ABSTRACT
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.
Subject(s)
Huntington Disease/metabolism , Magnetic Resonance Spectroscopy , Thalamic Diseases/metabolism , Thalamus/physiopathology , Adolescent , Adult , Aged , Aspartic Acid/analogs & derivatives , Aspartic Acid/analysis , Case-Control Studies , Creatine/analysis , Deuterium , Dipeptides/analysis , Female , Glycerylphosphorylcholine/analysis , Humans , Male , Middle Aged , Motor Activity , Phosphocreatine/analysis , Phosphorylcholine/analysis , Thalamic Diseases/diagnosis , Trinucleotide Repeats , Young AdultABSTRACT
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.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Huntington Disease/metabolism , Magnetic Resonance Spectroscopy , Thalamic Diseases/metabolism , Thalamus/physiopathology , Aspartic Acid/analysis , Aspartic Acid/analogs & derivatives , Case-Control Studies , Creatine/analysis , Deuterium , Dipeptides/analysis , Glycerylphosphorylcholine/analysis , Motor Activity , Phosphocreatine/analysis , Phosphorylcholine/analysis , Trinucleotide Repeats , Thalamic Diseases/diagnosisABSTRACT
OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.
Subject(s)
Multiple Sclerosis/epidemiology , Pregnancy Complications/epidemiology , Adolescent , Adult , Birth Weight/drug effects , Brazil/epidemiology , Data Interpretation, Statistical , Databases, Factual , Female , Glatiramer Acetate , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Interferon Type I/adverse effects , Interferon Type I/therapeutic use , Multiple Sclerosis/drug therapy , Peptides/adverse effects , Peptides/therapeutic use , Pregnancy , Pregnancy Outcome , Recombinant Proteins , Recurrence , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: The mechanisms guiding the progression of neuronal damage in patients with Huntington disease (HD) are not completely understood. It is unclear whether the genotype--that is, the length of the expanded CAG repeat--guides the location and speed of grey matter decline once HD is clinically manifested. Moreover, the relationship between cortical and subcortical grey matter atrophy and the severity of motor symptoms of HD is controversial. OBJECTIVES: In this article, we longitudinally studied, over the period of 1 year, a cohort of 49 patients with HD. We investigated: first, the clinical relevance of regional progressive grey matter atrophy; and second, the relationship between the ratio of atrophy progression and genotype. METHODS: The length of the expanded CAG repeat was quantified for all patients and the United Huntington's Disease Rating Scale (UHDRS) was used to rate the severity of clinical symptoms. Grey matter atrophy was determined using voxel-based morphometry (VBM) of brain MRI. Progression of atrophy was quantified in 37 patients who were submitted to two different MRI scans, the second scan 1 year later than the first. RESULTS: Overall, patients exhibited progressive atrophy involving the caudate, pallidum, putamen, insula, cingulate cortex, cerebellum, orbitofrontal cortex, medial temporal lobes and middle frontal gyri. Patients with a larger UHDRS score exhibited selective atrophy of the caudate, thalamus, midbrain, insula and frontal lobes. Patients with longer, expanded CAG repeat sequences showed faster rates and more widespread atrophy, particularly those patients with more than 55 expanded CAG repeats. CONCLUSIONS: These results confirm that brain atrophy progresses after the clinical onset of HD and that regional atrophy is related to symptom severity. Moreover, our results also indicate that intensity and rate of progression of brain atrophy are more pronounced in patients with larger, expanded CAG repeat sequences.
Subject(s)
Brain/pathology , DNA Repeat Expansion/genetics , Huntington Disease/genetics , Trinucleotide Repeats/genetics , Adolescent , Adult , Aged , Atrophy , Child , Child, Preschool , Cohort Studies , Disease Progression , Female , Genotype , Humans , Huntington Disease/diagnosis , Huntington Disease/pathology , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Neurologic Examination , Statistics as TopicABSTRACT
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.
Subject(s)
Brain/pathology , Huntington Disease/genetics , Huntington Disease/pathology , Trinucleotide Repeats/genetics , Adolescent , Adult , Aged , Atrophy , Case-Control Studies , Child , Child, Preschool , Female , Genotype , Humans , Magnetic Resonance Imaging , Male , Middle AgedABSTRACT
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.
