Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.72272

Derek Denny-brown: O Homem Por Detrás Dos Gânglios

The authors present an historical review about the main contributions of Professor Derek Denny-Brown to neurology. Some of his achievements include the first description of sensory neuronopathies, and some of the essential textbooks on the function and anatomy of the basal ganglia. In 2016, on the 35th anniversary of his death, modern neurologists are still strongly influenced by his legacy. © 2017, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.75212712

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations ofN-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh;t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence

Multimodal MRI-based study in patients with SPG4 mutations

Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our objective is to identify regions of the central nervous system damaged in patients with SPG4-HSP using a multi-modal neuroimaging approach. In addition, we aimed to identify possible clinical correlates of such damage. Eleven patients (mean age 46.0 ± 15.0 years, 8 men) with molecular confirmation of hereditary spastic paraplegia, and 23 matched healthy controls (mean age 51.4 ± 14.1years, 17 men) underwent MRI scans in a 3T scanner. We used 3D T1 images to perform volumetric measurements of the brain and spinal cord. We then performed tract-based spatial statistics and tractography analyses of diffusion tensor images to assess microstructural integrity of white matter tracts. Disease severity was quantified with the Spastic Paraplegia Rating Scale. Correlations were then carried out between MRI metrics and clinical data. Volumetric analyses did not identify macroscopic abnormalities in the brain of hereditary spastic paraplegia patients. In contrast, we found extensive fractional anisotropy reduction in the corticospinal tracts, cingulate gyri and splenium of the corpus callosum. Spinal cord morphometry identified atrophy without flattening in the group of patients with hereditary spastic paraplegia. Fractional anisotropy of the corpus callosum and pyramidal tracts did correlate with disease severity. Hereditary spastic paraplegia is characterized by relative sparing of the cortical mantle and remarkable damage to the distal portions of the corticospinal tracts, extending into the spinal cord.Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our is to identify regions of the central nervous system damag102FAPESP - FUNDAÇÃO DE AMPARO A PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR2011/21521-3sem informaçãoFink, J.K., Hereditary spastic paraplegia: Clinico-pathologic features and emerging molecular mechanisms (2013) Acta Neuropathol, 126, pp. 307-328. , PMID: 23897027Depienne, C., Fedirko, E., Forlani, S., Cazeneuve, C., Ribaï, P., Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia (2007) J Med Genet, 44, pp. 281-284. , PMID: 17098887Charvin, D., Cifuentes-Diaz, C., Fonknechten, N., Joshi, V., Hazan, J., Mutations of SPG4 are responsible for a loss of function of spastin, an abundant neuronal protein localized in the nucleus (2003) Hum Mol Genet, 12, pp. 71-78. , PMID: 12490534França, M.C., Jr., Dogini, D.B., D'Abreu, A., Teive, H.A., Munhoz, R.P., SPG4-related hereditary spastic paraplegia: Frequency and mutation spectrum in Brazil (2014) Clin Genet, 86, pp. 194-196. , PMID: 24033003Duning, T., Warnecke, T., Schirmacher, A., Schiffbauer, H., Lohmann, H., Specific pattern of early white-matter changes in pure hereditary spastic paraplegia (2010) MovDisord, 25, pp. 1986-1992França, M.C., Jr., Yasuda, C.L., Pereira, F.R., D'Abreu, A., Lopes-Ramos, C.M., White and grey matter abnormalities in patients with SPG11 mutations (2012) J NeurolNeurosurg Psychiatry, 83, pp. 828-833. , PMID: 22696581Le Bihan, D., Mangin, J.F., Poupon, C., Clark, C.A., Pappata, S., Diffusion tensor imaging: Concepts and applications (2001) J MagnReson Imaging, 13, pp. 534-546. , PMID: 11276097Schüle, R., Holland-Letz, T., Klimpe, S., Kassubek, J., Klopstock, T., The Spastic Paraplegia Rating Scale (SPRS): A reliable and valid measure of disease severity (2006) Neurology, 67, pp. 430-434. , PMID: 16894103Dale, A.M., Fischl, B., Sereno, M.I., Cortical surface-based analysis I: Segmentation and surface reconstruction (1999) NeuroImage, 9, pp. 179-194. , PMID: 9931268Fischl, B., Dale, A.M., Measuring the thickness of the human cerebral cortex from magnetic resonance images (2000) ProcNatlAcadSci U S A, 97, pp. 11050-11055. , PMID: 10984517Fischl, B., Salat, D.H., Busa, E., Albert, M., Dieterich, M., Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain (2002) Neuron, 33, pp. 341-355. , PMID: 11832223Desikan, R.S., Ségonne, F., Fischl, B., Quinn, B.T., Dickerson, B.C., An automated labeling system for subdividing the human cerebral cortex on mri scans into gyral based regions of interest (2006) NeuroImage, 31, pp. 968-980. , PMID: 16530430Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Ract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data (2006) Neuroimage, 31, p. 1487e505. , PMID: 16624579Lebel, C., Walker, L., Leemans, A., Phillips, L., Beaulieu, C., Microstructural maturation of the human brain from childhood to adulthood (2008) Neuroimage, 40, pp. 1044-1055. , PMID: 18295509Bergo, F.P.G., França, M.C., Jr., Chevis, C.F., Cendes, F., SpineSeg: A segmentation and measurement tool for evaluation of spinal cord atrophy (2012) CISTI'2012 (7? Conferencia Ibérica de Sistemas y Tecnologia de Información), pp. 400-403. , Madrid, Spain: IEEEFitzgibbon, A., Pilu, M., Fisher, R.B., Direct least square fitting of ellipses (1999) IEEE Trans Patt Anal Mach Intel, 21, pp. 476-480Kassubek, J., Sperfeld, A.D., Baumgartner, A., Huppertz, H.J., Riecker, A., Brain atrophy in pure and complicated hereditary spastic paraparesis: A quantitative 3D MRI study (2006) Eur J Neurol, 13, pp. 880-886. , PMID: 16879300Uttner, I., Baumgartner, A., Sperfeld, A.D., Kassubek, J., Cognitive performance in pure and complicated hereditary spastic paraparesis: A neuropsychological and neuroimaging study (2007) Neurosci Lett, 419, pp. 158-161. , PMID: 17485167McDermott, C., White, K., Bushby, K., Shaw, P., Hereditary spastic paraparesis: A review of new developments (2000) J Neurol Neurosurg Psychiatry, 69, pp. 150-160. , PMID: 10896685Garaci, F., Toschi, N., Lanzafame, S., Meschini, A., Bertini, E., Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia (2014) Int J Neurosci, 124, pp. 261-270. , PMID: 23968121Hedera, P., Eldevik, O.P., Maly, P., Rainier, S., Fink, J.K., Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia (2005) Neuroradiology, 47, pp. 730-734. , PMID: 16143870Salinas, S., Carazo-Salas, R.E., Proukakis, C., Schiavo, G., Warner, T.T., Spastin and microtubules: Functions in health and disease (2007) J Neurosci Res, 85, pp. 2778-2782. , PMID: 17348041Karle, K.N., Schüle, R., Klebe, S., Otto, S., Frischholz, C., Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP) (2013) Orphanet J Rare Dis, 9 (8), p. 158. , PMID: 24107482Sun, S.W., Liang, H.F., Cross, A.H., Song, S.K., Evolving Wallerian degeneration after transient retinal ischemia in mice characterized by diffusion tensor imaging (2008) Neuroimage, 40, pp. 1-10. , PMID: 18187343Concha, L., Gross, D.W., Wheatley, B.M., Beaulieu, C., Diffusion tensor imagingof time-dependent axonal and myelin degradation after corpus callosotomyin epilepsy patients (2006) Neuroimage, 32, pp. 1090-1099. , PMID: 16765064Murphy, S., Gorman, G., Beetz, C., Byrne, P., Dytko, M., Dementia in SPG4 hereditary spastic paraplegia: Clinical, genetic, and neuropathologic evidence (2009) Neurology, 73, pp. 378-384. , PMID: 19652142White, K.D., Ince, P.G., Lusher, M., Lindsey, J., Cookson, M., Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation (2000) Neurology, 55, pp. 89-94. , PMID: 10891911Branco, L.M., De Albuquerque, M., De Andrade, H.M., Bergo, F.P., Nucci, A., Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis (2014) Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 15, pp. 93-97. , PMID: 25382834Aghakhanyan, G., Martinuzzi, A., Frijia, F., Vavla, M., Hlavata, H., Brainwhitematterinvolvement in hereditaryspasticparaplegias: Analysis with multiplediffusiontensorindices (2014) AJNR Am J Neuroradiol, 35, pp. 1533-1538. , PMID: 24788132Verstraete, E., Van Den Heuvel, M.P., Veldink, J.H., Blanken, N., Mandl, R.C., Motor network degeneration in amyotrophic lateral sclerosis: A structural and functional connectivity study (2010) PLoS One, 5, p. e13664. , PMID: 2106068

Multimodal Mri-based Study In Patients With Spg4 Mutations

Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our objective is to identify regions of the central nervous system damaged in patients with SPG4-HSP using a multi-modal neuroimaging approach. In addition, we aimed to identify possible clinical correlates of such damage. Eleven patients (mean age 46.0 ± 15.0 years, 8 men) with molecular confirmation of hereditary spastic paraplegia, and 23 matched healthy controls (mean age 51.4 ± 14.1years, 17 men) underwent MRI scans in a 3T scanner. We used 3D T1 images to perform volumetric measurements of the brain and spinal cord. We then performed tract-based spatial statistics and tractography analyses of diffusion tensor images to assess microstructural integrity of white matter tracts. Disease severity was quantified with the Spastic Paraplegia Rating Scale. Correlations were then carried out between MRI metrics and clinical data. Volumetric analyses did not identify macroscopic abnormalities in the brain of hereditary spastic paraplegia patients. In contrast, we found extensive fractional anisotropy reduction in the corticospinal tracts, cingulate gyri and splenium of the corpus callosum. Spinal cord morphometry identified atrophy without flattening in the group of patients with hereditary spastic paraplegia. Fractional anisotropy of the corpus callosum and pyramidal tracts did correlate with disease severity. Hereditary spastic paraplegia is characterized by relative sparing of the cortical mantle and remarkable damage to the distal portions of the corticospinal tracts, extending into the spinal cord