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PURPOSE: To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes. MATERIALS AND METHODS: Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method. RESULTS: MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001). CONCLUSION: These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD.
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Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Atrofia de Múltiplos Sistemas/patologia , Transtornos Parkinsonianos/patologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system that can lead to long-term disability. The diagnosis of MS is not simple and requires many instrumental and clinical tests. Sampling easily collected biofluids using spectroscopic approaches is becoming of increasing interest in the medical field to integrate and improve diagnostic procedures. Here we present a statistical approach where we combine a number of spectral biomarkers derived from the ATR-FTIR spectra of blood plasma samples of healthy control subjects and MS patients, to obtain a linear predictor useful for discriminating between the two groups of individuals. This predictor provides a simple tool in which the contribution of different molecular components is summarized and, as a result, the sensitivity (80%) and specificity (93%) of the identification are significantly improved compared to those obtained with typical classification algorithms. The strategy proposed can be very helpful when applied to the diagnosis of diseases whose presence is reflected in a minimal way in the analyzed biofluids (blood and its derivatives), as it is for MS as well as for other neurological disorders.
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Multiple sclerosis (MS) is one of the most common neurodegenerative diseases showing various symptoms both of physical and cognitive type. In this work, we used attenuated total reflection Fourier transformed infrared (ATR-FTIR) spectroscopy to analyze plasma samples for discriminating MS patients from healthy control individuals, and identifying potential spectral biomarkers helping the diagnosis through a quick non-invasive blood test. The cohort of the study consists of 85 subjects, including 45 MS patients and 40 healthy controls. The differences in the spectral features both in the fingerprint region (1800-900 cm-1) and in the high region (3050-2800 cm-1) of the infrared spectra were highlighted also with the support of different chemometric methods, to capture the most significant wavenumbers for the differentiation. The results show an increase in the lipid/protein ratio in MS patients, indicating changes in the level (metabolism) of these molecular components in the plasma. Moreover, the multivariate tools provided a promising rate of success in the diagnosis, with 78% sensitivity and 83% specificity obtained through the random forest model in the fingerprint region. The MS diagnostic tools based on biomarkers identification on blood (and blood component, like plasma or serum) are very challenging and the specificity and sensitivity values obtained in this work are very encouraging. Overall, the results obtained suggest that ATR-FTIR spectroscopy on plasma samples, requiring minimal or no manipulation, coupled with statistical multivariate approaches, is a promising analytical tool to support MS diagnosis through the identification of spectral biomarkers.
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Esclerose Múltipla , Plasma , Espectroscopia de Infravermelho com Transformada de Fourier , Humanos , Esclerose Múltipla/sangue , Esclerose Múltipla/diagnóstico , Análise Multivariada , Plasma/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Biomarcadores/sangueRESUMO
In previous studies, beta-k distribution and distribution functions strongly related to that, have played important roles in representing extreme events. Among these distributions, the Beta-Singh-Maddala turned out to be adequate for modelling hydrological extreme events. Starting from this distribution, the aim of the paper is to express the model as a function of indexes of hydrological interest and simultaneously investigate on their dependence with a set of explanatory variables in such a way to explore on possible determinants of extreme hydrologic events. Finally, an application to a real hydrologic dataset is considered in order to show the potentiality of the proposed model in describing data and in understanding effects of covariates on frequently adopted hydrological indicators.
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HidrologiaRESUMO
PURPOSE: To study prognosis and prognostic predictors of sporadic non-lesional temporal lobe epilepsy (TLE). METHOD: 474 patients with TLE were consecutively seen from April 1987 to April 2004. 190 had a sporadic non-lesional TLE and a follow-up longer than 2 years. 284 patients were excluded because of family history for TLE, incomplete history, poor compliance with treatment, psychogenic seizures, no brain MRI study, presence of intracranial lesions except for scattered T2 hyperintense spots on hemispheric white matter or mesial temporal sclerosis (MTS). The following prognostic predictors were considered: age at onset of epilepsy, gender, family history of non-TLE or febrile seizures, perinatal factors, history of febrile seizures, ictal phenomena, MTS and interictal EEG. The end point was time to 24 month seizure freedom after treatment onset. The χ(2) test, Student's t test, Kaplan-Meier survival curves with log rank test (univariate analysis) and Cox proportional hazards regression models (multivariate analysis) were used to assess seizure prognosis and prognostic predictors. RESULTS: At univariate analysis, patients achieving 24 month seizure freedom had a significantly older age at onset of epilepsy (33.5 ± 19.9 vs 17.2 ± 14.4 years), and lower occurrence of febrile seizures (11.0% vs 24.4%) and MTS (19.0% vs 35.6%). The chance of remission was directly correlated to age at onset of seizures and inversely correlated to a history of febrile seizures and to the presence of MTS. At multivariate analysis, age at onset of epilepsy was the only significant prognostic predictor. CONCLUSION: Older age at onset predicts better prognosis in sporadic non-lesional TLE.
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Epilepsia do Lobo Temporal/diagnóstico , Lobo Temporal/patologia , Adolescente , Adulto , Idade de Início , Distribuição de Qui-Quadrado , Eletroencefalografia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Esclerose , Convulsões/diagnóstico , Convulsões/patologia , Lobo Temporal/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Combined measurements on conventional magnetic resonance imaging (MRI), such as midbrain area/pons area or magnetic resonance parkinsonism index (MRPI) (pons area/midbrain area × middle cerebellar peduncle width/superior cerebellar peduncle width), have been proposed as powerful tools in the differential diagnosis between progressive supranuclear palsy (PSP) and Parkinson disease (PD). In this study, we evaluated the accuracy of MRPI, compared with midbrain/pons ratio, in distinguishing PSP from probable and possible PD. METHODS: Forty-two PSP patients, 170 probable PD patients, 132 possible PD patients, and 38 control subjects underwent MRI and, for each patient, midbrain/pons ratio and MRPI were calculated. RESULTS: Midbrain/pons ratio showed low accuracy in distinguishing PSP patients from those with probable PD (92.9% sensitivity; 85.3% specificity; 86.8% diagnostic accuracy) or those with possible PD (88.1% sensitivity, 88.3% specificity, and 88.2% diagnostic accuracy) and control subjects (97.6% sensitivity, 92.1% specificity, and 95% diagnostic accuracy). By contrast, MRPI showed higher accuracy to distinguish PSP from probable PD (100% sensitivity, 99.4% specificity, and 99.5% diagnostic accuracy), from possible PD (100% sensitivity, 99.2% specificity, and 99.4% diagnostic accuracy), and from control subjects (sensitivity, specificity, and diagnostic accuracy of 100%). CONCLUSIONS: Our study confirms that MRPI is a more accurate measure than midbrain/pons ratio for differentiation of patients with PSP from those with probable and possible PD.
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Diagnóstico Diferencial , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Tronco Encefálico/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
A splice site variation (c.603-91G>A or rs3812718) in the SCN1A gene has been claimed to influence efficacy and dose requirements of carbamazepine and phenytoin. We investigated the relationship between c.603-91G>A polymorphism and response to antiepileptic drugs (AEDs) in 482 patients with drug-resistant and 401 patients with drug-responsive focal epilepsy. Most commonly used AEDs were carbamazepine and oxcarbazepine. The distribution of c.603-91G>A genotypes was similar among drug-resistant and drug-responsive subjects, both in the entire population and in the groups treated with carbamazepine or oxcarbazepine. There was no association between the c.603-91G>A genotype and dosages of carbamazepine or oxcarbazepine. These findings rule out a major role of the SCN1A polymorphism as a determinant of AED response.
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Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Proteínas do Tecido Nervoso/genética , Polimorfismo Genético , Canais de Sódio/genética , Adulto , Anticonvulsivantes/farmacologia , Carbamazepina/análogos & derivados , Carbamazepina/farmacologia , Carbamazepina/uso terapêutico , Resistência a Medicamentos , Epilepsias Parciais/genética , Feminino , Genótipo , Humanos , Itália/etnologia , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Oxcarbazepina , Farmacogenética , População Branca/genéticaRESUMO
Our aim was to develop a clinimetric scale evaluating motor phenomena, associated features, and severity of psychogenic nonepileptic seizures (PNES). Sixty video/EEG-recorded PNES induced by suggestion maneuvers were evaluated. We examined the relationship between results from this scale and results from the Clinical Global Impression (CGI) scale to validate this technique. Interrater reliabilities of the PNES scale for three raters were analyzed using the AC1 statistic, Kendall's coefficient of concordance (KCC), and intraclass correlation coefficients (ICCs). The relationship between the CGI and PNES scales was evaluated with Spearman correlations. The AC1 statistic demonstrated good interrater reliability for each phenomenon analyzed (tremor/oscillation, tonic; clonic/jerking, hypermotor/agitation, atonic/akinetic, automatisms, associated features). KCC and the ICC showed moderate interrater agreement for phenomenology, associated phenomena, and total PNES scores. Spearman's correlation of mean CGI score with mean total PNES score was 0.69 (P<0.001). The scale described here accurately evaluates the phenomenology of PNES and could be used to assess and compare subgroups of patients with PNES.
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Psicometria/métodos , Transtornos Psicofisiológicos/diagnóstico , Convulsões/diagnóstico , Convulsões/fisiopatologia , Convulsões/psicologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Transtornos Psicofisiológicos/complicações , Reprodutibilidade dos Testes , Estudos Retrospectivos , Convulsões/complicações , Pesos e Medidas , Adulto JovemRESUMO
At 1.5 T, T2*-weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*-weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify the magnetic resonance imaging (MRI) T2*-weighted sequence which more specifically detected putaminal hypointensities differentiating atypical parkinsonian syndromes from Parkinson's disease (PD) and control subjects. In a sample of 38 healthy subjects, we performed three T2*-weighted GE sequences at increasing time echo (TE; TE = 15 millisecond, TE = 25 millisecond, and echoplanar at TE = 40 millisecond; T2* sequences study). The sequence not showing any putaminal abnormality in the healthy subjects was then used to assess putaminal signal intensity in 189 patients with PD, 20 patients with multiple system atrophy (MSA), 41 patients with progressive supranuclear palsy (PSP), and in 150 age and sex-matched control subjects. In the T2* sequences study, the T2*-weighted TE = 15 (T2*/15) did not show any putaminal abnormalities in the healthy subjects. This sequence detected putaminal hypointensities in a significantly higher proportion of patients with MSA (35%, P < 0.05) and PSP (24.4%, P < 0.05) than in patients with PD (5.3%), but in none of the controls. The sensitivity of putaminal hypointensity in T2*/15 sequence was 25.4% for PD, 43.9% for PSP, and 55% for MSA versus controls whereas the specificity was 93.2% for all groups. Despite the suboptimal sensitivity, the high specificity of the T2*/15 sequence performed on routine MRI suggests its usefulness in clinical practice for identifying putaminal hypointensities associated with parkinsonian disorders.
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Imageamento por Ressonância Magnética , Transtornos Parkinsonianos/patologia , Putamen/patologia , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Paralisia Supranuclear Progressiva/patologiaRESUMO
The cooccurrence of rest and postural tremor (mixed tremor) as the predominant clinical manifestation in patients who do not fulfill diagnostic established criteria for essential tremor (ET) or Parkinson's disease (PD) poses a clinical diagnostic challenge. Twenty-two patients with mixed tremor and additional mild extrapyramidal features, such as bradykinesia and rigidity, 20 patients with probable PD, 10 patients with probable ET, and 18 controls were investigated through the combined use of dopamine transporter (123)I-FP-CIT-single-photon emission tomography (DAT-SPECT) and cardiac (123)metaiodobenzylguanidine (MIGB) scintigraphy. Six of the 22 mixed-tremor patients had normal DAT-SPECT, a condition usually found in patients with ET, whereas 16 patients showed damage to the nigrostriatal system. Cardiac MIBG allowed further differentiation between these 16 patients because eight of them had decreased tracer uptakes (heart/mediastinum [H/M] ratio in delayed image, H/M ratio delayed: 1.16 +/- 0.11, P < 0.001 vs controls), indicating a PD, whereas the remaining eight had normal cardiac tracer uptakes, a finding suggestive of a parkinsonian syndrome (H/M ratio delayed: 1.90 +/- 0.13). Both DAT-SPECT and cardiac MIBG scintigraphies were abnormal in the 20 patients with probable PD, whereas these were normal in both the patients with probable ET as well as in the controls. Our study suggests that the combined use of both DAT-SPECT and MIBG scintigraphy in mixed tremors with additional extrapyramidal features can help distinguish patients with ET from those with PD and parkinsonism.
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3-Iodobenzilguanidina , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Coração/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tremor/diagnóstico por imagem , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Cintilografia/métodos , Compostos Radiofarmacêuticos , TropanosRESUMO
PURPOSE: To prospectively assess sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) for differentiating progressive supranuclear palsy (PSP) from Parkinson disease (PD) and Parkinson variant of multiple system atrophy (MSA-P), with established consensus criteria as reference standard. MATERIALS AND METHODS: All study participants provided informed consent; study was approved by the institutional review board. Pons area, midbrain area, MCP width, and SCP width were measured in 33 consecutive patients with PSP (16 possible, 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 healthy control participants on T1-weighted MR images. The pons area-midbrain area ratio (P/M) and MCP width-SCP width ratio (MCP/SCP) were also used, and an index termed MR parkinsonism index was calculated [(P/M).(MCP/SCP)]. Differences in MR imaging measurements among groups were evaluated with Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction. RESULTS: Midbrain area and SCP width in patients with PSP (23 men, 10 women; mean age, 69.3 years) were significantly (P < .001) smaller than in patients with PD (62 men, 46 women; mean age, 65.8 years), patients with MSA-P (five men, 14 women; mean age, 64.0 years), and control participants (25 men, 25 women; mean age, 66.6 years). P/M and MCP/SCP were significantly larger in patients with PSP than in patients in other groups and control participants. All measurements showed some overlap of values between patients with PSP and patients from other groups and control participants. MR parkinsonism index value was significantly larger in patients with PSP (median, 19.42) than in patients with PD (median, 9.40; P < .001), patients with MSA-P (median, 6.53; P < .001), and control participants (median, 9.21; P < .001), without overlap of values among groups. No patient with PSP received a misdiagnosis when the index was used (sensitivity and specificity, 100%). CONCLUSION: The MR parkinsonism index can help distinguish patients with PSP from those with PD and MSA-P on an individual basis.
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Imageamento por Ressonância Magnética , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK1, and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in 1 of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK1 mutations, in 3 of the 6 unrelated patients with Gly2019Ser mutation in the LRRK2 gene, whereas it was impaired in all patients with idiopathic PD. MIBG was preserved in all control subjects. Our study shows that myocardial MIGB uptake was normal in 8 of 14 patients with genetic PD, suggesting that cardiac sympathetic denervation occurs less frequently in genetic PD than in idiopathic PD. Our findings also demonstrate that MIGB uptake has a heterogeneous pattern in genetic PD, because it was differently impaired in patients with different mutations in the same gene or with the same gene mutation.
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3-Iodobenzilguanidina/farmacocinética , Miocárdio/metabolismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Mutação Puntual/genética , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Resposta Galvânica da Pele/fisiologia , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Peptídeos e Proteínas de Sinalização Intracelular/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/epidemiologia , Proteínas Oncogênicas/sangue , Proteínas Oncogênicas/genética , Doença de Parkinson/epidemiologia , Transtornos Parkinsonianos/epidemiologia , Regiões Promotoras Genéticas , Proteína Desglicase DJ-1 , Proteínas Quinases/sangue , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/sangue , Proteínas Serina-Treonina Quinases/genética , Índice de Gravidade de Doença , Inquéritos e Questionários , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Ubiquitina-Proteína Ligases/sangue , Ubiquitina-Proteína Ligases/genéticaRESUMO
Recent studies have reported an association between the glucocerebrosidase (GBA) gene and Parkinson's disease (PD). To elucidate the role of this gene in our population, we screened 395 PD patients and 483 controls from southern Italy for the N370S and the L444P mutations. We found 11 patients (2.8%) carrying a heterozygous mutant GBA allele, whereas only one control subject (0.2%) had a heterozygous substitution (P = 0.0018). These results strongly suggest that Italian carriers of a GBA mutation have an increased risk of developing PD.
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Predisposição Genética para Doença , Glucosilceramidase/genética , Mutação/genética , Doença de Parkinson/genética , Idoso , Asparagina/genética , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Itália/epidemiologia , Leucina/genética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Prolina/genética , Serina/genéticaRESUMO
The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA-P in order to evaluate its differential diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 x 10(-3)mm(2)/s) than patients with PD (median 0.79 x 10(-3) mm(2)/s, P < 0.001), MSA-P (median 0.79 x 10(-3) mm(2)/s, P < 0.001), and healthy controls (median 0.80 x 10(-3) mm(2)/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA-P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms.
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Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética , Doença de Parkinson/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
The gene encoding the inducible form of Nitric Oxide Synthase (NOS2A) has been considered with interest in the evaluation of the genetic predisposition to Multiple Sclerosis (MS). The aim of the present study was to address the possible contribution of two microsatellites repeats of the NOS2A promoter region - (CCTTT)(n) and (AAAT)(n) - to MS susceptibility. One hundred and thirteen Italian patients with clinically definite RRMS and 237 age and sex matched healthy controls from Calabria (South Italy) were studied. The distribution analysis of the markers frequencies showed that the (CCTTT)(14) allele was found in 11.5% of the RRMS patients and in 25.3% of the healthy subjects, with a statistically significant difference (chi(2)=8.843, p=0.003). This data seems to confer a significant protection against MS (OR=0.348; 95% CI=0.174-0.693, corrected for age and gender). No association with MS susceptibility was observed for the bi-allelic (AAAT)(n) microsatellite. In conclusion, we found that the NOS2A (CCTTT)(14) allele was detected more frequently in the control group than in the RRMS patients, thus confirming the scientific interest on this marker.
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Predisposição Genética para Doença/genética , Repetições de Microssatélites/genética , Esclerose Múltipla Recidivante-Remitente/enzimologia , Esclerose Múltipla Recidivante-Remitente/genética , Óxido Nítrico Sintase Tipo II/genética , Regiões Promotoras Genéticas/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Frequência do Gene , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Itália , Masculino , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Polimorfismo Genético/genética , População BrancaRESUMO
BACKGROUND: In multiple sclerosis (MS), relationships between disease-related MRI changes, cognitive function and brain responses are complex and still unclear. This study addresses the relative effects of cognitive impairment and brain atrophy on the cortical reorganization associated with a visuo-motor task. METHODS: Multivariate analysis was applied to compare functional MRI brain responses of 28 relapsing-remitting (RR) MS patients (16 cognitively preserved and 12 cognitively impaired) to that of 35 matched healthy controls during the execution of visuo-motor integration task. Regression analysis was performed to test for linear effects of structural variables (grey matter (GM) and white matter (WM) volumes) and cognitive profiles--and their combined effect--on the same response. RESULTS: Compared to preserved MS patients or normal controls, cognitively impaired MS patients showed significant decreases of brain parenchymal and GM volumes, but only a trend for lower WM volume. Multivariate analysis showed that cognitive profile, GM and WM atrophy independently contributed to the activation of parieto-premotor cortices. Baseline cognition predicted the greatest response of the entire network, whereas WM and GM losses predicted selective responses of parietal and premotor regions. CONCLUSIONS: Visuo-motor function in MS is associated with altered patterns of brain activation that vary as a function of cognitive decline. This is confirmed by a larger effect size of the individual cognitive profile compared to the structural damage. Both effects contribute in an additive way to cortical reorganization, which is primarily driven by such a cognitive gradient in RR-MS patients.
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Atrofia/fisiopatologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Plasticidade Neuronal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Atrofia/etiologia , Atrofia/patologia , Encéfalo/patologia , Mapeamento Encefálico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Progressão da Doença , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/patologia , Análise Multivariada , Fibras Nervosas Mielinizadas/patologia , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Valor Preditivo dos Testes , Recuperação de Função Fisiológica/fisiologia , Análise de Regressão , Sensibilidade e EspecificidadeRESUMO
Specific variations in the prion protein gene (PRNP) are associated with, and prevalent in patients with intractable temporal lobe epilepsy (TLE) and influence the surgical outcome. We investigated whether or not the PRNP gene is a susceptibility gene in temporal lobe epileptic patients with mild epilepsy. We systematically screened the entire open reading frame of the PRNP gene and evaluated the genetic contribution of the functional PRNP M129V polymorphism in 289 patients with mild TLE compared with a neurologically unaffected age and sex matched control group (n=272). Statistical analysis revealed a moderate difference in the distribution at codon 129 of the PRNP gene between sporadic mild TLE patients and healthy controls (p=0.036; OR=1.30; 95% CI=1.01-1.68). Although, there was no statistically significant difference in the genotype distribution within the study groups (p=0.101), a further analysis showed that the 129V allele was highly represented only in women with TLE compared with control group (p=0.006, OR=1.632; 95%CI=1.15-2.31). This is the first publication of data that support the hypothesis that the common methionine/valine polymorphism at codon 129 of the PRNP gene may modify the susceptibility of women to mild TLE.
Assuntos
Epilepsia do Lobo Temporal/genética , Predisposição Genética para Doença , Metionina/genética , Polimorfismo Genético , Príons/genética , Caracteres Sexuais , Valina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas PriônicasRESUMO
Eleven postmenopausal women with Parkinson disease and levodopa-induced peak-dose dyskinesias underwent a double-blind, placebo-controlled, crossover study. The active treatment consisted of estrogen replacement therapy for 12 weeks, followed by medroxyprogesterone acetate for 2 weeks. Estrogen replacement therapy-medroxyprogesterone acetate administration significantly improved peak-dose dyskinesia without worsening motor disability, thus suggesting a possible benefit on dyskinesias in postmenopausal women with Parkinson disease.
Assuntos
Acatisia Induzida por Medicamentos/tratamento farmacológico , Antineoplásicos Hormonais/administração & dosagem , Antiparkinsonianos/efeitos adversos , Estrogênios/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Idoso , Acatisia Induzida por Medicamentos/etiologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Levodopa/efeitos adversos , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Pós-Menopausa , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from Parkinson's disease is difficult in the early stage of the disease. In order to identify objective markers for differential diagnosis, we studied these three groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16 with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, thalamus, white matter, pons and middle cerebellar peduncles (MCPs). rADC calculated in the MCP completely differentiated MSA-P patients (median: 0.93 x 10(-3) mm2/s) from PSP patients (median: 0.82 x 10(-3) mm2/s, P < 0.001), Parkinson's disease patients (median: 0.79 x 10(-3) mm2/s, P < 0.001) and healthy volunteers (median: 0.81 x 10(-3) mm2/s, P < 0.001). Other regions considered showed an overlapping among groups. DWI discriminates MSA-P from PSP and Parkinson's disease and healthy volunteers on the basis of MCP rADC values. These in vivo results confirm the pathological findings that the majority of MSA-P patients have moderate or severe degenerative changes not only in the nigrostriatal but also in the olivopontocerebellar systems. Our findings indicate that, in order to substantially contribute to the in vivo differential diagnosis of MSA-P, PSP and Parkinson's disease, rADC measurements should not be limited to the basal ganglia but should also include the MCP.
Assuntos
Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico , Idoso , Análise de Variância , Gânglios da Base/patologia , Tronco Encefálico/patologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To determine if the qualitative test (cytochemical) is more reliable than the quantitative test (differential pH-metry) in identifying heterozygous G6PD- subjects. DESIGN AND METHODS: Identification of heterozygous G6PD- subjects was done by the measurement of G6PD activity and by a cytochemical test. RESULTS: A cytochemical test is more sensitive than differential pH-metry to identify heterozygous G6PD- subjects. CONCLUSIONS: A cytochemical test is a reliable method for mass screening for G6PD deficiency to identify G6PD- heterozygotes.