RESUMO
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with Parkinson's disease (PD) in the advanced stage. Besides motor improvement, DBS of the STN may also modulate cognitive and attentional functions of the basal ganglia. In our study, 13 patients with PD and bilateral DBS of the STN were assessed with DBS switched on and off by the use of a wide range of neuropsychological tasks. This included reasoning, cognitive flexibility, phonemic and semantic word fluency, verbal and nonverbal short-term memory, learning, delayed verbal memory recall, and stimulus-response incompatibility. Special emphasis was put on basic attentional functions, in particular intrinsic and phasic alertness as well as visual search. DBS significantly improved intrinsic alertness, whereas phasic alertness and other neuropsychological domains were not affected. Additionally, the effects on intrinsic alertness were independent of motor improvements by DBS. The findings suggest that DBS modulates the fronto-parietal network of alertness.
Assuntos
Atenção/fisiologia , Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Adulto , Idoso , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Atenção/efeitos dos fármacos , Terapia Combinada , Feminino , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiopatologia , Humanos , Masculino , Processos Mentais/efeitos dos fármacos , Processos Mentais/fisiologia , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Testes Neuropsicológicos , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Distribuição Aleatória , Índice de Gravidade de Doença , Núcleo Subtalâmico/efeitos dos fármacosRESUMO
The pathogenesis of essential tremor (ET) is still under debate. Several lines of evidence indicate that ET is associated with cerebellar dysfunction. The aim of the present study was to find corroborating evidence for this claim by investigating balance and speech impairments in patients with ET. In addition, the effect of deep brain stimulation (DBS) on balance and speech function was studied. A group of 25 ET patients including 18 with postural and/or simple kinetic tremor (ETpt) and seven ET patients with additional clinical signs of cerebellar dysfunction (ETc) was compared to 25 healthy controls. In addition, 12 ET patients with thalamic DBS participated in the study. Balance control was assessed during gait and stance including tandem gait performed on a treadmill as well as static and dynamic posturography. Motor speech control was analyzed through syllable repetition tasks. Signs of balance impairment were found in early stages and advanced stages of ET. During locomotion, ET patients exhibited an increased number of missteps and shortened stride length with tandem gait. ETc patients and, to a lesser extent, ETpt patients had increased postural instability in dynamic posturography conditions that are sensitive to vestibular or vestibulocerebellar dysfunction. ETc but not ETpt patients exhibited significantly increased syllable durations. DBS had no discernable effect on speech performance or balance control. We conclude that the deficits in balance as well as the subclinical signs of dysarthria in a subset of patients confirm and extend previous findings that ET is associated with an impairment of the cerebellum.
Assuntos
Cerebelo/fisiopatologia , Estimulação Encefálica Profunda/métodos , Tremor Essencial/terapia , Equilíbrio Postural/fisiologia , Distúrbios da Fala/patologia , Distúrbios da Fala/terapia , Adulto , Idoso , Análise de Variância , Tremor Essencial/complicações , Tremor Essencial/patologia , Feminino , Marcha/fisiologia , Humanos , Testes de Linguagem , Masculino , Pessoa de Meia-Idade , Distúrbios da Fala/complicações , Estatística como Assunto , Adulto JovemRESUMO
BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan). Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots. CONCLUSION: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data.
Assuntos
Antígenos/metabolismo , Astrócitos/metabolismo , Gliose/metabolismo , Proteoglicanas/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo , Traumatismos da Medula Espinal/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrócitos/patologia , Contagem de Células , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Imunofluorescência , Gliose/patologia , Humanos , Imuno-Histoquímica , Lectinas Tipo C/metabolismo , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Neurocam , Oligodendroglia/metabolismo , Traumatismos da Medula Espinal/patologia , Fatores de Tempo , Versicanas/metabolismoRESUMO
Despite considerable progress in recent years, the underlying mechanisms responsible for the failure of axonal regeneration after spinal cord injury (SCI) remain only partially understood. Experimental data have demonstrated that a major impediment to the outgrowth of severed axons is the scar tissue that finally dominates the lesion site and, in severe injuries, is comprised of connective tissue and fluid-filled cysts, surrounded by a dense astroglial scar. Reactive astrocytes and infiltrating cells, such as fibroblasts, produce a dense extracellular matrix (ECM) that represents a physical and molecular barrier to axon regeneration. In the human situation, correlative data on the molecular composition of the scar tissue that forms following traumatic SCI is scarce. A detailed investigation on the expression of putative growth-inhibitory and growth-promoting molecules was therefore performed in samples of post-mortem human spinal cord, taken from patients who died following severe traumatic SCI. The lesion-induced scar could be subdivided into a Schwann cell dominated domain which contained large neuromas and a surrounding dense ECM, and a well delineated astroglial scar that isolated the Schwann cell/ECM rich territories from the intact spinal parenchyma. The axon growth-modulating molecules collagen IV, laminin and fibronectin were all present in the post-traumatic scar tissue. These molecules were almost exclusively found in the Schwann cell-rich domain which had an apparent growth-promoting effect on PNS axons. In the astrocytic domain, these molecules were restricted to blood vessel walls without a co-localization with the few regenerating CNS neurites located in this region. Taken together, these results favour the notion that it is the astroglial compartment that plays a dominant role in preventing CNS axon regeneration. The failure to demonstrate any collagen IV, laminin or fibronectin upregulation associated with the astroglial scar suggests that other molecules may play a more significant role in preventing axon regeneration following human SCI.
Assuntos
Astrócitos/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/fisiologia , Cicatriz/fisiopatologia , Colágeno Tipo IV/fisiologia , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Fibronectinas/fisiologia , Imunofluorescência/métodos , Proteína Glial Fibrilar Ácida/fisiologia , Humanos , Imuno-Histoquímica/métodos , Laminina/fisiologia , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/fisiologia , Neuroglia/fisiologia , Receptores de Fator de Crescimento Neural/fisiologia , Medula Espinal/química , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologiaRESUMO
In humans, hyperventilation (HV) has various effects on systemic physiology and, in particular, on neuronal excitability and synaptic transmission. However, it is far from clear how the effects of HV are mediated at the cortical level. In this study we investigated the effects of HV-induced hypocapnia on primary motor (M1) and visual cortex (V1) excitability. We used 1) motor threshold (MT) and phosphene threshold (PT) and 2) stimulus-response (S-R) curves (i.e., recruitment curves) as measures of excitability. In the motor cortex, we additionally investigated 3) the intrinsic inhibitory and facilitatory neuronal circuits using a short-interval paired-pulse paradigm. Measurements were performed before, during, and after 10 min of HV (resulting in a minimum end-tidal Pco(2) of 15 Torr). HV significantly increased motor-evoked potential (MEP) amplitudes, particularly at lower transcranial magnetic stimulation (TMS) intensities. Paired-pulse stimulation indicated that HV decreases intracortical inhibition (ICI) without changing intracortical facilitation. The results suggestthat low Pco(2) levels modulate, in particular, the intrinsic neuronal circuits of ICI, which are largely mediated by neurons containing gamma-aminobutyric acid. Modulation of MT probably resulted from alterations of Na(+) channel conductances. A significant decrease of PT, together with higher intensity of phosphenes at low stimulus intensities, furthermore suggested that HV acts on the excitability of M1 and V1 in a comparable fashion. This finding implies that HV also affects other brain structures besides the corticospinal motor system. The further exploration of these physiological mechanisms may contribute to the understanding of the various HV-related clinical phenomenona.
Assuntos
Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Hiperventilação/fisiopatologia , Córtex Motor/fisiologia , Córtex Visual/fisiologia , Adulto , Dióxido de Carbono/metabolismo , Eletromiografia , Feminino , Humanos , Hiperventilação/metabolismo , Masculino , Neurônios Motores/fisiologia , Neurônios Aferentes/fisiologia , Pressão Parcial , Estimulação Magnética TranscranianaRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that degrade the extracellular matrix and other extracellular proteins. Studies in experimental animals demonstrate that MMPs play a number of roles in the detrimental as well as in the beneficial events after spinal cord injury (SCI). In the present correlative investigation, the expression pattern of several MMPs and their inhibitors has been investigated in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In the unlesioned human spinal cord, MMP and TIMP immunoreactivity was scarce. After traumatic SCI, a lesion-induced bi-phasic pattern of raised MMP-1 levels could be found with an early up-regulation in macrophages within the lesion epicentre and a later induction in peri-lesional activated astrocytes. There was an early and brief induction of MMP-2 at the lesion core in macrophages. MMP-9 and -12 expression peaked at 24 days after injury and both molecules were mostly expressed in macrophages at the lesion epicentre. Whereas MMP-9 levels rose progressively from 1 week to 3 weeks, there was an isolated peak of MMP-12 expression at 24 days. The post-traumatic distribution of the MMP inhibitors TIMP-1, -2 and -3 was limited. Only occasional TIMP immuno-positive macrophages could be detected at short survival times. The only clear induction was detected for TIMP-3 at survival times of 8 months and 1 year in peri-lesional activated astrocytes. CONCLUSION: The involvement of MMP-1, -2, -9 and -12 has been demonstrated in the post-traumatic events after human SCI. With an expression pattern corresponding largely to prior experimental studies, they were mainly expressed during the first weeks after injury and were most likely involved in the destructive inflammatory events of protein breakdown and phagocytosis carried out by infiltrating neutrophils and macrophages, as well as being involved in enhanced permeability of the blood spinal cord barrier. Similar to animal investigations, the strong induction of MMPs was not accompanied by an expression of their inhibitors, allowing these proteins to exert their effects in the lesioned spinal cord.
Assuntos
Metaloproteinases da Matriz/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrócitos/metabolismo , Astrócitos/patologia , Cadáver , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Macrófagos/patologia , Microglia/patologia , Pessoa de Meia-Idade , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Fatores de Tempo , Distribuição TecidualRESUMO
We have studied grip force performance in a group of 10 patients who were in a stable state after implantation of bilateral stimulating electrodes in the subthalamic nuclei (Stn) to counter drug-resistant or drug-induced symptoms of advanced Parkinson's disease. The patients were required to use a precision grip to lift an object which recorded grip force development and lift dynamics. Lifting was performed with stimulation on and with stimulation off under optimal medication. Post-operatively, dyskinesia was absent in all patients in both conditions, but in the 'off' state the patients showed the profound bradykinesia and excessive levels of grip force development associated with Parkinson's disease from its early stages. In the stimulation 'on' state both the rate of grip force development and the speed of the lifting phase were increased significantly. The excessive levels of grip force present in the stimulation 'off' state, and present from the early stages of the disease, however, were even more marked with Stn stimulation on. It is suggested that this results from a failure to modify stored motor programs developed over a long period under the influence of bradykinesia, leading to an inappropriately prolonged duration of grip force development when this influence is removed by Stn stimulation. Thus although Stn stimulation achieved a dramatic improvement in the mobility of the patients in general, and in the dynamics of hand movements specifically, by improving rates of force development and lifting dynamics, it does not restore, and may even worsen, the ability to match lifting parameters to actual conditions.
Assuntos
Estimulação Encefálica Profunda/métodos , Força da Mão , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Recuperação de Função Fisiológica , Suporte de Carga , PunhoRESUMO
BACKGROUND: Interruption of mature axons activates a cascade of events in neuronal cell bodies which leads to various outcomes from functional regeneration in the PNS to the failure of any significant regeneration in the CNS. One factor which seems to play an important role in the molecular programs after axotomy is the stearoyl Coenzyme A-desaturase-1 (SCD-1). This enzyme is needed for the conversion of stearate into oleate. Beside its role in membrane synthesis, oleate could act as a neurotrophic factor, involved in signal transduction pathways via activation of protein kinases C. RESULTS: In situ hybridization and immunohistochemistry demonstrated a strong up-regulation of SCD at mRNA and protein level in regenerating neurons of the rat facial nucleus whereas non-regenerating Clarke's and Red nucleus neurons did not show an induction of this gene. CONCLUSION: This differential expression points to a functionally significant role for the SCD-1 in the process of regeneration.
Assuntos
Sistema Nervoso Central/enzimologia , Regeneração Nervosa/fisiologia , Sistema Nervoso Periférico/enzimologia , Estearoil-CoA Dessaturase/metabolismo , Traumatismos do Sistema Nervoso/enzimologia , Animais , Axotomia , Sistema Nervoso Central/lesões , Sistema Nervoso Central/patologia , Progressão da Doença , Traumatismos do Nervo Facial/enzimologia , Traumatismos do Nervo Facial/patologia , Nervo Hipoglosso/enzimologia , Nervo Hipoglosso/patologia , Traumatismos do Nervo Hipoglosso , Imuno-Histoquímica , Hibridização In Situ , Isoenzimas/metabolismo , Neurônios/enzimologia , Neurônios/patologia , Sistema Nervoso Periférico/lesões , Sistema Nervoso Periférico/patologia , Ponte/enzimologia , Ponte/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Núcleo Rubro/enzimologia , Núcleo Rubro/patologia , Traumatismos da Medula Espinal/enzimologia , Traumatismos da Medula Espinal/patologia , Traumatismos do Sistema Nervoso/patologia , Regulação para CimaRESUMO
BACKGROUND: It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood. RESULTS: To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (approximately 15%) have been demonstrated to be differentially expressed. CONCLUSIONS: The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues.
Assuntos
Traumatismos do Nervo Facial/genética , Perfilação da Expressão Gênica , Regeneração Nervosa/genética , Neurônios/metabolismo , Traumatismos da Medula Espinal/genética , Animais , Axotomia , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Traumatismos do Nervo Facial/patologia , Feminino , Regulação da Expressão Gênica , Hibridização In Situ , Neurônios/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Núcleo Rubro/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Estearoil-CoA Dessaturase/genética , Fatores de TempoRESUMO
In recent years it has been suggested that processing of visual information is divided between a ventral stream, responsible for object recognition and conscious processing of object properties, and a dorsal stream mediating automatic integration of visual information into a motor task. We used metacontrast masking to prevent conscious perception of visual cues concerning the load of an object to be lifted in a precision grip. It was found that when such non-consciously perceived cues warned of a load change, they allowed the subjects to produce the grip force profile appropriate to the new load. It is concluded that non-consciously perceived visual information can be utilised to adapt a functional motor task to actual conditions.
Assuntos
Percepção/fisiologia , Desempenho Psicomotor/fisiologia , Inconsciente Psicológico , Adulto , Estado de Consciência/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Estatísticas não ParamétricasRESUMO
Excitotoxicity plays a key role in ischemic neuronal death and is also one of the candidate mechanisms contributing to neurodegeneration in Huntington's disease (HD). Unexpectedly we have now found that transgenic mice expressing exon 1 of a mutant human HD gene (R6/1) are protected against global cerebral ischemia (GCI), installed by temporary bilateral occlusion of the carotid arteries. Whereas wild type mice showed a substantial neuronal damage in the hippocampus following 15, 20 and 60 min of GCI, transgenic mice were partially protected after 15 and 20 minutes of hypoxemia. This tolerance to ischemia is not blocked by pretreatment of mice with cycloheximide, an unspecific protein synthesis inhibitor. We conclude that this form of tolerance to ischemia in HD transgenic mice--although somewhat reminiscent of ischemic tolerance after ischemic preconditioning--is therefore independent of short term expression of endogenous neuroprotective proteins.
Assuntos
Hipocampo/patologia , Doença de Huntington/genética , Imunidade Inata/genética , Ataque Isquêmico Transitório/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Animais , Cicloeximida/farmacologia , Éxons , Predisposição Genética para Doença , Hipocampo/efeitos dos fármacos , Humanos , Proteína Huntingtina , Doença de Huntington/complicações , Doença de Huntington/imunologia , Doença de Huntington/patologia , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/imunologia , Ataque Isquêmico Transitório/patologia , Camundongos , Camundongos Transgênicos , MutaçãoRESUMO
BACKGROUND AND PURPOSE: The overall mortality rate of primary pontine hemorrhage (PPH) in recent studies is 40-50%. The aim of the present study was to analyze the predictive value of clinical and neuroradiologic parameters concerning the outcome of patients with PPH. METHODS: We reviewed the clinical data of 29 consecutive patients (mean age, 59 +/- 13.5 years; 12 women, 17 men) with PPH. National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were assessed on admission, and NIHSS, GCS, and Glasgow Outcome Scale (GOS) scores were assessed on discharge. The hemorrhage volume was calculated by using a previously published formula. Clinical manifestations, outcome, and volume and location of the bleeding were correlated. RESULTS: The mean GCS score on admission was 6.8 +/- 3.9 and increased to 9.0 +/- 3.9 on discharge. The NIHSS score improved from 29.1 +/- 12.5 to 12.1 +/- 7.3. Nine patients (31%) died as a result of PPH after 5 +/- 3 days. The mean GOS score was 3.0 +/- 1.5 (3.9 +/- 0.8 for patients who survived). Arterial hypertension was the most common risk factor (90%); other causes were anticoagulation therapy (7%) and amyloid angiopathy (3%). A high correlation was observed between a poor outcome (GOS score < 4) and hematoma volume greater than 4 mL (P =.006), ventral hemorrhage (P <.001), and necessity for mechanical ventilation (P <.001). Patients with dorsally located hematomas less than 4 mL in volume had a significantly better outcome. CONCLUSION: The prognosis of PPH is better than commonly expected. Most patients with moderate neurologic deficits on admission and dorsally located small hematomas are able to survive PPH with minor neurologic deficits.
Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Exame Neurológico , Ponte/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Volume Sanguíneo/fisiologia , Hemorragia Cerebral/mortalidade , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
BACKGROUND AND PURPOSE: Intracranial stenoses are associated with a considerable number of strokes each year. The clinical value of a workstation-based three-dimensional (3D) reconstruction system for transcranial color-coded sonography was evaluated in patients with intracranial stenosis or occlusion. METHODS: Twenty-six patients (13 men, 13 women; mean age, 57 years +/- 12 [SD]) with 36 intracranial stenoses or occlusions, as detected at two-dimensional (2D) color Doppler imaging (CDI) and digital subtraction angiography (DSA), underwent Levovist-enhanced power Doppler imaging (PDI), with subsequent 3D reconstruction. A workstation connected to a magnetic sensor capable of spatial localization of the probe was used to reconstruct 3D images of the circle of Willis from serial PDI images. RESULTS: At DSA, seven (19%) stenoses were estimated to less than 50%, 24 (67%) were 50% or more, and five (14%) were occluded. DSA and 3D-PDI estimates of the degree of stenosis agreed in 33 cases (92%), with a weighted kappa value of 0.86. Disagreement occurred with two subtotal basilar artery stenoses and one subtotal middle cerebral artery stenosis, which were evaluated as being complete occlusions at 3D-PDI. Interobserver agreement between two experienced 3D investigators in estimating the percentage of stenosis was high (correlation coefficient,.98). CONCLUSION: 3D-PDI enables the investigator to reconstruct virtually any arbitrary viewing angle. Compared with conventional CDI, 3D-PDI offers easier spatial assessment of intracranial stenoses, and its findings are sufficiently correlated with angiographic findings. Because different investigators can postprocess the same 3D data, improving reproducibility and reducing investigator dependency in transcranial color-coded sonography may be possible.
Assuntos
Transtornos Cerebrovasculares/diagnóstico por imagem , Meios de Contraste , Imageamento Tridimensional , Polissacarídeos , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler Transcraniana , Idoso , Angiografia Digital , Círculo Arterial do Cérebro/diagnóstico por imagem , Constrição Patológica/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador/normas , Masculino , Pessoa de Meia-IdadeRESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit unspecific morphological signs of a degenerative myopathy. We report on five unrelated patients who carried the pathogenic FSHD mutation on chromosome 4q35. Muscle biopsies revealed numerous rimmed vacuoles and filamentous cytoplasmic inclusions in all cases. Clinically, the patients suffered from weakness and atrophy predominantly of the lower limb muscles. In conclusion, we suggest considering FSHD in the differential diagnosis of adult-onset distal myopathies with rimmed vacuoles.
Assuntos
Perna (Membro)/patologia , Perna (Membro)/fisiopatologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular Facioescapuloumeral/patologia , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Fenótipo , Adulto , Idoso , Cromossomos Humanos Par 4/genética , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Distrofia Muscular Facioescapuloumeral/genética , Mutação/genética , Vacúolos/patologia , Vacúolos/ultraestruturaRESUMO
Prehension movements consist of distal (grasp) and proximal (reach, lift) components. The proximal lifting movements (achieved at the wrist) of patients with Parkinson's disease (PD) are characterized by bradykinesia. With respect to the distal component, PD patients show pathologically high grip forces (generated by the fingers) and slowing of force development indicative of disturbed sensorimotor adjustments during prehension. Combining kinematic and force analyses of prehension movements, we investigated whether PD differentially affects the adjustments of the distal or proximal prehension components to current load conditions. First, PD patients (n = 12) and healthy, age-matched control subjects grasped and lifted light and heavy objects without any load cues. Then, they were presented with cues that indicated changes in object load. These load cues were either consciously perceived or rendered subconscious through use of the technique of metacontrast masking. Consistent with the functional organization of the basal ganglia, patients with PD could adapt distal prehension components (grip force) to current load conditions using both types of cues. However, they were impaired in adjusting proximal prehension components (lift velocity). While controls were able to normalize lift velocity with the help of both conscious and subconscious load cues, the PD patients could use neither form of cue, and retained a pathological overshoot in lift velocity. Our results demonstrate that visuomotor integration during prehension movements differs at distal and more proximal joints and that deficits in this integration are pronounced for the latter in Parkinson's disease.
Assuntos
Doença de Parkinson/psicologia , Desempenho Psicomotor , Adulto , Idoso , Análise de Variância , Fenômenos Biomecânicos , Sinais (Psicologia) , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
Traumatic injury to the nervous system induces functional deficits as a result of axonal destruction and the formation of scar tissue, cystic cavitation, and physical gaps. Bioengineering bridging materials should ideally act as cell carriers for the implantation of axon growth-promoting glia, as well as supporting integration with host cell types. Here, we describe the cytocompatibility of a novel, micro-structured porcine collagen scaffold containing densely packed and highly orientated channels that, in three-dimensional (3D) tissue culture, supports attachment, proliferation, aligned process extension, and directed migration by populations of glial cells (olfactory nerve ensheathing cells and astrocytes) and orientated axonal growth by neurons (differentiated human SH-SY5Y neuroblastoma cell line). The seeded glia required several weeks to penetrate deeply into the highly porous scaffold, where they adopted an orientated morphology similar to that displayed in simple 2D cultures. The direct interaction between SH-SY5Y-derived nerve fibers and the collagen scaffold also resulted in highly orientated axonal growth. It is likely that biocompatible scaffolds that are capable of promoting glial cell attachment, migration, and highly orientated process outgrowth will be important for future repair strategies for traumatically injured nervous tissues.
Assuntos
Materiais Biocompatíveis/farmacologia , Colágeno/farmacologia , Teste de Materiais , Tecido Nervoso/citologia , Tecido Nervoso/efeitos dos fármacos , Alicerces Teciduais , Cicatrização/efeitos dos fármacos , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Colágeno/ultraestrutura , Reagentes de Ligações Cruzadas/farmacologia , Imunofluorescência , Indóis , Neurônios/citologia , Neurônios/ultraestrutura , Peroxidase/metabolismo , Ratos , Esterilização , Sus scrofaRESUMO
Traumatic spinal cord injury (SCI) causes severe and permanent functional deficits due to the primary mechanical insult followed by secondary tissue degeneration. The cascade of secondary degenerative events constitutes a range of therapeutic targets which, if successfully treated, could significantly ameliorate functional loss after traumatic SCI. During the early hours after injury, potent pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) are synthesized and released, playing key roles in secondary tissue degeneration. In the present investigation, the ability of rolipram and thalidomide (FDA approved drugs) to reduce secondary tissue degeneration and improve motor function was assessed in an experimental model of spinal cord contusion injury. The combined acute single intraperitoneal administration of both drugs attenuated TNF-alpha and IL-1beta production and improved white matter sparing at the lesion epicenter. This was accompanied by a significant (2.6 point) improvement in the BBB locomotor score by 6 weeks. There is, at present, no widely accepted intervention strategy that is appropriate for the early treatment of human SCI. The present data suggest that clinical trials for the acute combined application of rolipram and thalidomide may be warranted. The use of such "established drugs" could facilitate the early initiation of trials.
Assuntos
Imunossupressores/uso terapêutico , Locomoção/efeitos dos fármacos , Inibidores de Fosfodiesterase/uso terapêutico , Rolipram/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Talidomida/uso terapêutico , Animais , Modelos Animais de Doenças , Progressão da Doença , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/metabolismo , Masculino , Proteína Básica da Mielina/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Proteínas de Neurofilamentos/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Proprioceptive facilitation (PF) is a phenomenon occasionally seen during motor restoration following acute hemiplegia. At an early stage of recovery, a number of brief passive muscle stretches can facilitate voluntary contraction in the stretched muscles. Here we present a patient who during early recovery from a left hemispheric stroke causing right hemiplegia was able to develop maximum isometric arm force if, during this effort, large-amplitude passive stretches of the elbow were applied as conditioning stimuli. Based on clinical and positron emission tomography findings, possible physiological mechanisms of PF and the role of proprioception in stroke recovery are discussed.
Assuntos
Hemiplegia/fisiopatologia , Propriocepção/fisiologia , Recuperação de Função Fisiológica/fisiologia , Hemiplegia/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodosRESUMO
The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage.