They have shaped Alzheimer disease: the protagonists, well known and less well known     

Boller F  Bick K  Duyckaerts C 《Cortex; a journal devoted to the study of the nervous system and behavior》2007,43(4):565-569

This paper discusses the history of dementia and Alzheimer's disease (AD) with emphasis on the individuals who have shaped its development. In addition to the best known protagonists recognized as founders of the field, it will mention other figures who have provided important contributions but are sometimes overlooked. Many of these have also become famous for work unrelated to AD.  相似文献   

Neurologic improvement in a type 3 Gaucher disease patient treated with imiglucerase/miglustat combination   总被引：3，自引：0，他引：3  

Capablo JL  Franco R  de Cabezón AS  Alfonso P  Pocovi M  Giraldo P 《Epilepsia》2007,48(7):1406-1408

PURPOSE: Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a deficiency of glucocerebrosidase. The neurologic manifestations of GD patients have to date been refractory to any treatment approach. We present a report of a neuronopathic GD patient whose myoclonic epilepsy improved after combination therapy with imiglucerase and miglustat. METHODS: In an adult type 3 GD patient who, despite good visceral and analytic response to ERT, developed progressive neurologic deterioration with marked myoclonic epilepsy and dystonia, we added miglustat to the enzyme-replacement therapy. RESULTS: After 2 years of combined miglustat (200 mg, 3 t.i.d.) and imiglucerase (60 IU/kg every 2 weeks), generalized tonic-clonic seizures decreased, speech improved, and the general neurologic clinical picture improved markedly. The EEG showed a reduction in focal and generalized paroxysmal discharges. No significant adverse effects were observed. CONCLUSIONS: Combined imiglucerase and miglustat therapy may be beneficial for some neuronopathic forms of GD.  相似文献   

An anthropological study about epilepsy in native tribes from Central and South America     

Carod-Artal FJ  Vázquez-Cabrera CB 《Epilepsia》2007,48(5):886-893

PURPOSE: Epilepsy was a well-recognized disease in pre-Columbian cultures. However, anthropological studies about epilepsy in native cultures living at the present time are scarce. The objective of this paper was to study native perception and myths about epilepsy, their magic-religious healing rites and ceremonies, and the natural treatments that archaic cultures used. METHODS: An anthropological fieldwork was performed in Central and South America with Tzeltal Maya (Chiapas, Mexico, 1995), Kamayurá (Matto Grosso, Brazil, 1999) and Uru-Chipaya people (Bolivian Andes, 2004). We collected information from shamans and medicine men about epilepsy beliefs and the use of traditional treatments. RESULTS: Epilepsy is called tub tub ikal by Tzeltal people. It is caused by an attack suffered by the animal spirit who accompanies the person, after a fight between the spirits who serve the forces of good and evil. People with chronic epilepsy are considered witches. Epilepsy is called teawarup by Kamayurá, and is caused by the revenge of the spirit (mama'e) of the armadillo killed by a huntsman. It is treated with two roots, tsimó and wewurú, kneaded and diluted in water. Epilepsy is called tukuri by the Chipaya people, and is originated by a witchcraft that enters into the nose and the head, as a wind. Tukuri is treated with a ritual animal sacrifice called willancha, and by taking several dried insect infusions and bird's blood. CONCLUSION: These American native cultures have developed a system of orally transmitted knowledge about epilepsy based on magic-religious traditions.  相似文献   

Late effects of enriched environment (EE) plus multimodal early onset stimulation (MEOS) after traumatic brain injury in rats: Ongoing improvement of neuromotor function despite sustained volume of the CNS lesion     

Lippert-Gruener M  Maegele M  Garbe J  Angelov DN 《Experimental neurology》2007,203(1):82-94

Recently we showed that the combination between MEOS and EE applied to rats for 7-15 days after traumatic brain injury (TBI) was associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction. In a continuation of this work, we tested whether these effects persisted for longer post-operative periods, e.g. 30 days post-injury (dpi). Rats were subjected to lateral fluid percussion (LFP) or to sham injury. After LFP, one third of the animals (injured and sham) was placed under conditions of standard housing (SH), one third was kept in EE-only, and one third received EE+MEOS. Standardized composite neuroscore (NS) for neurological functions and computerized analysis of the vibrissal motor performance were used to assess post-traumatic neuromotor deficits. These were followed by evaluation of the cortical lesion volume (CLV) after immunostaining for neuron-specific enolase, caspase 3 active, and GFAP. Finally, the volume of cortical lesion containing regeneration-associated proteins (CLV-RAP) was determined in sections stained for GAP-43, MAP2, and neuronal class III beta-tubulin. We found (i) no differences in the vibrissal motor performance; (ii) EE+MEOS rats performed significantly better than SH rats in NS; (iii) EE-only and EE+MEOS animals, but not SH rats, showed better recovery at 30 dpi than at 15 dpi; (iv) no differences among all groups in CLV (larger than that at 15 dpi) and CLV-RAP, despite a clear tendency to reduction in the EE-only and EE+MEOS rats. We conclude that EE+MEOS retards, but cannot prevent the increase of lesion volume. This retardation is sufficient for a continuous restoration of neurological functions.  相似文献   

Brain neuroprotection by scavenging blood glutamate   总被引：3，自引：0，他引：3  

Zlotnik A  Gurevich B  Tkachov S  Maoz I  Shapira Y  Teichberg VI 《Experimental neurology》2007,203(1):213-220

Excess glutamate in brain fluids characterizes acute brain insults such as traumatic brain injury and stroke. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As blood glutamate scavenging has been demonstrated to increase the efflux of excess glutamate from brain into blood, we tested the prediction that oxaloacetate-mediated blood glutamate scavenging causes neuroprotection in a pathological situation such as closed head injury (CHI), in which there is a well established deleterious increase of glutamate in brain fluids. We observed highly significant improvements of the neurological status of rats submitted to CHI following an intravenous treatment with 1 mmol oxaloacetate/100 g rat weight which decreases blood glutamate levels by 40%. No detectable therapeutic effect was obtained when rats were treated IV with 1 mmol oxaloacetate together with 1 mmol glutamate/100 g rat. The treatment with 0.005 mmol/100 g rat oxaloacetate was no more effective than saline but when it was combined with the intravenous administration of 0.14 nmol/100 g of recombinant glutamate-oxaloacetate transaminase, recovery was almost complete. Oxaloacetate provided neuroprotection when administered before CHI or at 60 min post CHI but not at 120 min post CHI. Since neurological recovery from CHI was highly correlated with the decrease of blood glutamate levels (r=0.89, P=0.001), we conclude that blood glutamate scavenging affords brain neuroprotection Blood glutamate scavenging may open now new therapeutic options.  相似文献   

Marked recovery of functional metabolic activity and laminar volumes in the rat hippocampus and dentate gyrus following postnatal hypothyroid growth retardation: a quantitative cytochrome oxidase study     

Farahvar A  Darwish NH  Sladek S  Meisami E 《Experimental neurology》2007,204(2):556-568

Similar to cretinism in human children, absence or deficiency of thyroid hormones in rats and mice during early postnatal development results in marked retardation of brain development along with behavioral and cognitive deficits. Less is known about brain recovery from postnatal hypothyroidism. [Farahvar, A., Meisami, E., 2007. Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation. Experimental Neurology.] found, by means of morphometric maps, that surface areas of hippocampal cortex and its CA1-CA4 regions which were significantly reduced in developing hypothyroid rats, show nearly complete growth recovery upon restoration of thyroid function. Here we explore the ability of hippocampal synapse-rich neuronal fiber layers to show recovery from early hypothyroid growth retardation. Rat pups were made hypothyroid from birth to day 25 (weaning) or up to young adulthood (day 90) by a treatment with the reversible goitrogen, PTU (n-propylthiouracil), in the drinking water. Recovery was induced by withdrawal of PTU at weaning and analysis of cytochrome oxidase (CytOx)-stained serial sections of the hippocampus and dentate gyrus at the ages of 25 and 90 days. CytOx stains the synapse-rich fiber layers of the hippocampal formation (HCF). Volumetric growth of molecular layer, stratum oriens and radiatum and dentate hilar region showed complete or nearly complete recovery from marked and significant growth retardation induced by early postnatal hypothyroidism. Also the reduced CytOx staining intensity in the hypothyroid rat HCF layers showed marked recovery following hormonal restoration. Results indicate remarkable growth plasticity of the HCF and ability of the synapse-rich fiber layers to show complete recovery of metabolic and functional neural activity from deleterious effects of early hypothyroidism. Mitochondrial CytOx is highly localized to the synapse-rich fiber layers of the HCF and its activity and histochemical staining intensity correlates positively with functional metabolic activity of neural tissue. Thus hippocampus and dentate gyrus neuronal fiber layers and their oxidative activity show remarkable ability to recover from the postnatal hypothyroid growth retardation. The results indicate that some brain regions are less vulnerable to early developmental insults and can recover.  相似文献   

Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation     

Farahvar A  Meisami E 《Experimental neurology》2007,204(2):541-555

Effects of postnatal hypothyroidism and recovery from this condition on regional growth of the rat hippocampus (HC) were studied using two-dimensional (2D) foldout, morphometric maps of HC and its constituent CA1-CA4 regions. The maps were derived from unfolding serial coronal sections of the rat forebrain, consisting of the entire rostrocaudal extent of HC pyramidal cell layer in the normal control and hypothyroid weanling (P25, postnatal day 25) and young adult (P90) male rats, as well as animals allowed to recover from hypothyroid-induced growth retardation at weaning. The maps revealed novel views of HC regions for assessment of topological relationships and measurement of surface areas of the HC cortical sheet (pyramidal cell layer). In normal control P90 rats, the unfolded HC on each side extended 4 times more laterally than rostrocaudally; total HC surface area was about 40 mm(2), compared to 30 mm(2) in the weanling, indicating 35% growth from P25 to P90; CA1 took up 52% of the total HC surface area, followed by CA3 (31%) and CA2 and CA4, 8% each. Hypothyroidism resulted in significant (p<0.01) 11% and 20% reductions in the HC surface area in P25 and P90 rats, respectively; CA1 and CA4 regions suffered the most reductions while CA3 and CA2 regions the least. Recovering rats examined at P90 exhibited remarkable growth plasticity and recovery in HC regions, as evident by their near normal HC cortical surface area values, compared to age-matched controls. The 2D maps also revealed growth deficits in all HC regions of the hypothyroid rats; recovery in these parameters occurred across all dimensions, although the anterior-posterior growth was more severely affected than the mediolateral one. These results are confirmed and extended by volumetric analysis of laminar volumes of HC regions presented in a companion paper [Farahvar, A., Darwish, N., Sladek, S., Meisami, E., in press. Marked recovery of functional metabolic activity and laminar volumes in the rat hippocampus and dentate gyrus following postnatal hypothyroid growth retardation: a quantitative cytochrome oxidase study. Exp. Neurol.]. These results imply that HC regions, in contrast to whole brain, possess exceptional growth plasticity, as shown by ability to dramatically recover from early hypothyroid retardation; also 2D morphometric maps are useful tools to visualize complex and convoluted regional sheet of HC cortex and depict quantitative aspects of growth in normal and experimental conditions.  相似文献   

Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal     

Arrieta-Cruz I  Pfaff DW  Shelley DN 《Experimental neurology》2007,205(2):449-460

Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controlled periods had a surprising bifurcate effect: about half the mice survived with neurological measures that were virtually normal while the other half died. The new assay detected behavioral deficits unrevealed by neurological screening. Two important features of the results were that (i) deficits were not equal across the circadian cycle, and (ii) deficits were not equal across all the measures within the operational definition of arousal. Specific voluntary motor measurements were decreased in a manner that depended on the phase of the circadian cycle. Sensory responses were also decreased, with an emphasis on vertical movement responses; but, interestingly, fear learning was not damaged. This study establishes the first useful approach to diffuse brain damage in a genetically tractable animal. The model and its outcome measurements will be useful during future attempts at amelioration of acquired neurological disabilities following hypoxic-ischemic injuries.  相似文献   

Tailored psychotherapy for patients with functional neurological symptoms: a pilot study     

Reuber M  Burness C  Howlett S  Brazier J  Grünewald R 《Journal of psychosomatic research》2007,63(6):625-632

OBJECTIVE: The objective of this study was to assess whether individually tailored psychotherapy for patients with functional neurological symptoms is associated with improvements in patient-centered measures of emotional well-being, quality of life, as well as somatic symptoms and whether this treatment modality is likely to be cost-effective. METHODS: We conducted an uncontrolled prospective pilot study of consecutive patients with functional symptoms referred from neurology outpatient clinics to a single psychotherapist using validated questionnaires [Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), Short Function (SF)-36 Health Survey, and Patient Health Questionnaire (PHQ)-15]. Patients had a median of 6 treatment sessions (range=1-24). Ninety-one patients completed questionnaires at referral, 63 did at the end of treatment, and 34 did at follow-up after 6 months. Significant improvements were seen on all measures and were maintained at follow-up (CORE-OM, P=.003; SF-36, P<.001; PHQ-15, P=.001). Significance was not lost in an intention-to-treat analysis. Of all the patients, 49.2% improved by at least 1 S.D. in at least one of the measures. The number of patients needed to be treated to see an improvement of at least 1 S.D. in one of the three outcome measures was 2; that in two measures, 3.9; and that in all measures, 7. The mean cost of the intervention was pound231; the cost per quality-adjusted life year was estimated as pound5,328. RESULTS: Psychotherapy was associated with significant improvements in patient-centered measures, which seemed to be achieved at a comparatively low cost. CONCLUSIONS: The results indicate that psychotherapy may be a cost-effective intervention for patients presenting with functional neurological symptoms. The findings warrant further assessment of this treatment with a randomized and controlled trial.  相似文献   

Putative neural substrate of normal and abnormal general movements     

Hadders-Algra M 《Neuroscience and biobehavioral reviews》2007,31(8):1181-1190

During the last decade it has become clear that the assessment of the quality of general movements (GMs) in foetus and young infant is a sensitive tool to evaluate the integrity of the young nervous system. GMs are movements in which all parts of the body participate. The hallmark of typical GMs is movement complexity and variation; in abnormal GMs movement complexity and variation is reduced or absent. Abnormal GMs may predict developmental outcome. Prediction on the basis of longitudinal series of GM assessments is best. Second best is prediction on the basis of an assessment at ‘fidgety’ GM age, i.e. at 2–4 months post-term. Definitely abnormal GMs at ‘fidgety’ age are related to cerebral palsy, mildly abnormal GMs to minor neurological dysfunction at school age. In the present paper the hypothesis is advanced that GM complexity and variation are brought about by the transiently present cortical subplate and that abnormal GMs are the result of damage or dysfunction of the subplate and its efferent motor connections in the periventricular white matter.  相似文献