Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.

Distinct Patterns of Brain Atrophy associated with Mild Behavioral Impairment in Cognitively Normal Elderly Adults.

A cross-sectional study was conducted to evaluate patterns of gray matter changes in cognitively normal elderly adults with mild behavioral impairment (MBI). Sixteen MBI patients and 18 healthy controls were selected. All the participants underwent a neuropsychological assessment battery, including the Mini-mental State Examination (MMSE), Geriatric Depression Scale (GDS), Self-rating Anxiety Scale (SAS), and Chinese version of the mild behavioral impairment-checklist scale (MBI-C), and magnetic resonance imaging (MRI) scans. Imaging data was analyzed based on voxel-based morphometry (VBM). There was no significant difference in age, gender, MMSE score, total intracranial volume, white matter hyperdensity, gray matter volume, white matter volume between the two groups (p > 0.05). MBI group had shorter education years and higher MBI-C score, GDS and SAS scores than the normal control group (p < 0.05). For neuroimaging analysis, compared to the normal control group, the MBI group showed decreased volume in the left brainstem, right temporal transverse gyrus, left superior temporal gyrus, left inferior temporal gyrus, left middle temporal gyrus, right occipital pole, right thalamus, left precentral gyrus and left middle frontal gyrus(uncorrected p < 0.001). The grey matter regions correlated with the MBI-C score included the left postcentral gyrus, right exterior cerebellum, and left superior frontal gyrus. This suggests a link between MBI and decreased grey matter volume in cognitively normal elderly adults. Atrophy in the left frontal cortex and right thalamus in MBI patients is in line with frontal-subcortical circuit deficits, which have been linked to neuropsychiatric symptoms (NPS) in dementia. These initial results imply that MBI might be an early harbinger for subsequent cognitive decline and dementia.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

OBJECTIVE: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. DESIGN: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. SETTING: KU Leuven, Belgium. SAMPLE: Twenty-four ewes. METHODS: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. MAIN OUTCOME MEASURES: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. RESULTS: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. CONCLUSIONS: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. TWEETABLE ABSTRACT: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

Clinician knowledge, attitudes, and barriers to management of vulvovaginal atrophy: variations in primary care and gynecology.

OBJECTIVE: Vulvovaginal atrophy is a common, but under-recognized condition affecting postmenopausal women. To guide development of an intervention to boost its detection and treatment, we surveyed primary care and gynecology clinicians practicing in an integrated healthcare system. METHODS: We constructed a three-part survey that contained (1) eight multiple-choice knowledge questions; (2) three Likert-scale questions regarding clinicians' likelihood of assessing for vulvovaginal atrophy symptoms at a routine (well) visit, confidence in advising patients about symptoms and counseling about therapy; and (3) a 12-item check list of potential barriers to diagnosis and treatment. Analyses were performed using multiple regression. RESULTS: Of the 360 clinicians who were sent an e-mail request, 119 (90 primary care, 29 gynecology) completed the survey (33%). Responders and nonresponders did not differ by age, specialty, or clinician type. The proportion with correct responses to knowledge questions differed between primary care (63%) and gynecology (77%) (adjusted mean difference [AMD] =16, 95% CI [10-22]). Primary care clinicians were less likely than gynecology clinicians to assess for symptoms (AMD = 1.04, 95% CI [0.55-1.52]), and were less confident about their ability to advise on symptoms (AMD = 0.66, 95% CI [0.33-0.99]) and to counsel patients about treatment (AMD = 0.76, 95% CI [0.42-1.10]). Lack of time (71%) and educational materials (44%) were the most common barriers to diagnosis and treatment. CONCLUSIONS: Primary care and gynecology clinicians differ in their knowledge and confidence in managing vulvovaginal atrophy but report similar practice barriers. Addressing identified knowledge deficits and practice barriers may lead to improved management of vulvovaginal atrophy.

Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines.

BACKGROUND: Cerebral atrophy is common in multiple sclerosis (MS) and selectively involves gray matter (GM). Several fully automated methods are available to measure whole brain and regional deep GM (DGM) atrophy from MRI. OBJECTIVE: To assess the sensitivity of fully automated MRI segmentation pipelines in detecting brain atrophy in patients with relapsing-remitting (RR) MS and normal controls (NC) over five years. METHODS: Consistent 3D T1-weighted sequences were performed on a 3T GE unit in 16 mildly disabled patients with RRMS and 16 age-matched NC at baseline and five years. All patients received disease-modifying immunotherapy on-study. Images were applied to two pipelines to assess whole brain atrophy [brain parenchymal fraction (BPF) from SPM12; percentage brain volume change (PBVC) from SIENA] and two other pipelines (FSL-FIRST; FreeSurfer) to assess DGM atrophy (thalamus, caudate, globus pallidus, putamen). MRI change was compared by two sample t-tests. Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) change was compared by repeated measures proportional odds models. RESULTS: Using FreeSurfer, the MS group had a ~10-fold acceleration in on-study volume loss than NC in the caudate (mean decrease 0.51 vs. 0.05 ml, p = 0.022). In contrast, caudate atrophy was not detected by FSL-FIRST (mean decrease 0.21 vs. 0.12 ml, p = 0.53). None of the other pipelines showed any difference in volume loss between groups, for whole brain or regional DGM atrophy (all p>0.38). The MS group showed on-study stability on EDSS (p = 0.47) but slight worsening of T25FW (p = 0.054). CONCLUSIONS: In this real-world cohort of mildly disabled treated patients with RRMS, we identified ongoing atrophy of the caudate nucleus over five years, despite the lack of any significant whole brain atrophy, compared to healthy controls. The detectability of caudate atrophy was dependent on the MRI segmentation pipeline employed. These findings underscore the increased sensitivity gained when assessing DGM atrophy in monitoring MS.

Blood markers of fatty acids and vitamin D, cardiovascular measures, body mass index, and physical activity relate to longitudinal cortical thinning in normal aging.

We hypothesized that higher levels of omega-3 fatty acids, vitamin D, and physical activity relate to cortical sparing, whereas higher levels of cholesterol, systolic blood pressure, and body mass index (BMI) relate to increased atrophy in the adult lifespan. Longitudinal measures of cortical thickness were derived from magnetic resonance imaging scans acquired (mean interval 3.6 years) from 203 healthy persons aged 23-87 years. At follow-up, measures of BMI, blood pressure, and physical activity were obtained. Blood levels of docosahexaenoic acid, eicosapentaenoic acid, vitamin D, and cholesterol were measured in a subsample (n = 92). Effects were tested in cortical surface-based analyses, with sex, age, follow-up interval, and the interactions between each included as covariates. Higher levels of docosahexaenoic acid, vitamin D, and physical activity related to cortical sparing. Higher cholesterol and BMI related to increased cortical thinning. Effects were independent, did not interact with age, and the cholesterol effect was restricted to males. Eicosapentaenoic acid and blood pressure showed no effects. The observed effects show promise for potential factors to reduce cortical atrophy in normal aging.

Sacral nerve stimulation for fecal incontinence related to external sphincter atrophy.

BACKGROUND: Atrophy of the external anal sphincter, a pathologic muscle volume anomaly associated with fecal incontinence, has been shown to be a negative predictor of the outcome of surgery for defects of the external anal sphincter. It is unclear whether external anal sphincter atrophy also affects the outcome of sacral nerve stimulation for fecal incontinence. OBJECTIVE: Our aim was to assess the effectiveness of sacral nerve stimulation in patients with fecal incontinence and external anal sphincter atrophy and to determine whether severity of atrophy and concomitant presence of a sphincter defect are negative predictors of outcome. DESIGN: This was a prospective observational study of treatment outcome. SETTING: The study was conducted from November 2004 through November 2010 at a regional hospital in Italy. PATIENTS: Consecutive patients with fecal incontinence and external anal sphincter atrophy were included. By means of MRI, patients were determined to have either moderate (<50%) or severe (≥ 50%) thinning of and/or replacement of sphincter muscle by fat. The concomitant presence of defects of the external anal sphincter was also detected by MRI. INTERVENTION: All patients underwent sacral nerve stimulation through a staged implantation procedure. MAIN OUTCOME MEASURES: The main outcome measures were improvement in the Cleveland Clinic Florida Fecal Incontinence Scale (Wexner score), number of episodes of incontinence per week, and the Fecal Incontinence Quality of Life Scale. RESULTS: A total of 28 patients underwent definitive implantation of the sacral nerve stimulation device. Wexner scores decreased from a median of 16 (range, 10-20) at baseline to 3 (range, 0-8) at 6-month follow-up (p < 0.001). Weekly incontinence episodes decreased from a mean (SD) of 14.7 (12.5) to 0.40 (0.82); p < 0.001. Improvement was significantly related to severity of fecal incontinence (r = 0.86; p < 0.001). Overall quality-of-life scores improved from a mean of 1.8 (0.6) to 3.8 (0.4);p < 0.001. Sacral nerve stimulation was effective in both moderate (n = 16) and severe (n = 12) atrophy and in patients with (n = 8) or without (n = 20) external anal sphincter defects. LIMITATIONS: The study was limited by its observational nature and relatively small sample size. CONCLUSIONS: Sacral nerve stimulation can be effective in restoring continence and improving quality of life in patients with fecal incontinence related to atrophy of the external anal sphincter, regardless of the severity of atrophy. Moreover, the presence of EAS atrophy does not influence the success of the outcome of SNS in patients with a sphincter defect. These findings are consistent with the hypothesis that the effects of SNS are not achieved solely by its action on the anal sphincter complex.

Atrofia de íris após tratamento estético facial com luz intensa pulsada / Iris atrophy after aesthetic treatment with intense pulsed light

Relato de um caso de complicação ocular, em consequência do uso de luz intensa pulsada, para tratamento facial cosmético. A lesão consistiu em atrofia iriana no setor temporal, com grande área de transiluminação, sinéquias posteriores, deformidade e redução da dilatação pupilar. O objetivo é alertar para os riscos do procedimento para os olhos, caso não sejam tomadas as medidas adequadas de proteção ocular.

The authors report a case of ocular complication, following Intense Pulsed Light for cosmetic facial treatment.The lesion was iris atrophy with a large transilumination area, posterior synechiae, deformity and reduced dilation of the pupil, on the temporal side. The aim is to alert for the risk of ocular lesion related to this procedure, if adequate measures to protect the eyes are not taken.

Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy.

Mutations within Presenilin 1 (PSEN1) represent the most common cause of monogenic Alzheimer Disease (AD). The clinical phenotype is highly variable, even if early onset disease with an autosomal dominant pattern of inheritance and presenting memory deficits usually occur. In the present work, we described the case of a late-onset AD patient, without any positive family history for dementia, and associated with seizures and behavioural symptoms. Structural and functional neuroimaging showed frontotemporal changes without posterior biparietal brain abnormalities. Cerebrospinal analysis was consistent with AD pattern, with decreased Aß42 and increased Tau and phospho-Tau. A novel pathogenetic mutation within PSEN1 gene was detected within exon 8, leading to a substitution from arginine to tryptophan (AGG > TGG: R377W), affecting a splice junction and protein function. The case herein reported further confirms the heterogeneity of PSEN1 mutations and the need to take into account genetic screening in those cases with atypical presentation.

A case of catatonia resembling frontotemporal dementia and resolved with electroconvulsive therapy.

We describe a case of catatonia in a 51-year-old man in whom the catatonic symptoms could not be distinguished from symptoms of frontotemporal dementia (FTD) until they were resolved with electroconvulsive therapy (ECT). When it is difficult to distinguish between catatonia and FTD in patients with frontal dysfunction associated with frontal lobe atrophy, we believe that sequential administration of benzodiazepines and ECT is important for therapeutic diagnosis because the risk of missing a diagnosis of catatonia outweighs the risks associated with administration of benzodiazepines and/or ECT.

Mild cognitive impairment and event-related potentials in patients with cerebral atrophy and leukoaraiosis.

OBJECTIVE: The influence of cerebral atrophy and leukoaraiosis (LA) on the degree and profile of cognitive impairment remains unclear. DESIGN: The aim of the study was to assess neuropsychological features of cognitive performance and parameters of event-related potentials (ERP) in subjects with generalised cerebral atrophy and LA. SETTING: Department of Neurology, University of Medicine. PATIENTS AND PARTICIPANTS: Forty-two patients with LA and/or cerebral atrophy and twenty controls. MEASUREMENTS AND RESULTS: Neuropsychological testing (NT) included Mini Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT) and Trail Making Test (TMT). Auditory ERPs were performed and parameters of the N2 and P3 components were compared in the patients and controls. Relationships were analysed between radiological indices of atrophy and LA, and NT and ERP results. Results of NT suggested generalised mild cognitive impairment in all the patients. P3 and N2 latencies were longer in the patients than in controls, especially in the LA subgroup. Correlations were found for indices of atrophy, AVLT and ERP parameters. There was a predominant influence of age upon ERP parameters and radiological indices. CONCLUSIONS: Cerebral atrophy and LA result in deficits in memory and attention. NT and ERP may be used as complementary methods in the assessment of cognitive impairment in patients with cerebral atrophy and LA.

Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction.

OBJECTIVE: To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease. METHODS: We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated. RESULTS: Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups. DISCUSSION: PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.

Thalamic atrophy and cognition in multiple sclerosis.

OBJECTIVES: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function. METHODS: We studied 79 patients with MS and 16 normal subjects. A subgroup of 31 MS subjects underwent cognitive testing. The thalamus was segmented in whole from three-dimensional MRI scans. We also determined whole brain atrophy (brain parenchymal fraction), third ventricular width, and whole brain T2-weighted (fluid-attenuated inversion recovery) hyperintense, T1 hypointense, and gadolinium-enhanced lesion volumes. RESULTS: Normalized thalamic volume was 16.8% lower in the MS group (p < 0.0001) vs controls. Cognitive performance in all domains was moderately to strongly related to thalamic volume in the MS group (r = 0.506 to 0.724, p < 0.005), and thalamic volume entered and remained in all regression models predicting cognitive performance. Thalamic volume showed a weak relationship to physical disability score (r = -0.316, p = 0.005). CONCLUSION: These findings suggest that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.

Posterior cingulate neurometabolite profiles and clinical phenotype in frontotemporal dementia.

Proton magnetic resonance spectroscopy was used to compare metabolite levels from a posterior cingulate voxel in a group of patients with 2 syndromic subtypes of frontotemporal dementia (n=10) and an age and education-matched group with Alzheimer disease (n=10). Overall, frontotemporal dementia was indistinguishable from Alzheimer disease, though differences in N-acetylaspartate emerged between patients with the SD and progressive nonfluent aphasia subtypes, attributable to 2 atypical results among the latter. Such values may index cases with atrophy in posterior cortical regions presenting with progressive nonfluent aphasia.

Transcranial magnetic stimulation. A case report and review of the literature.

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. CASE REPORT: A 2-years-old male infant was referred to our department with a history of Epstein-Barr virus (EBV) encephalitis, treated with foscarnet and steroids, for he developed mutism and ataxia and loss of the ability to eat, walk and talk. Brain imaging revealed loss of white matter around ventricles and progressive global brain atrophy, findings consistent with encephalopathy. Serology for antibodies against EBV infection was positive and the diagnosis of acute and prolonged EBV infection was made. There was an improvement of the clinical findings after the application of TMS with proper field characteristics (intensity: 1-7.5 pT, frequency: 8-13 Hz). CONCLUSIONS: Our case illustrates the possibility of therapeutic applications of TMS (in the order of pT) with proper field characteristics to normalize pathologically decreased levels of brain cortex activity. TMS might provide novel insights into the pathophysiology of the neural circuitry, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases.

A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD.

OBJECTIVE: To investigate the patterns of MRI brain atrophy in patients with ALS with and without clinically evident frontotemporal lobar dementia (FTLD) using voxel-based morphometry (VBM). METHODS: Voxel-based morphometry was used to compare T1-weighted MRI images obtained from ten ALS patients with FTLD, ten ALS patients who were cognitively and behaviorally normal, and 22 control subjects. Images from patients and controls were spatially pre-processed using a study-specific, customized template and a priori images. A statistical threshold of p < 0.05 corrected for multiple comparisons determined significance. RESULTS: A common pattern of gray matter atrophy was seen in both ALS and ALS/FTLD patients when compared to controls that involved the bilateral motor/premotor cortices, the left middle and inferior frontal gyri, the anterior portion of the superior frontal gyri, the superior temporal gyri, the temporal poles and left posterior thalamus. Most of the frontal regions were significantly more atrophied in the ALS/FTLD group than in the ALS group. No significant differences were found in white matter volumes. CONCLUSIONS: Patients with ALS and ALS associated with frontotemporal lobar degeneration exhibit widespread gray matter atrophy in frontotemporal regions. This finding supports the idea of a clinical and anatomic continuum between ALS and frontotemporal lobar degeneration.

In vivo evidence of neuronal loss in the hypothalamus of narcoleptic patients.

A dysfunction of the orexin (hypocretin) system in the hypothalamus has recently been linked to the pathogenesis of narcolepsy. The authors used in vivo proton MR spectroscopy to assess the N-acetylaspartate (NAA) content in the hypothalamus of narcoleptic patients. Hypothalamic NAA/creatine-phosphocreatine was reduced in narcoleptic patients compared with control subjects (p < 0.01). Hypothalamic neuronal loss/damage is a central pathogenetic feature in narcolepsy.

Predominant telangiectatic erythema in linear atrophoderma of Moulin: novel variant or separate entity?

Linear atrophoderma of Moulin is a distinctive disease originally described in 1992 and characterized by acquired, mildly atrophic, non-sclerotic, slightly hyperpigmented lesions following the lines of Blaschko. Here, we describe a 15-year-old girl with a 13-year history and a 29-year-old male with a 6-year history of prominent linear telangiectatic erythema and mild atrophoderma following the lines of Blaschko that involved the right leg and hip, and both legs, the trunk and both arms, respectively. As pronounced telangiectatic erythema within lesions of atrophoderma of Moulin has not hitherto been described, we propose that the disease in our patients represents a novel variant of linear atrophoderma of Moulin. Due to considerable overlap, we do not favour the notion that our cases constitute an entity entirely separate from linear atrophoderma of Moulin.