Atypical antipsychotic effects of quetiapine fumarate in animal models.
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AIM: To evaluate the effect of quetiapine fumarate in animal models of schizophrenia and its possibility to induce extrapyramidal side effects (EPSE). METHODS: The enhancement of immobility in a forced swimming test of mice induced by repeated treatment with phencyclidine and amphetamine swimming "normalization" test of mice were used as animal models of negative and positive symptoms of schizophrenia, respectively. The paw test of rats was used to evaluate the possibility by quetiapine fumarate to induce EPSE. RESULTS: After treatment with phencyclidine (10 mg.kg-1.d-1, s.c., 14 d), the immobility time in the forced swimming test of mice was increased (P < 0.01). Quetiapine fumarate (20, 40, and 80 mg.kg-1, ig) and clozapine (10 and 30 mg.kg-1, ig) attenuated the enhanced immobility in the forced swimming test induced by repeated treatment with phencyclidine (P < 0.01), whereas haloperidol (0.3 and 1 mg.kg-1, ig) had no effect. In amphetamine swimming "normalization" test, quetiapine fumarate ameliorated the disorder induced by amphetamine in a dose-dependent manner. In paw test, quetiapine fumarate was much less effective in increasing the forelimb retraction time (FRT) than the hindlimb retraction time (HRT). The minimal effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) of quetiapine fumarate was 20 mg.kg-1 and 100 mg.kg-1, respectively, and the ratio of MEDFRT to MEDHRT was 5. CONCLUSION: The effects of quetiapine fumarate in these models indicated its clinical effect on schizophrenia with a reduced liability to produce EPSE. (+info)
Preclinical syndromes predict dementia: the Sydney older persons study.
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OBJECTIVES: To identify if preclinical syndromes for Alzheimer's disease, vascular dementia, and Parkinson's disease and related dementias exist. Identification of dementia at early or even preclinical stages has important implications for treatment. METHODS: A community dwelling sample of 647 subjects aged 75 and over at recruitment were followed up for a mean period of 3.19 years (range 2.61 to 4.51 years). Each subject was asked to participate in a medical assessment which included a standardised medical history examining both past and current health and medication usage; a neuropsychological battery (mini mental state examination, Reid memory test, verbal fluency, subsets of the Boston naming test and similarities, clock drawing and copied drawings) and physical examination. Preclinical syndromes for the three predominant dementias (Alzheimer's disease, vascular dementia and Parkinson's disease, and related dementias) and their combinations were defined using cognitive, motor, and vascular features. Their longitudinal outcome as defined by death and dementia incidence was examined. RESULTS: Preclinical syndromes affected 55.7% (n=299) of subjects. Preclinical syndromes showed a trend for an increased odds of death (odds ratio 1.72, p=0.056) and a significantly increased odds of developing dementia (odds ratio 4.81, p<0.001). Preclinical syndromes were highly sensitive, detecting 52 of 58 (89.7%) incident dementias. Two hundred and sixteen of 268 (80.6%) preclinical subjects did not show dementia over the 3 year period (positive predictive value 19.4%). Subjects defined as having a combination of cognitive, extrapyramidal, and vascular features were at greatest risk of progressing to dementia. CONCLUSIONS: Preclinical syndromes were sensitive and significant predictors of dementia. In view of their poor positive predictive value, the preclinical syndromes as defined in this study remain a research tool needing both definitional refinement and greater periods of observation. Multiple coexistent preclinical disorders resulted in a greater incidence of dementia, providing evidence for an additive role between multiple disorders. (+info)
MR imaging and histologic features of capillary telangiectasia of the basal ganglia.
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Capillary telangiectasias are being recognized with increasing frequency on MR imaging studies. Most are located in the brain stem and show slightly increased signal intensity on T2-weighted images, low signal intensity on T2*-weighted images (reflecting the presence of deoxyhemoglobin), and contrast enhancement. These findings are considered fairly typical for capillary telangiectasia, and pathologic correlation is not generally pursued. We present a case of a proven capillary telangiectasia in the basal ganglia. The imaging features of the lesion were identical to those described for capillary telangiectasias in the brain stem. (+info)
Involuntary hand levitation associated with parietal damage: another alien hand syndrome.
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The alien hand syndrome (AHS) usually consists of an autonomous motor activity perceived as an involuntary and purposeful movement, with a feeling of foreignness of the involved limb, commonly associated with a failure to recognise ownership of the limb in the absence of visual clues. It has been described in association to lesions of the frontal lobes and corpus callosum. However, parietal damage can promote an involuntary, but purposeless, hand levitation, which, sometimes, resembles AHS. In the present study, four patients (cortico-basal ganglionic degeneration - n=2; Alzheimer's disease - n=1 and parietal stroke - n=1) who developed alien hand motor behaviour and whose CT, MRI and/or SPECT have disclosed a major contralateral parietal damage or dysfunction are described. These results reinforce the idea that parietal lobe lesions may also play a role in some patients with purposeless involuntary limb levitation, which is different from the classic forms of AHS. (+info)
Reversible neurologic manifestations after glycerol: a short report.
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A 46 year old male inadvertently consumed 500 ml of glycerol and presented with altered sensorium, focal neurologic signs and generalised seizures. He was managed conservatively and recovered fully within 48 hours. The case highlights the rare presentations of overdosage and neurologic effects with glycerol, an otherwise safe drug used in neurology. (+info)
Efficacy and safety of risperidone oral solution in agitation associated with dementia in the elderly.
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BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) contribute to caregiver burden and institutionalization of elderly. Neuroleptics are prescribed to control agitation. Side effects of typical neuroleptics are harmful, making atypical neuroleptics an indication. OBJECTIVES: To evaluate efficacy and tolerability of risperidone oral solution (ROS) given once daily to demented elderly outpatients with BPSD (agitation). METHOD: Patients (n=26), 76.35+/-8.63 years, Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for dementia. RSO was given, starting dose of 0.25 mg and increments of 0.25 mg every week. Mini-Mental State Examination (MMSE) assessed cognitive status, Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) and Clinical Global Impression (CGI) measured BPSD, Extrapiramidal Symptom Rating Scale (ESRS) evaluated extrapyramidal symptoms. Cardiovascular side effects were evaluated clinically. RESULTS: There was a 26% reduction in agitation and no cardiovascular side effects in the range from 1.0 to 1.25 mg. Side effects were more prevalent above 2.5 mg. CONCLUSION: Risperidone oral solution improved agitation with good tolerability from 0.5 to 1.25 mg. A single dose with increments of 0.25 mg may be more acceptable to patients and caregivers. (+info)
Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion.
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BACKGROUND AND PURPOSE: Postoperative brain dysfunction, such as delirium, is a common complication of anesthesia and is sometimes prolonged, especially in patients with cerebrovascular disease. In the present study we investigated the effect of hypocapnia during anesthesia on neuronal damage using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced by clipping the bilateral common carotid arteries in male Wistar rats. Fourteen days after the operation, these animals were mechanically ventilated for 2 hours and then kept in suitable conditions for an additional 14 days. Twenty-four rats were assigned to 4 groups: those with chronic cerebral hypoperfusion with either hypocapnia or normocapnia during anesthesia, and those given sham operation with either hypocapnia or normocapnia. White matter lesions in the brain sections were evaluated with Kluver-Barrera staining. Proliferation of glial cells was estimated with the use of immunohistochemistry of glial fibrillary acidic protein, a marker for astroglia, and CD11b, a marker for microglia. Computer-assisted morphometry was applied to the immunohistochemical results of microtubule-associated protein 2 to evaluate the loss of neurons. RESULTS: The histological damage was localized almost exclusively in the white matter in the rats subjected to chronic cerebral hypoperfusion but without hypocapnia. Neuronal damage and astroglial proliferation occurred with aggravated white matter lesions in the caudoputamen in the rats with chronic cerebral hypoperfusion and hypocapnia. No lesions were observed in sham-operated rats with either hypocapnia or normocapnia. CONCLUSIONS: These results indicate that hypocapnia during anesthesia causes tissue damage in the caudoputamen, which may be responsible for long-lasting postoperative delirium in patients with stroke and/or dementia. (+info)
Neuropsychiatry of the basal ganglia.
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This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are important links between parts of the brain that have classically been considered to be related to emotional functioning and brain regions previously considered to have largely motor functions. The basal ganglia have a role in the development and integration of psychomotor behaviours, involving motor functions, memory and attentional mechanisms, and reward processes. (+info)