RESUMO
The original version of this article contains an error in Table 2. The Authors realized that they submitted the previous version of Table 2. The correct version of Table 2 is shown here.
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The primary endpoint of this work was to evaluate the effect of safinamide on non-motor symptoms (NMS) in patients affected by idiopathic Parkinson's disease (PD) complicated by motor fluctuations. We retrospectively collected data from 20 subjects affected by idiopathic PD in treatment with L-dopa alone or in combination with dopamine agonists, who began to be treated with safinamide due to the occurrence of motor fluctuations. Secondary endpoints included SCales for Outcomes in Parkinson's disease (SCOPA) Motor Scale, cognitive assessment, the Hoehn and Yahr stage, Clinical Impression of Severity Index for Parkinson's Disease, Hospital Anxiety And Depression Scale, Physical and Mental Fatigue, Parkinson's disease Sleep Scale, Parkinson's Disease Questionnaire-8 (PDQ-8) and EQ-5D. Each one of these scales/questionnaires was performed at baseline and T1. For efficacy analyses, continuous variables were treated with descriptive statistics, using mean and standard deviations. A non-parametric test (the Friedman test) was carried out to evaluate the statistical significance of the results observed. We found a statistically significant reduction of the total score of NMS, of 6 domains out of 9, and 13 items out of 30. A statistically significant reduction of SCOPA Motor Scale, PDQ-8, and CISI was also detected. In conclusion, our data showed a positive effect of safinamide on NMS and confirm its positive effect on motor symptomatology.
Assuntos
Alanina/análogos & derivados , Antiparkinsonianos/uso terapêutico , Benzilaminas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Alanina/uso terapêutico , Feminino , Humanos , Masculino , Doença de Parkinson/psicologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Área Postrema , Neuromielite Óptica , Espasmo , Humanos , Feminino , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/diagnóstico por imagem , Idoso , Espasmo/etiologia , Espasmo/diagnóstico , Área Postrema/diagnóstico por imagem , Imageamento por Ressonância Magnética , Dor/etiologia , Dor/diagnósticoRESUMO
L-dopa-induced dyskinesia (LID) is a frequent motor complication of Parkinson's disease (PD), associated with a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and LID, the results of which have not been confirmed. The present study is aimed to determine whether genetic differences of DR are associated with LID in a small but well-characterized cohort of PD patients. To this end we enrolled 100 PD subjects, 50 with and 50 without LID, matched for age, gender, disease duration and dopaminergic medication in a case-control study. We conducted polymerase chain reaction for single nucleotide polymorphisms (SNP) in both D1-like (DRD1A48G; DRD1C62T and DRD5T798C) and D2-like DR (DRD2G2137A, DRD2C957T, DRD3G25A, DRD3G712C, DRD4C616G and DRD4nR VNTR 48bp) analyzed genomic DNA. Our results showed that PD patients carrying allele A at DRD3G3127A had an increased risk of LID (OR 4.9; 95% CI 1.7-13.9; p = 0.004). The present findings may provide valuable information for personalizing pharmacological therapy in PD patients.
Assuntos
Discinesias/etiologia , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/genética , Polimorfismo Genético , Receptores Dopaminérgicos/genética , Idoso , Alelos , Animais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Prevalence estimates for the 2 forms of myotonic dystrophy types 1 and 2 (DM1 and DM2) are not exhaustive or non-available. Our aim was to estimate the minimum prevalence of DM1 and DM2 in Italy in the Rome province, applying standards of descriptive epidemiology. METHODS: All patients with a molecular diagnosis of DM1/DM2 and residents in the Rome province in 2013 have been enrolled, and the age-standardized prevalence has been calculated, assuming a Poisson distribution and adjusting for age. RESULTS: We identified 395 DM1 patients: the age-standardized prevalence for total, females and males was 9.65, 8.35 and 11.07/100,000, respectively. The mean age of subjects differed considerably according to CTG repeat length (p = 0.001). Forty DM2 patients were identified. The age-standardized prevalence for total, females and males was 0.99, 1.07 and 0.90/100,000, respectively. The mean age was 57.05. CONCLUSIONS: We estimated for the first time the age-standardized prevalence and the sex and age distribution of DM1 and DM2 in a general population. A higher prevalence of males in DM1 and females in DM2 and a higher mean age of DM2 patients (+8 years) were ascertained. Prevalence of DM2 was 10% that of DM1. These prevalence values are probably lower than mutational rates due to the incomplete penetrance of DM1 mutations and to the clinical elusiveness of DM2. Our findings will be useful in designing cohort studies and for developing a disease registry.
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Distrofia Miotônica/diagnóstico , Distrofia Miotônica/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Cidade de Roma/epidemiologia , Distribuição por Sexo , Adulto JovemRESUMO
BACKGROUND: Myotonic dystrophy type 1 (MD1) is reported to be associated with internal malignancies. The association of myotonic dystrophy with cutaneous tumors is not fully understood. OBJECTIVE: We sought to explore the total nevi count and the presence of atypical nevi, cutaneous melanoma, and other skin neoplasms in a representative cohort of patients with MD1 and to compare the findings with age- and sex-matched control subjects. METHODS: In all, 90 patients with MD1 and 103 age- and sex-matched control subjects were assessed for cutaneous neoplasms by clinical skin and epiluminescence examination (dermoscopy). Where indicated, subsequent excisions were performed. In patients with MD1, leukocyte n(CTG) expansion was measured. RESULTS: Patients with MD1 showed significantly higher numbers of nevi, dysplastic nevi, and melanomas despite a significantly greater proportion of the control subjects reporting sunburns. In addition, we found a significantly greater number of pilomatrixoma in patients with MD1. LIMITATIONS: Our study is limited by the fact that there is no agreed-upon standardized technique to assess for prior sun exposure. Further research in the association of cutaneous neoplasms and MD1 including vitamin D and molecular biological techniques are also recommended. CONCLUSION: MD1 itself may predispose to development of skin tumors.
Assuntos
Síndrome do Nevo Displásico/complicações , Síndrome do Nevo Displásico/epidemiologia , Melanoma/complicações , Melanoma/epidemiologia , Distrofia Miotônica/complicações , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
AIMS: The pathogenesis of myotonic dystrophy type 1 (DM1) and type 2 (DM2) has been related to the aberrant splicing of several genes, including those encoding for ryanodine receptor 1 (RYR1), sarcoplasmatic/endoplasmatic Ca(2+)-ATPase (SERCA) and α1S subunit of voltage-gated Ca(2+) channels (Cav 1.1). The aim of this study is to determine whether alterations of these genes are associated with changes in the regulation of intracellular Ca(2+) homeostasis and signalling. METHODS: We analysed the expression of RYR1, SERCA and Cav 1.1 and the intracellular Ca(2+) handling in cultured myotubes isolated from DM1, DM2 and control muscle biopsies by semiquantitative RT-PCR and confocal Ca(2+) imaging respectively. RESULTS: (i) The alternative splicing of RYR1, SERCA and Cav 1.1 was more severely affected in DM1 than in DM2 myotubes; (ii) DM1 myotubes exhibited higher resting intracellular Ca(2+) levels than DM2; (iii) the amplitude of intracellular Ca(2+) transients induced by sustained membrane depolarization was higher in DM1 myotubes than in controls, whereas DM2 showed opposite behaviour; and (iv) in both DM myotubes, Ca(2+) release from sarcoplasmic reticulum through RYR1 was lower than in controls. CONCLUSION: The aberrant splicing of RYR1, SERCA1 and Cav 1.1 may alter intracellular Ca(2+) signalling in DM1 and DM2 myotubes. The differing dysregulation of intracellular Ca(2+) handling in DM1 and DM2 may explain their distinct sarcolemmal hyperexcitabilities.
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Processamento Alternativo , Sinalização do Cálcio/genética , Cálcio/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Distrofia Miotônica/genética , Adulto , Idoso , Canais de Cálcio/genética , Canais de Cálcio Tipo L , Homeostase , Humanos , Pessoa de Meia-Idade , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genéticaRESUMO
PURPOSE: Myotonic dystrophy types 1 (DM1) and 2 (DM2) are the most common muscular dystrophies in adulthood. A high prevalence of excessive daytime sleepiness (EDS) and sleep disordered breathing was documented in DM1; however, there are limited data available regarding DM2. Goals of the study were: (1) to evaluate the prevalence of sleep apnea in a large cohort of patients (71 DM1 and 14 DM2) and (2) to analyze correlations among such disorders and clinical features of myotonic dystrophies. METHODS: All patients underwent clinical examination, subjective sleep evaluation, and home based cardiorespiratory monitoring, and most of them performed pulmonary function tests and oropharyngeal-oesophageal scintigraphy (OPES). RESULTS: Almost 45% of patients reported poor sleep quality; only 20% of them referred EDS. Sleep studies documented sleep apnea, mostly obstructive, in 69% DM1 patients and 43% DM2 patients; overall, 28% of cases needed non-invasive ventilation. Neither age, gender, illness duration, body mass index, muscle involvement, OPES respiratory function indexes, nor n(CTG) in leukocytes were predictive of sleep apnea in DM1 patients. Conversely, in DM1 the central apnea-hypopnea index is correlated with the oral transit time estimated by OPES, whereas in DM2 apnea indexes are correlated with pulmonary function parameters. CONCLUSIONS: Sleep apnea is highly prevalent in both forms of myotonic dystrophies. In DM1, no clinical parameters appear to be predictive, while age appears to influence the severity of the obstructive variant; in DM2, the severity of sleep apnea is correlated with the degree of respiratory muscle involvement. Considering the harmful consequences of sleep apnea on cardiorespiratory function, our findings suggest including PSG in the follow-up of myotonic dystrophies.
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Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/epidemiologia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Estatística como Assunto , Capacidade Vital/fisiologia , Adulto JovemRESUMO
INSR, one of those genes aberrantly expressed in myotonic dystrophy type 1 (DM1) and type 2 (DM2) due to a toxic RNA effect, encodes for the insulin receptor (IR). Its expression is regulated by alternative splicing generating two isoforms: IR-A, which predominates in embryonic tissue, and IR-B, which is highly expressed in adult, insulin-responsive tissues (skeletal muscle, liver, and adipose tissue). The aberrant INSR expression detected in DM1 and DM2 muscles tissues, characterized by a relative increase of IR-A versus IR-B, was pathogenically related to the insulin resistance occurring in DM patients. To assess if differences in the aberrant splicing of INSR could underlie the distinct fiber type involvement observed in DM1 and DM2 muscle tissues, we have used laser capture microdissection (LCM) and RT-PCR, comparing the alternative splicing of INSR in type I and type II muscle fibers isolated from muscle biopsies of DM1, DM2 patients and controls. In the controls, the relative amounts of IR-A and IR-B showed no obvious differences between type I and type II fibers, as in the whole muscle tissue. In DM1 and DM2 patients, both fiber types showed a similar, relative increase of IR-A versus IR-B, as also evident in the whole muscle tissue. Our data suggest that the distinct fiber type involvement in DM1 and DM2 muscle tissues would not be related to qualitative differences in the expression of INSR. LCM can represent a powerful tool to give a better understanding of the pathogenesis of myotonic dystrophies, as well as other myopathies.
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Processamento Alternativo , Antígenos CD/genética , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Distrofia Miotônica/genética , Receptor de Insulina/genética , Adenosina Trifosfatases/metabolismo , Adulto , Biópsia , Expressão Gênica , Histocitoquímica , Humanos , Concentração de Íons de Hidrogênio , Microdissecção e Captura a Laser/métodos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Transtornos Miotônicos/genética , Transtornos Miotônicos/metabolismo , Transtornos Miotônicos/patologia , Distrofia Miotônica/metabolismo , Distrofia Miotônica/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The Andersen-Tawil syndrome (ATS) is characterized by hypo-normokaliemic muscle periodic paralysis, dysmorphic features and ventricular arrhythmias. Most cases are caused by mutations in KCNJ2, encoding for the potassium inwardly rectifying channel, Kir2.1 (ATS1). Although KCNJ2 mutations show no obvious genotype-phenotype correlations and incomplete penetrance, signs of cardiac involvement are usually present in most ATS1 cases. In contrast, here we describe an Italian ATS1 patient, carrying a c.574AâG mutation in KCNJ2, who had both facial dysmorphisms and muscle periodic paralysis but who did not manifest any cardiac involvement, although the same mutation was originally described in a Japanese kindred, in which all affected individuals manifested a severe cardiac phenotype.
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Síndrome de Andersen/genética , Mutação/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Arritmias Cardíacas/genética , Eletrocardiografia , Humanos , Masculino , PenetrânciaRESUMO
The purpose of the study is to evaluate retinal involvement in a cohort of patients affected by Myotonic Dystrophy type 1 (DM1). Both eyes of 30 patients and one eye of a 31st patient with genetically proven diagnosis of DM1 and both eyes of 20 healthy age- and gender-matched subjects were enrolled. All patients underwent complete ophthalmologic examination including best-corrected visual acuity, intraocular pressure measurement, fundoscopy, fundus autofluorescence, infrared imaging and spectral-domain optical coherence tomography with central macular thickness measurement. DM1 patients showed statistically significant higher central macular thickness values than controls. In the DM1 group, butterfly (14.8%) and reticular (13.1%) pigment abnormalities were found with corresponding drusenoid deposit and focal disruption of photoreceptor and retinal pigment epithelium layers. Compared with the controls, DM1 group had higher prevalence of epiretinal membrane. In the DM1 group, the prevalence of epiretinal membrane and retinal pigment epithelium alterations were directly correlated with age, whereas no correlation was found with disease duration, CTG expansion and MIRS score. In conclusion, in addition to the typical retinal pigment epithelium changes, DM1 is also associated with abnormalities of the vitreoretinal interface, particularly epiretinal membrane, resulting in central macular thickness increase. Both inner and outer retinal alterations were associated with increasing age, suggesting that DM1 may cause a premature aging of the retina.
Assuntos
Membrana Epirretiniana/patologia , Macula Lutea/patologia , Distrofia Miotônica/patologia , Epitélio Pigmentado da Retina/patologia , Descolamento do Vítreo/patologia , Adulto , Fatores Etários , Idoso , Senilidade Prematura/patologia , Membrana Epirretiniana/diagnóstico por imagem , Membrana Epirretiniana/etiologia , Feminino , Seguimentos , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/complicações , Distrofia Miotônica/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Descolamento do Vítreo/diagnóstico por imagem , Descolamento do Vítreo/etiologia , Adulto JovemRESUMO
Recent studies documented an increased risk of neoplasm in patients with myotonic dystrophies (DM). Yet, none of these studies evaluated the contribution of common cancer risk factors in such observation. In this study, we included a cohort of patients (n = 255) with an established molecular diagnosis of DM type 1 (DM1), and who receives their treatment in one of the four centers with recognized expertise in neuromuscular disorders in Rome. We estimated the prevalence of benign and malignant tumors, and assessed if lifestyle factors and/or specific disease features would be associated to their occurrence. Overall, 59 benign tumors in 54 patients and 19 malignant tumors in 17 patients were diagnosed. The most common malignant neoplasms were cancers of the skin (31.6%), thyroid (21.0%), ovary (10.5%), and breast (10.5%). Uterine fibroid was the most common benign tumor (37.6%) in women, while pilomatricoma was the most common in men (28.6%). Age at enrollment (OR = 1.02, 95% CI 1.00-1.05), and female gender (OR = 5.71, 95% CI 2.90-11.22) were associated with tumor development in DM1 patients, while thyroid disorders was associated with malignant tumors only in women (OR = 5.12, 95% CI 1.35-19.37). There was no association between tumor development and evaluated lifestyle factors. In conclusion, the lack of association between common cancer risk factors and tumor development in DM1 support a pathogenic link between tumors and DM1 itself, emphasizing the need for a systematic surveillance. Our observation of an association between thyroid diseases in women and cancer development needs confirmation.
Assuntos
Estilo de Vida , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/psicologia , Neoplasias/epidemiologia , Neoplasias/psicologia , Adolescente , Adulto , Distribuição por Idade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Fatores de Risco , Estatísticas não Paramétricas , Adulto JovemRESUMO
OBJECTIVE: Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, is characterized by a multisystem involvement. Cognitive involvement predominantly affecting frono-temporal functions is an established clinical feature in this disorder. Brain imaging and metabolic studies showed a predominant involvement of fronto-temporal regions in DM1 patients, yet correlation studies among these findings and neuropsychological data gave contrasting results. In order to contribute to clarify the relationship between the metabolic changes documented in the frontal cortex of DM1 patients and a related cognitive task, we applied the functional near-infrared spectroscopy (fNIRS) during the execution of a phonemic verbal fluency task (pVFT). METHODS: We enrolled 29 consecutive right-handed DM1 patients and 30 controls. A 2-channel fNIRS imaging system was used to investigate changes in oxygenated [O2Hb] and deoxygenated [HHb] hemoglobin concentrations in the prefrontal cortex (PFC) during a pVFT. [O2Hb] and [HHb] baseline-corrected activation values were calculated (respectively [O2Hb]c and [HHb]c). RESULTS: In the control group [O2Hb] significantly increased and [HHb] significantly decreased during the pVFT, in the DM1 group no significant variation was found for both parameters revealing no activation of both PFCs during the task. On the other hand, in the DM1 sample, statistical analysis revealed a direct correlation between [O2Hb]c of the left PFC and the pVFT score, while no correlation was observed in the control group. CONCLUSIONS: Our study reveals that DM1 patients show prefrontal hypometabolism during a specific frontal cognitive task compared to controls. Moreover the rapid temporal discrimination of fNIRS allows revealing the correlation between the PFC hypometabolism and the cognitive performance in DM1 patients. SIGNIFICANCE: fNIRS can be helpful to understand the functional correlates of the frontal cognitive impairment in DM1.