Sex Differences in the Treatment of Sexual Dysfunction

Purpose of Review

Sex differences in the treatment of sexual dysfunction are partly due to neurobiological differences, as well as, the central and peripheral physiological effects of hormones and neurotransmitter actions on reproductive systems in men and women. Differences in epidemiology of complaints and diagnostic considerations, variance in medical comorbidities, and interference from related medications also contribute to the need for different strategies for treatments of sexual dysfunction according to gender.

Recent Findings

Flibanserin and ospemifene are new medication treatment options that may help some women with symptoms of sexual dysfunction.

Summary

Various therapies are available to address sexual dysfunction and sex differences are relevant to consider, in terms of diagnosis, effectiveness of treatments, and side effect profiles that may help determine indication, safety, and outcomes for specific treatments.

     

Sleep Disturbance and Cognitive Dysfunction in Multiple Sclerosis: a Systematic Review

Purpose of Review

The present review summarizes recent research on the association between sleep disturbance and cognitive dysfunction in MS. Assessment methodology, domain-specific associations between sleep disturbance and cognitive dysfunction, and implications for future research and treatment are discussed.

Recent Findings

All 12 studies included in this review found significant associations between sleep disturbance and cognitive dysfunction; however, results varied considerably depending on the assessment method used and the cognitive domain assessed. Self-reported sleep disturbance generally predicted self-report but not objective measures of cognitive dysfunction. Objective sleep measures (e.g., polysomnography, actigraphy) generally predicted objective impairments in processing speed and attention; however, objective sleep disturbance was more variable in predicting performance in other cognitive domains (e.g., memory, executive function).

Summary

Sleep disturbance may help predict future cognitive decline in MS. Results highlight the need to integrate sleep assessment into routine MS care. Interventions aimed treating sleep disturbance may offer promise for improving cognitive dysfunction in MS.

     

Onset of bladder and motor symptoms in multiple system atrophy: differences according to phenotype

Purpose

To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.

Methods

Medical records were retrospectively reviewed in 144 patients.

Results

Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).

Conclusions

Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.

     

Urological dysfunction in synucleinopathies: epidemiology,pathophysiology and management

Objective

Parkinson’s disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA.

Method

A systematic review.

Results

The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention. These bladder dysfunctions presumably reflect the different nervous system pathologies. Overactive bladder in PD reflects lesions in the brain, e.g., in the prefrontal-nigrostriatal D1 dopaminergic bladder-inhibitory pathway. Overactive bladder in MSA reflects lesions similar to PD and the cerebellum (bladder-inhibitory), and the urinary retention in MSA presumably reflects lesions in the pontine micturition center and the sacral intermediolateral nucleus of the spinal cord (bladder-facilitatory). Bladder dysfunction not only impairs an individual’s quality of life, it can also cause emergency hospitalizations due to acute retention and early institutionalization. Anticholinergics are the first-line treatment for bladder dysfunction in PD and MSA patients, but care should be taken for the management of bladder dysfunction—particularly in MSA patients due to the high prevalence of difficult emptying, which needs clean, intermittent catheterization.

Conclusions

This review summarizes the epidemiology, pathophysiology, and management of bladder dysfunction in individuals with PD or MSA.

     

Autonomic dysfunction,immune regulation,and multiple sclerosis

Objective

To review existing evidence regarding interactions between the autonomic nervous system and the immune system functions in multiple sclerosis.

Methods

We reviewed the literature regarding new insights linking autonomic dysfunction to immune deregulation in multiple sclerosis, with particular focus on the specific influence of sympathetic and parasympathetic dysfunction on inflammatory and neurodegenerative processes.

Results

Autonomic dysfunction is common in multiple sclerosis, representing a significant cause of disability. Several connections between pathologic immune pathways and the autonomic nervous system function were found.

Conclusions

Autonomic dysfunction may enhance inflammatory and neurodegenerative pathways that are of major importance in multiple sclerosis. Autonomic dysfunction can present with highly variable manifestations. Sympathetic and parasympathetic dysfunction displays different patterns in multiple sclerosis, with specific impact on inflammation and neurodegeneration.

     

Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives

Purpose of Review

Parkinson’s disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction.

Recent Findings

Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions.

Summary

Recent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development.

     

Psychotherapy for Borderline Personality Disorder: Progress and Remaining Challenges

Purpose

The main purpose of this review was to critically evaluate the literature on psychotherapies for borderline personality disorder (BPD) published over the past 5 years to identify the progress with remaining challenges and to determine priority areas for future research.

Method

A systematic review of the literature over the last 5 years was undertaken.

Results

The review yielded 184 relevant abstracts, and after applying inclusion criteria, 16 articles were fully reviewed based on the articles’ implications for future research and/or clinical practice.

Conclusion

Our review indicated that patients with various severities benefited from psychotherapy; more intensive therapies were not significantly superior to less intensive therapies; enhancing emotion regulation processes and fostering more coherent self-identity were important mechanisms of change; therapies had been extended to patients with BPD and posttraumatic stress disorder; and more research was needed to be directed at functional outcomes.

     

Serum anti-JCV antibody indexes in Japanese patients with multiple sclerosis: elevations along with fingolimod treatment duration

Background

The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood.

Objective

In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs.

Methods

JCVAb indexes were measured in 149 serum samples from 105 patients with MS. JCVAb indexes and seropositivity, and their correlation with age, sex, disease duration, Kurtzke expanded disability status scale and the duration of the DMTs were evaluated in each patient.

Results

JCVAb was positive in 73 of 105 MS patients. Within 40 fingolimod-treated patients, 27 were positive for JCVAb and JCVAb indexes were positively correlated with the duration of fingolimod treatment. No significant relation was found between JCVAb indexes and the duration of treatment for the other disease-modifying drugs.

Conclusion

JCVAb seropositivity was comparatively high in Japanese MS patients. Fingolimod treatment is likely to increase serum JCVAb index, possibly leading to the development of PML. Therefore, it is advised that JCVAb index should be serially monitored during fingolimod treatment to decrease PML risk.

     

Link between overweight/obese in children and youngsters and occurrence of multiple sclerosis

Background/aims

The prevalence of overweight/obesity is a major problem in the world, and the number of MS cases is increasing. This literature study examines the relationship between overweight/obesity in children and adolescents and later occurrence of MS.

Method

This is a complete literature survey. The search database is primarily Pubmed using MeSH terms “multiple sclerosis”, “obesity”, and “overweight”, and text words not to restrict searches.

Results

All included studies show a link between being overweight/obese and the presence of MS among people below 20 years of age. The relation is especially true for young girls. The same relation in boys is not significant.

Conclusion

The literature survey convincingly revealed a link between young overweight/obese and occurrence of MS, in particular for girls. There is a need for more and larger studies to investigate the molecular mechanisms that link obesity and MS.

     

A Review of Environmental Influences on Food Choices

Background

Diet-related environmental and policy interventions are being advocated at a population level because individual change is more likely to be facilitated and sustained if the environment within which choices are made supports healthful food options.

Purpose

This study aims to review research that examines factors having an influence on food choices in social environments, physical environments, and macroenvironments.

Methods

A snowball strategy was used to identify relevant peer-reviewed studies and reviews, with a focus on research completed in the US and published within the past 10 years.

Results

Research has identified a number of environmental factors associated with dietary intake; however, the majority of completed studies have methodological limitations which limit their credibility to guide interventions and policy changes.

Conclusions

Future research will need to emphasize multilevel investigations, examine how associations vary across population subgroups, develop a standard set of measures for assessing food environments and policies, and improve dietary assessment methodology.

     

Caring for Women with Multiple Sclerosis Across the Lifespan

Purpose of Review

Caring for women with multiple sclerosis (MS), whose first symptoms typically begin during the childbearing years, requires a comprehensive approach to management across a range of reproductive exposures, and beyond through menopause.

Recent Findings

This article summarizes what is known about the disease course in women with MS, how it differs from men, and the current state of knowledge regarding effects of reproductive exposures (menarche, childbearing, menopause) on MS-related inflammation and neurodegeneration. Recent findings regarding pregnancy-associated relapses in the treatment era, protective effects of breastfeeding, and care for women during the menopausal transition are reviewed. Then, updated recommendations to guiding women during childbearing—including pre-conception counseling, discontinuation of MS therapies, and management of postpartum relapses—are provided. Whenever possible, areas of uncertainty and avenues for future research are highlighted.

Summary

From childhood through the postreproductive life stages, gender and hormonal exposures appear to shape an individual’s risk for MS, as well as the experience of living with MS.

     

Changes in disability in people with multiple sclerosis: a 10-year prospective study

Background

Little is known about the long-term course of disability in relation with disease severity in people with multiple sclerosis (PwMS).

Objective

To explore changes in a broad spectrum of disability over 10 years in relation with disease severity in PwMS.

Methods

We conducted a longitudinal study of 155 PwMS who attended the MS Centre at Karolinska University Hospital, Stockholm. Disease severity was determined by the use of the Expanded Disability Status Scale (EDSS) and classified as mild MS (EDSS score 0–3.5) or moderate/severe MS (EDSS score 4–9.5). Ten-year changes in perceived physical and psychological impacts of MS, walking, cognition, manual dexterity, participation in social/lifestyle activities, and signs of depression were compared between PwMS with mild and moderate/severe MS at baseline.

Results

Although walking, manual dexterity, and cognition declined in both groups, only the moderate/severe group demonstrated that long-term increased physical impact of MS, increased wheel-chair dependency, and reduced participation in social/lifestyle activities. Perceived psychological impact of MS declined in both groups, while signs of depression were experienced by fewer in the mild group and remained unaltered in the moderate/severe group.

Conclusion

We found a more pronounced increase in disability across 10 years in individuals with moderate/severe MS compared to mild MS. These findings accentuate the importance of developing a variety of interventions that can be applied across the spectrum of disease severity.

     

Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case–control MRI study

Background

Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes.

Objectives

To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case–control MS population.

Methods

A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX.

Results

The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p?=?0.038) and cortical GM (p?=?0.036) volumes, independent from MS clinical features and related to T1D duration (p?<?0.01), while no association was observed with AT and celiac disease.

Conclusions

Our data support the importance of considering T1D as possible factors influencing the brain atrophy in MS. Further studies are needed to confirm our data and to clarify the underlying mechanisms.

     

Idiopathisch generalisierte Epilepsien

Background

Although the sociomedical importance of epilepsies has been extensively investigated, data regarding social long-term outcome and quality of life of people with idiopathic generalized epilepsies (IGE) are lacking.

Objectives

Predictors for the psychosocial outcome and the quality of life in patients with IGE are identified and discussed.

Materials and methods

The findings of existing studies on the social outcome in patients with various IGE syndromes are analyzed and discussed.

Results

Patients with absence epilepsy or juvenile myoclonic epilepsy (JME) are reported to have an unfavorable psychosocial outcome. While in JME a lower seizure frequency or remission of the epilepsy correlates with a favorable psychosocial outcome and a higher quality of life, remission of epilepsy is not predictive for a better social outcome among patients with absence epilepsy. Compared to other IGE syndromes, IGE with generalized, tonic–clonic seizures on awakening appears have a more favorable psychosocial outcome.

Conclusion

Several predictors for the psychosocial outcome and the quality of life have been identified and may potentially increase the clinicians’ ability and confidence to recommend different treatment options to patients with IGE.

     

Immunosenescence: the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis

Purpose of Review

This review highlights some of the important changes in the immune system that occur in the process of normal aging. Immunosenescence as a concept is directly relevant to the world of neuro-inflammation, as it may be a contributing factor to the risks associated with some of the current immunosuppressive and immunomodulatory therapies used in treating multiple sclerosis (MS) and other inflammatory disorders.

Recent Findings

Profound qualitative and quantitative changes occur in the adaptive and innate immunity compartments during aging. These changes may explain why patients of older age are at an increased risk of infections and infection-associated mortality.

Summary

Immunosenescence-associated changes may be additive or synergistic with the effects produced by immunomodulatory and immunosuppressive medications. Clinicians should exercise a high level of vigilance in monitoring the risk of infections in older patients on these treatments.

     

Affective Personality Traits in Olfactory Dysfunction: the Role of Dysthymia and Arousal

Introduction

Olfactory dysfunction can have a negative impact on emotional well-being. The aim of the present study was to examine associations between olfactory deficits and two affective personality characteristics (trait anxiety/trait depression).

Methods

A questionnaire study was conducted with a total of 116 participants (33 classified as anosmic, 40 as hyposmic, and 39 as normosmic). All participants gave self-reports on two facets of trait depression (dysthymia, euthymia) and trait anxiety (arousal, worrying). Due to the fact that in all three groups, trait depression and anxiety were substantially correlated, analyses of covariance were conducted.

Results

After controlling for trait depression, anosmic and hyposmic patients showed lower trait arousal compared to normosmic controls (partial η ²?=?.05). After controlling for trait anxiety, patients scored higher on dysthymia (partial η ²?=?.06).

Conclusions

This study underlines the importance of statistically isolating specific associations between each of these affective personality characteristics and olfactory dysfunction.

Implications

The present findings suggest that olfactory dysfunction can have opposite effects on facets of trait depression and trait anxiety.

     

An Up to Date Review of Pseudotumor Cerebri Syndrome

Purpose of Review

Idiopathic intracranial hypertension (IIH), pseudotumor cerebri syndrome (PTCS), and benign intracranial hypertension are all terms that have been used for a neurologic syndrome consisting of elevated intracranial pressure (ICP), headache and vision loss without mass lesion or underlying infection or malignancy. In this review article, categorization, diagnostic criteria, symptom management strategies, and disease treatment options for pseudotumor cerebri syndrome will be discussed.

Recent Findings

The Idiopathic Intracranial Hypertension Treatment Trial has now proven that acetazolamide should be the first line therapy in primary PTCS, but other treatment options exist in patients who cannot tolerate acetazolamide or in selected cases, which requires surgical intervention for PTCS which acutely threatens vision. Headache has also been shown to require focused treatment beyond therapies that lower ICP, specifically targeting coexistent primary headache disorders and medication overuse.

Summary

Advances in treatment and diagnostic modalities have improved understanding of PTCS types and their treatment. The pathophysiology of primary PTCS, however, remains incompletely understood, but continued evaluation of cerebrospinal fluid flow dynamics, aquaporins, hormones, natriuretic peptides, and the link with female gender and obesity may lead to future answers.

     

Single-Session Behavioral Interventions for Sexual Risk Reduction: A Meta-Analysis

Background

Evidence-based, single-session STI/HIV interventions to reduce sexual risk taking are potentially effective options for implementation in resource-limited settings and may solve problems associated with poor participant retention.

Purpose

The purpose of the study is to estimate the efficacy of single-session, behavioral interventions in reducing unprotected sex or increasing condom use.

Methods

Data sources were searched through April 2013 producing 67 single-session interventions (52 unique reports; N?=?20,039) that included outcomes on condom use and/or unprotected sex.

Results

Overall, participants in single-session interventions reduced sexual risk taking relative to control groups (d ₊ ?=?0.19, 95 % CI?=?0.11, 0.27). Within-group effects of the interventions were larger than the between-groups effects when compared to controls.

Conclusions

Brief, targeted single-session sexual risk reduction interventions demonstrate a small but significant effect and should be prioritized.

     

Therapeutic coma for the treatment of status epilepticus

Background

There are scarce data available on the treatment of refractory status epilepticus (SE) where general anesthetics are recommended. However, these may be related to increased morbidity (and possibly mortality).

Question

When and how should therapeutic coma be used in this clinical setting?

Methods

Critical review of available international literature in the past 50 years as well as of personal experience.

Results

Patients with generalized convulsive or nonconvulsive SE in coma not responding to benzodiazepines and an antiepileptic drug should be treated under electroencephalographic (EEG) monitoring with coma induction and general anesthetics. Initially, midazolam/propofol seem to represent the safest options. A progressive weaning attempt should be made after 24?h without EEG seizures. Patients with absence SE should never be treated with coma, and in those with focal SE with preserved consciousness coma should be deferred after the trial of other nonsedating compounds. In cases of super-refractory SE, ketamine and/or a ketogenic diet may be considered.

Conclusion

In view of the limited current evidence, it seems reasonable to avoid indiscriminate use of general anesthetics in SE.

     

Treating Immune-Related Epilepsy

Purpose of Review

This review explores different treatment modalities for immune-mediated epilepsy, including epilepsy caused by autoantibodies as well as epilepsy in the context of systemic autoimmune disease.

Recent Findings

Autoimmune epilepsy is an increasingly recognized entity. Conventional treatments for epilepsy, such as antiseizure medications and epilepsy surgery, are less successful in treating epilepsy caused by autoimmune disease. Immunomodulatory therapies such as corticosteroids, intravenous immunoglobulin, and plasma exchange are generally more successful in treating immune-mediated epilepsy than conventional epilepsy therapies.

Summary

Autoimmune epilepsy should be considered as a possible etiology for patients with frequent seizures of unknown etiology. The response to immunotherapies is often promising, particularly in patients with antibodies to neuronal cell surface antigens.