Neuropsychiatric symptoms in a European Huntington's disease cohort (REGISTRY).

BACKGROUND: The majority of Huntington's disease (HD) mutation carriers experience some psychopathology during their lifetime, varying from irritability to psychosis, but prevalences of particular symptoms vary widely due to diverse study populations in different stages of HD and the use of different assessment methods. METHODS: The study population consisted of 1993 HD mutation carriers from 15 European countries, all participating in the observational REGISTRY study. The behavioural section of the Unified HD Rating Scale was used to examine the prevalence and correlates of five neuropsychiatric features: depression, irritability/aggression, obsessive/compulsive behaviours, apathy and psychosis. RESULTS: Twenty-seven per cent of the participants did not have any neuropsychiatric symptom in the last month. Moderate to severe apathy occurred in 28.1% of the participants, whereas moderate to severe depression was found in 12.7%. Irritable/aggressive symptoms were present in 13.9% of the participants, and 13.2% showed obsessive/compulsive behaviours. Moderate to severe psychotic symptoms were found in only 1.2%. Only 54.9% of all participants with moderate to severe depression used antidepressants, suggesting undertreatment of depression. Obsessive/compulsive behaviours and irritability/aggression were inversely correlated with the Total Functional Capacity score, but with apathy showing the strongest inverse association. CONCLUSIONS: A variety of neuropsychiatric symptoms are highly prevalent in different stages of HD in this European HD population, with apathy as the most frequent symptom. Depression, irritability/aggression and OCBs are prevalent in all stages of HD. Apathy was the key neuropsychiatric symptom occurring most often in advanced HD stages. Due to possible selection of relatively healthy participants, prevalences reported in this study might be an underestimation of prevalence in the entire HD population.

Mental disorders, religion and spirituality 1990 to 2010: a systematic evidence-based review.

Religion/spirituality has been increasingly examined in medical research during the past two decades. Despite the increasing number of published studies, a systematic evidence-based review of the available data in the field of psychiatry has not been done during the last 20 years. The literature was searched using PubMed (1990-2010). We examined original research on religion, religiosity, spirituality, and related terms published in the top 25 % of psychiatry and neurology journals according to the ISI journals citation index 2010. Most studies focused on religion or religiosity and only 7 % involved interventions. Among the 43 publications that met these criteria, thirty-one (72.1 %) found a relationship between level of religious/spiritual involvement and less mental disorder (positive), eight (18.6 %) found mixed results (positive and negative), and two (4.7 %) reported more mental disorder (negative). All studies on dementia, suicide, and stress-related disorders found a positive association, as well as 79 and 67 % of the papers on depression and substance abuse, respectively. In contrast, findings from the few studies in schizophrenia were mixed, and in bipolar disorder, indicated no association or a negative one. There is good evidence that religious involvement is correlated with better mental health in the areas of depression, substance abuse, and suicide; some evidence in stress-related disorders and dementia; insufficient evidence in bipolar disorder and schizophrenia, and no data in many other mental disorders.

Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant differences in both patient groups, displaying higher sexual desire and activity in HD patients, but MS patients also reported fewer sexual problems compared to the norming values. Conversely, the MS patients' relationships seemed to be stable despite subjectively perceived lower initiative on sexual activities. The results are discussed under the possible influences of the underlying organic changes and the psychosocial consequences of chronic progressive disorders.

Impaired ideomotor limb apraxia in cortical and subcortical dementia: a comparison of Alzheimer's and Huntington's disease.

BACKGROUND: Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). METHODS: To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. RESULTS: There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. CONCLUSIONS: Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful.

Comparative EEG mapping studies in Huntington's disease patients and controls.

Huntington's disease (HD) is a devastating neurodegenerative disorder with prominent motor and cognitive decline. Previous studies with small sample sizes and methodological limitations have described abnormal electroencephalograms (EEG) in this cohort. The aim of the present study was to investigate objectively and quantitatively the neurophysiological basis of the disease in HD patients as compared to normal controls, utilizing EEG mapping. In 55 HD patients and 55 healthy controls, a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Evaluation of 36 EEG variables was carried out by spectral analysis and visualized by EEG mapping techniques. To elucidate drug interference, the analysis was performed for the total group, unmedicated patients only and between treated and untreated patients. Statistical overall analysis by the omnibus significance test demonstrated significant (p < 0.01 and p < 0.05) EEG differences between HD patients and controls. Subsequent univariate analysis revealed a general decrease in total power and absolute alpha and beta power, an increase in delta/theta power, and a slowing of the centroids of delta/theta, beta and total power. The slowing of the EEG in HD reflects a disturbed brain function in the sense of a vigilance decrement, electrophysiologically characterized by inhibited cortical areas (increased delta/theta power) and a lack of normal routine and excitatory activity (decreased alpha and beta power). The results are similar to those found in other dementing disorders. Medication did not affect the overall interpretation of the quantitative EEG analysis, but certain differences might be due to drug interaction, predominantly with antipsychotics. Spearman rank correlations revealed significant correlations between EEG mapping and cognitive and motor impairment in HD patients.

Is there a cortical blood flow redistribution pattern related with perseverative error in schizophrenia?

BACKGROUND: We studied relative cortical blood flow (relCBF) patterns associated to correct performance (CP) and perseverative error (PE) during Wisconsin Card Sorting Test (WCST) execution, in controls and patients with schizophrenia. SUBJECTS AND METHODS: relCBF (regional cortical blood flow (rCBF) / whole cortex blood flow) of 10 well defined cortical regions was measured in 18 patients with schizophrenia and 13 healthy controls by a Technetium - 99 - HMPAO - SPECT, at rest and while they performed WCST. RESULTS: Patients made significantly more PE than controls during WCST performance. In patients, we found a significant correlation between PE and relCBF in right occipital cortex. In controls, we found a significant correlation between CP and relCBF of several cortical regions during WCST execution: left orbitofrontal cortex and left global frontal cortex positively and parietal bilateral cortex negatively. PE was inversely correlated with relCBF in left temporal cortex. CONCLUSIONS: Successful WCST performance is associated to a high left frontal activity in controls but not in patients. The severity of PE during WCST performance is associated to a low left frontal-temporal activity in controls and to a high right parietal-occipital activity in schizophrenia. This may represent a cortical activity redistribution pattern related to perseveration in schizophrenia.

Philosophical considerations on brain death and the concept of the organism as a whole.

Since intensive care medicine enables us to maintain blood circulation and respiration artificially for some time, the usual criteria for death, such as cardiac arrest and cessation of respiration, are not applicable in all cases. Thus, the irreversible breakdown of the brain functions have come to be accepted as the most prominent factor for the occurrence of death. This criterion is linked primarily to the disintegration of the organism as a whole. Yet the controversy surrounding the moment when a man can be declared dead has not yet been resolved. The decisive weak point in this controversial discussion seems to be that the notion of the "organism as a whole" is inadequately defined. The aim of this work is to fill this void. We developed four general criteria of life: integration, coordination, dynamics, and immanency. Moreover, four additional characteristics are necessary for a living being (organism as a whole): completion, indivisibility, autofinality, and identity. If one of these four characteristics is missing we can only speak of derivative life but not of a living being. In a brain dead body one finds a number of signs of life. These signs of life, however, are not signs of an organism as a whole but signs of a physiological combination of organs whose parts - directed from the outside - are dependent on each other. The brain dead body lacks the four criteria of a living being. Thus it is no longer a living person but purely derivated biological life.

Ideomotor limb apraxia in Huntington's disease: a case-control study.

INTRODUCTION: Ideomotor limb apraxia is the disturbance of planning and of execution of motor activity,which is not caused by a dysfunction of the motor or sensory nervous system. Apraxia is a diagnostic criterion in dementialike Alzheimer's disease. However, this symptom may also occur in dementia with subcortical lesions like Huntington's disease (HD), a hereditary, devastating neurodegenerative disease leading to neurological and psychiatric dysfunction. The aim of our study is to determine the correlation between the occurrence of ideomotor limb apraxia and neuropsychological deficits in HD. METHODS: To assess the correlation between apraxia and neuropsychological abilities in HD, 41 patients with HD and 33 age- and sex-matched controls were examined. The De Renzi test for apraxia and an apraxia test battery containing tests of i) imitation of meaningless gestures of hands, ii) imitation of meaningless gestures of fingers, iii) performance of meaningful gestures on demand, and iv) pantomime of tool use were used to assess apraxia. Moreover, neuropsychological function was rated by the Mini Mental State Examination (MMSE), the Rey Complex Figure Memory Test, the Trail Making Test A and B, the California Verbal Learning Test (German version), the Stroop Color and Word Test, the Controlled Oral Word Association Test, and the Mehrfachwahl- Wortschatz-Intelligenztest for measuring verbal intelligence. Motor function was assessed in all HD patients by the Unified HD Rating Scale (UHDRS), rating oculomotor and orolingual function, fine motor tasks, parkinsonism, dystonia, chorea and statics and gait. RESULTS: Apraxic HD patients showed worse results than non-apraxic HD patients in three items of the Rey Complex Figure Memory Test (Organisation, short-term and longterm memory), but not in other assessed neuropsychological tests. In assessment of meaningful gestures on demand 39.3% of HD patients were apraxic, in assessment of pantomime of tool use 67.9% of HD patients showed apraxia. Patients with HD showed highly significant worse results than controls in the De Renzi test, in hands' and fingers' imitation, in performance of gestures on demand, in pantomime of tool use and every neuropsychological test except for the test measuring verbal intelligence. Apraxic HD patients showed worse results than non-apraxic HD patients in the UHDRS total motor score and the score for oculomotor function. CONCLUSION: This is the largest study on apraxia in HD. Ideomotor limb apraxia is a common sign in HD patients, occurring in a high percentage. In contrast to the opinion of several authors, occurrence of apraxia in HD is independent from neuropsychological decline and the severity of most neurological symptoms.

Frontal-subcortical dementias.

Frontal-subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychologic impairment. Their clinical presentation is characterized by memory disorders, an impaired ability to manipulate acquired knowledge, important changes of personality (apathy, inertia, or depression), and slowed thought processes (or bradyphrenia). It also has marked frontal dysfunction. Classic frontal-subcortical dementias include Huntington chorea, Parkinson disease dementia, progressive supranuclear palsy, thalamic degeneration, subcortical vascular dementia, multiple sclerosis, the acquired immunodeficiency syndrome dementia complex, depressive pseudodementia, and some other rare dementias like spinocerebellar degenerative syndromes, Hallervorden-Spatz disease, choreoacanthocytosis, idiopathic basal ganglia calcification, Guamanian parkinsonism-dementia complex, corticobasal degeneration multiple system atrophy, Wilson disease, metachromatic leukodystrophy, adrenoleukodystrophy, hypoparathyroidism, sarcoidosis, and other CNS inflammatory disorders. Anatomic data suggest that the frontal signs result from a disconnection of the frontal cortex from the basal ganglia. However, most frontal-subcortical dementias show cortical atrophy in later stages, and cortical dementias have subcortical pathology at some point. In fact, the concept might be seen as a continuum, and only the 2 extremes would be represented by pure cortical or subcortical pathology. Anyway, subcortical disorders may still be more similar to one another than they are to AD. Possibly, frontal-subcortical and cortical dementias are the description of the prior main target of the disease process, ending up in both cases in a global dementia. Although the dichotomy cortical versus frontal-subcortical dementia is not strict, the 2 concepts still seem to have advantages.

Sexuality in Huntington's disease.

Sexuality and partnership have an important influence on the quality of life of patients with chronic disorders. There are just a few studies in literature about sexuality in Huntington's disease which conclude that up to 85% men and up to 75% of women experience high levels of sexual problems, most of them having prevalent symptoms of a hypoactive sexual disorder but also increased sexual interest and paraphilia were found. There is no evidence that sexual dysfunction is mainly a specific symptom of HD and may be associated with the specific brain lesion itself or if it is chiefly related to the psychosocial factors caused by the steadily worsening of the disease. Further studies should focus on asymptomatic patients to explore sexual changes preceding neurological and motor symptoms and should incorporate partners to objectify sexual distinctive features. Investigations on the context of sexual dysfunction with depression, irritability and dementia symptoms are needed to better understand reasons for sexual changes in HD. Treatment options for HD patients with sexual disorder are only reported sporadically, guidelines can only be obtained from non-HD patients and further research is needed.

Structural neuroimaging of the basal ganglia in schizophrenic patients: a review.

The basal ganglia structures have quickened interests in schizophrenia research for several reasons: On the one hand, schizophrenic patients are successfully treated with neuroleptics acting on dopamine receptors, which are highly concentrated in the basal ganglia structures. On the other hand, basal ganglia play an important role in higher cognitive functions such as attention, working memory and goal-directed behavior, which are impaired in schizophrenia. Magnetic resonance imaging allows non-invasive in vivo volumetric measurement of these brain structures. In this review, we studied all available papers on MRI research of the basal ganglia in schizophrenic patients. We found a possibly decreased caudate volume in first-episode schizophrenic patients, whereas studies on chronic patients mostly reveal volume increases in caudate, putamen and pallidum. Data from longitudinal studies suggest on the one hand that typical and atypical neuroleptics may produce different effects on brain morphology and on the other hand, that these changes are dynamic and might be reversible. Further studies are warranted for a better understanding of the mechanisms, which may lead to structural basal ganglia abnormalities, with medication effects demanding particular attention.

Frontal-subcortical circuitry and behavior.

The neuropsychiatric manifestations of neurodegenerative diseases are closely linked to neurocircuitry defects. Frontal-subcortical circuits, in particular, are effector mechanisms that allow the organism to act on its environment. In this paper, we present the three main frontal-subcortical circuits: the dorsolateral prefrontal circuit allows the organization of information to facilitate a response; the anterior cingulate circuit is required for motivated behavior; and the orbitofrontal circuit allows the integration of limbic and emotional information into behavioral responses. Impaired executive functions, apathy, and impulsivity are hallmarks of frontal-subcortical circuit dysfunction. A variety of other neuropsychiatric disorders, such as Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, schizophrenia, and mood disorders may result from disturbances that have a direct or indirect impact on the integrity or functioning of these loops.

Pharmacological management of Huntington's disease: an evidence-based review.

INTRODUCTION: Despite the increasing body of published reports on pharmacological interventions in Huntington's disease (HD), an evidence based review (EBR) of treatment studies has not yet been published. METHOD: Systematic literature searches were done using Medline (1965-August 2005), the central database in the Cochrane Library (1969-August 2005), and reference lists published in review articles and other clinical reports. Randomized controlled trials (RCTs) were classified as level-I-studies in this paper. Level-II evidence was assigned to non-randomized, controlled clinical studies. Level-III-studies comprised open label trials excluding case reports. Measures of efficacy as well as safety and tolerability were considered for each compound. RESULTS: We identified 218 publications on pharmacological interventions in HD since 1965. Among them were 20 level-I, 55 level-II, 54 level-III trials, and 89 case reports. All these papers are listed and analyzed. Chorea was the primary end point in all level-I and level-II symptomatic intervention trials. There is some evidence for treating chorea with haloperidol or fluphenazine, and less evidence for olanzapine. These three drugs have been considered "possibly useful" for the treatment of chorea in this analysis. Other substances (e.g. amantadine, riluzole, and tetrabenazine) are considered "investigational" for chorea. There is very low evidence for the treatment of other problems: "possibly useful" drugs are L-dopa and pramipexole for rigidity; amitryptiline and mirtazapine for depression; risperidone for psychosis; and olanzapine, haloperidol, and buspirone for behavioral symptoms in HD. Three substances are considered "investigational" for possible neuroprotection: coenzyme Q10, minocycline, and unsaturated fatty acids. CONCLUSION: There is poor evidence in management of HD today. The analysis of the twenty level-I studies fails to result in any treatment recommendation of clinical relevance. High-quality RCT are highly warranted to advance HD treatment in clinical practice.

Apoptotic cascades as possible targets for inhibiting cell death in Huntington's disease.

Huntington's disease (HD) is a devastating autosomal dominant disorder characterized by progressive motor and neuropsychological symptoms. Evidence implicating the apoptotic cascades as a possible cause for the neurodegeneration seen in HD has directed researchers toward investigating therapeutic treatments targeting caspases and other proapoptotic factors. Cellular and murine models, which have demonstrated that caspase-mediated cleavage could be the cause for the neurodegeneration seen in HD, have evoked more research investigating the possible inhibition of apoptosis in HD. In particular, minocycline, a tetracycline-derived antibiotic that has been shown to increase survival in transgenic mouse models of HD, exhibits a neuroprotective feature in HD and demonstrates an anti-inflammatory as well as an anti-microbial effect by inhibiting microglial activation known to cause apoptosis.

[Limb apraxia]. / Die Gliedmassenapraxie.

Apraxia is the disturbance of planning and of execution of motor activity. It is not caused by a lesion or a disturbance of the motor or sensory nervous system, it is elicited by a dysfunction of an area in the left cortex of the brain. This area in the left fronto-parietotemporal hemisphere is located right beside the area for speech. Therefore it is not unusual that patients with apraxia suffer from aphasia as well. The two different types of limb apraxia are ideomotor apraxia and ideational apraxia. Ideomotor apraxia is apraxia without tool use, it includes imitation of positions of hands and fingers, performance of gestures on demand, and pantomime of object use. Ideational apraxia is apraxia with tool use like cutting with a knife or utilizing a pencil.

[Religiosity and Mental Health]. / Religiosität und psychische Gesundheit ­ was ist wissenschaftlich belegt?

Since 1978, two systematic evidence-based reviews of the available data on religiosity and mental health in the field of psychiatry have been done. More than 70 % found a relationship between level of religious/spiritual involvement and less mental disorder (positive), some found mixed results (positive and negative), and only about 5 % reported more mental disorder (negative), as was originally suggested by Sigmund Freud. There is good evidence that religious involvement is correlated with better mental health in the areas of depression, substance abuse, and suicide; some evidence in stress-related disorders and dementia; insufficient evidence in bipolar disorder and schizophrenia, and no data in many other mental disorders.

The influence of psychotropic drugs on cerebral cell death: female neurovulnerability to antipsychotics.

Tissue transglutaminase (tTG) is a marker for apoptosis, and its protein level is known to be increased in post-mortem Alzheimer's and Huntington's disease brains. tTG is increased in the cerebrospinal fluid of patients with Alzheimer's disease. However, the influence of psychotropic medication on acute cell death has not been studied so far in vivo, although some experiments performed in vitro suggest that antipsychotic drugs are neurotoxic. The protein level of tTG was examined in the cerebrospinal fluid obtained from 29 patients under neuroleptic medication in the last 24 h before lumbar puncture (eight patients diagnosed with Alzheimer's disease and 21 patients with other neurological diseases), and compared with those from 55 patients without antipsychotic medication (25 Alzheimer's patients and 30 others). In addition, the influence of several other psychotropic drugs on apoptosis was analysed. A significant influence (P<0.01) of antipsychotic drugs for both the Alzheimer's and the non-Alzheimer's group was found with respect to tTG protein levels in cerebrospinal fluid. By contrast to the male subgroups, the female groups showed a strong influence of neuroleptics on cerebral cell death. Surprisingly, atypical antipsychotics did not differ from typical neuroleptics in neurotoxicity. By contrast, no influence of antidepressants, cholinesterase-inhibitors, nootropics, tranquilizers and tramadol on cerebral cell death was found. The results suggest that typical and atypical antipsychotic drugs may induce cerebral cell death, especially in female patients. Subjects with Alzheimer's disease might be even more vulnerable to any antipsychotic. Therefore, subsequent research should aim to identify atypical neuroleptics without neurotoxicity. A limit on the use of first- and second-generation antipsychotics in elderly patients is proposed. Finally, the possible connection between the observed increased cerebral cell death and tardive dyskinesia, the most threatening side-effect in antipsychotic therapy, is discussed.

Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis.

Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be of autoimmune origin the correlation of these two diseases is of special interest. The aim of this study was to determine whether there are differences in the prevalence of thyroid disease with special emphasis on AIT compared with MS and normal subjects and whether the presence of thyroid disease correlates with disability, disease course, age, and disease duration. 353 consecutive patients with clinically definite MS, without interferon-beta treatment and 308 patients with low back pain or headache were extensively examined for the presence of non-immune or autoimmune thyroid disease. We found a significantly higher prevalence of AIT in male MS patients (9.4 %) than in male controls (1.9 %; p = 0.03). The prevalence of AIT in female MS patients (8.7 %) did not differ from female controls (9.2 %). Hypothyroidism, caused by AIT in almost all cases, showed a tendency to be more severe and more often present in patients with MS. There was no association between relapsing-remitting and secondary progressive disease course of MS and the prevalence of AIT. MS patients with AIT were significantly older but did not differ in disease duration and expanded disability status scale (EDSS). Further studies are warranted, to see if there is a difference in sex-hormone levels between MS patients with and without AIT and healthy controls. Longitudinal studies comparing MS patients with or without AIT could show whether there is an influence of AIT on the disease course or progression.

Cerebrospinal fluid tissue transglutaminase in vascular dementia.

The enzyme tissue transglutaminase (tTG), an indicator of acute cell death, is found in brains of Alzheimer's and Huntington's disease patients. tTG, as a specific marker for apoptosis, may therefore be a powerful biochemical marker of the acute degenerating process in vivo and may be useful in discrimination between vascular dementia (VaD) and Alzheimer's disease (AD). It may serve as completion of CSF analysis in diagnosis of dementing disorders and be a simple way of assessing the efficacy of possible new anti-apoptotic drugs.

Ziprasidone in Huntington's disease: the first case reports.

Huntington's disease (HD) is a relentlessly progressive neuropsychiatric disorder with an underlying autosomal dominantly inherited genetic defect. Classical antipsychotics (i.e. phenothiazines or butyrophenones) are the most used medication to reduce the (probably dopamine-born) choreiform hyperkinesias. Ziprasidone is the latest of a new class of atypical antipsychotics; it has not been studied so far in this indication. We report three genetically confirmed HD patients who improved significantly in several categories of the motor scale of the Unified HD Rating Scale.