Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.
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Acquired cerebellar lesions in adults have been shown to produce impairments in higher function as exemplified by the cerebellar cognitive affective syndrome. It is not yet known whether similar findings occur in children with acquired cerebellar lesions, and whether developmental factors influence their presentation. In studies to date, survivors of childhood cerebellar tumours who demonstrate long-term deficits in cognitive functions have undergone surgery as well as cranial irradiation or methotrexate treatment. Investigation of the effects of the cerebellar lesion independent of the known deleterious effects of these agents is important for understanding the role of the cerebellum in cognitive and affective development and for informing treatment and rehabilitation strategies. If the cerebellar contribution to cognition and affect is significant, then damage in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on. In this study we evaluated neuropsychological data in 19 children who underwent resection of cerebellar tumours but who received neither cranial irradiation nor methotrexate chemotherapy. Impairments were noted in executive function, including planning and sequencing, and in visual-spatial function, expressive language, verbal memory and modulation of affect. These deficits were common and in some cases could be dissociated from motor deficits. Lesions of the vermis in particular were associated with dysregulation of affect. Behavioural deficits were more apparent in older than younger children. These results reveal that clinically relevant neuropsychological changes may occur following cerebellar tumour resection in children. Age at the time of surgery and the site of the cerebellar lesion influence the neurobehavioural outcome. The results of the present study indicate that the cerebellar cognitive affective syndrome is evident in children as well as in adults, and they provide further clinical evidence that the cerebellum is an essential node in the distributed neural circuitry subserving higher-order behaviours. (+info)
The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours.
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We present data on the intellectual, language and executive functions of 26 children who had undergone surgery for the removal of cerebellar hemisphere or vermal tumours. The children with right cerebellar tumours presented with disturbances of auditory sequential memory and language processing, whereas those with left cerebellar tumours showed deficits on tests of spatial and visual sequential memory. The vermal lesions led to two profiles: (i) post-surgical mutism, which evolved into speech disorders or language disturbances similar to agrammatism; and (ii) behavioural disturbances ranging from irritability to behaviours reminiscent of autism. These data are consistent with the recently acknowledged role of the cerebellum as a modulator of mental and social functions, and suggest that this role is operative early in childhood. (+info)
Neuroleptics ameliorate phencyclidine-induced impairments of short-term memory.
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1. Phencyclidine (PCP), a non-competitive NMDA-receptor antagonist, is able to induce schizophrenia-like symptoms in animals and in humans. It is known that schizophrenic patients have deficits in memory processes. 2. Therefore, it was investigated whether subchronic pulsatile or continuous application of 5.0 mg kg(-1) PCP over 5 days induce short-term memory deficits in holeboard learning and the action of two different neuroleptics on this behavioural test. 3. First, an impairment in the holeboard task was described when the animals were tested 24 h after the last application but not after 15 min or 1 h after the last injection. Secondly, the influence of haloperidol and risperidone on the PCP-induced short-term memory changes was tested. 4. The combined application of PCP and risperidone led to a complete antagonism of the short-term deficits, but the combined treatment with haloperidol was accompanied by a partial abolishment of the PCP-induced deficits. 5. PCP led to an upregulation of the glutamate binding sites in striatum and nucleus accumbens whereas the D(2) binding sites were reduced in striatum. The D(1) binding sites seem to be unchanged. The receptor protein expression of glutamate receptors mGluR1, GluR2, GluR5/7 and NMDAR1 were not modified in response to PCP treatment. 6. The determination of a subpopulation of GABAergic interneurons shows a decrease of the cells within the CA3 of the hippocampal formation. 7. These findings indicate that PCP induced impairments in short term memory can be detected by holeboard learning and may provide an interesting tool for the search of new neuroleptics. (+info)
Deficits in memory and motor performance in synaptotagmin IV mutant mice.
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Synaptotagmin (Syt) IV is a synaptic vesicle protein. Syt IV expression is induced in the rat hippocampus after systemic kainic acid treatment. To examine the functional role of this protein in vivo, we derived Syt IV null [Syt IV(-/-)] mutant mice. Studies with the rotorod revealed that the Syt IV mutants have impaired motor coordination, a result consistent with constitutive Syt IV expression in the cerebellum. Because Syt IV is thought to modulate synaptic function, we also have examined Syt IV mutant mice in learning and memory tests. Our studies show that the Syt IV mutation disrupts contextual fear conditioning, a learning task sensitive to hippocampal and amygdala lesions. In contrast, cued fear conditioning is normal in the Syt IV mutants, suggesting that this mutation did not disrupt amygdala function. Conditioned taste aversion, which also depends on the amygdala, is normal in the Syt IV mutants. Consistent with the idea that the Syt IV mutation preferentially affects hippocampal function, Syt IV mutant mice also display impaired social transmission of food preference. These studies demonstrate that Syt IV is critical for brain function and suggest that the Syt IV mutation affects hippocampal-dependent learning and memory, as well as motor coordination. (+info)
Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.
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The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments. (+info)
Body burden of aluminum in relation to central nervous system function among metal inert-gas welders.
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OBJECTIVES: The relationship between elevated internal aluminum loads and central nervous system function was studied among aluminum welders, and the threshold level for adverse effect was defined. METHODS: For 65 aluminum welders and 25 current mild steel welders body burden was estimated, and the aluminum concentrations in serum (S-Al) and urine (U-Al) were analyzed with graphite furnace atomic absorption spectrometry with Zeeman background correction. Referents and low-exposure and high-exposure groups were defined according to an aggregated measure of aluminum body burden, the group median S-Al levels being 0.08, 0.14, and 0.46 micromol/l, respectively, and the corresponding values for U-Al being 0.4, 1.8, and 7.1 micromol/l. Central nervous system functions were assessed with a neuropsychological test battery, symptom and mood questionnaires, a visual and quantitative analysis of electroencephalography (EEG), and P3 event-related potentials with pitch and duration paradigms. RESULTS: Subjective symptoms showed exposure-related increases in fatigue, mild depression, and memory and concentration problems. Neuropsychological testing revealed a circumscribed effect of aluminum, mainly in tasks demanding complex attention and the processing of information in the working memory system and in the analysis and recall of abstract visual patterns. The visual EEG analysis revealed pathological findings only for aluminum welders. Mild, diffuse abnormalities were found in 17% of the low-exposure group and 27% of the high-exposure group, and mild to moderate epileptiform abnormalities at a frequency of 7% and 17%, respectively. CONCLUSIONS: Both objective neurophysiological and neuropsychological measures and subjective symptomatology indicated mild but unequivocal findings dose-dependently associated with increased aluminum body burden. The study indicates that the body burden threshold for adverse effect approximates an U-Al value of 4-6 micromol/l and an S-Al value of 0.25-0.35 micromol/l among aluminum welders. (+info)
Surveillance for possible estuary-associated syndrome--six states, 1998-1999.
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Pfiesteria piscicida (Pp) is an alga that has been associated with fish kills in estuaries (where fresh water mixes with salty seawater) along the eastern seaboard and possibly with human health effects. Since June 1, 1998, surveillance for possible estuary-associated syndrome (PEAS), including possible Pp-related human illness, has been conducted in Delaware, Florida, Maryland, North Carolina, South Carolina, and Virginia. This report summarizes passive surveillance for PEAS during June 1, 1998-December 31, 1999, which indicated no persons had illnesses that met PEAS criteria. (+info)
Comparison of microembolism detected by transcranial Doppler and neuropsychological sequelae of carotid surgery and percutaneous transluminal angioplasty.
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BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty (PTA) is currently being assessed for the treatment of carotid stenosis. In comparison with carotid endarterectomy (CEA), there is evidence of an increased risk of cerebral microembolism during the procedure. We have sought evidence of any neuropsychological sequelae of carotid PTA and compared it with CEA to demonstrate the relative safety of the 2 treatment options. METHODS: The neuropsychological outcomes after CEA and PTA were compared in 2 matched groups of patients with severe symptomatic carotid stenosis, 96% of whom had been randomized in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), at a single center. Transcranial Doppler insonation of the middle cerebral artery was used to measure cerebral reactivity in response to carbon dioxide inhalation before treatment and then to detect microembolization of the ipsilateral cerebral hemisphere and measure changes in blood flow velocity during the procedures. The performance on a neuropsychological test battery administered before, 6 weeks after, and 6 months after the procedure was compared in 20 patients undergoing PTA and 26 having CEA. RESULTS: At 6 weeks, 5 patients in each group showed a similar decline in neuropsychological performance; global measures showed no significant difference between the 2 procedures, despite a significantly higher incidence of microemboli during PTA. Both groups showed a marked reduction in anxiety after treatment. CONCLUSIONS: The findings provide some reassurance that PTA is not associated with greater cerebral complications than CEA, despite the higher embolic load recorded by transcranial Doppler ultrasonography during angioplasty. (+info)