The use of atypical antipsychotics in the management of schizophrenia.
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Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: an estimated quarter to one third of patients are treatment-resistant; conventional antipsychotics have only a modest impact upon negative symptoms (poverty of thought, social withdrawal and loss of affect); and adverse effects, particularly extrapyramidal symptoms (EPS). Newer, so-called atypical, antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old drug which was re-introduced in 1990) are claimed to address these limitations. Atypical agents are, at a minimum, at least as effective as conventional drugs such as haloperidol. They also cause substantially fewer extrapyramidal symptoms. However, some other adverse effects are more common than with conventional drugs. For example, clozapine carries a significant risk of serious blood disorders, for which special monitoring is mandatory; it also causes troublesome drowsiness and increased salivation more often than conventional agents. Some atypical agents cause more weight gain or QT prolongation than older agents. The choice of therapy is, therefore, not straightforward. At present, atypical agents represent an advance for patients with severe or intolerable EPS. Most published evidence exists to support the use of clozapine, which has also been shown to be effective in schizophrenia refractory to conventional agents. However, the need for compliance with blood count monitoring and its sedative properties make careful patient selection important. The extent of any additional direct benefit offered by atypical agents on negative symptoms is not yet clear. The lack of a depot formulation for atypical drugs may pose a significant practical problem. To date, only two double-blind studies in which atypical agents were compared directly have been published. Neither provides compelling evidence for the choice of one agent over another. Atypical agents are many times more expensive than conventional drugs. Although drug treatment constitutes only a small proportion of the costs of managing schizophrenia, the additional annual cost of the use of atypical agents in, say, a quarter of the likely U.K. schizophrenic population would be about 56 M pound sterling. There is only limited evidence of cost-effectiveness. Atypical antipsychotics are not currently licensed for other conditions where conventional antipsychotics are commonly used, such as behaviour disturbance or dementia in the elderly. Their dose, and place in treatment in such cases have yet to be determined. (+info)
Bilateral basal ganglial necrosis after allogeneic bone marrow transplantation in a child with Kostmann syndrome.
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A 6-year-old girl underwent allogeneic BMT from a matched sibling donor for the treatment of Kostmann syndrome. She suddenly became drowsy on day 30 after BMT, and lost consciousness 2 days later. Cranial CT scan showed symmetrical lesions suggesting bilateral necrosis in the basal ganglia. Clinical and laboratory investigations failed to reveal any evidence of neurometabolic disease. (+info)
Non-typhoid Salmonella meningitis complicated by a infarction of basal ganglia.
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A previously healthy 16-month-old Korean girl with symptoms of fever, vomiting, and generalized tonic seizure was diagnosed to have Group D non-typhoid Salmonella meningitis. The patient was treated with ceftriaxone (100 mg/kg/day) and amikin (22.5 mg/kg/day) initially and ciprofloxacin (30 mg/kg/day) was added later because of clinical deterioration and disseminated intravascular coagulation. Brain CT performed on the second day showed a well-demarcated low density lesion in the right lentiform nucleus and both caudate nuclei, without evidence of increased intracranial pressure. MRI performed on the 11th day confirmed CT scan findings as well as right subdural fluid collection, brain atrophy, and ventriculomegaly. She underwent subdural drainage and later ventriculo-peritoneal shunt operation. Despite receiving intensive treatment, she still has severe neurologic sequelae. Our case shows that infarctions of basal ganglia and thalami are not specific for tuberculous meningitis and that meningitis complicated by infarction is indicative of grave prognosis. (+info)
Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease).
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Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative syndrome that is associated with a variety of movement disorders and neurobehavioral and cognitive manifestations. Despite numerous clinical, pathological, and biochemical investigations, its etiology remains unknown. We have identified a multigenerational family with dominantly inherited IBGC and, in 24 members of this family, performed a whole-genome scan using polymorphic microsatellite markers to identify the first chromosomal locus for this disorder (IBGC1). A maximum two-point LOD score of 3.37 was obtained at marker D14S1014, and a maximum multipoint LOD score of 4.95 was obtained between D14S75 and D14S306. The minimal haplotype shared by affected patients extended over a 17.1-cM region bounded by D14S70 and D14S66, which is potentially further narrowed to a 13.3-cM region by a recombination observed in a patient with probable affected status. The age at onset appeared to be decreasing by an average of >20 years with each transmission, which is consistent with genetic anticipation. (+info)
Dyspraxia in a patient with corticobasal degeneration: the role of visual and tactile inputs to action.
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OBJECTIVES: To investigate the roles of visual and tactile information in a dyspraxic patient with corticobasal degeneration (CBD) who showed dramatic facilitation in miming the use of a tool or object when he was given a tool to manipulate; and to study the nature of the praxic and neuropsychological deficits in CBD. METHODS: The subject had clinically diagnosed CBD, and exhibited alien limb behaviour and striking ideomotor dyspraxia. General neuropsychological evaluation focused on constructional and visuospatial abilities, calculation, verbal fluency, episodic and semantic memory, plus spelling and writing because impairments in this domain were presenting complaints. Four experiments assessed the roles of visual and tactile information in the facilitation of motor performance by tools. Experiment 1 evaluated the patient's performance of six limb transitive actions under six conditions: (1) after he described the relevant tool from memory, (2) after he was shown a line drawing of the tool, (3) after he was shown a real exemplar of the tool, (4) after he watched the experimenter perform the action, (5) while he was holding the tool, and (6) immediately after he had performed the action with the tool but with the tool removed from his grasp. Experiment 2 evaluated the use of the same six tools when the patient had tactile but no visual information (while he was blindfolded). Experiments 3 and 4 assessed performance of actions appropriate to the same six tools when the patient had either neutral or inappropriate tactile feedback-that is, while he was holding a non-tool object or a different tool. RESULTS: Miming of tool use was not facilitated by visual input; moreover, lack of visual information in the blindfolded condition did not reduce performance. The principal positive finding was a dramatic facilitation of the patient's ability to demonstrate object use when he was holding either the appropriate tool or a neutral object. Tools inappropriate to the requested action produced involuntary performance of the stimulus relevant action. CONCLUSIONS: Tactile stimulation was paramount in the facilitation of motor performance in tool use by this patient with CBD. This outcome suggests that tactile information should be included in models which hypothesise modality specific inputs to the action production system. Significant impairments in spelling and letter production that have not previously been reported in CBD have also been documented. (+info)
Progressive frontal gait disturbance with atypical Alzheimer's disease and corticobasal degeneration.
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OBJECTIVES: The clinical neuropsychological, neuroradiological, and neuropathological description of two patients presenting with a frontal gait disturbance. METHODS: Clinical case note review, neuropsychological assessment, functional imaging with (15)O(2) and (18)F-fluorodopa PET, and neuropathology. RESULTS: Both patients presented with frontal gait impairment and only later developed more widespread cognitive impairment. In both cases (15)O(2) PET disclosed focal hypometabolism in the medial frontal lobes and in one patient (18)F-fluorodopa uptake into the caudate and putamen was normal. The neuropathological examination in one patient showed Alzheimer's histopathology together with large swollen eosinophilic neurons characteristic of corticobasal degeneration, which were particularly prominent in the medial frontal lobes. CONCLUSION: Focal degeneration of the medial frontal lobes may present as an isolated gait disturbance and should be considered in the differential diagnosis of patients who present without an obvious structural abnormality on neuroimaging. (+info)
Extrapyramidal type rigidity in rheumatoid arthritis.
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OBJECTIVES: We had noted cogwheel rigidity in a number of patients with rheumatoid arthritis (RA). Based on this finding, we aimed to investigate formally the presence of rigidity and cogwheeling in RA patients. Our secondary aim was to survey the co-existence of RA and Parkinson's disease (PD). METHODS: A total of 87 consecutive patients with a diagnosis of RA, 78 patients with PD and 67 otherwise healthy patients attending a dedicated headache clinic participated in the study. RESULTS: Rigidity was observed in 24% of RA, 60% of PD and 2% of headache patients. The frequency among the RA patients was significantly higher compared to that of patients with headache (chi 2 = 15.2; P = 0.00009). The frequency of PD among the RA patients was 2/87 (2.3%), while the frequency of RA among the PD patients was 6/78 (7.7%). CONCLUSION: Rigidity can be observed in approximately a quarter of patients with RA. (+info)
Enhanced association of mutant triosephosphate isomerase to red cell membranes and to brain microtubules.
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In a Hungarian family with triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate keto-isomerase, EC 5.3.1.1) deficiency, two germ-line identical, but phenotypically differing compound heterozygote brothers (one of them with neurological disorder) have been identified with the same very low (<5%) TPI activity and 20- or 40-fold higher erythrocyte dihydroxyacetone phosphate levels as compared with normal controls. Our present studies with purified TPI and hemolysates revealed the binding of TPI, and the binding of human wild-type and mutant TPIs in hemolysate, to the red cell membrane, and the interference of binding with other hemolysate proteins. The binding of the mutant TPI is enhanced as compared with the wild-type enzyme. The increased binding is influenced by both the altered structure of the mutant and the changes in the red cell membrane. Compared with binding of glyceraldehyde-3-phosphate dehydrogenase, the isomerase binding is much less sensitive to ionic strength or blocking of the N-terminal tail of the band-3 transmembrane protein. The binding of TPIs to the membrane decreases the isomerase activity, resulting in extremely high dihydroxyacetone phosphate levels in deficient cells. In cell-free brain extract, tubulin copolymerizes with TPI and with other cytosolic proteins forming highly decorated microtubules as shown by immunoblot analysis with anti-TPI antibody and by electron microscopic images. The efficacy order of TPI binding to microtubules is propositus > brother without neurological disorder > normal control. This distinct microcompartmentation of mutant proteins may be relevant in the development of the neurodegenerative process in TPI deficiency and in other, more common neurological diseases. (+info)