ABSTRACT
Gender is an important factor influencing epidemiological and clinical features of Parkinson's disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs (miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman's correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62; p < 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44; p < 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.
Subject(s)
MicroRNAs , Parkinson Disease , Humans , Male , Female , Levodopa/therapeutic use , Sex Factors , Biomarkers , MicroRNAs/genetics , Parkinson Disease/drug therapy , Parkinson Disease/geneticsABSTRACT
We aimed to characterize in vivo α-synuclein (α-syn) aggregates in skin nerves to ascertain: 1) the optimal marker to identify them; 2) possible differences between synucleinopathies that may justify the clinical variability. We studied multiple skin nerve α-syn deposits in 44 patients with synucleinopathy: 15 idiopathic Parkinson's disease (IPD), 12 dementia with Lewy Bodies (DLB), 5 pure autonomic failure (PAF) and 12 multiple system atrophy (MSA). Ten healthy subjects were used as controls. Antibodies against native α-syn, C-terminal α-syn epitopes such as phosphorylation at serine 129 (p-syn) and to conformation-specific for α-syn mature amyloid fibrils (syn-F1) were used. We found that p-syn showed the highest sensitivity and specificity in disclosing skin α-syn deposits. In MSA abnormal deposits were only found in somatic fibers mainly at distal sites differently from PAF, IPD and DLB displaying α-syn deposits in autonomic fibers mainly at proximal sites. PAF and DLB showed the highest p-syn load with a widespread involvement of autonomic skin nerve fibers. IN CONCLUSION: 1) p-syn in skin nerves was the optimal marker for the in vivo diagnosis of synucleinopathies; 2) the localization and load differences of aggregates may help to identify specific diagnostic traits and support a different pathogenesis among synucleinopathies.
Subject(s)
Protein Aggregation, Pathological/genetics , Skin Diseases/genetics , Skin/metabolism , alpha-Synuclein/genetics , Aged , Aged, 80 and over , Amyloid/genetics , Amyloid/metabolism , Brain/metabolism , Brain/pathology , Female , Humans , Lewy Body Disease/genetics , Lewy Body Disease/metabolism , Lewy Body Disease/pathology , Male , Multiple System Atrophy/genetics , Multiple System Atrophy/metabolism , Multiple System Atrophy/pathology , Nerve Fibers/metabolism , Nerve Fibers/pathology , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Pure Autonomic Failure/genetics , Pure Autonomic Failure/metabolism , Pure Autonomic Failure/pathology , Skin/innervation , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/metabolism , Skin Diseases/pathologyABSTRACT
BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.
Subject(s)
Dystonia/diagnosis , Dystonic Disorders/diagnosis , Laryngeal Diseases/diagnosis , Age Factors , Age of Onset , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Italy , Male , Middle Aged , Registries , Sex FactorsABSTRACT
In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.
ABSTRACT
The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.
Subject(s)
Dystonia/diagnosis , Dystonia/epidemiology , Registries , Adult , Age of Onset , Aged , Aged, 80 and over , Disease Progression , Dystonia/physiopathology , Dystonia/psychology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Optic nerve involvement is frequent in mitochondrial disease, and retinal abnormalities are described in Parkinson's disease (PD). METHODS: We evaluated retinal nerve fiber layer (RNFL) thickness by optical coherence tomography in 43 patients with PD and in 86 age-matched controls. We considered separately the eyes ipsilateral and contralateral to the most affected body side in patients with PD. ancova analysis, Pearson test, and multiple regression analysis were used (P < 0.05). RESULTS: Patients with PD showed significantly thinner temporal RNFL thickness compared to controls (P = 0.004), more evident in the eye contralateral to the most affected body side. Average RNFL thickness significantly correlated with age in both controls and patients with PD (P-values ranging from 0.001 to 0.019), whereas in patients with PD RNFL thickness did not correlate with clinical variables. CONCLUSIONS: Our study reveals a loss of retinal nerve fibers in the temporal quadrant in PD, which is typically susceptible in mitochondrial optic neuropathies.
Subject(s)
Nerve Fibers/pathology , Optic Nerve Diseases/etiology , Optic Nerve/pathology , Parkinson Disease/complications , Retina/pathology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 , Male , Middle Aged , Mutation/genetics , Protein Serine-Threonine Kinases/genetics , Tomography, Optical CoherenceABSTRACT
BACKGROUND: Essential tremor (ET) is the most common movement disorder worldwide. Three susceptibility loci on chromosomes 3q13, 2p24.1, and 6p23 have been reported, but no causative genes were found. The Ser9Gly variant of dopamine D3 receptor (DRD3) receptor was found associated to ET in a French and US population. METHODS: A case-control study to evaluate the association between the Ser9Gly variant and ET was performed in a cohort of 116 Italian patients with familial ET and in 158 normal controls. RESULTS: No significant difference in allele and genotype frequencies was found between the two groups. CONCLUSIONS: These results do not support an association between DRD3 Ser9Gly and susceptibility to ET in Italian patients.
Subject(s)
Amino Acid Substitution , Essential Tremor/genetics , Polymorphism, Single Nucleotide , Receptors, Dopamine D3/genetics , Adult , Aged , Alleles , Case-Control Studies , Essential Tremor/epidemiology , Female , Gene Frequency , Genetic Linkage , Genetic Predisposition to Disease , Genotype , Humans , Italy/epidemiology , Male , Middle AgedABSTRACT
Primary cutaneous aspergillosis is a rare cutaneous disease that usually affects immunodepressed patients of any age. The most common associated disorders in children are leukemias and lymphomas although it can also occur in neonates and preterms due to their intrinsic immunological immaturity. We report the case of a 4-year-old boy diagnosed of acute lymphoblastic leukemia that, during chemotherapy, developed an ulceronecrotic inflammatory cutaneous lesion in the venopuncture area of the left forearm, and whose microbiological culture was positive for Aspergillus flavus.
Subject(s)
Aspergillosis/etiology , Aspergillus flavus/isolation & purification , Dermatomycoses/etiology , Opportunistic Infections/etiology , Phlebotomy/adverse effects , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Wound Infection/etiology , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child, Preschool , Humans , Immunocompromised Host , Male , Neutropenia/chemically induced , Neutropenia/complications , Opportunistic Infections/microbiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Skin Ulcer/etiology , Skin Ulcer/microbiology , Wound Infection/microbiologyABSTRACT
La aspergilosis cutánea primaria es una enfermedad cutánea infrecuente que suele presentarse en individuos inmunodeprimidos de cualquier edad. En los niños, las patologías asociadas con mayor frecuencia son las leucemias y los linfomas, aunque también puede ocurrir en neonatos y prematuros debido a su inmadurez inmunológica intrínseca. Presentamos el caso de un varón de 4 años diagnosticado de leucemia linfoblástica aguda que durante el tratamiento quimioterápico presentó una lesión cutánea inflamatoria ulceronecrótica en la zona de venopunción del antebrazo izquierdo, y cuyo cultivo microbiológico fue positivo para Aspergillus flavus
Primary cutaneous aspergillosis is a rare cutaneous disease that usually affects immunodepressed patients of any age. The most common associated disorders in children are leukemias and lymphomas although it can also occur in neonates and preterms due to their intrinsic immunological immaturity. We report the case of a 4-year-old boy diagnosed of acute lymphoblastic leukemia that, during chemotherapy, developed an ulceronecrotic inflammatory cutaneous lesion in the venopuncture area of the left forearm, and whose microbiological culture was positive for Aspergillus flavus
Subject(s)
Male , Child, Preschool , Humans , Aspergillosis/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Dermatomycoses/complications , Immunocompromised Host , Aspergillus flavus/pathogenicityABSTRACT
Parkinsonism is a rare feature of immunological diseases. We describe a 67-year-old man with Caplan's syndrome (CS) and parkinsonism. CS is an immunologic disease characterised by the presence of rheumatoid arthritis associated with a specific form of pneumoconiosis. Parkinsonism as a manifestation of involvement of the central nervous system in this condition has never been reported. Following immunosuppressive treatment both the CS and the parkinsonian signs and symptoms showed a marked improvement. The role of immune mechanisms in these parkinsonian syndromes is discussed.
Subject(s)
Brain/pathology , Brain/physiopathology , Caplan Syndrome/complications , Caplan Syndrome/immunology , Encephalitis/immunology , Parkinson Disease/immunology , Aged , Anti-Inflammatory Agents/therapeutic use , Atrophy/diagnosis , Atrophy/immunology , Atrophy/physiopathology , Brain/immunology , Caplan Syndrome/drug therapy , Encephalitis/drug therapy , Encephalitis/physiopathology , Humans , Immunosuppressive Agents/therapeutic use , Lung/immunology , Lung/pathology , Lung/physiopathology , Magnetic Resonance Imaging , Male , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Silicosis/complications , Treatment OutcomeABSTRACT
The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.
Subject(s)
Parkinson Disease/complications , Parkinson Disease/diagnosis , REM Sleep Behavior Disorder/complications , REM Sleep Behavior Disorder/diagnosis , Surveys and Questionnaires , Aged , Confidence Intervals , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Parkinson Disease/physiopathology , REM Sleep Behavior Disorder/physiopathologyABSTRACT
We present the case of an 11 year-old Caucasian girl who presented chest pain of 12 weeks evolution, with no other symptoms and a negative physical examination. Lactate dehydrogenase levels were increased to 797 U/l, whereas beta-2-microglobulin (BM2) levels were normal. The thoracic CT showed a bulky mediastinal mass that occupied the pretracheal, paratracheal and right prevascular regions. The gallium scintigraphy showed high uptake in the mediastinic region; the bone scintigraphy was negative. Biopsy of the mediastinal mass revealed the presence of diffuse large B-cell non-Hodgkin's lymphoma. Treatment included 4 cycles of chemotherapy followed by 7 days of subcutaneous granulocyte colony-stimulating factor (G-CSF, Lenogastrim) at a dose of 5 mg/Kg/day. Following treatment, a CT scan was performed to evaluate response, finding a calcification of the mass without significant reduction of the overall size. Because CT was inconclusive in the assessment of response to therapy, a 18F-FDG PET scan was performed. The 18F-FDG PET scan did not show any pathological uptake in the mediastinum but revealed a splenic and bone marrow diffusely increased 18F-FDG uptake. The differential diagnosis included a secondary effect induced by G-CSF therapy as one of the main possibilities, but other possibilities such as a malignant infiltration by lymphoma could not be discarded. Therefore, a second 18F-FDG PET scan was performed 3 months later. This study showed no pathological findings, with a normal 18F-FDG uptake in the spleen and bone marrow. Thus, the benign and reactive nature of the splenic and bone marrow 18F-FDG increased uptake found in the previous study was confirmed. We consider that the stimulating effect that G-CSF therapy has on the spleen and bone marrow must be taken into account when performing a 18F-FDG PET scan, as it can be an important source of false-positive results.
Subject(s)
Bone Marrow/diagnostic imaging , Bone Marrow/metabolism , Fluorodeoxyglucose F18/metabolism , Granulocyte Colony-Stimulating Factor/adverse effects , Radiopharmaceuticals/metabolism , Spleen/diagnostic imaging , Spleen/metabolism , Tomography, Emission-Computed , Child , Female , HumansABSTRACT
This is a multiparametric MR study of the first reported patient with adult-onset genetically confirmed vanishing white matter (VWM) disease. It shows that, despite the presence of a severe and diffuse damage of the brain WM, brain gray matter, and cervical cord tissue, the cortical adaptive capacities were relatively preserved. Interpatient variability of brain plasticity may contribute to the known phenotypic variation of patients with VWM disease.
Subject(s)
Brain Diseases/pathology , Brain/pathology , Heredodegenerative Disorders, Nervous System/pathology , Magnetic Resonance Imaging/methods , Basal Ganglia/pathology , Brain/physiopathology , Brain Diseases/genetics , Brain Mapping , Eukaryotic Initiation Factor-2B/genetics , Female , Genes, Recessive , Humans , Middle Aged , Mutation, Missense , Psychomotor PerformanceABSTRACT
Two sisters from an Italian family shared progressive motor symptoms, preceding the onset of sensory and autonomic disturbances. The familial occurrence of axonal and slowly progressive polyneuropathy led us to consider these patients as candidates for TTR molecular analysis. We found a missense mutation causing Ile68Leu TTR substitution in both. The aims of this work are to report the possibility of a motor onset of amyloid polyneuropathy and to suggest the search for TTR mutations in familial cases of axonal polyneuropathy. Second, to stress the possible occurrence of amyloid within the spinal canal as the potential pathogenesis and responsible for motor presentation.
Subject(s)
Amyloid Neuropathies, Familial/genetics , Motor Activity/physiology , Point Mutation , Prealbumin/genetics , Adult , Age of Onset , Base Sequence , Female , Humans , Middle Aged , Molecular Sequence Data , Motor Activity/genetics , PedigreeABSTRACT
We examined the potential sex-related differences in levodopa pharmacokinetics and their relation with the presence of dyskinesias in a group of 115 patients (67 men, 49 women) with Parkinson's disease. The patients were given a standard oral dose of levodopa plus benserazide (100/25 mg). The area under the levodopa plasma concentration time curve, corrected for the levodopa test dose (in mg/kg body weight), (AUC(w)) was significantly higher in women than in men, with a reduced oral clearance. No difference in the proportion of men and women experiencing dyskinesias was observed.
Subject(s)
Antiparkinson Agents/blood , Dyskinesias/etiology , Levodopa/blood , Parkinson Disease/blood , Sex Characteristics , Aged , Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Area Under Curve , Benserazide/therapeutic use , Case-Control Studies , Dyskinesias/blood , Female , Half-Life , Humans , Levodopa/adverse effects , Levodopa/therapeutic use , Linear Models , Male , Metabolic Clearance Rate , Middle Aged , Parkinson Disease/drug therapyABSTRACT
Antecedentes: Topotecán es un quimioterápico alcaloide derivado de la planta Camptotheca acuminata (originaria de China) con capacidad de inhibir la enzima topoisomerasa I y de reciente uso en el tratamiento del cáncer pediátrico. Objetivos: Evaluar nuestra experiencia preliminar con el topotecán en el tratamiento de segunda línea de tumores sólidos refractarios en la edad pediátrica.Pacientes y métodos Estudio retrospectivo de 10 pacientes con tumores sólidos refractarios o recidivantes a la primera línea de tratamiento que reciben topotecán en monoterapia o en asociación con otros agentes quimioterápicos. Resultados: Se incluyeron 10 pacientes con tumores sólidos refractarios o recidivantes al tratamiento convencional (dos neuroblastomas, tres rabdomiosarcomas, dos tumores neuroectodérmicos primitivos (PNET)/Ewing, un astrocitoma anaplásico, un tumor desmoplásico y un sarcoma sinovial). Obtuvieron respuesta favorable 5 pacientes (dos remisiones completas, dos remisiones parciales y un estabilización de la enfermedad). En 5 pacientes no se consiguió ninguna respuesta. Todos los pacientes presentaron toxicidad hematológica de grado III-IV. Conclusiones: En nuestra experiencia, topotecán sería beneficioso en determinados tumores sólidos refractarios o recidivantes, sobre todo neuroblastomas y sarcomas de partes blandas, con una aceptable tolerancia a la toxicidad hematopoyética con el uso de factores estimulantes de colonias granulocíticas. Los pacientes en remisión completa de su enfermedad tras topotecán podrían beneficiarse de una intensificación de quimioterapia con rescate autólogo de progenitores hematopoyéticos (AU)
Subject(s)
Child, Preschool , Child , Adolescent , Male , Infant , Female , Humans , Drug Resistance, Neoplasm , Topotecan , Remission Induction , Retrospective Studies , Antineoplastic Agents , Drug Administration Schedule , Neoplasm Staging , NeoplasmsABSTRACT
BACKGROUND: Topotecan is a cytotoxic drug isolated from the Camptotheca acuminata tree (from China). It is able to block the enzyme DNA topoisomerase I and has recently been used in the treatment of pediatric cancer. OBJECTIVES: To evaluate our preliminary experience with topotecan in the second line treatment of refractory solid tumors in the pediatric age group. PATIENTS AND MEHTODS: We performed a retrospective study of 10 patients with various recurrent solid tumors resistant to first line treatment who were treated with topotecan alone or in association with other chemotherapeutic agents. RESULTS: Ten patients with recurrent solid tumors or tumors that were refractory to conventional treatment (two neuroblastomas, three rhabdomyosarcoma, two PNET/Ewing's sarcoma, one anaplastic astrocytoma, one soft tissue sarcoma and one synovial sarcoma) were included. Five patients showed favorable responses (two had complete responses, two had partial responses and one had stable disease). Five patients showed no response. All patients showed grade II-IV hematological toxicity. CONCLUSIONS: In our experience, topotecan is beneficial in some refractory or recurrent solid tumors, especially neuroblastomas and soft tissue sarcomas. Myelosuppression was tolerable with the use of granulocyte colony-stimulating factors. Patients with a complete response to topotecan could benefit from high-dose chemotherapy and autologous stem cell rescue therapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Topotecan/therapeutic use , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Infant , Male , Neoplasm Staging , Remission Induction , Retrospective StudiesABSTRACT
La listeriosis, infección sistémica causada por Listeria monocytogenes, es una enfermedad poco frecuente. Se ha observado que la inmunosupresión celular predispone a sufrir esta infección con mayor frecuencia, siendo ejemplo de este tipo de afectación la producida en los pacientes sometidos a tratamiento quimioterápico. Por este motivo se ha observado un aumento de su frecuencia en los últimos años. Presentamos el caso de una niña diagnosticada de leucemia linfoblástica aguda, que desarrolló una sepsis y meningitis por Listeria tratada con ampicilina y gentamicina, con evolución favorable (AU)