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Biomedical subjects

Raphael M Bonelli

Publications and source records attributed to Raphael M Bonelli.

At least 19 recordsLinked to original sources
PubMed2006

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.

Animals↗
PubMed2006

[Limb apraxia].

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.

Aphasia↗
PubMed2006

Cortical blood flow during rest and Wisconsin Card Sorting Test performance in schizophrenia.

BACKGROUND: The aim of this study is to examine if patients with schizophrenia differ in prefrontal, orbitofrontal, temporal, parietal and occipital blood flow from healthy controls during performance of the Wisconsin Card Sorting Test (WCST). METHODS: We conducted a 99mTc-hexamethylpropylene amine oxime-SPECT study in patients with schizophrenia (n = 21) and in healthy controls (n = 18). The assessment of relative regional cerebral blood flow (relCBF) was achieved by comparing blood flow of well-defined cortical regions to whole brain blood flow. relCBF at rest and during WCST was compared between the groups and in the groups. RESULTS: Significant bilateral prefrontal and right-sided parietal increases of relCBF were found in patients (p < 0.05) during resting conditions, while prefrontal and parietal interhemispheric asymetry were higher in patients (p < 0.005). However, patients failed to increase right prefrontal and frontobasal relCBF as well as orbitofrontal interhemispheric asymetry during WCST performance in contrast to the control group (p < 0.05). The right occipital relCBF increased significantly in patients only (p < 0.05). CONCLUSIONS: In our study we could confirm the common hypothesis of schizophrenic hypofrontality at rest and during WCST performance. Moreover, due to our method, we identified significant frontal and parietal interhemispheric asymmetries in schizophrenia at rest as well as right occipital hyperperfusion during WCST.

Adult↗
PubMed2006

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.

Antipsychotic Agents↗
PubMed2005

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.

Aged↗
PubMed2004

Amantadine in the akinetic-rigid variant of Huntington's disease.

OBJECTIVE: To report the effects of amantadine on an akinetic-rigid variant of Huntington's disease (HD). CASE SUMMARY: We describe a 36-year-old woman with HD who was treated with intravenous amantadine for 5 days. The woman was evaluated with the Unified Huntington's Disease Rating Scale before and after treatment. Parkinsonism, bradykinesia, and dystonia improved significantly. DISCUSSION: Amantadine is a noncompetitive N-methyl d-aspartate receptor antagonist. It is mainly used in the treatment of Parkinson's disease, as it increases dopamine levels in the brain. This effect is said to ameliorate akinesia. Although the effect of amantadine on choreatic dystonia in HD has been reported in several studies, to the best of our knowledge, this is the first report of the ameliorative effects of amantadine on the rigid form of HD. Our patient showed improvements of gait, parkinsonism, and dystonia. Fine-motor tasks and eye movement did not change significantly. CONCLUSIONS: We suggest that amantadine treatment might be of value to patients with the akinetic-rigid variant of HD.

Adult↗
PubMed2004

Huntington's disease: present treatments and future therapeutic modalities.

Huntington's disease (HD) is a devastating neuropsychiatric disorder for which therapeutic interventions have been rather fruitless to date, except in a slight symptomatic relief. Even the discovery of the gene related to HD in 1993 has not effectively advanced treatments. This article is essentially a review of available double-blind, placebo-controlled trials of therapy for this condition which also includes relevant open label trials. Unfortunately, HD research has tended to concentrate on the motor aspects of the disorder, whereas the major problems are behavioural (e.g. dementia, depression, psychosis), and the chorea is often least relevant in terms of management. We conclude that there is definitely poor evidence in management of HD. The analysis of the 24 best studies fails to result in a treatment recommendation of clinical relevance. Based on data of open-label studies, or even case reports, we recommend riluzole, olanzapine and amantadine for the treatment of the movement disorders associated with HD, selective serotonin reuptake inhibitors and mirtazapine for the treatment of depression, and atypical antipsychotic drugs for HD psychosis and behavioural problems. Moreover, adjuvant psychotherapy, physiotherapy and speech therapy should be applied to supply the optimal management. Finally, some cellular mechanisms are discussed in this paper because they are essential for future neuroprotective modalities, such as minocycline, unsaturated fatty acids or riluzole.

Antipsychotic Agents↗
PubMed2004

Neuroprotection in Huntington's disease: a 2-year study on minocycline.

Huntington's disease (HD), a relentlessly progressive neurodegenerative disorder, is characterized by a clinical triad of psychiatric, cognitive and motor disturbances. The antibiotic minocycline, a caspase inhibitor exhibiting antiapoptotic properties, has been shown to prolong survival in the transgenic mouse model of HD. We administrated minocycline to 14 patients with genetically confirmed HD. The patients were psychiatrically, neurologically and neuropsychologically evaluated at baseline, and after 6 and 24 months of treatment, using the Unified HD Rating Scale and a neuropsychological test battery. After 12 months, three patients were lost to follow-up so that 11 patients were analysed at the endpoint. Minocycline was well tolerated. Unlike the expected natural course of HD, patients exhibited stabilization in general motor and neuropsychological function at endpoint, after improving in the first 6 months. Moreover, we found a significant amelioration of psychiatric symptoms that was not apparent after the first 6 months. In detail, the Mini-Mental State Examination, the Total Motor Score, the Total Functional Capacity Scale and the Independence Scale, as the most prominent scales in HD, were stabilized after 3 years of treatment. Our results confirm previous animal studies and indicate a neuroprotective effect of this agent in HD. A long-term, double-blind, placebo-controlled trial appears highly warranted for definitively establishing the value of minocycline in HD.

Adult↗
PubMed2004

A review of the treatment options for Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, inherited, neuropsychiatric disease which gives rise to progressive motor, cognitive and behavioural symptoms. Its core pathology involves degeneration of the basal ganglia, in particular, the caudate and putamen, and is caused by a single autosomal gene coding for a mutated form of the protein, huntingtin. At the present time, the only treatment options available in HD are symptomatic. There are several substances available today for the treatment of chorea. Other neurological symptoms, such as dystonia, can be treated, but treatment is associated with a high risk of adverse events. Psychiatric symptoms, on the other hand, are often amenable to treatment and relief of these symptoms may provide significant improvement in quality of life.

Antipsychotic Agents↗
PubMed2004

Transient hypoglycemic abducens palsy.

Since 1928, among the thousands of patients treated for insulinoma, only 32 cases with peripheral neuropathy have been reported. None of these described an affection of the cranial nerves. We present a 56 old woman, who suffered from chronic hyperinsulinism due to an insulinoma. For ten years, the patient has developed progressively marked hypoglycemic attacks of up to 20 mg/dl. Recently we have observed the development of a paresis of the right abducens nerve lasting for 6 weeks.

Abducens Nerve Diseases↗
PubMed2003

Zotepine in Huntington's disease.

The authors report a patient with Huntington's disease (HD) presenting with severe chorea. The motor scale of the unified HD rating scale (UHDRS-I) revealed 81 points. Motor function clearly improved with zotepine, until she reached an UHDRS-I of 34 points on day 7 of treatment. The patient was stable for at least 12 weeks. The improvement includes all seven categories of the UHDRS-I, especially chorea, gait and oral function. This is the first description of zotepine in HD. Our findings suggest that zotepine is useful in the treatment of HD chorea. Controlled trials of its use in HD would be welcome.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

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.

Adult↗