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BACKGROUND: Breast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. METHODS: The ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. RESULTS: Twenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive. Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. CONCLUSIONS: Secondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40-57 vs. 31-41 months).
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Neoplasias de la Mama/mortalidad , Hemangiosarcoma/mortalidad , Neoplasias Primarias Secundarias/mortalidad , Complicaciones Posoperatorias/mortalidad , Anciano , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Hemangiosarcoma/complicaciones , Hemangiosarcoma/etiología , Hemangiosarcoma/cirugía , Humanos , Italia/epidemiología , Escisión del Ganglio Linfático/efectos adversos , Linfangiosarcoma/complicaciones , Mastectomía/mortalidad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/cirugía , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Cirujanos/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess whether different patterns of EEG rhythms during a Go/No-go motor task characterize patients with cortical myoclonus (EPM1) or with spinocerebellar ataxia (SCA). METHODS: We analyzed event-related desynchronization (ERD) and synchronization (ERS) in the alpha and beta-bands during visually cued Go/No-go task in 22 patients (11 with EPM1, 11 with SCA) and 11 controls. RESULTS: In the Go condition, the only significant difference was a reduced contralateral beta-ERS in the EPM1 patients compared with controls; in the No-go condition, the EPM1 patients showed prolonged alpha-ERD in comparison with both controls and SCA patients, and reduced or delayed alpha- and beta-ERS in comparison with controls. In both conditions, the SCA patients, unlike EPM1 patients and controls, showed minimal or absent lateralization of alpha- and beta-ERD. CONCLUSIONS: EPM1 patients showed abnormal ERD/ERS dynamics, whereas SCA patients mainly showed defective ERD lateralization. SIGNIFICANCE: A different behavior of ERS/ERD distinguished the two patient groups: the pattern observed in EPM1 suggests a prominent defect of inhibition occurring in motor cortex contralateral to activated segment, whereas the pattern observed in SCA suggested a defective lateralization attributable to the damage of cerebello-cortical network, which is instead marginal in patients with cortical myoclonus.
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Corteza Cerebral/fisiopatología , Potenciales Evocados/fisiología , Actividad Motora/fisiología , Movimiento/fisiología , Mioclonía/fisiopatología , Ataxias Espinocerebelosas/fisiopatología , Adulto , Sincronización Cortical/fisiología , Electroencefalografía , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Disease severity varies considerably among patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to investigate the role of androgen receptor (AR) polymorphic repeats in SBMA phenotype. METHODS: We analyzed the length of AR polyQ and polyG tracts in 159 SBMA patients. RESULTS: No relationship between polyG size or polyG/polyQ haplotypes and clinical phenotype was found. An independent negative correlation between polyQ-length and onset of weakness was confirmed (P < 0.001). CONCLUSIONS: The negative results of our study prompt to continue the search for potential disease modifiers in SBMA outside the AR gene.
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Atrofia Muscular Espinal/genética , Polimorfismo de Nucleótido Simple , Receptores Androgénicos/genética , Alelos , Haplotipos , Humanos , Péptidos/genética , Fenotipo , Poli G/genéticaRESUMEN
AIM The aim of this study is to evaluate long-term efficacy of intravitreal injections of aflibercept as primary treatment for subfoveal/juxtafoveal myopic choroidal neovascularisation (CNV).METHODS Thirty-eight treatment-naive eyes of thirty-eight patients with subfoveal/juxtafoveal myopic CNV received initial intravitreal aflibercept injections and were followed for at least 18 months. Aflibercept was applied again for persistent or recurrent CNV, as required. Statistical analysis was carried out using SPSS.RESULTS Mean patient age was 45.8 years, and mean eye refractive error was -7.79 D. For the total patient group (n=38 eyes), mean logMAR best-corrected visual acuity (BCVA) significantly improved from 0.69 at baseline to 0.15 at 18 months (P<0.01). Over half of the treated eyes obtained resolution with one aflibercept injection. Patients were also grouped according to age, as <50 years (n=20 eyes) and ≥50 years (n=18 eyes). Mean BCVA improvement was significantly greater in eyes of the younger myopic CNV group, compared with those of ≥50 years (0.21 vs 0.35; P<0.05). The mean number of aflibercept injections was 1.8 for the <50 years myopic CNV group, and 3.6 for the ≥50 years myopic CNV group (P<0.001). Correlation between spherical equivalent refraction and final visual acuity reached statistical significance only for the <50 years myopic CNV group (P<0.001; Levene's correlation).CONCLUSIONS Intravitreal aflibercept provides long-term visual acuity improvement in myopic CNV. The <50 years old myopic CNV group had significantly fewer injections, with greater visual acuity improvement. Intravitreal aflibercept in myopic CNV does not require the three-injection loading phase used for aflibercept treatment of neovascular age-related macular degeneration.
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Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Miopía Degenerativa/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Adulto , Anciano , Neovascularización Coroidal/fisiopatología , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Miopía Degenerativa/fisiopatología , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacos , Adulto JovenRESUMEN
PURPOSE: To determine the predictive value of markers for persistent subretinal fluid (SRF) absorption and the influence of subfoveal fluid on visual outcome after scleral buckle (SB) surgery for rhegmatogenous retinal detachment (RRD). PATIENTS AND METHODS: This was a retrospective, observational study. We reviewed the medical records of 64 eyes of 64 patients who underwent SB surgery for macula-off RRD. Patients underwent clinical examination and spectral-domain optical coherence tomography before surgery, at 1 month and every 3 months postoperatively. The height and width of SRF bleb(s) were measured over time. RESULTS: Persistent SRF at 1 month was observed in 40 eyes (62.5%). SRF blebs were first detected 1.7 ± 2.2 months postoperatively. In 29 cases that could be fully followed up, SRF blebs were completely absorbed 7.8 ± 4.4 months postoperatively. Resolution of fluid was associated with an improvement of VA (P = 0.003). Serial measurements of SRF bleb size showed that bleb width decreased significantly at all time points during the 12-month follow-up period (P < 0.05), while significant bleb height decrease occurred from postoperative sixth month only (P < 0.05). There was no correlation between VA outcomes and subfoveal bleb height or width (P > 0.05). The cut-off value of the bleb width-to-height ratio level for predicting bleb absorption at 6 months was 7, with 89% sensitivity and 83% specificity. CONCLUSIONS: Visual improvement may occur with late resolution of residual subfoveal fluid. A bleb width-to-height ratio >7 indicates a higher risk of SRF to persist beyond 6 months after surgery.
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Desprendimiento de Retina/cirugía , Curvatura de la Esclerótica/efectos adversos , Líquido Subretiniano , Adulto , Anciano , Biomarcadores/análisis , Femenino , Humanos , Mácula Lútea/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Líquido Subretiniano/metabolismo , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
The ocular involvement in psoriasis is not a completely well-known problem. The ophthalmologic involvement occurs in about 10 % of patients, particularly in case of arthropathic or pustular psoriasis. Ocular lesions are more common in males, and they often occur during psoriasis exacerbations. Our study aimed to assess the prevalence and type of ocular involvement in psoriasis, by a comparison between psoriasis and healthy subjects, and if/how a 12-week long systemic immunosuppressive therapy is able to modify them. This study involved thirty-two psoriatic patients and thirty-two healthy subjects. Dermatological evaluation was done using Psoriasis Area and Severity Index, Physician Global Assessment, and Dermatology Life Quality Index (PASI, PGA, and DLQI score). Ophthalmological evaluation included ocular surface involvement (Schirmer, Jones, break-up time--BUT, DR-1 camera), retinal pathologies, and ocular surface disease index. Laboratory investigations including the C-reactive protein (CRP) of all the patients were performed. At baseline, the values of Schirmer, Jones, and BUT tests in the patient group were significantly lower compared to controls; moreover, conjunctival hyperemia was more frequent in psoriatic patients than in healthy subjects. Ocular involvement was more prominent in the subset of psoriatic patients with sebo-psoriasis than in general psoriatic population. A statistically significant correlation was found in sebo-psoriasis between PASI and Schirmer, between PASI and Jones, and between PASI and BUT. On the other hand, the results obtained from DR1 camera showed statistically significant difference between psoriatic and sebo-psoriatic patients at the end of the follow-up. After 12 weeks of treatment, the mean values of PASI, PGA, DLQI, CRP, and BUT showed significant changes in psoriatic patients. Our findings suggest a high rate of ocular involvement in psoriatic patients, emphasizing the need of performing periodic ophthalmological examinations in order to avoid underestimating eye diseases and to allow early diagnosis and treatment of patients.
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Oftalmopatías/etiología , Psoriasis/complicaciones , Adulto , Anciano , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Oftalmopatías/tratamiento farmacológico , Oftalmopatías/epidemiología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Estudios Prospectivos , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Psoriasis/patología , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
Purpose. Myopic macular holes can be difficult to close with surgery and are frequently associated with retinal detachment. We report on a case of a macular hole in a severely myopic eye that underwent spontaneous closure. Methods. An observational case study. Results. A 55-year-old female was referred to Ophthalmology for a central scotoma and metamorphopsia in the right eye. Visual acuity was 1/20 in both eyes. Fundus examination showed loss of the foveal depression, with a small yellow ring in the center of the fovea in the right eye, and a tilted optic disc and peripapillary staphyloma bilaterally. Spectral domain optical coherence tomography (SD-OCT) revealed a fully developed macular hole with a rim of thickened and slightly elevated retina in the right eye. The patient refused surgery. After 4 years of follow-up, her visual acuity improved to 20/40 in the right eye, and SD-OCT revealed spontaneous sealing of the macular hole without bare retinal pigment epithelium. Conclusions. Myopic macular holes represent a challenge regarding their management, and the prognosis is often poor.
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BACKGROUND AND OBJECTIVES: The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer-reviewed evidence-based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. METHODS: This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force. DIAGNOSIS: If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia (SCA) 1, 2, 3, 6, 7 and 17 (level B), and in Asian patients also for dentatorubral-pallidoluysian atrophy (DRPLA). In the case of recessive disease, a stepwise diagnostic work-up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at Friedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene (POLG gene, various mutations), autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and ataxia with oculomotor apraxia (AOA) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work-up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 FMR1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work-up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work-up, or even whole exome and genome sequencing for selected cases. TREATMENT: Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in Friedreich's ataxia (level A). Riluzole (level B) and amantadine (level C) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA3 patients (level B) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.
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Ataxia/diagnóstico , Ataxia/terapia , Consenso , Guías como Asunto/normas , Ataxia/genética , Enfermedad Crónica , Bases de Datos Factuales/estadística & datos numéricos , HumanosRESUMEN
Vitamin E possesses potent beneficial effects on mammalian spermatogenesis and sperm quality. Subjects affected by cerebellar ataxia due to congenital isolated vitamin E deficiency (AVED) show vitamin E deficiency caused by a selective impaired gastrointestinal absorption of vitamin E for a mutation in the gene for α-tocopherol transfer protein leading to impairment of vitamin E absorption and decreased vitamin E plasma levels. Here, we present a 34-year-old male patient with AVED showing normal seminal parameters and normal gonadotrophins, testosterone and inhibin B plasma levels. The normal standard seminal parameters of this patient with AVED possibly question the role of vitamin E in human spermatogenesis.
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Ataxia Cerebelosa/etiología , Ataxia Cerebelosa/fisiopatología , Espermatogénesis , Deficiencia de Vitamina E/congénito , Adulto , Proteínas Portadoras/genética , Humanos , Masculino , Mutación , Espermatogénesis/genética , Espermatogénesis/fisiología , Espermatozoides/fisiología , Vitamina E/fisiología , Deficiencia de Vitamina E/complicaciones , Deficiencia de Vitamina E/genéticaRESUMEN
PURPOSE: To report on the long-term outcomes and risk factors for failure with the EX-PRESS shunt implanted under a scleral flap. SETTINGS: Eye Department, University of Ancona, Ancona, Italy and the Oxford Eye Center, University of Witwatersrand, Johannesburg, South Africa. METHODS: The medical records of glaucoma patients who underwent consecutive EX-PRESS implantations under a scleral flap between 2000 and 2009 were reviewed. The operations were performed by two experienced surgeons using an identical surgical technique. The potential risk factors for failure that were analysed included age, sex, race, glaucoma type, previous antiglaucoma medications, previous glaucoma surgeries, diabetes, and smoking. Complete success was defined as postoperative intraocular pressure (IOP) 5 mm Hg>IOP<18 mm Hg without antiglaucoma medications. Qualified success was defined as 5 mm Hg>IOP<18 mm Hg with or without antiglaucoma medications. RESULTS: Two hundred and forty-eight eyes of 211 consecutive patients were included. The mean IOP was reduced from 27.63 ± 8.26 mm Hg preoperatively (n=248) to 13.95 ± 2.70 mm Hg at 5 years (n=95). The mean follow-up was 3.46 ± 1.76 years. Complete and qualified success rates decreased gradually from 83% and 85% at 1 year to 57% and 63% at 5 years follow-up, respectively. The risk factors for failure were diabetes, non-Caucasian race, and previous glaucoma surgery. Complete success rates of diabetic patients and non-Caucasian patients decreased from 63% and 75% at 1 year to 42% and 40% at 5 years follow-up, respectively. CONCLUSIONS: EX-PRESS success rates decrease over time but compare favourably with trabeculectomy literature data. The main identifiable risk factors for failure are diabetes, non-Caucasian race, and previous glaucoma surgery.
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Implantes de Drenaje de Glaucoma , Glaucoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Femenino , Estudios de Seguimiento , Glaucoma/tratamiento farmacológico , Glaucoma/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Implantación de Prótesis , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: Interactions between blood pressure control, sleep and headache have been largely studied, although not well understood. We designed a study trying to simultaneously evaluate all three aspects in the same subjects. We particularly concentrated on the observation of physiological blood pressure circadian rhythm, and the presence of cutaneous allodynia correlated to headache. Objective of the study was to investigate blood pressure during nocturnal sleep in patients that underwent a blood pressure 24 hours monitoring, and at the same time the presence of headache and of sleep behavioural alterations. METHODS: Blood pressure 24 hours monitoring was performed by an ambulatory blood pressure (ABP) monitor (Space Labs) with its ad hoc software. Headache diagnosis was made according to ICHD-II criteria. Presence of allodynia and sleep behavior were evaluated through semi-structured ad hoc questionnaires. RESULTS: A total of 195 subjects were included, of which 122 without headache (mean age 60.4±11.6 years, 78 men and 44 women) and 73 with history of headache, (mean age 54.2±12.5 years, 18 men and 55 women). Fifty-one headache patients had migraine (mean age 52.6±11.7 years, 11 men and 40 women) and 22 tension type headache (TTH - mean age 58.0±13.5 years, 7 men and 15 women). Allodynia was found in 30 out of 73 headache patients: 23 out of 51 in the migraine group and in 7 out of 22 in the tension-type one. The physiological reduction of blood pressure during night (dipping) was more conserved among headache patients (34 dippers out of 73 subjects, 46,6%) with respect to subjects without headache (40 dippers out of 122, 32,8%) and that this border-line difference was more strongly significant comparing allodynic subjects (19 dippers out of 30, 63.3%) with both non-headache (40 dippers out of 122, 32.8%, P<0.001) and non-allodynic (15 out of 43, 34.9%, P<0.05) ones. No significant difference was observed between headache patients and subjects without headache in terms of mean systolic and diastolic pressure, neither between migraine and TTH. CONCLUSION: Allodynic headache patients seem to maintain a more physiologic pressure circadian rhythm. While considering the possibility of selection bias, the hypothesis of an allostatic function of headache and allodynia in patients with unbalanced blood pressure could be made.
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Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Cefalea/fisiopatología , Hiperalgesia/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño/fisiología , Cefalea de Tipo Tensional/fisiopatología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Femenino , Humanos , Hiperalgesia/diagnóstico , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/fisiopatologíaRESUMEN
The aim of the present study was to investigate the possible relationships between the presence of headache-related photophobia and migraine-associated allodynia--a hallmark of central sensitization--among patients with different migraine types. A sample of 456 migraineurs was studied. Our results showed that photophobia was present in a high proportion of patients, with similar figures in patients with episodic migraine or CM, and confirmed that the prevalence of allodynia was higher among CM patients than in those with episodic migraine. We found a clear association between migraine-related allodynia and photophobia only in CM patients. Overall, these findings suggest that light stimulation may contribute to central sensitization of pain pathways in migraineurs, possibly contributing to progression into chronic forms. The possible connections underlying this type of sensitization is offered by the recently published data on a non-image-forming visual retino-thalamo-cortical pathway which may allow photic signals to converge on a thalamic region which is selectively activated during migraine headache.
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Sensibilización del Sistema Nervioso Central/fisiología , Trastornos Migrañosos/fisiopatología , Fotofobia/fisiopatología , Vías Visuales/fisiopatología , Adulto , Encéfalo/fisiopatología , Femenino , Humanos , Hiperalgesia/epidemiología , Hiperalgesia/fisiopatología , Masculino , Fotofobia/epidemiología , PrevalenciaRESUMEN
Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.
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Examen Neurológico , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/diagnóstico , Área Bajo la Curva , Europa (Continente) , Femenino , Humanos , Estudios Longitudinales , Masculino , Psicometría , Reproducibilidad de los Resultados , Ataxias Espinocerebelosas/clasificación , Ataxias Espinocerebelosas/genética , Estadística como AsuntoRESUMEN
BACKGROUND AND PURPOSE: The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. The disease, first described in Canadian families from Québec, is characterized by cerebellar ataxia, pyramidal tract involvement and peripheral neuropathy. METHODS: Analysis of SACS gene allowed the identification of 14 patients with ARSACS from 13 unrelated Italian families. Clinical phenotype, gene mutations and magnetic resonance imaging (MRI) findings were analysed. RESULTS: We found 16 novel SACS gene mutations, including a large in-frame deletion. The age at onset was in infancy, but one patient presented the first symptoms at age 32. Progression of the disease was variable, and increased muscle tone was mostly recognized in later stages. Structural MRI showed atrophy of the superior cerebellar vermis, a bulky pons exhibiting T2-hypointense stripes, identified as the corticospinal tract (CST), thinning of the corpus callosum and a rim of T2-hyperintensity around the thalami in 100% of cases. The presence of iron or other paramagnetic substances was excluded. Diffusion tensor imaging (DTI) revealed grossly over-represented transverse pontine fibres (TPF), which prevented reconstruction of the CST at this level (100% of cases). In all patients, significant microstructural alterations were found in the supratentorial white matter of forceps, cingulum and superior longitudinal fasciculus. CONCLUSIONS: Our findings further enlarge the genetic spectrum of SACS mutations and widen the study of clinical phenotype. MRI characteristics indicate that pontine changes and supratentorial abnormalities are diagnostic. The over-representation of TPF on DTI suggests a developmental component in the pathogenesis of the disease.
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Cerebelo/patología , Imagen por Resonancia Magnética , Espasticidad Muscular/patología , Puente/patología , Ataxias Espinocerebelosas/congénito , Adolescente , Adulto , Niño , Imagen de Difusión por Resonancia Magnética , Salud de la Familia , Femenino , Trastornos Neurológicos de la Marcha/etiología , Genes Recesivos , Proteínas de Choque Térmico/genética , Humanos , Italia , Masculino , Espasticidad Muscular/complicaciones , Espasticidad Muscular/genética , Mutación/genética , Tractos Piramidales/patología , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Adulto JovenRESUMEN
BACKGROUND: Hereditary spastic paraplegias (HSP) are heterogeneous neurodegenerative disorders, genetically classified according to the identified disease gene or locus. Clinically, HSP are distinguished in pure and complicated forms. Mutations in the spastin gene (SPAST) are responsible for SPG4 and account approximately for 50% of the dominantly inherited paraplegias with a pure HSP phenotype. METHODS: Molecular screening of the SPAST gene allowed the identification of 31 Italian mutation carriers, from 19 unrelated families. Genetic testing was performed by direct sequencing and multiplex ligation-dependent probe amplification. Subjects carrying SPAST mutations were retrospectively evaluated for clinical phenotype and disability score assessment. RESULTS: We found 12 recurrent mutations, and 7 novel SPAST mutations. Twenty-eight patients exhibited a pure spastic paraplegia phenotype, while 3 subjects were asymptomatic mutation carriers. Four patients were sporadic cases. Age at onset ranged from 10 to 61 years. Disability score increased with age at examination and disease duration. Patients with onset >38 years presented a faster disease progression, and a higher disability functional index, than the patients with earlier onset (p<0.04). CONCLUSIONS: Our study enlarges the number of pathogenic SPAST mutations, and confirms the association with a pure spastic paraplegia phenotype. Age at onset was highly variable and correlates with the rate of disease progression. Future longitudinal clinical studies are needed to confirm these observations.
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Adenosina Trifosfatasas/genética , Mutación , Paraplejía Espástica Hereditaria/genética , Adolescente , Adulto , Edad de Inicio , Niño , Evaluación de la Discapacidad , Femenino , Heterocigoto , Humanos , Italia , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Linaje , Fenotipo , Paraplejía Espástica Hereditaria/complicaciones , Espastina , Población Blanca/genética , Adulto JovenRESUMEN
Following an allostatic perspective, episodic migraine (M) may be considered as an adaptive behavioural response to endogenous or exogenous stressors, while its progression to a daily or nearly daily form (chronic migraine) may represent the failure of adaptive strategies. Multiple factors may enhance the progression/chronification of M, and among these the presence of cutaneous allodynia (CA) as well as alterations in blood pressure and in sleep. The working hypothesis of the study was that subjects with M, and particularly those with CA, could show a tendency towards high blood pressure levels and/or to alterations in the circadian rhythm of blood pressure. We studied 235 subjects consecutively attending a centre for blood pressure control for a blood pressure 24 h monitoring. Headache diagnosis was made according to the ICHD-II criteria. The presence of CA was evaluated through a semi-structured ad hoc questionnaire. Blood pressure 24 h monitoring was performed by an ambulatory blood pressure monitor (Space Labs) with its ad hoc software. Seventy-eight subjects had a history of headache (mean age 54.0 ± 12.4 years, 18 men and 60 women); 56 of them had M, 22 had tension-type headache; among them, CA was found in 24/56 subjects with M, and in 6/22 with tension-type headache; 157 subjects did not suffer from headache (mean age 60.5 ± 11.5 years, 99 men and 58 women). No significant difference was observed between headache subjects and subjects without headache in terms of mean systolic and diastolic pressure, neither in the M nor in tension-type subgroups. With regard to the circadian rhythm of blood pressure, the physiological reduction during night (dipping) was more evident among headache subjects than in subjects without headache; this border-line difference was more strongly significant in subjects with CA than both non-headache (p = 0.003) and non-CA (p = 0.05) ones. The difference between allodynic and non-allodynic subjects was present also in the M sub-group (7 dippers out of 32 non-allodynic migraineurs vs. 12 dippers out of 24 allodynic migraineurs, p = 0.03) notwithstanding the reduction of the sample size. Despite the initial hypothesis, subjects with primary headaches did not show differences in terms of mean blood pressure values and they showed a more physiologic blood pressure daily rhythm than those without headaches. Also the presence of CA, a marker of progression to chronic headache forms, was associated neither with hypertension nor with increased frequency of loss of dipping. M, particularly when associated with allodynia, may improve breathing during nocturnal sleep and consequently counteract possible blood pressure alterations, suggesting an allostatic function of allodynic headache.
Asunto(s)
Presión Sanguínea/fisiología , Cefaleas Primarias/epidemiología , Cefaleas Primarias/fisiopatología , Hiperalgesia/epidemiología , Hiperalgesia/fisiopatología , Adulto , Anciano , Ritmo Circadiano/fisiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.