RESUMO
BACKGROUND AND PURPOSE: We hypothesized that 3D T1-TSE "black-blood" images may carry an increased risk of contrast-enhancing lesion misdiagnosis in patients with MS because of the misinterpretation of intraparenchymal vein enhancement. Thus, the occurrence of true-positive and false-positive findings was compared between standard MPRAGE and volumetric interpolated brain examination techniques. MATERIALS AND METHODS: Sampling perfection with application-optimized contrasts by using different flip-angle evolution (SPACE) images obtained from 232 patients with MS, clinically isolated syndrome, or radiologically isolated syndrome were compared with standard MPRAGE and volumetric interpolated brain examination images. The intraparenchymal vein contrast-to-noise ratio was estimated at the level of the thalami. Contrast-enhancing lesions were blindly detected by 2 expert readers and 1 beginner reader. True- and false-positives were determined by senior readers' consensus. True-positive and false-positive frequency differences and patient-level diagnosis probability were tested with the McNemar test and OR. The contrast-to-noise ratio and morphology were compared using the Mann-Whitney U and χ2 tests. RESULTS: The intraparenchymal vein contrast-to-noise ratio was higher in SPACE than in MPRAGE and volumetric interpolated brain examination images (P < .001, both). There were 66 true-positives and 74 false-positives overall. SPACE detected more true-positive and false-positive results (P range < .001-.07) but did not increase the patient's true-positive likelihood (OR = 1 1.29, P = .478-1). However, the false-positive likelihood was increased (OR = 3.03-3.55, P = .008-.027). Venous-origin false-positives (n = 59) with contrast-to-noise ratio and morphology features similar to small-sized (≤14 mm3 P = .544) true-positives occurred more frequently in SPACE images (P < .001). CONCLUSIONS: Small intraparenchymal veins may confound the diagnosis of enhancing lesions on postgadolinium black-blood SPACE images.
Assuntos
Esclerose Múltipla , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Meios de Contraste , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologiaRESUMO
BACKGROUND AND PURPOSE: Demyelinating lesions in the anterior visual pathways represent an underestimated marker of disease dissemination in patients with MS. We prospectively investigated whether a dedicated high-resolution MR imaging technique, the 3D-T2-STIR-ZOOMit, improves demyelinating lesion detection compared with the current clinical standard sequence, the 2D-T2-STIR. MATERIALS AND METHODS: 3T MR imaging of the anterior visual pathways (optic nerves, chiasm, and tracts) was performed using 3D-T2-STIR-ZOOMit and 2D-T2-STIR, in patients with MS and healthy controls. Two experienced neuroradiologists assessed, independently, demyelinating lesions using both sequences separately. 3D-T2-STIR-ZOOMit scan-rescan reproducibility was tested in 12 patients. The Cohen κ was used for interrater agreement, and the intraclass correlation coefficient for reproducibility. Between-sequence detection differences and the effects of location and previous acute optic neuritis were assessed using a binomial mixed-effects model. RESULTS: Forty-eight patients with MS with (n = 19) or without (n = 29) past optic neuritis and 19 healthy controls were evaluated. Readers' agreement was strong (3D-T2-STIR-ZOOMit: 0.85; 2D-T2-STIR: 0.90). The 3D-T2-STIR-ZOOMit scan-rescan intraclass correlation coefficient was 0.97 (95% CI, 0.96-0.98; P < .001), indicating excellent reproducibility. Overall, 3D-T2-STIR-ZOOMit detected more than twice the demyelinating lesions (n = 89) than 2D-T2-STIR (n = 43) (OR = 2.7; 95% CI, 1.7-4.1; P < .001). In the intracranial anterior visual pathway segments, 33 of the 36 demyelinating lesions (91.7%) detected by 3D-T2-STIR-ZOOMit were not disclosed by 2D-T2-STIR. 3D-T2-STIR-ZOOMit increased detection of demyelinating lesion probability by 1.8-fold in patients with past optic neuritis (OR = 1.8; 95% CI, 1.2-3.1; P = .01) and 5.9-fold in patients without past optic neuritis (OR = 5.9; 95% CI, 2.5-13.8; P < .001). No false-positive demyelinating lesions were detected in healthy controls. CONCLUSIONS: Dedicated 3D-T2-STIR-ZOOMit images improved substantially the detection of MS disease dissemination in the anterior visual pathways, particularly in the intracranial segments and in patients without past optic neuritis.
Assuntos
Esclerose Múltipla , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/diagnóstico por imagem , Neurite Óptica/diagnóstico por imagem , Reprodutibilidade dos Testes , Vias Visuais/diagnóstico por imagemRESUMO
Larger body parts are somatotopically represented in the primary motor cortex (M1), while smaller body parts, such as the fingers, have partially overlapping representations. The principles that govern the overlapping organization of M1 remain unclear. We used transcranial magnetic stimulation (TMS) to examine the cortical encoding of thumb movements in M1 of healthy humans. We performed M1 mapping of the probability of inducing a thumb movement in a particular direction and used low intensity TMS to disturb a voluntary thumb movement in the same direction during a reaction time task. With both techniques we found spatially segregated representations of the direction of TMS-induced thumb movements, thumb flexion and extension being best separated. Furthermore, the cortical regions corresponding to activation of a thumb muscle differ, depending on whether the muscle functions as agonist or as antagonist for flexion or extension. In addition, we found in the reaction time experiment that the direction of a movement is processed in M1 before the muscles participating in it are activated. It thus appears that one of the organizing principles for the human corticospinal motor system is based on a spatially segregated representation of movement directions and that the representation of individual somatic structures, such as the hand muscles, overlap.
Assuntos
Potenciais Evocados/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Rede Nervosa/fisiologia , Polegar/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polegar/inervaçãoRESUMO
BACKGROUND AND PURPOSE: Postgadolinium MR imaging is crucial for brain tumor diagnosis and morphometric assessment. We compared brain tumor enhancement visualization and the "target" object morphometry obtained with the most commonly used 3D MR imaging technique, MPRAGE, with 2 other routinely available techniques: sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) and volumetric interpolated brain examination (VIBE). MATERIALS AND METHODS: Fifty-four contrast-enhancing tumors (38 gliomas and 16 metastases) were assessed using MPRAGE, VIBE, and SPACE techniques randomly acquired after gadolinium-based contrast agent administration on a 3T scanner. Enhancement conspicuity was assessed quantitatively by calculating the contrast rate and contrast-to-noise ratio, and qualitatively, by consensus visual comparative ratings. The total enhancing tumor volume and between-sequence discrepancy in the margin delineation were assessed on the corresponding 3D target objects contoured with a computer-assisted software for neuronavigation. The Wilcoxon signed rank and Pearson χ2 nonparametric tests were used to investigate between-sequence discrepancies in the contrast rate, contrast-to-noise ratio, visual conspicuity ratings, tumor volume, and margin delineation estimates. Differences were also tested for 1D (Response Evaluation Criteria in Solid Tumors) and 2D (Response Assessment in Neuro-Oncology) measurements. RESULTS: Compared with MPRAGE, both SPACE and VIBE obtained higher contrast rate, contrast-to-noise ratio, and visual conspicuity ratings in both gliomas and metastases (P range, <.001-.001). The between-sequence 3D target object margin discrepancy ranged between 3% and 19.9% of lesion tumor volume. Larger tumor volumes, 1D and 2D measurements were obtained with SPACE (P range, <.01-.007). CONCLUSIONS: Superior conspicuity for brain tumor enhancement can be achieved using SPACE and VIBE techniques, compared with MPRAGE. Discrepancies were also detected when assessing target object size and morphology, with SPACE providing more accurate estimates.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Adulto , Idoso , Neoplasias Encefálicas/patologia , Meios de Contraste , Feminino , Glioma/patologia , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. METHODS: Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). RESULTS: The results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. CONCLUSIONS: The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the 'off'-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5-6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.
Assuntos
Estimulação Encefálica Profunda/métodos , Globo Pálido , Doença de Parkinson/terapia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.
Assuntos
Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/estatística & dados numéricos , Distúrbios Distônicos/terapia , Adulto , Encéfalo/cirurgia , Estimulação Encefálica Profunda/métodos , Estimulação Encefálica Profunda/normas , Distonia/fisiopatologia , Distonia/terapia , Distúrbios Distônicos/fisiopatologia , Feminino , Seguimentos , Globo Pálido/fisiologia , Humanos , Masculino , Síndrome de Meige/fisiopatologia , Síndrome de Meige/terapia , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Marca-Passo Artificial , Tálamo/fisiologia , Tempo , Torcicolo/fisiopatologia , Torcicolo/terapia , Resultado do TratamentoRESUMO
Several lines of evidence suggest that GABA-ergic neurotransmission plays a role in the pathogenesis of primary dystonia in humans. In this study, we tested the hypothesis that mutations in the GABRA1, GABRB3, and GABRG2 genes encoding the alpha1, beta3, and gamma subunits of the GABA(A) receptor are involved in familial primary dystonia. All exons and exon-intron boundaries of the above genes were amplified by PCR from genomic DNA in 28 patients who had primary dystonia and a positive family history but had no mutation in any other genes known to be involved in primary dystonia. The PCR products were analyzed by single strand conformation polymorphism followed by sequencing of variant conformers compared with normal controls (n = 54). We found no mutations in these genes. We did, however, find a new polymorphism, 559 + 80G>A in intron 5 of GABRA1, and we also confirmed several that were previously reported, including 315C>T in exon 3 and 588C>T in exon 5 of GABRG2, but there were no significant differences between controls and patients in the allele and genotype frequencies of these polymorphisms. In conclusion, mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia.
Assuntos
Distúrbios Distônicos/genética , Testes Genéticos/métodos , Mutação/genética , Receptores de GABA-A/genética , Adulto , Distúrbios Distônicos/diagnóstico , Feminino , Humanos , Masculino , Polimorfismo Genético/genéticaRESUMO
Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason for this renewal in surgical treatment for PD is the "deep brain stimulation" (DBS) that replaced the previously used stereotactic lesions in most centers. DBS allows a focal specific electrical stimulation of basal ganglia target instead of an irreversible lesion. Mainly bilateral DBS of the nucleus subthalamicus is now an established surgical treatment for PD. But DBS of the Globus pallidus internus and of the thalamus should still be considered in selected patients. DBS is an efficient treatment for motor complication of PD that can no longer be controlled by drug treatment. Dyskinesia, bradykinesia, tremor and rigor can be improved by DBS and the medication can be reduced. It is still unclear, however, how the improvement in motor symptoms affects quality of life in the long term. Furthermore, patients with severe cognitive and psychiatric symptoms as well as patients with severe axial symptoms should not be operated since these symptoms may worsen after surgery.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/cirurgia , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Estimulação Elétrica , Globo Pálido/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Seleção de Pacientes , Complicações Pós-Operatórias , Qualidade de Vida , Medição de Risco , Fatores de Risco , Núcleo Subtalâmico/fisiopatologia , Tálamo/fisiopatologia , Fatores de TempoRESUMO
OBJECTIVE: To investigate whether levetiracetam (LTC) alters corticospinal excitability in humans. BACKGROUND: Although the antiepileptic activity of LTC is well recognized, its mechanism of action has yet to be determined. Transcranial magnetic stimulation (TMS) has been used to investigate the pharmacologic effects of various antiepileptic drugs on human corticospinal excitability. METHODS: The authors performed TMS before and after double-blind administration of 3000 mg LTC or placebo in six healthy volunteers. TMS measurements included resting and active motor threshold (MT), recruitment curve of motor-evoked potential amplitudes, intracortical inhibition, and facilitation using the paired-pulse technique and silent period. F-wave and compound muscle action potential (CMAP) were also measured. RESULTS: In recruitment curve measurements, motor-evoked potential amplitude was reduced for LTC with high stimulation intensity (130% and 140% of resting MT) compared with placebo (p < 0.05 and p < 0.01), but not with relatively low stimulation intensity (110% and 120%). The changes in other TMS measurements as well as F-wave and CMAP after LTC did not differ significantly from those observed after placebo administration. CONCLUSION: These results suggest that LTC reduces the corticospinal neuronal response to magnetic stimulation, preferentially affecting less excitable neurons. The lack of change in F-wave and CMAP suggests that this effect is mainly derived from the motor cortex.
Assuntos
Anticonvulsivantes/farmacologia , Potencial Evocado Motor/efeitos dos fármacos , Piracetam/farmacologia , Tratos Piramidais/efeitos dos fármacos , Adulto , Método Duplo-Cego , Fenômenos Eletromagnéticos , Eletromiografia/efeitos dos fármacos , Eletromiografia/métodos , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Levetiracetam , Masculino , Piracetam/análogos & derivados , Tratos Piramidais/fisiologiaRESUMO
Although botulinum toxin is an effective treatment for focal dystonia, the importance of electromyography (EMG) in identifying muscles and guiding injections is unclear. The authors examined the accuracy of muscle localization in 38 muscles in patients with focal hand dystonia without EMG guidance. Only 37% of needle placement attempts reached the target muscles or muscle fascicles. This study demonstrates that EMG guidance is needed for correct localization of desired muscles.
Assuntos
Distonia/fisiopatologia , Eletromiografia , Injeções Intramusculares/métodos , Músculo Esquelético/fisiopatologia , Animais , Toxinas Botulínicas/uso terapêutico , Distonia/tratamento farmacológico , HumanosRESUMO
Transcranial magnetic (TMS) and electrical (TES) stimulation of the human brain have become useful tools in neurophysiological and neuropsychological research. Here we describe an integrated system that allows experimental control, data recording and analysis of neurophysiological and neuropsychological TMS and TES procedures (including motor thresholds, recruitment curves, intracortical inhibition and facilitation with paired pulses). The system uses a multifunction input/output board and a set of virtual instruments (VI) programmed with the Labview graphical programming language. It also includes online curve fitting of recruitment curves using the Boltzmann sigmoid function and monitoring of the preinnervation grade of the target muscle. Modules for neuropsychological stimulus presentation or faster repetitive stimulation can be easily added. This system yields more accurate data recording and analysis in a user friendly and unified environment.
Assuntos
Estimulação Elétrica , Potencial Evocado Motor/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Magnetismo , Computadores , Condicionamento Clássico/fisiologia , Processamento Eletrônico de Dados , Humanos , Córtex Motor/fisiologia , Software , Design de SoftwareRESUMO
Neurotropin, an inhibitor of the kallikrein-kinin system, was therapeutically i.p. administered to mice with brain inflammation induced by subarachnoidal injection of carrageenan. Brain water content was determined by the wet/dry weight ratio. The concentrations of cerebral Ca, K, Mn, Fe, Cu, Zn, Se, Rb, and Sr were measured by particle-induced X-ray emission. It was found that neurotropin dose dependently reduced brain water content. The mean concentration of cerebral calcium was significantly lower in the neurotropin-treated group than that in the non-treated group, suggesting less cell damage. Since it has been reported that dexamethasone and some prostaglandin inhibitors have no effect on brain swelling in this model and that, in contrast to these drugs, neurotropin has only a weak inhibiting activity on carrageenan-induced paw swelling, it is hypothesized that the kallikrein-kinin system is differently implicated in cerebral and peripheral inflammation.
Assuntos
Analgésicos/uso terapêutico , Edema Encefálico/tratamento farmacológico , Cálcio/metabolismo , Polissacarídeos/uso terapêutico , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Aracnoide-Máter/efeitos dos fármacos , Aracnoide-Máter/metabolismo , Edema Encefálico/induzido quimicamente , Carragenina/administração & dosagem , Carragenina/toxicidade , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Cobre/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Ferro/metabolismo , Sistema Calicreína-Cinina/efeitos dos fármacos , Modelos Lineares , Masculino , Manganês/metabolismo , Camundongos , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Potássio/metabolismo , Rubídio/metabolismo , Selênio/metabolismo , Espectrometria por Raios X , Água/metabolismo , Zinco/metabolismoRESUMO
The adenosine A2a receptors (A2aR) play an important role in the purinergic mediated neuromodulation. The presence of A2aR in the brain is well established. In contrast, little is known about their expression in the periphery. The purpose of this study was to investigate the expression of A2aR gene in the autonomic (otic, sphenopalatine, ciliary, cervical superior ganglia and carotid body) and in the dorsal root ganglia of normal rat. Hybridization histochemistry with S35-labelled radioactive oligonucleotide probes was used. An expression of A2aR gene was found in the large neuronal cells of the rat dorsal root ganglia. The satellite cells showed no expression of A2aR gene. In the superior cervical ganglion, isolated ganglion cells expressed A2aR. In the carotid body clusters of cells with a strong A2aR gene expression were found. In contrast, the ciliary and otic ganglia did not expressed A2aR gene, and only few small sized A2aR expressing cells were demonstrated in the sphenopalatine ganglion. The discrete distribution of A2aR gene expression in the peripheral nervous system speaks for a role of this receptor in the purinergic modulation of sensory information as well as in the sympathetic nervous system.
Assuntos
Gânglios Autônomos/metabolismo , Gânglios Espinais/metabolismo , Receptores Purinérgicos P1/genética , Animais , Feminino , Hibridização In Situ , Masculino , Sondas de Oligonucleotídeos , Ratos , Ratos Wistar , Receptor A2A de Adenosina , Receptores Purinérgicos P1/biossínteseRESUMO
The expression of adenosine A2a receptors (A2aR) in the mammalian striatum is well known. In contrast the exact distribution of A2aR in other regions of the central nervous system remains unclear. The aim of this study was to investigate the A2aR gene expression in the rat olfactory bulb and spinal cord, two regions which are seldom included in mapping studies. Secondly, we compared the A2aR expression in the rat and in the mouse brain. Hybridization histochemistry was performed with an S35-labelled radioactive oligonucleotide probe. The results show strong expression of A2aR in the mouse and rat striatum in accordance with previous reports. In the olfactory bulb a weak but specific expression of A2aR was found in the granular cell layer in both species. In contrast, no significant expression of the A2aR gene was observed in other parts of the brain or the rat spinal cord. The presence of the A2aR in the mammalian olfactory bulb suggests a functional role for this receptor in olfaction.
Assuntos
Bulbo Olfatório/metabolismo , Receptores Purinérgicos P1/biossíntese , Receptores Purinérgicos P1/genética , Medula Espinal/metabolismo , Animais , Feminino , Hibridização In Situ , Camundongos , Sondas de Oligonucleotídeos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptor A2A de Adenosina , Especificidade da EspécieRESUMO
To identify cholinergically mediated components in the optic nerve response (ONR) we studied effects of cholinergic agonists and antagonists in the arterially perfused cat eye. Acetylcholine, carbachol, scopolamine, quinuclidinylbenzilate and mecamylamine were applied intra-arterially in micromolar concentrations. Recordings of rod- and cone-driven ERG accompanied those of the ONR and revealed: (i) cholinergic agonists enhanced the b-wave, particularly under photopic conditions, whereas scopolamine decreased the b-wave. Mecamylamine induced biphasic effects (decrease followed by increase) in the amplitudes of the rod- and cone-driven b-waves. The effects on the cone-driven ERG were more marked than those on the rod-driven ERG. (ii) The ON-component of the ONR was increased, then decreased by acetylcholine. The cholinergic antagonists exerted complex changes in the ONR-ON component depending on dosage and adaptation. Scopolamine increased, then decreased the rod-driven ON-component, but mainly increased the cone-driven ON-component. Mecamylamine tended to increase the cone-driven, but to decrease the rod-driven ON-component of the ONR. (iii) The configuration of the rod- as well as for the cone-driven ONR, in particular the early plateau and OFF-components, were consistently and reversibly changed by cholinergic agonists, as well as by both muscarinic and nicotinic antagonists. Agonists decreased, and antagonists increased the amplitude of the plateau-component. We conclude that the ERG b-wave was enhanced by acetylcholine, but decreased by cholinergic antagonists. Cholinergic agonists and antagonists affect the same specific components of the ONR in a dose-related and reversible fashion, indicating a major contribution of cholinergic mechanisms to information processing in the cat retina.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Agonistas Colinérgicos/farmacologia , Antagonistas Colinérgicos/farmacologia , Nervo Óptico/fisiologia , Retina/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Carbacol/farmacologia , Gatos , Eletrorretinografia/efeitos dos fármacos , Técnicas In Vitro , Mecamilamina/farmacologia , Células Fotorreceptoras/fisiologia , Quinuclidinil Benzilato/farmacologia , Retina/fisiologia , Escopolamina/farmacologia , Fatores de TempoRESUMO
The function of A1- and A2a-adenosine receptors in the control of vascular resistance and in the modulation of light-evoked neuronal activity was investigated in the isolated perfused cat eye. The A1 agonist CCPA, the A1 antagonist CPT, the A2a agonist CGS 21680 and the A2 antagonist DMPX were used. The agents were applied intra-arterially at concentrations in the low nanomolar to micromolar range during rod-selective photic stimulation. The flow rate of perfusate, reflecting vascular resistance and the light-evoked optic nerve response (ONR) were recorded. Our results show a vasodilating effect of both A1 and A2 agonists and a vasoconstricting effect of the respective antagonists. The dose-effect relationships are suggestive, however, of an A2a receptor-mediated mechanism. The amplitude of the ONR-ON component was decreased during application of both adenosine-agonists. Analysis of the dose-effect relationships and the blockade of the CCPA-induced decrease by CPT suggests that inhibition is mediated by A1 receptors. However, CGS 21680-mediated inhibition cannot be explained by unspecific binding at A1 receptors alone and suggests the involvement of inhibitory A2a receptors.
Assuntos
Adenosina/farmacologia , Nervo Óptico/efeitos dos fármacos , Agonistas do Receptor Purinérgico P1 , Retina/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Adenosina/análogos & derivados , Animais , Gatos , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Eletrofisiologia , Feminino , Nervo Óptico/efeitos da radiação , Perfusão , Fenetilaminas/farmacologia , Estimulação Luminosa , Antagonistas de Receptores Purinérgicos P1 , Retina/metabolismo , Teobromina/análogos & derivados , Teobromina/farmacologia , Teofilina/análogos & derivados , Teofilina/farmacologiaRESUMO
Parkinson's disease (PD) is an asymmetric neurodegenerative disorder, and secondary adaptive mechanisms of the less-affected side could potentially compensate for parkinsonian symptoms. Here, we analyzed gene expression changes on the healthy side of a unilateral PD rat model and correlated these changes with locomotor velocity, which is known to be decreased in PD. Four weeks after a unilateral 6-hydroxydopamine lesion, the spontaneous locomotor velocity of rats was recorded just prior to brain extraction. We then analyzed the gene expression levels of markers of the direct (dynorphin and D1-class dopamine receptors) and indirect (enkephalin and D2-class dopamine receptors) pathways in the contralateral healthy striatum by in situ hybridization histochemistry. In addition, we analyzed the expression of several striatal and cortical glutamatergic markers, as well as nigral tyrosine hydroxylase (TH) and nigral dopamine transporter (DAT). We found a significant positive correlation between the mRNA expression levels of contralateral D1-class dopamine receptors and the mean locomotor velocity, at 4 weeks after surgery in parkinsonian rats but not in controls. Moreover, we observed a significant increase in the level of dynorphin mRNA in the lateral part of the contralateral striatum of parkinsonian rats compared to the controls. In contrast, no contralateral changes were observed in the striatal indirect pathway. We also did not find any significant contralateral modifications of TH, DAT or glutamatergic markers in PD animals, indicating that changes in direct pathway genes are not due to nigrostriatal dopaminergic or corticostriatal glutamatergic innervation. In conclusion, our results suggest a role of the healthy striatal direct pathway in counteracting dopaminergic denervation effects on motor symptoms.
Assuntos
Córtex Cerebral/metabolismo , Dinorfinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transtornos Parkinsonianos/metabolismo , Receptores de Dopamina D1/metabolismo , Adaptação Fisiológica , Adrenérgicos , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Dinorfinas/genética , Encefalinas/genética , Encefalinas/metabolismo , Feminino , Lateralidade Funcional , Perfilação da Expressão Gênica , Locomoção/fisiologia , Neostriado/metabolismo , Neostriado/patologia , Proteínas do Tecido Nervoso/genética , Vias Neurais/fisiologia , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , RNA Mensageiro/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.
Assuntos
Estimulação Elétrica/métodos , Guias como Assunto/normas , Doenças do Sistema Nervoso/diagnóstico , Estimulação Magnética Transcraniana/métodos , Estimulação Magnética Transcraniana/normas , Biofísica , Depressão Alastrante da Atividade Elétrica Cortical , Eletromiografia , Potencial Evocado Motor , Lateralidade Funcional , Humanos , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Condução NervosaRESUMO
Primary dystonia is a movement disorder characterized by involuntary and sustained muscle contractions causing twisting or abnormal postures and mutations in several genes have been identified. Our goal was to investigate, whether the clinical presentation would differ between patients with a positive family history, and patients without. Furthermore, we have performed mutation analysis in the subgroup of patients with a positive family history. A total of 175 patients with primary dystonia were evaluated. Data on gender, presence and frequency of pain and tremor, age of onset, and the distribution of affected body parts were compared between patients with positive and negative family history. All exons of the torsion dystonia 1, GTP cyclohydrolase 1 and epsilon-sarcoglycan genes were examined in 40 patients by SSCP analysis of PCR products followed by sequencing of variant conformers. Dystonia patients with a positive family history of dystonia had an earlier age of onset and those with a positive family history of tremor more often associated tremor than those with a negative family history. Four new polymorphisms in the epsilon-sarcoglycan gene were found and others confirmed, but no known or new mutations could be detected. Our study supports the notion that primary dystonia is a genetically heterogeneous disease.
Assuntos
Distúrbios Distônicos/genética , Distúrbios Distônicos/fisiopatologia , Adulto , Idade de Início , Feminino , GTP Cicloidrolase/genética , Humanos , Masculino , Chaperonas Moleculares/genética , Mutação , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Sarcoglicanas/genéticaRESUMO
BACKGROUND: Electrophysiological measurements in the mammalian eye in vivo or in vitro, i.e. in the arterially perfused cat eye, require storage and analysis of a large amount of data: light-evoked signals, including the electroretinogram (ERG) and the optic nerve response (ONR) are stimulus-related and have to be measured in a triggered mode, whereas the DC-standing potential and flow rate of perfusion medium should be measured continuously. METHOD AND RESULT: In order to facilitate the analysis of these various signals, we developed a computer program, that allows an on-line data analysis and a trend indication for pharmacologically induced changes in signal size as well as efficient storage. The flexible system is based on a "labview" program, the application and efficiency of which are discussed.