The effect of pelvic floor muscle training alone or in combination with electrostimulation in the treatment of sexual dysfunction in women with multiple sclerosis.

BACKGROUND: Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. OBJECTIVES: The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. METHODS: Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. RESULTS: After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. CONCLUSION: This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.

Monthly variation of multiple sclerosis activity in the southern hemisphere: analysis from 996 relapses in Brazil.

BACKGROUND AND PURPOSE: Seasonal variations of multiple sclerosis (MS) activity have been reported, however, most data come from studies in the northern hemisphere. METHODS: We reviewed medical records of MS patients living in Campinas region, Brazil. The first symptoms' date was defined as the relapse month. Climatic information included UV radiation index, median temperature, rainfall, and humidity. RESULTS: Two hundred and nine patients were included. The incidence of relapses was highest in January (11.2%) and December (10.4%) and lowest in November (5.7%) and October (7.0%) (P < 0.015). The months with highest incidence of relapses (December-January) had higher UV radiation index and humidity rates (P = 0.032 and 0.040, respectively). CONCLUSION: Most exacerbations were in the spring/summer transition, which also showed higher UV radiation index and humidity rate. Along with other environmental factors, seasonal fluctuation contributes to MS activity.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

MR imaging texture analysis of the corpus callosum and thalamus in amnestic mild cognitive impairment and mild Alzheimer disease.

BACKGROUND AND PURPOSE: TA is a branch of image processing that seeks to reduce image information by extracting texture descriptors from the image. TA of MR images of anatomic structures in mild AD and aMCI is not well-studied. Our objective was to attempt to find differences among patients with aMCI and mild AD and normal-aging subjects, by using TA applied to the MR images of the CC and the thalami of these groups of subjects. MATERIALS AND METHODS: TA was applied to the MR images of 17 patients with aMCI, 16 patients with mild AD, and 16 normal-aging subjects. The TA approach was based on the GLCM. MR images were T1-weighted and were obtained in the sagittal and axial planes. The CC and thalami were manually segmented for each subject, and 44 texture parameters were computed for each of these structures. RESULTS: TA parameters showed differences among the 3 groups for the CC and thalamus. A pair-wise comparison among groups showed differences for AD-control and aMCI-AD for the CC; and for AD-control, aMCI-AD, and aMCI-control for the thalamus. CONCLUSIONS: TA is a useful technique to aid in the detection of tissue alterations in MR images of mild AD and aMCI and has the potential to become a helpful tool in the diagnosis and understanding of these pathologies.

Global aphasia as a predictor of mortality in the acute phase of a first stroke / Afasia global prediz mortalidade na fase aguda de um primeiro acidente vascular cerebral isquêmico

OBJECTIVE: To establish whether vascular aphasic syndromes can predict stroke outcomes. METHOD: Thirty-seven adults were evaluated for speech and language within 72 hours after a single first-ever ischemic brain lesion, in blind association to CT and/or MR. RESULTS: Speech or language disabilities were found in seven (87.5 percent) of the eight deceased patients and twenty-six (89.7 percent) of the twenty-nine survivors. Global aphasia was identified in eleven patients, all with left hemisphere lesions (nine mute; five deceased), consisting on a risk factor for death in the acute stroke phase (ρ=0.022). Age (z=1.65; ρ>0.09), thrombolysis (ρ=0.591), infarct size (ρ=0.076) and side (ρ=0.649) did not significantly influence survival. Absence of aphasia did not predict a better evolution, regardless of the affected hemisphere. Prevalence of cardiovascular risk factors was similar for all patient groups. CONCLUSION: Global aphasia in acute stroke can adversely affect prognosis, translated into impairment of dominant perisylvian vascular territories, with mutism as an important semiological element.

OBJETIVO: Determinar se síndromes afásicas na fase aguda do infarto cerebral influenciam o prognóstico. MÉTODO: Avaliação para fala e linguagem de 37 adultos dentro de 72 horas após um primeiro infarto cerebral, em associação topográfica cega com TC e/ou RM. RESULTADOS: Detectaram-se afasias ou disartria em 7 (87,5 por cento) dos 8 pacientes falecidos, e em 26 (89,7 por cento) dos 29 sobreviventes. Afasia global foi identificada em 11 pacientes, todos com lesões no hemisfério esquerdo (cinco óbitos; mutismo em nove), consistindo em fator de risco para mortalidade na fase aguda do acidente vascular cerebral isquêmico (ρ=0,022). Idade (z=1,65; ρ>0,09), trombólise (ρ=0,591), dimensões da lesão (ρ=0,076) e lado (ρ=0,649) não afetaram significativamente a sobrevivência. Ausência de afasia não prenunciou melhor evolução. Fatores de risco cardiovascular tiveram similar prevalência para todos os grupos de pacientes. CONCLUSÃO: Afasia global na fase aguda do infarto cerebral pode aumentar mortalidade, demonstrando envolvimento de território vascular perisylviano dominante, tomando-se mutismo como importante elemento semiológico.

Microemulsão: um promissor carreador para moléculas insolúveis / Microemulsion: a promising carrier system for insoluble compounds

Microemulsão (ME) é um sistema que foi descoberto por Hoar e Schulman no ano de 1943 e que é termodinamicamente estável e isotropicamente translúcido de dois líquidos imiscíveis (óleo/água), estabilizados por um filme interfacial de tensoativos. O estudo de sistemas microemulsionados se baseia nas suas três teorias de formação: (1) teoria da solubilização, (2) teoria da tensão interfacial e (3) teoria termodinâmica. A estrutura formada é influenciada pelas propriedades físico-químicas dos componentes utilizados e da razão entre os componentes. O objetivo desta revisão foi avaliar o estado da arte de sistemas microemulsionados enfatizando uma abordagem teórica. Além disso, os recentes avanços sobre a aplicabilidade clínca e utilização como carreador de moléculas insolúveis foram discutidas.

Microemulsions (ME) are thermodynamically stable and isotropic systems of two immiscible liquids (oil/water), stabilized by an interfacial film of surfactants, discovered by Hoar and Schulman in 1943. The study of ME formation is based on three areas of theory: (1) solubilization, (2) interfacial tension and (3) thermodynamics. ME structures are influenced by the physicochemical properties and proportions of their ingredients. The goal of this review is to assess the state of the art of microemulsified systems, from a theoretical viewpoint. Also, recent progress on their clinical application and use as carriers for insoluble compounds is discussed.

Administração cutânea de fármacos: desafios e estratégias para o desenvolvimento de formulações transdérmicas / Cutaneous administration of drugs: challenges and strategies for the development of transdermal formulations

O desenvolvimento de formulações para aplicação na pele é uma estratégia interessante para transportar fármacos cuja ação é a própria pele, representando uma alternativa para superar aspectos indesejados relacionados às características farmacocinéticas e farmacodinâmicas dos fármacos. No entanto, a pele apresenta camadas que formam uma barreira à penetração de fármacos. Desse modo, estratégias têm sido pesquisadas e os modernos estudos farmacêuticos apontam para o uso de métodos físicos e químicos, norteados no desenvolvimento de novas formas farmacêuticas, as quais devem apresentar propriedades físico-químicas e parâmetros farmacotécnicos adequados para o uso transdérmico.

The development of formulations for skin application is a good strategy for the delivery of drugs whose target is the skin itself, which avoids some unwanted effects of treatment arising from the pharmacokinetic and pharmacodynamic properties of drugs. However, the skin has layers that resist the penetration of drugs. Thus, new strategies have been researched and the latest pharmaceutical studies point to the use of physical and chemical methods aimed at the development of new drug delivery systems, exhibiting physicochemical properties and pharmaceutical parameters suitable for transdermal administration.

Relationship between environmental factors and gray matter atrophy in refractory MTLE.

OBJECTIVE: To investigate clinical, neuropsychological, and MRI abnormalities (gray matter atrophy [GMA] and white matter atrophy [WMA]) in surgical mesial temporal lobe epilepsy (MTLE) patients with and without familial antecedent for epilepsy. METHODS: A cohort study including 69 operated patients with unilateral MTLE, divided into a group of 29 patients (mean age 35.8 +/- 10.4 years) with a negative family history (FH) of epilepsy and a group of 40 patients (32.8 +/- 10 years) with a positive FH. We performed voxel-based morphometry (VBM) on preoperative MRIs and investigated possible clinical and neuropsychological differences between the 2 groups. We also performed VBM and t tests to compare the patients' groups with normal controls. RESULTS: The negative-FH group had lower IQ scores (p = 0.004), performed poorer on the Boston Naming Test (p = 0.02) and on delayed recall (p = 0.03), and presented a more prominent asymmetry index of hippocampal volume (p = 0.04) and more frequent initial precipitating injuries (p = 0.023). VBM showed a more restricted pattern of GMA in the positive-FH group and a more bilateral and widespread pattern of GMA in the negative-FH group, involving thalami, temporal, frontal, parietal, and occipital lobes. WMA was widespread and bilateral in both groups. CONCLUSIONS: The more widespread structural voxel-based morphometry abnormalities and worse IQ performance identified in the negative-family history (FH) group may result from a stronger environmental influence, including initial precipitating injuries. This is further support for the hypothesis that hippocampal sclerosis in mesial temporal lobe epilepsy with positive FH is determined by a stronger genetic predisposition with less influence of environmental factors compared with patients in the negative-FH group.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model.

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model--experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease.

BACKGROUND: Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. METHODS: We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. RESULTS: Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. DISCUSSION: We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.

SolEmuls technology: a way to overcome the drawback of parenteral administration of insoluble drugs.

In this article, a nanosuspension of AmB was prepared and mixed with the preformed parenteral emulsion Lipofundin and subjected to high-pressure homogenization (SolEmuls technology). Characterization was performed by photon correlation spectroscopy (PCS), laser diffractometry (LD), and zeta potential measurements. Drug incorporation was studied by using light microscopy. The produced emulsions were further investigated by comparing them with the commercially available Fungizone in regard to antifungal efficiency and toxicity. Results suggest that through the SolEmuls process the AmB forms a reservoir, out of which it is released in such a manner that it is more efficient and less toxic than Fungizone.

Differences in memory performance and other clinical characteristics in patients with mesial temporal lobe epilepsy with and without hippocampal atrophy.

Mesial temporal lobe epilepsy (MTLE) is usually accompanied by memory deficits due to damage to the hippocampal system. In most studies, however, the influence of hippocampal atrophy (HA) is confounded with other variables, such as: type of initial precipitating injury and pathological substrate, effect of lesion (HA) lateralization, history of febrile seizures, status epilepticus, age of seizure onset, duration of epilepsy, seizure frequency, and antiepileptic drugs (AEDs). To investigate the relationship between memory deficits and these variables, we studied 20 patients with MTLE and signs of HA on MRI and 15 MTLE patients with normal high-resolution MRI. The findings indicated that (1) HA, earlier onset of seizures, longer duration of epilepsy, higher seizure frequency, and AEDs (polytherapy) are associated with memory deficits; and (2) there is a close relationship between deficits of verbal memory and left HA, but not between visual memory and right HA.

Congenital destructive hemispheric lesions and epilepsy: clinical features and relevance of associated hippocampal atrophy.

We studied the clinical, EEG and MRI findings in 19 patients with epilepsy secondary to congenital destructive hemispheric insults. Patients were divided in two groups: 10 with cystic lesions (group 1), and 9 with atrophic lesions (group 2). Seizure and EEG features, as well as developmental sequelae were similar between the two groups, except for the finding that patients of group 2 more commonly presented seizures with more than one semiological type. MRI showed hyperintense T2 signal extending beyond the lesion in almost all patients of both groups, and it was more diffuse in group 2. Associated hippocampal atrophy (HA) was observed in 70% of group 1 patients and 77.7% of group 2, and it was not correlated with duration of epilepsy or seizure frequency. There was a good concordance between HA and electroclinical localization. The high prevalence of associated HA in both groups suggests a common pathogenesis with the more obvious lesion. Our findings indicate that in some of these patients with extensive destructive lesions, there may be a more circumscribed epileptogenic area, particularly in those with cystic lesions and HA, leading to a potential rationale for effective surgical treatment.

Pattern of cytokine secretion by peripheral blood cells of patients with multiple sclerosis in Brazil.

Autoimmune T cells play a key role as regulators and effectors of organ-specific autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components produce a plethora of inflammatory cytokines and mediators that contribute to myelin damage. The production of proinflammatory and regulatory cytokines by peripheral blood cells from patients with active and stable MS and healthy controls were examined. The results show that TNF alpha production was somewhat elevated in active MS with no significant increase in the level IFN gamma, whereas in the chronic phase the anti-inflammatory cytokines IL-10 and TGF beta increased, accompanied by a reduction in IFN gamma when stimulated by myelin basic protein. Multiple Sclerosis (2000) 6 293 - 299

De novo psychogenic seizures after epilepsy surgery: case report.

The occurrence of de novo psychogenic seizures after epilepsy surgery is rare, and is estimated in 1.8% to 3.6%. Seizures after epilepsy surgery should be carefully evaluated, and de novo psychogenic seizures should be considered especially when there is a change in the ictal semiology. We report a patient with de novo psychogenic seizures after anterior temporal lobe removal for refractory temporal lobe epilepsy. Once psychogenic seizures were diagnosed and psychiatric treatment was started, seizures stopped.

Magnetic resonance imaging in the evaluation of patients with aseptic meningoencephalitis and connective tissue disorders.

OBJECTIVE: To describe the role of magnetic resonance imaging (MRI) in the evaluation of patients with chronic and recurrent aseptic meningitis. METHOD: A retrospective study of five patients with aseptic meningoencefalitis diagnosed by clinical and CSF findings. CT scans showed without no relevant findings. RESULTS: MRI showed small multifocal lesions hyperintense on T2 weighted images and FLAIR, with mild or no gadolinium enhancement, mainly in periventricular and subcortical regions. Meningoencephalitis preceded the diagnosis of the underlying disease in four patients (Behçet's disease or systemic lupus erythematosus). After the introduction of adequate treatment for the rheumatic disease, they did not present further symptoms of aseptic meningoencephalitis. CONCLUSION: Aseptic meningoencephalitis can be an early presentation of an autoimmune disease. It is important to emphasize the role of MRI in the diagnosis and follow-up of these patients.

Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults.

INTRODUCTION: Several recent studies have analyzed a possible effect of thrombophilia risk factors such as factor V Leiden, the prothrombin variant (allele 20210 A), and homozygosity for thermolabile methylenetetrahydrofolate reductase (MTHFR-T) on the development of ischemic stroke (IS). In the present study, we determined the role of these prothrombotic polymorphisms in the early onset of arterial IS or cerebral venous thrombosis (CVT) in a group of young Brazilian adults of Caucasian and African descent. MATERIALS AND METHODS: We conducted a cross-sectional study of 167 survivors of IS (153 patients with arterial IS and 14 cases of CVT; 66 men: 101 women; 124 of Caucasian and 43 of African origin; median age: 32.6 years; range: 15 to 45 years) and compared the prevalence of inherited thrombophilia risk factors with a control group of 225 sex and age matched individuals of the same ethnic background. To determine the interaction with atherogenic risk factors, the following diagnoses were considered: hypertension, hyperlipoproteinemia, diabetes mellitus, smoking status and use of oral contraceptives. RESULTS: In the arterial IS group, no significant variation was found between patients and controls of Caucasian origin regarding the prevalence of factor V Leiden (P = 0.92), the prothrombin variant (P = 0.13) or homozygosity for MTHFR-T (P = 0.61). Among Brazilians of African descent, 10.3% were homozygous for MTHFR-T, which was significantly elevated, odds ratio of 5.9 (95% CI: 0.88 to 49.15). In the CVT group, two Caucasian patients (20%) were heterozygous for the prothrombin variant, odds ratio of 9.7 (95% CI: 0.95 to 89.71) and one patient was carrier of factor V Leiden (P = 0.49). No prothrombotic polymorphism was identified in patients with CVT of African descent. All women in the CVT group were in use of oral contraceptives or in the post-partum state. DISCUSSION: Inherited thrombophilia risk factors were not found to increase the risk of arterial IS among young patients of Caucasian descent. However, a potential role of homozygosity for MTHFR-T was observed in a small group of patients of African origin. The analysis of patients with CVT revealed an increased risk due to the prothrombin gene variant or oral contraceptive use. Further studies including all incoming patients with IS are necessary to evaluate the impact of inherited thrombophilia risk factors on early mortality.