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AIM: Small fibre neuropathy (SFN) diagnosis represents a challenge for neurologists. The diagnostic gold standard is intraepidermal nerve fibre (IENF) density, but in about 10-20% of patients with symptoms/signs and abnormalities on functional tests, it remains within normal range. We propose an adjunctive parameter to improve the efficiency of skin biopsy diagnosis. METHODS: We recruited 31 patients with SFN symptoms/signs, normal nerve conduction study, abnormal quantitative sensory testing and normal IENF density. We also included 31 healthy controls and 31 SFN patients with reduced IENF density as control groups. RESULTS: We measured the distance between consecutive IENFs in the three groups. Mean inter-fibre distances did not differ between patients with normal counts and healthy controls (66.7 ± 14.5 µm vs. 76.7 ± 13.4 µm; P = 0.052), while the relative standard deviation was significantly (P < 0.001) higher in patients (79.3 ± 29.9) compared to controls (51.6 ± 12.2). Using ROC analysis, we identified an inter-fibre distance of 350 µm as the measure that better differentiated patients from controls (AUC = 0.85, sensitivity: 74%, specificity: 94%). At least one such segment was also observed in all patients with reduced IENF count. CONCLUSION: Irregular spatial distribution is an SFN intrinsic feature preceding actual nerve loss. The presence of a stretch of denervated epidermis longer than 350 µm is a parameter able to increase the diagnostic efficiency of skin biopsy.
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Pele/inervação , Pele/patologia , Neuropatia de Pequenas Fibras/diagnóstico , Adulto , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologiaRESUMO
BACKGROUND AND PURPOSE: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. METHODS: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. RESULTS: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty-seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). CONCLUSIONS: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.
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Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Bases de Dados Factuais , Humanos , Condução Nervosa , Nervos Periféricos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.
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Comportamento Alimentar , Estilo de Vida , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/epidemiologia , Adulto , Criança , Bases de Dados Factuais , Feminino , Humanos , Infecções/complicações , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Objective: The aim of the study was to investigate endothelial function in treatment-naïve polymyalgia rheumatica (PMR) patients and its modification during steroid therapy, in relation to changes in clinical and laboratory parameters.Method: This prospective observational study involved patients with a new diagnosis of PMR according to provisional American College of Rheumatology/European League Against Rheumatism 2012 criteria, who were naïve to steroid therapy, and control subjects matched for age, gender, and comorbidities. All participants underwent clinical and vascular ultrasound evaluations at baseline and after 1, 3, 6, and 12 months of steroid therapy. For the study of endothelial function, we evaluated the brachial artery reactivity, which has emerged as the most well-established technique used in adults, by assessing flow-mediated dilatation (FMD), which measures the endothelium-dependent vasodilatation.Results: Sixteen newly diagnosed PMR patients were compared with a population of 16 matched controls. FMD values in all subjects showed an inverse correlation with the values of erythrocyte sedimentation rate and C-reactive protein. At baseline, the FMD of PMR patients was significantly lower than controls and remained significantly lower with respect to controls until the sixth month of therapy, despite a clinical improvement already being evident after 1 month of therapy.Conclusions: PMR is characterized by an important chronic subclinical inflammatory component. This pilot study demonstrates that affected patients show endothelial dysfunction that slowly responds to steroid therapy. Further studies are needed to investigate the clinical relevance of these observations and, in particular, to monitor the cardiovascular risk profile of PMR patients.
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Aterosclerose/etiologia , Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Polimialgia Reumática/complicações , Vasodilatação/fisiologia , Idoso , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Artéria Braquial/diagnóstico por imagem , Endotélio Vascular/diagnóstico por imagem , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Projetos Piloto , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/fisiopatologia , Estudos Prospectivos , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. The lack of in vitro models able to recapitulate the intrinsic heterogeneity of primary NB tumours has hindered progress in understanding disease pathogenesis and therapy response. METHODS: Here we describe the establishment of 6 patient-derived organoids (PDOs) from cells of NB tumour biopsies capable of self-organising in a structure resembling the tissue of origin. RESULTS: PDOs recapitulate the histological architecture typical of the NB tumour. Moreover, PDOs expressed NB specific markers such as neural cell adhesion molecules, NB84 antigen, synaptophysin (SYP), chromogranin A (CHGA) and neural cell adhesion molecule NCAM (CD56). Analyses of whole genome genotyping array revealed that PDOs maintained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Furthermore, the PDOs showed stemness features and retained cellular heterogeneity reflecting the high heterogeneity of NB tumours. CONCLUSIONS: We were able to create a novel preclinical model for NB exhibiting self-renewal property and allowing to obtain a reservoir of NB patients' biological material useful for the study of NB molecular pathogenesis and to test drugs for personalised treatments.
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Doenças do Sistema Nervoso Autônomo/genética , Doenças do Sistema Nervoso Autônomo/patologia , Modelos Biológicos , Neuroblastoma/genética , Neuroblastoma/patologia , Organoides/patologia , Doenças do Sistema Nervoso Autônomo/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia , Criança , Pré-Escolar , Cromogranina A/metabolismo , Aberrações Cromossômicas , Amplificação de Genes/genética , Humanos , Lactente , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/metabolismo , Organoides/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sinaptofisina/metabolismoRESUMO
BACKGROUND AND PURPOSE: The aim of our study was to describe, by a case-control and cross-sectional design, the correlation between clinical impairment and age in Charcot-Marie-Tooth type 1A (CMT1A) patients. METHODS: Seventy CMT1A patients and 70 sex- and age-matched healthy controls were enrolled. Motor performance was assessed through the 10-m walk test, the 6-min walk test and the 9-hole peg test of the dominant and non-dominant side, and muscle strength was measured by using the Medical Research Council score. In the CMT1A group, disability and quality of life were evaluated using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Short Form 36 (SF-36) questionnaire. Cross-sectional relationships between age and all clinical measures were analyzed and differences in the slopes between cases and controls were calculated. The occurrence of a structural change in the age-related progression of clinical measures was explored. RESULTS: The deterioration of motor performance correlated with age in both groups with a greater slope in CMT1A patients than controls. The deterioration of CMTNS and SF-36 correlated with age in the CMT1A group. The deterioration of all clinical measures with the exception of the SF-36 questionnaire showed a structural change at the 50th year of age. The rate of deterioration was no different between patients and controls until 50 years of age, whereupon it became significantly greater in CMT1A patients. CONCLUSION: Our study supports that the disease progression in CMT1A patients is an age-related process and the 50th year of age represents a critical moment after which the clinical decline becomes faster.
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Doença de Charcot-Marie-Tooth/fisiopatologia , Progressão da Doença , Atividade Motora/fisiologia , Força Muscular/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: We aimed to test the clinical utility of the leg:thigh intraepidermal nerve-fiber (IENF) density ratio as a parameter to discriminate between length-dependent small-fiber neuropathy (SFN) and small-fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small-fiber pathology. METHODS: We retrospectively evaluated thigh and leg IENF density in 314 subjects with small-fiber pathology (173 with distal symmetrical length-dependent SFN and 141 with non-length-dependent SFSG). A group of 288 healthy subjects was included as a control group. The leg:thigh IENF density ratio was calculated for all subjects. We used receiver operating characteristic curve analyses to assess the ability of this parameter to discriminate between length-dependent SFN and SFSG, and the decision curve analysis to estimate its net clinical benefit. RESULTS: In patients with neuropathy, the mean IENF density was 14.8 ± 6.8/mm at the thigh (14.0 ± 6.9/mm in length-dependent SFN and 15.9 ± 6.7/mm in patients with SFSG) and 7.5 ± 4.5/mm at the distal leg (5.4 ± 3.2/mm in patients with length-dependent SFN and 10.1 ± 4.6/mm in patients with SFSG). The leg:thigh IENF density ratio was significantly (P < 0.01) lower in patients with length-dependent SFN (0.44 ± 0.23) compared with patients with SFSG (0.68 ± 0.28). The area under the curve of the receiver operating characteristic analysis to discriminate between patients with length-dependent SFN and SFSG was 0.79. The decision curve analysis demonstrated the clinical utility of this parameter. CONCLUSIONS: The leg:thigh IENF ratio represents a valuable tool in the differential diagnosis between SFSG and length-dependent SFN.
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Fibras Nervosas/patologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Pele/patologia , Neuropatia de Pequenas Fibras/diagnóstico , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Neuropatia de Pequenas Fibras/patologiaRESUMO
Casertana is an endangered autochthonous pig breed (raised in south-central Italy) that is considered to be the descendant of the influential Neapolitan pig population that was used to improve British breeds in the 19th century. Casertana pigs are characterized by a typical, almost complete, hairless phenotype, even though a few Casertana pigs are normal haired. In this work, using Illumina PorcineSNP60 BeadChip data, we carried out a genome-wide association study and an FST analysis with this breed by comparing animals showing the classical hairless phenotype (n = 81) versus pigs classified as haired (n = 15). Combining the results obtained with the two approaches, we identified two significant regions: one on porcine chromosome (SSC) 7 and one on SSC15. The SSC7 region contains the forkhead box N3 (FOXN3) gene, the most plausible candidate gene of this region, considering that mutations in another gene of the same family (forkhead box N1; Foxn1 or FOXN1) are responsible for the nude locus in rodents and alopecia in humans. Another potential candidate gene, rho guanine nucleotide exchange factor 10 (ARHGEF10), is located in the SSC15 region. FOXN3 and ARHGEF10 have been detected as differentially expressed in androgenetic and senescent alopecia respectively. This study on an autochthonous pig breed contributes to shed some light on novel genes potentially involved in hair development and growth and demonstrates that local animal breeds can be valuable genetic resources for disclosing genetic factors affecting unique traits, taking advantage of phenotype variability segregating in small populations.
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Cruzamento , Fenótipo , Sus scrofa/genética , Animais , Feminino , Fatores de Transcrição Forkhead/genética , Estudos de Associação Genética/veterinária , Cabelo , Itália , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Troca de Nucleotídeo Guanina Rho/genéticaRESUMO
AIMS: To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS). METHODS: We enrolled 41 patients (M = 20, aged 63.5 ± 11.8 years), and 41 age- and gender-matched healthy volunteers (M = 20, aged 63.5 ± 11.8 years). Disease severity and sensory and autonomic symptoms were scored using dedicated rating scales. Skin biopsies obtained from thigh, leg and fingertip were processed using indirect immunofluorescence. Intraepidermal nerve fibres, Meissner corpuscles (MCs), intrapapillary myelinated endings, cholinergic and noradrenergic pilomotor nerves and dermal vessels were quantified on confocal images. Intraepidermal nerve fibres, pilomotor nerves and vessels were also assessed on distal leg skin samples of 10 spinal cord injury patients to compare our findings with those of a chronic hypomobility condition. RESULTS: Compared to healthy controls skin biopsies showed: (i) non-length-dependent loss of intraepidermal nerve fibres (P < 0.01) and loss of MCs (P < 0.01); (ii) reduced (P < 0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (P < 0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (P < 0.01). Moreover, we observed signs of nerve regeneration coexisting with nerve degeneration and increased complexity of the dermal vessels. In patients with posttraumatic spinal cord injury, the density of intraepidermal nerve fibres, pilomotor nerves and of the vascular bed did not differ from controls (P > 0.05). CONCLUSIONS: We demonstrated a cutaneous sensory and autonomic denervation in ALS and a previously undescribed relationship between autonomic and vascular involvement that appeared to be linked to the disease progression rate.
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Esclerose Lateral Amiotrófica/patologia , Vias Autônomas/patologia , Vasos Sanguíneos/patologia , Células Receptoras Sensoriais/patologia , Adulto , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/patologia , Pele/patologiaRESUMO
This study evaluates the prevalence of sarcopenia among older people admitted to a rehabilitation unit after hip fracture and the association between sarcopenia and functional outcomes. The results show that sarcopenia had a negative impact on functional recovery. The assessment of sarcopenia among older adults receiving rehabilitation programs is crucial. INTRODUCTION: Sarcopenia is a highly prevalent geriatric syndrome associated with adverse outcomes, including falls, disability, institutionalization, and mortality. Few studies assessed sarcopenia among older adults receiving rehabilitation programs. METHODS: Patients aged 70 years or more consecutively admitted to in-hospital rehabilitation programs that had suffered from hip fracture entered the study. Sarcopenia was defined according to the Foundation for National Institutes of Health (FNIH) criteria. Multivariable linear regression models were used to analyze the association between the sarcopenia and functional recovery. RESULTS: The recruited population was composed of 127 patients, with a mean age of 81.3 ± 4.8 years, predominantly females (64.6%). Using the criteria proposed by the FNIH, patients with a diagnosis of sarcopenia were 43 (33.9%). After adjustment for potential confounders, participants with sarcopenia had a significant increased risk of incomplete functional recovery compared with non-sarcopenic patients (OR 3.07, 95% CI 1.07-8.75). Compared with participants without sarcopenia, those with sarcopenia showed lower Barthel index scores at the time of discharge from the rehabilitation unit (69.2 versus 58.9, respectively; p < 0.001) and after 3 months of follow-up (90.9 versus 80.5, respectively; p = 0.02). CONCLUSIONS: These findings support the systematic assessment of sarcopenia among older adults receiving rehabilitation programs to assist in the development of personalized treatment plans aimed at improving functional outcomes.
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Fraturas do Quadril/complicações , Fraturas do Quadril/reabilitação , Sarcopenia/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Indicadores Básicos de Saúde , Fraturas do Quadril/fisiopatologia , Hospitalização , Humanos , Masculino , Recuperação de Função Fisiológica , Centros de Reabilitação , Sarcopenia/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. METHODS: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. RESULTS: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. CONCLUSIONS: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique.
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Epiderme/inervação , Perna (Membro)/inervação , Fibras Nervosas , Adulto , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/diagnóstico , Valores de ReferênciaRESUMO
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy, but therapeutic options have been limited to symptom management. Past pharmacological trials have failed, possibly due to insensitive outcome measures (OMs). The aim of the current study was to evaluate the validity and reliability of the 6-min walk test (6MWT) and StepWatch(™) Activity Monitoring (SAM) with other previously validated OMs in CMT disease. METHODS: A prospective multicenter study was performed, consecutively enrolling 168 CMT patients (104 with CMT1A, 27 with CMT1B, 37 with X-linked CMT) from Italian centers specializing in CMT care. RESULTS: Statistical analysis showed that the 6MWT was highly related with all previously used OMs. Some, but not all, SAM parameters were related to commonly used OMs but may provide more information about quality of life. CONCLUSIONS: The current study demonstrated the validity and reliability of the 6MWT and SAM as OMs for CMT. Moreover, SAM provides data that correlate better with quality of life measures, making it useful in future rehabilitation trials.
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Doença de Charcot-Marie-Tooth/diagnóstico , Qualidade de Vida , Caminhada , Adolescente , Adulto , Idoso , Doença de Charcot-Marie-Tooth/fisiopatologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Reprodutibilidade dos Testes , Teste de Caminhada , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. METHODS: Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot-Marie-Tooth Examination Score (CMTES). RESULTS: NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. CONCLUSIONS: This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.
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Potenciais de Ação/fisiologia , Doença de Charcot-Marie-Tooth/fisiopatologia , Condução Nervosa/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder to the upper urinary tract. It is the most common congenital urological anomaly affecting 1-2% of children and 30-40% of patients with urinary tract infections. VUR is a major risk factor for pyelonephritic scarring and chronic renal failure in children. It is the result of a shortened intravesical ureter with an enlarged or malpositioned ureteric orifice. An ectopic embryonal ureteric budding development is implicated in the pathogenesis of VUR, which is a complex genetic developmental disorder. Many genes are involved in the ureteric budding formation and subsequently in the urinary tract and kidney development. Previous studies demonstrate an heterogeneous genetic pattern of VUR. In fact no single major locus or gene for primary VUR has been identified. It is likely that different forms of VUR with different genetic determinantes are present. Moreover genetic studies of syndromes with associated VUR have revealed several possible candidate genes involved in the pathogenesis of VUR and related urinary tract malformations. Mutations in genes essential for urinary tract morphogenesis are linked to numerous congenital syndromes, and in most of those VUR is a feature. The Authors provide an overview of the developmental processes leading to the VUR. The different genes and signaling pathways controlling the embryonal urinary tract development are analyzed. A better understanding of VUR genetic bases could improve the management of this condition in children.
RESUMO
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.
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Doença de Charcot-Marie-Tooth/diagnóstico , Teste de Esforço/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Adulto , Doença de Charcot-Marie-Tooth/tratamento farmacológico , Ensaios Clínicos como Assunto , Teste de Esforço/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normasRESUMO
Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.
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Toxinas Botulínicas/administração & dosagem , Disfonia/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Adulto , Idoso , Disfonia/fisiopatologia , Eletromiografia/métodos , Feminino , Seguimentos , Humanos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Exame Neurológico , Índice de Gravidade de Doença , Espectrografia do Som , Acústica da Fala , Inquéritos e Questionários , Resultado do Tratamento , Gravação em Vídeo/métodos , Prega VocalRESUMO
Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.
Assuntos
Glucosamina/urina , Heparitina Sulfato/urina , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Mucopolissacaridoses/genética , Mucopolissacaridoses/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Glucosamina/química , Heparitina Sulfato/química , Humanos , Lactente , Masculino , Peso Molecular , Mucopolissacaridose I/genética , Mucopolissacaridose I/psicologia , Mucopolissacaridose III/genética , Mucopolissacaridose III/psicologia , Valores de Referência , Adulto JovemRESUMO
PURPOSE: To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. MATERIALS AND METHODS: The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen's kappa statistics. RESULTS: In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT-simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were -0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and -1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa >0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six comparisons. CONCLUSIONS: CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Posicionamento do Paciente/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador/métodos , Técnica de Subtração , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. RESULTS: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. DISCUSSION: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients.
Assuntos
Doença de Charcot-Marie-Tooth/complicações , Debilidade Muscular/etiologia , Adolescente , Adulto , Idoso , Doença de Charcot-Marie-Tooth/fisiopatologia , Transtornos Traumáticos Cumulativos/etiologia , Transtornos Traumáticos Cumulativos/fisiopatologia , Feminino , Lateralidade Funcional/fisiologia , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. METHODS: Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2â years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. RESULTS: At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. CONCLUSIONS: Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up.