'Wind-up' in Parkinson's disease: A functional magnetic resonance imaging study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder mainly marked by selective degeneration of dopaminergic neurons that leads to disabling motor and cognitive impairment. This condition is less widely appreciated as a disease associated with a substantial variety of pain syndromes, although the prevalence of pain is relatively high. Repeated painful stimulation of peripheral nerves can cause pain 'wind-up' if the frequency of the stimulation is adequate and specifically stimulates the afferent C-fibres. We presumed that in case of PD, pain or pain severeness might be frequently caused by the aggravation of the 'wind-up' phenomenon due to any central or peripheral lesions or functional alterations. METHODS: To test for this hypothesis, we compared three groups (patients with left- and right-dominant PD and control subjects) using functional magnetic resonance imaging and thermally induced pain. RESULTS: Patient showed higher average 'wind-up' scores, compared to the healthy subjects, with lower values on the more affected sides compared to the less affected ones. In group level comparisons, patients had higher activation during 'wind-up' compared to control subjects in two main areas; these were the posterior division of cingulate gyrus and the precuneus cortex. In case of patients, further analyses showed that applied heat pain on the less affected side elicited higher activation in the supramarginal and postcentral gyri. CONCLUSIONS: These differences may arise from the deficiency in the efferent information, as well as the alterations in the central processing. It is highly likely that both processes contribute to this phenomenon simultaneously.

Cortical involvement during myotonia in myotonic dystrophy: an fMRI study.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is a common adulthood muscular dystrophy, characterized by muscle wasting, myotonia, and multisystemic manifestations. The phenomenon of involuntary muscle contraction during myotonia offers a unique possibility of investigating brain motor functions. This study explores cortical involvement during grip myotonia in DM1. MATERIALS AND METHODS: Sixteen DM1 patients were enrolled in the study. Eight patients had apparent grip myotonia, while eight patients did not (control subjects). All patients underwent functional MRI grip task examination twice: prior a warm-up procedure (myotonia was elicited in patients with apparent grip myotonia) and after a warm-up procedure (myotonia was attenuated in patients with apparent grip myotonia). No myotonia was elicited during either examination in patients without apparent grip myotonia. Cerebral blood oxygen level-dependent (BOLD) signals were compared both between groups with and without apparent myotonia, and between pre- and post-warm-up sessions. RESULTS: Significantly higher BOLD signal was found during myotonia phase in patients with apparent grip myotonia compared to corresponding non-myotonia phase of patients without apparent grip myotonia in the supplementary motor area and in the dorsal anterior cingulate cortex. Significant differences in BOLD signal levels of very similar pattern were detected between prewarm-up session myotonia phase and post-warm-up session myotonia absent phase in the group of patients with apparent grip myotonia. CONCLUSION: We showed that myotonia is related to cortical function in high-order motor control areas. This cortical involvement is most likely to represent action of inhibitory circuits intending motor termination.

A statistical model for intervertebral disc degeneration: determination of the optimal T2 cut-off values.

PURPOSE: The aim of this study was to investigate the possibility of quantitative classification in intervertebral disc degeneration using spin-spin relaxation time (T2) cut-off values with regard to morphological classifications. METHODS: Lumbar magnetic resonance (MR) imaging was performed on 21 subjects (a total of 104 lumbar disks). The T2 relaxation time was measured in the nucleus pulposus using a sagittal multi-echo spin-echo sequence. The morphological classification of disc degeneration was assessed independently by three experienced neuroradiologists according to the Pfirrmann and Schneiderman classifications. Receiver operating characteristic analysis was performed among grades to determine T2 cut-off values in each classification. Intra- and interobserver differences were calculated using kappa statistics. RESULTS: Moderate overall interobserver agreement was found between observers in both the Pfirrmann and Schneiderman classification schemes (kappa 0.46 and 0.51), while intraobserver reliability was substantial to almost perfect. The interobserver reliability was only fair in Pfirrmann grades III and IV (kappa 0.33 and 0.36), but the T2 cut-off values still indicated a significant difference between grades (p<0.05). CONCLUSIONS: Interobserver agreement of MR evaluation in patients with intervertebral disc degeneration was only fair to moderate on the classification of more severe disc degeneration in the Pfirrmann and Schneiderman schemes. Based on our results, quantitative T2 cut-off values seem to be a more reliable method to define the degree of disc degeneration, which may help staging intervertebral disc degeneration (IVDD) even if the interobserver reliability is low.

Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicentre study.

OBJECTIVE: To assess the risk of adverse perinatal events of vaccination of pregnant women with an MF59 adjuvanted vaccine. DESIGN: Cross sectional multicentre study. SETTING: 49 public hospitals in major cities in Argentina, from September 2010 to May 2011. PARTICIPANTS: 30,448 mothers (7293 vaccinated) and their 30,769 newborns. MAIN OUTCOME MEASURE: Primary composite outcome of low birth weight, preterm delivery, or fetal or early neonatal death up to seven days postpartum. RESULTS: Vaccinated women had a lower risk of the primary composite outcome (7.0% (n=513) v 9.3% (n=2160); adjusted odds ratio 0.80, 95% confidence interval 0.72 to 0.89). The propensity score analysis showed similar results. Adjusted odds ratios for vaccinated women were 0.74 (0.65 to 0.83) for low birth weight, 0.79 (0.69 to 0.90) for preterm delivery, and 0.68 (0.42 to 1.06) for perinatal mortality. These findings were consistent in further subgroup analysis. No significant differences in maternal outcomes were found. CONCLUSION: This large study using primary data collection found that MF59 adjuvanted A/H1N1 influenza vaccine did not result in an increased risk of adverse perinatal events and suggested a lower risk among vaccinated women. These findings should contribute to inform stakeholders and decision makers on the prescription of vaccination against influenza A/H1N1 in pregnant women.

Lateralisation of non-metric rhythm.

There are contradictory results on lateralisation and localisation of rhythm processing. Our aim was to test whether there is a hemispheric dissociation of metric and non-metric rhythm processing. We created a non-metric rhythm stimulus without a sense of metre and we measured brain activities during passive rhythm perception. A total of 11 healthy, right-handed, native female Hungarian speakers aged 21.3 ± 1.1 were investigated by functional magnetic resonance imaging (fMRI) using a 3T MR scanner. The experimental acoustic stimulus consisted of comprehensive sentences transformed to Morse code, which represent a non-metric rhythm with irregular perceptual accent structure. Activations were found in the right hemisphere, in the posterior parts of the right-sided superior and middle temporal gyri and temporal pole as well as in the orbital part of the right inferior frontal gyrus. Additional activation appeared in the left-sided superior temporal region. Our study suggests that non-metric rhythm with irregular perceptual accents structure is confined to the right hemisphere. Furthermore, a right-lateralised fronto-temporal network extracts the continuously altering temporal structure of the non-metric rhythm.

Quantitative proton MRI and MRS of the rat brain with a 3T clinical MR scanner.

OBJECTIVE: To demonstrate the capability of a clinical 3T human scanner in performing quantitative MR experiments in the rat brain. MATERIAL AND METHODS: In vivo, measurements on eight Wistar rats were performed. Longitudinal relaxation time (T1) and transverse relaxation time (T2) measurements were set up at a spatial resolution of 0.3×0.3×1mm(3). Diffusion-weighted imaging was also applied and the evaluation included both mono- and biexponential approaches (b-value up to 6000s/mm(2)). Besides quantitative imaging, the rat brain was also scanned at a microscopic resolution of 130×130×130µm(3). Quantitative proton spectroscopy was also carried out on the rat brain with water as internal reference. RESULTS: T1 and T2 for the rat brain cortex were 1272±85ms and 75±2ms, respectively. Diffusion-weighted imaging yielded accurate diffusion coefficient measurements at both low and high b-value ranges. The concentrations of MR visible metabolites were determined for the major resonances (i.e., N-acetyl-aspartate, choline and creatine) with acceptable accuracy. CONCLUSION: The results suggest that quantitative imaging and spectroscopy can be carried out on small animals on high-field clinical scanners.

1H-MRS experiences after bilateral DBS of the STN in Parkinson's disease.

UNLABELLED: The objective of this study was to evaluate the changes in the concentrations of certain brain metabolites in 13 patients with Parkinson's disease before and after bilateral subthalamic nucleus (STN DBS). The N-acetylaspartate (NAA)/choline (Chol), NAA/creatine (Cr), Chol/Cr ratios were determined by single voxel Proton magnetic resonance spectroscopy ((1)H-MRS) studies on 1.0T unit using short TE stimulated echo acquisition mode (STEAM) sequence. Spectra were obtained from the right and left globus pallidus, and left fronto-basal cortex. The patients were also assessed according to the UPDRS part III, in the "medication-on and off" conditions. CONCLUSIONS: after STN DBS cortical NAA/Cho, NAA/Cr ratios increased significantly, which were highly correlated with the significant improvements of the UPDRS scores.

Fast method for longitudinal relaxation time and water content mapping of the human brain on a clinical MR scanner.

BACKGROUND: Longitudinal relaxation time (T(1)) map generation from human brain slices renders possible the in vivo follow-up of the changes in T(1) values during the course of several pathologies such as stroke, multiple sclerosis, traumatic brain injury etc. T(1) values can be converted to water contents, thus brain oedema reducing therapy can be non-invasively evaluated. The purpose of the study was to work out a fast and simple MRI method to obtain T(1) and water maps of the human brain. METHOD: The T(1) values of Gadolinium solutions with different concentrations were determined by means of MRI methods at a clinical MR scanner operating at 1 Tesla. In order to validate these measurements, T(1) values of the same Gadolinium solutions were also quantified with a relaxometer operating at the same field strength. T(1) and water maps from the brains of healthy volunteers were obtained with an inversion prepared spoiled gradient echo sequence (turbo-FLASH). FINDINGS: The T(1) values of Gadolinium solutions measured with the relaxometer showed a strong correlation (r > 0.999) with those determined with MRI sequences on the whole body scanner. The fastest MRI method to produce T(1) and consequent water maps from human brain was the inversion prepared turbo-FLASH sequence. CONCLUSIONS: The implemented turbo-FLASH method can produce T(1) and water map of a single virtual brain slice within 2 minutes. However, brain tissue containing haemorrhage should be excluded from the measurement due to the large influence of excessive haemoglobin concentration on longitudinal relaxation. The proposed method is available on most of the MR scanners, thus T(1) and water mapping of human brain can be routinely performed.

Fast in vivo water quantification in rat brain oedema based on T(1) measurement at high magnetic field.

BACKGROUND: In vivo water content determination based on magnetic resonance (MR) method is of importance in clinical practice as well as in animal studies to follow up the treatment given in order to reduce brain oedema. The methods proposed in the literature so far are largely time consuming. The aim of this study was to find a fast in vivo water quantification method having real advantage for patients suffering from critical conditions. METHOD: Cold injury was applied to provoke brain oedema in fourteen rats. T(1) values of both the oedematous area and the contralateral normal cortex were determined by two independent methods 24 hours after the cold impact. First, from a series of images recorded by inversion recovery spin echo (IRSE) sequence and then by progressive saturation experiment performed by localised MR spectroscopy using stimulated echo acquisition mode (STEAM). To reduce the acquisition time, a two-element repetition time array was optimised for the STEAM experiment, whereas four inversion times were used for T(1) mapping. Both methods were validated against gel phantoms with known T(1) values. After the MR measurements the animals were sacrificed and the water contents of the regions of interest were determined by gravimetric wet-dry method. FINDINGS: The reciprocals of the in vivo measured T(1) values were correlated with the reciprocals of the brain water contents. STEAM experiment showed stronger correlation (r=0.96) than IRSE (r=0.93). In addition, STEAM provided more accurate T(1) values in the phantom study. Determination of brain water content based on T1 measurement does work also at high magnetic field. Determination of brain water content by Magnetic Resonance Spectroscopy is feasible within 2 minutes. INTERPRETATION: Using the presented fast method, water content can be determined within a couple of minutes in animal experiments as well as in the daily clinical practice.

In vivo water quantification in mouse brain at 9.4 Tesla in a vasogenic edema model.

The aim of our study was to establish a simple in vivo method for water quantification in vasogenic edema, and provide data on imaging of mouse brain at 9.4 Tesla. Apparent T1 and spin density values determined by MRI were found to strongly correlate with the gravimetric water content of mouse brain undergoing cold injury. Using a two-point calibration line between the spin density values for pure water and cortex of mouse brain, as well as the corresponding water contents in vivo, water could be quantified with satisfactory accuracy.

Mortalidad perinatal en la provincia de Chubut / Perinatalmortality in the province of Chubut

Se analizarona través de un método clasificatorio sencillo las muertes perinatales (n:115) ocurridas en los hospitales de Comodoro Rivadavia, Trelew, Puerto Madryn y Esquelen 1994. El método empleado puede agrupar rápidamente las causas evitables con el objetivo de desarrollar futuras acciones preventivas o curativas del sistema de salud. En la mortalidad fetal predominaron los fetos macerados con peso menora 2500 grs. En la mortalidad neonatal las causas más comunes fueron: bajo peso y prematurez (66 por ciento) y muy bajo peso (45 por ciento). Casi la mitad de la mortalidad neonatal ocurrió en el primer día de vida. Se comprobó una muy elevada frecuencia (43 por ciento) de falta de control del embarazo en la| mortalidad fetal y neonatal. Los resultados obtenidos con el método clasificatorio propuesto permiten inferir la necesidad de mejorar los niveles de atención primaria dela embarazada y los estándares de atención del neonato de bajo peso para disminuir la mortalidad perinatal (AU)

Mortalidad perinatal en la provincia de Chubut / Perinatalmortality in the province of Chubut

Se analizarona través de un método clasificatorio sencillo las muertes perinatales (n:115) ocurridas en los hospitales de Comodoro Rivadavia, Trelew, Puerto Madryn y Esquelen 1994. El método empleado puede agrupar rápidamente las causas evitables con el objetivo de desarrollar futuras acciones preventivas o curativas del sistema de salud. En la mortalidad fetal predominaron los fetos macerados con peso menora 2500 grs. En la mortalidad neonatal las causas más comunes fueron: bajo peso y prematurez (66 por ciento) y muy bajo peso (45 por ciento). Casi la mitad de la mortalidad neonatal ocurrió en el primer día de vida. Se comprobó una muy elevada frecuencia (43 por ciento) de falta de control del embarazo en la- mortalidad fetal y neonatal. Los resultados obtenidos con el método clasificatorio propuesto permiten inferir la necesidad de mejorar los niveles de atención primaria dela embarazada y los estándares de atención del neonato de bajo peso para disminuir la mortalidad perinatal