RESUMO
INTRODUCTION: In posterior fossa tumor survivors, lower white matter integrity (WMI) in the right cerebellar-left frontal pathway has been well documented and appears to be related to proximity to the cerebellum, radiation treatment, as well as time since treatment in both cranial radiation and surgery-only treatment groups. The current study investigated theories of transneural degeneration following cerebellar tumor resection that may underlie or relate to reductions in WMI and regional brain volumes using correlations. We hypothesized a positive relationship between the volume of the right cerebellum and known white matter output pathways, as well as with the volume of structures that receive cerebellar projections along the pathway. METHODS: Adult survivors of childhood brain tumors were recruited (nâ¯=â¯29; age, Mâ¯=â¯22â¯years, SDâ¯=â¯5; 45% female). Age- and gender-matched controls were also included (nâ¯=â¯29). Participants completed 3â¯T diffusion-weighted and T1 MPRAGE MRI scans. Brain structure volume relative to intracranial vault served as regional volumetric measures. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. In the survivor group, partial correlations between WMI and regional volume included controlling for disease severity. RESULTS: In posterior fossa tumor survivors, the volumes of the cerebellum, thalamus, and frontal lobe were correlated with WMI of the thalamic-frontal segment of the cerebellar-frontal pathway (râ¯=â¯0.41-0.49, pâ¯<â¯.05). Cerebellar atrophy was correlated with reduced WMI in the cerebellar-rubral segment (FA, râ¯=â¯-0.32 pâ¯>â¯.05; RD, râ¯=â¯0.53, pâ¯<â¯.01). In the no-radiation survivor group, the regional volume of each structure along the pathway was associated with WMI in the cerebellar-rubral segment. In the radiation survivor group, significant correlations were found between the regional brain volume of each structure and the thalamic-frontal segment of the pathway. DISCUSSION: The results of this multimodal neuroimaging study provide correlational evidence that the mechanism of injury subsequent to brain tumor treatment may be different depending on type of treatment(s). Without radiation, the primary mechanism of injury is cerebellar tumor growth, resection, and hydrocephalus. Therefore, the most proximal connection to that injury (cerebellar-rubral pathway) was correlated with reductions in volume along the pathway. In contrast, the survivor group treated with radiation may have had possible radiation-induced demyelination of the thalamic-frontal portion of the pathway, based on a strong correlation with volume loss in the cerebellum, red nucleus, thalamus, and frontal lobe.
Assuntos
Sobreviventes de Câncer , Cerebelo/patologia , Lobo Frontal/patologia , Neoplasias Infratentoriais/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Lesões por Radiação/patologia , Núcleo Rubro/patologia , Tálamo/patologia , Substância Branca/patologia , Adolescente , Adulto , Atrofia/patologia , Cerebelo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/terapia , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Lesões por Radiação/diagnóstico por imagem , Núcleo Rubro/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. METHODS: The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. RESULTS: Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. CONCLUSION: The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.
Assuntos
Mapeamento Encefálico/métodos , Globo Pálido/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Núcleo Rubro/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Casos e Controles , Feminino , Globo Pálido/efeitos dos fármacos , Globo Pálido/metabolismo , Globo Pálido/patologia , Humanos , Interpretação de Imagem Assistida por Computador , Ferro/metabolismo , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Núcleo Rubro/efeitos dos fármacos , Núcleo Rubro/metabolismo , Núcleo Rubro/patologia , Índice de Gravidade de Doença , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Tálamo/efeitos dos fármacos , Tálamo/metabolismo , Tálamo/patologiaRESUMO
INTRODUCTION: The aim of this study is to identify disease-specific changes of the thalamus, basal ganglia, pons, and midbrain in patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD), and multiple system atrophy with predominant parkinsonism (MSA-P) using diffusion tensor imaging and volumetric analysis. METHODS: MRI diffusion and volumetric data were acquired in a derivation of 30 controls and 8 patients with PSP and a validation cohort comprised of controls (n = 21) and patients with PSP (n = 27), PD (n = 10), and MSA-P (n = 11). Analysis was performed using regions of interest (ROI), tract-based spatial statistic (TBSS), and tractography and results compared between diagnostic groups. RESULTS: In the derivation cohort, we observed increased mean diffusivity (MD) in the thalamus, superior cerebellar peduncle, and the midbrain in PSP compared to controls. Furthermore, volumetric analysis showed reduced thalamic volumes in PSP. In the validation cohort, the observations of increased MD were replicated by ROI-based analysis and in the thalamus by TBSS-based analysis. Such differences were not found for patients with PD in any of the cohorts. Tractography of the dentatorubrothalamic tract (DRTT) showed increased MD in PSP patients from both cohorts compared to controls and in the validation cohort in PSP compared to PD and MSA patients. Increased MD in the thalamus and along the DRTT correlated with disease stage and motor function in PSP. CONCLUSION: Patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. These changes are associated with disease stage and impaired motor function.
Assuntos
Núcleos Cerebelares/patologia , Doença de Parkinson/patologia , Núcleo Rubro/patologia , Paralisia Supranuclear Progressiva/patologia , Tálamo/patologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas , Vias Neurais/patologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.
Assuntos
Doenças Cerebelares/fisiopatologia , Estimulação Encefálica Profunda , Núcleo Rubro/fisiopatologia , Tremor/terapia , Doenças Cerebelares/diagnóstico , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Núcleo Olivar/patologia , Núcleo Olivar/fisiopatologia , Núcleo Rubro/patologia , Tálamo/patologia , Tálamo/fisiopatologia , Tremor/diagnósticoRESUMO
Atrophy of the dentate nucleus is one of the major neuropathological changes in Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM) degeneration in FRDA. In this study, we used advanced tractography techniques to quantitatively measure WM changes in the dentato-thalamic and dentato-rubral tracts, and correlated these changes with cognitive profiles of FRDA. We also analysed diffusivity changes of the thalamo-cortical tract to assess whether neurological degeneration of WM extends beyond the primary site of involvement in FRDA. Twelve genetically proven individuals with FRDA and 14 controls were recruited. Sixty directions diffusion tensor images were acquired. The WM bundles from the dentate nucleus were estimated using a constrained spherical deconvolution method and the diffusivity characteristics measured. The Simon task was used to assess cognitive profile of FRDA. The dentato-rubral, dentato-thalamic and thalamo-cortical tracts manifested significantly lower fractional anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA compared with controls. There was no difference in axial diffusivity between the two groups. The mean and radial diffusivity of the dentato-rubral tract was positively correlated with choice reaction time, congruent reaction time, incongruent reaction time and Simon effect reaction time and negatively with the larger GAA repeat. Significant changes in diffusivity characteristics were observed in the dentato-thalamic and thalamo-cortical tracts, suggesting extensive WM degeneration and affected WM structures in FRDA. Correlation of WM changes in the dentato-rubral tract with the cognitive assessment suggested that this tract is an important contributor to cognitive disturbances in FRDA.
Assuntos
Núcleos Cerebelares/patologia , Transtornos Cognitivos/patologia , Ataxia de Friedreich/patologia , Núcleo Rubro/patologia , Adulto , Anisotropia , Córtex Cerebral/patologia , Transtornos Cognitivos/etiologia , Imagem de Tensor de Difusão , Feminino , Ataxia de Friedreich/complicações , Ataxia de Friedreich/genética , Humanos , Masculino , Degeneração Neural , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/patologia , Testes Neuropsicológicos , Tempo de Reação , Tálamo/patologiaRESUMO
BACKGROUND: In addition to neuronal injury, inflammatory, and demyelinating processes, evidence suggests multiple sclerosis (MS) is also associated with increased iron deposition in the basal ganglia. Magnetic resonance imaging (MRI), particularly at very high field strengths, is sensitive to iron accumulation and may enable visualization and quantification of iron associated with MS. OBJECTIVES: To investigate the sub-cortical gray matter in patients with early-stage relapsing-remitting MS using multiple, and novel, quantitative MRI measures at very high field. METHODS: In total, 22 patients with relapsing-remitting MS and 22 control subjects were imaged at 4.7 Tesla. Transverse relaxation rates (R2 and R2*) and susceptibility phase were quantified in four basal ganglia nuclei, the thalamus, and the red nuclei. Parameters in patients with MS were compared with those in healthy subjects and correlated with clinical scores. RESULTS: Significant abnormalities were observed in most structures, most notably in the pulvinar sub-nucleus. Significant correlations with disability were observed in the pulvinar; marginally significant correlations were also observed in the thalamus and red nucleus. No significant correlations were observed with duration since index relapse. CONCLUSIONS: Widespread abnormalities are present in the deep gray matter nuclei of patients recently diagnosed with MS; these abnormalities can be detected via multi-modal high-field MRI. Imaging metrics, particularly R2*, relate to disease severity in the pulvinar and other gray matter regions.
Assuntos
Ferro/metabolismo , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/metabolismo , Núcleo Rubro/metabolismo , Núcleo Rubro/patologia , Tálamo/metabolismo , Tálamo/patologiaRESUMO
In vivo and post-mortem studies have demonstrated that increased nigral iron content in patients with Parkinson's disease is a prominent pathophysiological feature. However, the mechanism and risk factors associated with nigral iron deposition in patients with Parkinson's disease have not been identified and represent a key challenge in understanding its pathogenesis and for its diagnosis. In this study, we assessed iron levels in patients with Parkinson's disease and in age- and gender-matched control subjects by measuring phase values using magnetic resonance based susceptibility-weighted phase imaging in a 3T magnetic resonance system. Phase values were measured from brain regions including bilateral substantia nigra, globus pallidus, putamen, caudate, thalamus, red nucleus and frontal white matter of 45 patients with Parkinson's disease with decreased or normal serum ceruloplasmin levels, together with age- and gender-matched control subjects. Correlative analyses between phase values, serum ceruloplasmin levels and disease severity showed that the nigral bilateral average phase values in patients with Parkinson's disease were significantly lower than in control subjects and correlated with disease severity according to the Hoehn and Yahr Scale. The Unified Parkinson's Disease Rating Scale motor scores from the clinically most affected side were significantly correlated with the phase values of the contralateral substantia nigra. Furthermore, nigral bilateral average phase values correlated highly with the level of serum ceruloplasmin. Specifically, in the subset of patients with Parkinson's disease exhibiting reduced levels of serum ceruloplasmin, we found lowered nigral bilateral average phase values, suggesting increased nigral iron content, while those patients with normal levels of serum ceruloplasmin exhibited no changes as compared with control subjects. These findings suggest that decreased levels of serum ceruloplasmin may specifically exacerbate nigral iron deposition in patients with Parkinson's disease. Combining susceptibility-weighted phase imaging with serum ceruloplasmin determination is likely to be useful for the diagnosis and assessment of a subset of patients with Parkinson's disease.
Assuntos
Ceruloplasmina/metabolismo , Ferro/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/metabolismo , Adulto , Idoso , Análise de Variância , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Núcleo Rubro/metabolismo , Núcleo Rubro/patologia , Substância Negra/patologia , Tálamo/metabolismo , Tálamo/patologiaRESUMO
Secondary dystonia is well known subsequent to lesions of the basal ganglia or the thalamus. There is evidence that brainstem lesions may also be associated with dystonia, but little is known about pathoanatomical correlations. Here, we report on a series of four patients with acquired dystonia following brainstem lesions. There were no basal ganglia or thalamic lesions. Three patients suffered tegmental pontomesencephalic hemorrhage and one patient diffuse axonal injury secondary to severe craniocerebral trauma. Dystonia developed with a delay of 1 to 14 months, at a mean delay of 6 months. The patients' mean age at onset was 33 years (range 4-56 years). All patients presented with hemidystonia combined with cervical dystonia, and two patients had craniofacial dystonia in addition. Three patients had postural or kinetic tremors. Dystonia was persistent in three patients, and improved gradually in one. There was little response to medical treatment. One patient with hemidystonia combined with cervical dystonia improved after thalamotomy. Overall, the phenomenology of secondary dystonia due to pontomesencephalic lesions is similar to that caused by basal ganglia or thalamic lesions. Structures involved include the pontomesencephalic tegmentum and the superior cerebellar peduncles. Such lesions are often associated with fatal outcome. While delayed occurrence of severe brainstem dystonia appears to be rare, it is possible that mild manifestations of dystonia might be ignored or not be emphasized in the presence of other disabling deficits.
Assuntos
Hemorragia do Tronco Encefálico Traumática/complicações , Hemorragia Cerebral/complicações , Distúrbios Distônicos/etiologia , Mesencéfalo/patologia , Ponte/patologia , Adulto , Dano Encefálico Crônico/diagnóstico por imagem , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/patologia , Hemorragia do Tronco Encefálico Traumática/diagnóstico por imagem , Hemorragia do Tronco Encefálico Traumática/patologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Pré-Escolar , Doenças dos Nervos Cranianos/etiologia , Lesão Axonal Difusa/etiologia , Progressão da Doença , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/patologia , Distúrbios Distônicos/fisiopatologia , Seguimentos , Traumatismos Cranianos Fechados/complicações , Hematoma Subdural/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Mesencéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Ponte/diagnóstico por imagem , Núcleo Rubro/diagnóstico por imagem , Núcleo Rubro/lesões , Núcleo Rubro/patologia , Estudos Retrospectivos , Tegmento Mesencefálico/diagnóstico por imagem , Tegmento Mesencefálico/lesões , Tegmento Mesencefálico/patologia , Tálamo/cirurgia , Tomografia Computadorizada por Raios X , Tremor/etiologia , Tremor/fisiopatologiaAssuntos
Encéfalo/metabolismo , Ceruloplasmina/genética , Ferro/metabolismo , Mutação , Gânglios da Base/patologia , Encéfalo/patologia , Portador Sadio , Feminino , Triagem de Portadores Genéticos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Núcleo Rubro/patologia , Irmãos , Substância Negra/patologia , Tálamo/patologiaRESUMO
T2 hypointensity (black T2, BT2) in the deep grey matter of multiple sclerosis (MS) patients correlate weakly with disability at 1.5 T. BT2 is likely to be caused by abnormal iron deposition. We compared the correlation between disability and deep grey matter BT2 measured on 3 T MRI and on 1.5 T MRI in 17 MS patients. We observed a significant correlation between expanded disability status scale and signal intensity on 3 T MRI in the globus pallidus and the caudate nucleus (r = -0.5, P < 0.05). BT2 at 3 T may be a useful MRI measure associated with disability in MS and warrants further study.
Assuntos
Encéfalo/patologia , Avaliação da Deficiência , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Biomarcadores/metabolismo , Encéfalo/metabolismo , Núcleo Caudado/metabolismo , Núcleo Caudado/patologia , Feminino , Globo Pálido/metabolismo , Globo Pálido/patologia , Humanos , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Putamen/metabolismo , Putamen/patologia , Núcleo Rubro/metabolismo , Núcleo Rubro/patologia , Substância Negra/metabolismo , Substância Negra/patologia , Tálamo/metabolismo , Tálamo/patologiaAssuntos
Neoplasias Encefálicas/diagnóstico , Síndrome de Korsakoff/diagnóstico , Linfoma de Células B/diagnóstico , Núcleo Rubro/patologia , Ataxia/etiologia , Ataxia/patologia , Ataxia/fisiopatologia , Neoplasias Encefálicas/complicações , Diagnóstico Diferencial , Diplopia/etiologia , Diplopia/patologia , Diplopia/fisiopatologia , Disartria/etiologia , Disartria/patologia , Disartria/fisiopatologia , Feminino , Humanos , Síndrome de Korsakoff/tratamento farmacológico , Síndrome de Korsakoff/fisiopatologia , Linfoma de Células B/complicações , Pessoa de Meia-Idade , Mutismo/etiologia , Mutismo/patologia , Mutismo/fisiopatologia , Núcleo Rubro/fisiopatologia , Tálamo/patologia , Tálamo/fisiopatologia , Tiamina/uso terapêutico , Transcetolase/sangueRESUMO
OBJECTIVE: To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography. BACKGROUND: Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both. METHODS: Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99. RESULTS: There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious. CONCLUSIONS: This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern demonstrated in hemicrania continua mirrors the clinical phenotype, with its overlap with trigeminal autonomic headaches and migraine.
Assuntos
Hipotálamo/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Ponte/fisiopatologia , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Circulação Cerebrovascular , Método Duplo-Cego , Feminino , Humanos , Hipotálamo/patologia , Indometacina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/tratamento farmacológico , Ponte/patologia , Tomografia por Emissão de Pósitrons , Núcleo Rubro/patologia , Núcleo Rubro/fisiopatologia , Substância Negra/patologia , Substância Negra/fisiopatologiaRESUMO
This paper describes the toxic effects of chloromycetin on the motor neurons of the Chinese tree shrew (Tupaia belangeri chinensis) with horse radish peroxidase (HRP) as the labeling enzyme. When chloromycetin was administered orally at 2.5 mg/kg (body weight)/day for 3 days, Chinese tree shrews showed evidence of neurotoxicity. This included damage in cortical motor neuron synapses ending on neurons of the red nucleus and the ultrastructural changes in the mitochondria such as swelling of these organelles and blurring of their cristae. There was an increase of the mitochondrial matrix density and of the thickness of the synaptic membranes. These observations indicate that chloromycetin can lead to ultrastructural change of terminals of the cortical motor axons, and that Chinese tree shrews are sensitive animal model for chloromycetin neurotoxicity.
Assuntos
Cloranfenicol/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/ultraestrutura , Tupaiidae/fisiologia , Administração Oral , Animais , Anorexia/induzido quimicamente , Cloranfenicol/administração & dosagem , Cloranfenicol/sangue , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Peroxidase do Rábano Silvestre , Masculino , Microscopia Eletrônica/instrumentação , Microscopia Eletrônica/métodos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Neurônios Motores/patologia , Transtornos Neuróticos/induzido quimicamente , Núcleo Rubro/patologia , Núcleo Rubro/ultraestrutura , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/ultraestrutura , Vesículas Sinápticas/efeitos dos fármacos , Vesículas Sinápticas/ultraestrutura , Fatores de TempoRESUMO
AIM: Deep brain stimulation (DBS) is the treatment of choice for advanced Parkinson's disease. The target co-ordinates are traditionally calculated in relation to the intercommissural distance. Anterior (AC) and posterior commissures (PC) may be visualised by the means of ventriculography, CT or MRI. METHODS: We have studied the efficacy of direct visualisation of the subthalamic-red nucleus complex on MRI, the advantage of fusion of stereotactic CT and MR images (Multiple Sequences Image Fusion - MuSIF). These methods are combined with double check of indirect calculation of the target co-ordinates based on AC-PC line, as well as the corrispondence to the stereotactic electronic atlas. RESULTS: Subthalamic nucleus (STN) was well recognisable in fused images in all 22 sides. At 3 months from surgery it was possible to reduce 76% of L-dopa equivalent daily dose. Dyskine-sias reduced to 50% and motor fluctuation up to 45%. CONCLUSION: In our experience MuSIF offers very high rate of accuracy in calculation of target co-ordinates. Direct visualisation of STN in MR and MuSIF are reliable and facilitate the accuracy of identification of target co-ordinates. Intraoperative neurophysiological recording increases the accuracy of microelectrode position.
Assuntos
Terapia por Estimulação Elétrica , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/patologia , Tomografia Computadorizada por Raios X , Antiparkinsonianos/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Levodopa/administração & dosagem , Masculino , Doença de Parkinson/tratamento farmacológico , Período Pós-Operatório , Núcleo Rubro/patologia , Técnicas EstereotáxicasRESUMO
The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.
Assuntos
Gânglios da Base/patologia , Terapia por Estimulação Elétrica , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Doença de Parkinson/terapia , Técnicas Estereotáxicas , Adulto , Idoso , Gânglios da Base/fisiopatologia , Mapeamento Encefálico , Eletrodos Implantados , Feminino , Globo Pálido/patologia , Globo Pálido/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Núcleo Rubro/patologia , Núcleo Rubro/fisiopatologia , Valores de Referência , Substância Negra/patologia , Substância Negra/fisiopatologia , Núcleo Subtalâmico/patologia , Núcleo Subtalâmico/fisiopatologiaRESUMO
CONTEXT: While gray matter T2 hypointensity in multiple sclerosis (MS) has been associated with physical disability and clinical course, previous studies have relied on visual magnetic resonance imaging (MRI) assessments. OBJECTIVE: To quantitatively determine if T2 hypointensity is associated with conventional MRI and clinical findings in MS. DESIGN: Case-control study. SETTING: University-affiliated community-based hospital. SUBJECTS: Sixty patients with MS and 50 controls. MAIN OUTCOME MEASURES: T2 intensities of the substantia nigra, red nucleus, thalamus, putamen, globus pallidus, and caudate; third ventricular width; total brain T1 (hypointense) and T2 (hyperintense) lesion volumes; Expanded Disability Status Scale (physical disability) score; and disease course. RESULTS: Deep gray matter T2 hypointensity was present in patients with MS in all structures (P<.005) except for the substantia nigra. T2 hypointensity was associated with third ventricle enlargement and higher T2 but not T1 plaque load. The regression model predicting third ventricle width included caudate T2 hypointensity (P =.006). The model predicting T2 lesion load included globus pallidus T2 hypointensity (P =.001). Caudate T2 hypointensity was the only variable associated with disability score in regression modeling (P =.03). All T2 hypointensities differentiated the secondary progressive from the relapsing-remitting clinical courses. The final model (P<.001) predicting clinical course retained T2 hypointensity of the thalamus, caudate, and putamen but not MRI plaques or atrophy. CONCLUSIONS: Gray matter T2 hypointensity in MS is associated with brain atrophy and is a stronger predictor of disability and clinical course than are conventional MRI findings. While longitudinal studies are warranted, these results suggest that pathologic iron deposition is a surrogate marker of the destructive disease process.
Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Atrofia , Gânglios da Base/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Rubro/patologia , Substância Negra/patologia , Tálamo/patologia , Terceiro Ventrículo/patologiaRESUMO
Orthotopic liver transplantation (OLT) has been applied to patients with Wilson's disease (WD) for correction of irreversible liver cirrhosis. However, the neurological outcome and the correlation between clinical manifestations and neuroimage findings after OLT remain uncertain. We present a WD patient who showed an improvement in both liver functions and neurological manifestations after OLT. Serum levels of ceruloplasmin and copper returned to normal rapidly after the operation. His ataxic gait was improved 5 months later and dysmetria and tremor disappeared 11 months later. The high signal intensities on T2-weighted brain magnetic resonance images regressed at bilateral thalami 5 months later and disappeared in bilateral thalami and red nuclei 16 months after OLT. We conclude that the neurological improvement could be expected in WD patients after OLT. The improvement was correlated with the MRI changes in red nuclei and bilateral thalami.
Assuntos
Encéfalo/patologia , Discinesias/etiologia , Discinesias/terapia , Degeneração Hepatolenticular/cirurgia , Transplante de Fígado , Adulto , Discinesias/patologia , Discinesias/fisiopatologia , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/patologia , Degeneração Hepatolenticular/fisiopatologia , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Masculino , Recuperação de Função Fisiológica , Núcleo Rubro/patologia , Tálamo/patologia , Resultado do TratamentoRESUMO
OBJECT: Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance. METHODS: Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure-posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately. Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted. CONCLUSIONS: At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the "off' and "on" medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopa-induced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.
Assuntos
Terapia por Estimulação Elétrica/métodos , Eletroencefalografia , Imageamento por Ressonância Magnética , Doença de Parkinson/terapia , Radiologia Intervencionista , Técnicas Estereotáxicas , Núcleo Subtalâmico , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Discinesia Induzida por Medicamentos/prevenção & controle , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Levodopa/efeitos adversos , Masculino , Mesencéfalo/patologia , Pessoa de Meia-Idade , Monitorização Intraoperatória , Movimento , Doença de Parkinson/tratamento farmacológico , Planejamento de Assistência ao Paciente , Núcleo Rubro/patologia , Segurança , Núcleo Subtalâmico/patologia , Tremor/fisiopatologia , Tremor/terapiaRESUMO
Described herein is a patient with Wilson's disease who had tremor as a prominent neurological manifestation. T2-weighted magnetic resonance imaging showed abnormal high signal intensities in the bilateral lenticular nuclei, thalami, and red nuclei of the midbrain. Improvement of tremor with copper chelating agents was well correlated with a decrease of the abnormal signals in the thalami and the red nuclei.
Assuntos
Degeneração Hepatolenticular/patologia , Imageamento por Ressonância Magnética , Adolescente , Quelantes/uso terapêutico , Cobre , Corpo Estriado/patologia , Feminino , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/fisiopatologia , Humanos , Núcleo Rubro/patologia , Tálamo/patologia , Tremor/tratamento farmacológico , Tremor/fisiopatologiaRESUMO
We evaluated the magnetic resonance images of the patients with intention tremor. Five patients out of seven had some atrophic structures or changes in signal intensity in the cerebello-rubral thalamic tract. Moreover, the T2-weighted images of the patients group detected the dentate and red nuclei more poorly than those of our control group. From these results, the etiological significance of the tract was confirmed and the mechanism of the intention tremor onset was discussed.