment of acute AIMD could be associated with improved treatment outcomes.

[Genuine motor phenomena in schizophrenic psychoses : Theoretical background and definition of context]. / Genuine motorische Phänomene bei schizophrenen Psychosen : Theoretischer Hintergrund und Kontextdefinition.

Besides positive and negative symptoms, motor abnormalities have been increasingly recognized as central symptoms of schizophrenia. Recent investigations of antipsychotic-naive first-episode patients with schizophrenia found significantly higher rates of genuine motor abnormalities (GMA) when compared to healthy individuals. The first part of this article introduces the historical and clinical background of GMA in schizophrenia. In the second part the relevance of scientific research and clinical implication of GMA in schizophrenia are discussed. Finally, this article aims at presenting a conceptual framework and a reference system involving both genuine and drug-induced motor abnormalities. The future clinical implications of GMA research are presented and multimodal and transdiagnostic studies are advocated. Future research on GMA will not only essentially enrich the formation of psychiatric theories but also promote progress in clinical neuroscience.

[Genuine motor phenomena in schizophrenia : Neuronal correlates and pathomechanisms]. / Genuine motorische Phänomene bei schizophrenen Psychosen : Neuronale Korrelate und Pathomechanismen.

Despite a growing body of evidence on motor dysfunction in schizophrenia spectrum disorders, the neuronal correlates of genuine motor abnormalities (GMA) are not fully elucidated at present. Moreover, the clinical relevance of a potential "motor intermediate phenotype" remains controversial. This systematic review aims at characterizing a "motor intermediate phenotype" in schizophrenia spectrum disorders. The second goal of this systematic review is to discuss GMA-associated brain alterations as potential biomarkers of psychosis risk syndrome and manifest motor symptoms against the background of current neuroimaging evidence. The detailed clinical assessment of GMA in the context of multimodal imaging could, in the future promote the early recognition of psychotic disorders and the initiation of disorder-oriented and individualized treatment. Taken as a whole the data provide initial evidence that motor dysfunction in schizophrenic spectrum disorders must be considered dimensionally. The predictive value of neurobiological results with respect to the transition to a life-threatening catatonia or the development of chronic dyskinesia, cannot currently be conclusively assessed.

[German version of the Northoff catatonia rating scale (NCRS-dv) : A validated instrument for measuring catatonic symptoms]. / Deutsche Version der Northoff Catatonia Rating Scale (NCRS-dv) : Ein validiertes Messinstrument zur Erfassung katatoner Symptome.

The clinical picture of catatonia includes impressive motor phenomena, such as rigidity, dyskinesia, festination, negativism, posturing, catalepsy, stereotypies and mannerisms, along with affective (e. g. aggression, anxiety, anhedonism or emotional lability) and behavioral symptoms (e.g. mutism, autism, excitement, echolalia or echopraxia). In English speaking countries seven catatonia rating scales have been introduced, which are widely used in clinical and scientific practice. In contrast, only one validated catatonia rating scale is available in Germany so far. In this paper, we introduce the German version of the Northoff catatonia rating scale (NCRS-dv). The original English version of the NCRS consists of 40 items describing motor (13 items), affective (12 items) and behavioral (15 items) catatonic symptoms. The NCRS shows high internal reliability (Crombachs alpha = 0.87), high interrater (r = 0.80-0.96) and high intrarater (r = 0.80-0.95) reliability. Factor analysis of the NCRS revealed four domains: affective, hyperactive or excited, hypoactive or retarded and behavior with individual eigenvalues of 8.98, 3.61, 2.98 and 2.82, respectively, which explained 21.5 %, 9.3 %, 7.6 % and 7.2 % of variance, respectively. In conclusion, the NCRS-dv represents a second validated instrument which can be used by German clinicians and scientists for the assessment of catatonic symptoms.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

BACKGROUND: Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. METHOD: Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. RESULTS: Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. CONCLUSIONS: This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

[Electroconvulsive therapy in depression: insights from fMRI, PET and SPECT studies]. / Elektrokonvulsive Therapie bei Depression: Welche Erkenntnisse erbringen fMRT-, PET- und SPECT-Untersuchungen?

Electroconvulsive therapy (ECT) is the most potent and rapidly acting of all antidepressant treatments in major depressive disorder (MDD). Nuclear and functional magnetic (fMRI) brain imaging studies of ECT have substantially contributed to the neurobiological understanding of this treatment modality. Neuroimaging methods may also validate potential mechanisms of antidepressant action. Models of neural dysfunction in MDD suggest impaired modulation of activity within a cortico-limbic circuitry, along with alterations in the functional organisation of multiple brain networks implicated in emotional processes. Nuclear imaging techniques have demonstrated consistent patterns of ECT-induced ictal changes in brain activity that appear to be linked to efficacy and side effects of ECT. Interictally, widespread alterations of brain function have been reported, however, results remain inconclusive. FMRI studies of ECT have demonstrated longer-lasting, interictal changes of neural activity in multiple cerebral regions that are in accordance with functional neuroanatomical models of mood disorders. Future research detailing ECT interactions with brain pathophysiology in MDD could potentially provide a clinically useful framework to better predict ECT treatment response and/or side effects, and may also facilitate the development of more focused brain stimulation techniques.

Frequency noise of free-running 4.6 µm distributed feedback quantum cascade lasers near room temperature.

The frequency noise properties of commercial distributed feedback quantum cascade lasers emitting in the 4.6 µm range and operated in cw mode near room temperature (277 K) are presented. The measured frequency noise power spectral density reveals a flicker noise dropping down to the very low level of <100 Hz(2)/Hz at 10 MHz Fourier frequency and is globally a factor of 100 lower than data recently reported for a similar laser operated at cryogenic temperature. This makes our laser a good candidate for the realization of a mid-IR ultranarrow linewidth reference.

[Mild cognitive impairment: diagnostic value of different MR techniques]. / "Mild cognitive impairment": Diagnostische Wertigkeit verschiedener MR-Techniken.

In view of an increasingly aging population the prevalence of dementia is also expected to increase rapidly. As well as clinical, neuropsychological and laboratory procedures magnetic resonance imaging (MRI) plays an important role in the early diagnosis of dementia which is important in the precursor stage of mild cognitive impairment (MCI). On the one hand this stage is associated with an increased risk of dementia and on the other hand an early treatment in this stage could attenuate development of the disease. In addition to morphological changes different functional MRI techniques can help in the early diagnosis of dementia and the precursor stages. Moreover, it is important to detect those MCI patients who are at particularly risk for developing dementia. In the differentiation of converters to non-converters initial studies suggest that particularly voxel-based morphometry, MR spectroscopy and diffusion tensor imaging can provide important additional information.

Effects of yoga in inflammatory bowel diseases and on frequent IBD-associated extraintestinal symptoms like fatigue and depression.

Quality of life (QoL) of persons with inflammatory bowel diseases (IBD) is often impaired by symptoms that do not primarily relate to intestinal inflammation. Among the most challenging extraintestinal symptoms are depression and fatigue, which are also frequent in other chronic diseases like multiple sclerosis, rheumatoid arthritis and cancer. Yoga as an ancient Indian tradition containing postures, breathing exercises and meditation may positively influence those symptoms. This review evaluates the current literature with regard to the effect of yoga-based interventions in persons with IBD and with regard to QoL, depression and fatigue in other somatic disorders. A systematic literature search yielded three trials examining the effects of yoga in patients with IBD and 37 trials addressing depressive syndromes or fatigue in somatic disorders. In summary, both in-person and video-based yoga classes are feasible, acceptable and safe as complementary treatment in patients with IBD and significantly improve anxiety and impaired quality of life. Current literature does not provide information on the effect of yoga on depression and fatigue in patients with IBD, but research from other somatic disorders or patients with depressive disorders implies the potential of yoga in this regard for persons with IBD. This should be specifically addressed in interventional trials with standardized yoga modules including patients with IBD suffering from fatigue, depression and/or impaired QoL.

An electrostatic glass actuator for ultrahigh vacuum: A rotating light trap for continuous beams of laser-cooled atoms.

This article describes the design, characterization, and performance of an electrostatic glass actuator adapted to an ultrahigh vacuum environment (10(-8) mbar). The three-phase rotary motor is used to drive a turbine that acts as a velocity-selective light trap for a slow continuous beam of laser-cooled atoms. This simple, compact, and nonmagnetic device should find applications in the realm of time and frequency metrology, as well as in other areas of atomic, molecular physics and elsewhere.

Temporal horn index and volume of medial temporal lobe atrophy using a new semiautomated method for rapid and precise assessment.

BACKGROUND AND PURPOSE: Quantitative markers of Alzheimer disease (AD), particularly in the early stages, are needed for clinical assessment and monitoring. We have evaluated a novel method to segment and visualize the ventricular system and obtain volumetric measures thereof. The temporal horn volume (THV) and index in patients with mild cognitive impairment (MCI) and in those with AD were evaluated. METHODS: High-resolution T1-weighted volume imaging was performed in 52 subjects (21 patients with MCI, 10 with AD, and 21 healthy control subjects). An interactive watershed transformation and semiautomated histogram analysis were implemented to produce segmented THV and temporal horn indices (THI) (ratio of THV to lateral ventricular volume). RESULTS: Cerebral ventricular and temporal horn size could be semiautomatically quantified from all 52 datasets. The method was fast and rater-independent. Qualitative ventricular inspections using surface rendering shading could uncover atrophic process with enlargement of the whole and especially temporal horn volume. Both THV and THI of patients with AD were significantly larger than those of patients with MCI or control subjects (P < .005). There was no significant difference in THV and THI between patients with MCI or control subjects (P > .05). There was a significant correlation between the neuropsychologic performance and both THI and THV across groups (P < .01). CONCLUSION: THV and THI could be used as markers of AD in the clinical environment and are expected to be helpful in monitoring therapeutic intervention.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab]. / Maladie de Castleman : désensibilisation rapide après une réaction d'hypersensibilité au rituximab.

INTRODUCTION: Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. CASE REPORT: We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). CONCLUSION: Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative.

Two-dimensional DNA-fingerprinting in animals.

DNA-fingerprinting has become, during the last five years, an important method of genetic analysis in medicine, veterinary medicine and other disciplines. The power of this technique, especially for genetic linkage analysis, may be enhanced in humans by using the two dimensional DNA-fingerprinting method. Here we show that this procedure can successfully be applied to different animal species, e.g. pig, dog and mouse. Optimal conditions, however, have to be determined for each species tested. With the use of marker systems as well as computer programs it will be possible to evaluate complex two-dimensional spot patterns in a short time and with high reliability.

Preparation and in vivo testing of porous alumina ceramics for cell carrier applications.

Microporous alumina was used to develop implantable cell carriers shaped as a hollow-sphere with a central opening to allow ingrowth of vascularised tissues. The carriers were produced by suspending the ceramic raw materials in water, homogenising and dropping the resulting slurry onto a heated plate (hot plate moulding, HPM). Morphological characteristics of the cell carriers were investigated by SEM and optical microscopy. Produced carriers had an average diameter of 4.9 mm. The material was highly porous (56 +/- 8%). For in vivo testing the cell carriers were implanted into abdominal wall of Zur: SIV rats for up to 50 weeks and investigated by light microscopy, SEM and TEM. The surface of the hollow carriers was in close contact with unirritated muscle tissue; no inflammation or capsule formation was observed. Loose connective tissue had grown into the hollow cell carrier, and after prolonged implantation >20 weeks adipocytes were observed. The absence of scar tissue formation around the implant and the vitality within the cavity of the hollow carriers indicate that porous alumina may be used for cell transplantation devices.

Laboratory values and vital signs in male smokers and nonsmokers in phase I trials: a retrospective comparison.

In a retrospective analysis of 13 phase I multiple-dose trials, clinical data from 100 volunteers who received placebo were investigated for differences in routine safety laboratory parameters and vital signs between smokers and nonsmokers. Of the 100 subjects, 47 were classified as smokers (cigarettes only) and 53 were classified as nonsmokers. Objectives of the analysis were to offer a basis for decision whether certain deviations of laboratory values or vital signs might be related to smoking rather than to a study drug or some external influence, and to explore whether smokers tend to present changes in laboratory values or vital signs during a trial that are different from changes that occur in nonsmokers. Regarding baseline values, which were defined as the mean of values at screening and the first day of the in-house stay, clinically and statistically significant differences between smokers and nonsmokers were found for total leukocytes and triglycerides (mean greater for smokers than nonsmokers), and total bilirubin (mean greater for nonsmokers than smokers). Comparison of changes during the study in smokers and nonsmokers showed a statistically and clinically significant difference only for triglyceride levels. Smokers had a slight decrease in triglyceride levels, whereas nonsmokers showed a marked increase in the respective values during the trials. Prospective studies with sufficiently large sample sizes are required to confirm the results of this retrospective analysis on a wider basis, and to possibly achieve significance for further differences between smokers and nonsmokers.

Correlated nerve conduction, somatosensory evoked potential and neuropathological studies in clioquinol and 2,5-hexanedione neurotoxicity in the baboon.

Observations have been made on 10 baboons receiving a high-dose regimen of clioquinol administered orally, 6 receiving a low-dose regimen and 6 treated with 2,5-hexanedione. The results were compared with those obtained from 10 control animals. Motor and sensory nerve conduction velocity was markedly reduced in the hexanedione-treated animals but only very minor abnormalities were detected in the clioquinol-treated baboons. Cervical and Rolandic somatosensory evoked potentials to lower and upper limb stimulation were delayed in both the high-dose clioquinol-treated and the hexanedione-treated animals, particularly in the latter. Histopathological studies in the low-dose clioquinol-treated group showed no abnormalities. In the high-dose group; axonal degeneration was confined to the spinal cord, cerebellar vermis and optic tract. It was most marked in the rostral portions of the dorsal spinal columns and the caudal parts of the direct and crossed corticospinal tracts. Occasional dorsal column fibres had degenerated back to the root entry zone in the cord. The distribution was that of a selective central distal axonopathy. There appeared to be no correlation with estimated blood levels of unaltered clioquinol. In hexanedione-treated animals there was also degeneration in the distal optic tracts and peripheral nerves in a pattern of central-peripheral distal axonopathy.

Clioquinol toxicity in the dog.

A number of instances have been reported in the scientific literature in which acute intoxication with halogenated oxyquinolines has led in some species to convlusions, often followed by death. The toxicity of repeated doses of clioquinol has been investigated extensively in the dog. The clinical syndrome induced in this species is characterized by anorexia, weight loss, extremem muscle weakness and emaciation. In some animals surviving this impairment of condition for several weeks, neuropathy of the central nervous system, but not of the peripheral nerves ensued. It is suggested that these toxicological manifestations are less dependent on the dose-level than on the degree of absorption. Some suggestions regarding the aetiology of the lesions are made.

Pyridoxine megavitaminosis produces degeneration of peripheral sensory neurons (sensory neuronopathy) in the dog.

Pyridoxine, a water-soluble vitamin, produces a sensory neuronopathy when administered in high doses to dogs. Beagles who received a daily oral dose of 300 mg/kg of pyridoxol hydrochloride developed a swaying gait within 9 days. They eventually became unable to walk, but were not weak. Animals were sacrificed at intervals up to 78 days. Morphological examination revealed widespread neuronal degeneration in the dorsal root ganglia and the Gasserian ganglia. Cytoplasmic changes were first observed after 8 days and consisted of small, electronlucent vacuoles that subsequently coalesced leading to death of the cells. Degeneration of sensory nerve fibers in peripheral nerves, dorsal columns of the spinal cord and the descending spinal tract of the trigeminal nerve was apparent. The pathogenesis of these changes is unclear, but may, in part, reflect the selective permeability of blood vessels in the peripheral ganglia. It is apparent that the peripheral neuropathy previously attributed to pyridoxine actually represents a toxic, peripheral sensory neuronopathy.

Early effects of high-dosed absorbable amoscanate on rat brain.

An oily suspension of the absorbable form of amoscanate was administered to young adult albino rats in single or repeated oral doses of 25, 125 and 500 mg/kg. At least 3 consecutive doses of 125 or 500 mg/kg were needed to induce a brain lesion. The early change consisted of necrosis of the ependyma of the lateral ventricles, indicating that intoxication may have occurred via the cerebrospinal fluid.