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Alice in Wonderland syndrome (AIWS) is a paroxysmal, perceptual, visual and somesthetic disorder that can be found in patients with migraine, epilepsy, cerebrovascular disease or infections. The condition is relatively rare and unique in its hallucinatory characteristics. OBJECTIVE To discuss the potential pathways involved in AIWS. Interest in this subject arose from a patient seen at our service, in which dysmetropsia of body image was reported by the patient, when she saw it in her son. METHODS We reviewed and discussed the medical literature on reported patients with AIWS, possible anatomical pathways involved and functional imaging studies. RESULTS A complex neural network including the right temporoparietal junction, secondary somatosensory cortex, premotor cortex, right posterior insula, and primary and extrastriate visual cortical regions seem to be involved in AIWS to varying degrees. CONCLUSIONS AIWS is a very complex condition that typically has been described as isolated cases or series of cases.

Background: Fingolimod is an effective therapy for multiple sclerosis (MS). Isolated reports of very aggressive MS rebound after discontinuation of fingolimod are drawing neurologists' attention to this potentially severe complication of the drug., Objective: Our objective was to collect literature data on cases of MS rebound following fingolimod withdrawal. In addition, we report six new cases of this adverse event in Brazil., Methods: We carried out a systematic review of published data on cases of MS rebound after fingolimod was discontinued. In addition, the study reports a retrospective data series of Brazilian patients presenting this rebound reaction., Results: Twenty papers have been published reporting on 52 patients with severe MS rebound after fingolimod withdrawal. Six new patients are included in the present paper, all of them with aggressive rebound and accumulated disability sequelae., Conclusion: We recommend gradual discontinuation of fingolimod with replacement by other treatment. The washout period should not exceed 4 weeks.

Neuromyelitis optica spectrum disorder is a severe and disabling disease that manifests with severe relapses of optic neuritis, longitudinally extensive myelitis, and/or brainstem syndromes. The disease is complex and, although onset typically occurs in middle age, children and adolescents may be affected. The present study adds to the literature through detailed clinical data from 36 Brazilian patients with neuromyelitis optica spectrum disorder starting before age 21. This was a retrospective assessment of medical records from 14 specialized units in Brazil. The results showed that the course of neuromyelitis optica spectrum disorder was worse in patients with disease onset before the age of 12 years. Gender and ethnic background did not influence disability accumulation. Over a median period of 8 years, 14% of the patients who presented the initial symptoms of neuromyelitis optica spectrum disorder before the age of 21 years died. In conclusion, the present study adds to the reports from other authors examining the severity of early-onset neuromyelitis optica spectrum disorder.

The latest revision of the McDonald criteria for the diagnosis of multiple sclerosis (MS) was published online in 2017. New features of the criteria, which were designed to facilitate earlier diagnosis of MS, include the recognition of oligoclonal bands in the cerebrospinal fluid as a possible marker of dissemination of MS pathology in time, the introduction of symptomatic lesions as a parameter to demonstrate spatial or temporal pathology dissemination, and the use of cortical lesions to demonstrate dissemination in space. In this Viewpoint, a panel of world-renowned MS specialists share their personal experiences of the new criteria to date.

Previous infection with John Cunningham virus (JCV) increases the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) undergoing treatment with natalizumab. Patients who test negative for JCV antibodies must be assessed every six months due to the risk of seroconversion. Data from the United States of America, Portugal, Holland, France, United Kingdom and Sweden have shown a strong correlation between the use of natalizumab and JCV seroconversion. The authors present now data on patients from Brazil, as there are no data from Latin American countries published on this subject yet. A group of 86 patients with MS with negative results for antibodies against JCV were included in this analyses with at least two JCV antibodies testing. Twenty-five patients (29% of the total group) did not use natalizumab at any time, while the remaining 71% used natalizumab for a median period of 800 days (equivalent to 28 monthly infusions). Seroconversion was observed in 19 patients (22.1%). There was no association of seroconversion with gender, age, previous pulses of corticosteroid or specific MS-modifying drugs. The use of natalizumab was strongly associated to seroconversion (p < 0.0001). The present results confirm the influence of natalizumab therapy on JCV antibodies in several countries and continents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The 2015 criteria for diagnosing neuromyelitis optica spectrum disorder (NMOSD) have encouraged several groups across the world to report on their patients using these criteria. The disease typically manifests with severe relapses of optic neuritis, longitudinally extensive myelitis and/or brainstem syndromes, often leading to severe disability. Some patients are seropositive for antibodies against aquaporin-4 (AQP4), others are positive for anti-myelin oligodendrocyte glycoprotein (MOG), while a few are negative for both biomarkers. The disease is complex, and only now are specific therapeutic clinical trials being carried out. The present study adds to the literature through detailed clinical data from 153 medical records of Brazilian patients., Methods: Retrospective assessment of medical records from nine specialized units in Brazil., Results: NMOSD was more prevalent in females (4.1:1), who had significantly fewer relapses than males (p = 0.007) but presented similar levels of disability over time. African ancestry was associated with higher levels of disability throughout the disease course (p < 0.001), although the number of relapses was similar to that observed in white patients. Concomitant autoimmune diseases were relatively rare in this population (6.5%). Positivity for anti-AQP4 antibodies was identified in 62% of the patients tested, while 3% presented anti-MOG antibodies. Anti-AQP4 antibodies were not associated to worse disease course. The last medical record showed that six patients had died and 13 were wheelchair-bound. Seventy percent of the patients did not respond to first-line therapy (azathioprine and/or corticosteroids), and five patients continued to relapse even after four different courses of treatment., Conclusion: The present study adds to the reports from other countries presenting original data on Brazilian patients diagnosed with NMOSD according to the 2015 criteria., (Copyright © 2018. Published by Elsevier B.V.)

Multiple sclerosis (MS) management presently aims to reach a state of no (or minimal) evidence of disease activity. The development and commercialization of new drugs has led to a renewed interest in family planning, since patients with MS may face a future with reduced (or no) disease-related neurological disability. The advice of neurologists is often sought by patients who want to have children and need to know more about disease control at conception and during pregnancy and the puerperium. When MS is well controlled, the simple withdrawal of drugs for patients who intend to conceive is not an option. On the other hand, not all treatments presently recommended for MS are considered safe during conception, pregnancy and/or breastfeeding. The objective of the present study was to summarize the practical and evidence-based recommendations for family planning when our patients (women and men) have MS.Funding TEVA Pharmaceutical Brazil.

Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV)., Objective: To identify the serologic profile of JCV in patients with MS., Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program., Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months., Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

Objective: Involuntary hospitalization for acute psychiatry cases can be acceptable when there is potential harm. However, there are few reasons for a patient committed on these grounds to stay in an institution for a long period. The objective of the present study was to identify the profile and costs of compulsory hospitalizations over 20 days in a public psychiatric hospital in the coastal region of the state of São Paulo., Methods: Retrospective data were collected from the medical records of 1,064 patients admitted between July 2013 and June 2016 from an intensive mental healthcare unit in Santos, state of São Paulo, Brazil., Results: Records were found of 527 patients who had been hospitalized for at least 21 days during the study period. Long-term hospitalization related to judicial mandates represented 5.9% of the total sample. These patients stayed in the hospital for an average period of 142 days, while patients hospitalized for any other reason stayed an average period of 35 days (p < 0.001). The cost of a long-term court-ordered hospitalization averaged US$ 21,311 per patient., Conclusion: Judicial mandate has been an important reason for the long-term hospitalization of chronic psychiatric patients in Santos, Brazil.

Objective: Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disease of the central nervous system. Since MS affects mostly fertile women, pregnancy issues often arise in daily practice. The present study assessed the use of postpartum intravenous immunoglobulin (IVIG) in MS., Methods: The authors individually searched for records using PubMed, Medline, EMBASE, Cochrane, SciELO, LILACS, and Google Scholar, using the terms "multiple sclerosis" OR "MS" AND "pregnancy" OR "gestation" OR "partum" OR "post-partum" OR "puerperium" AND "immunoglobulin"., Results: The initial search returned 321 papers. There were 11 eligible articles selected for the review. In total, 380 patients had received post-natal IVIG to reduce the number of postpartum relapses. The unadjusted number needed to treat was 6.3 for the quantitative and 5.8 for the qualitative analyses., Conclusion: The therapeutic effect of IVIG for prevention of postnatal relapses in MS could not clearly be established in this meta-analysis.

Background: Multiple sclerosis (MS) is an autoimmune disease, for which the forms of treatment are medication and rehabilitation. However, in vitro and in vivo studies have demonstrated that photobiomodulation can be an effective treatment modality for inflammatory diseases, including MS. Photobiomodulation has a broad range of benefits, such as the avoidance of cell and tissue death, the stimulation of healing and injury repair, reductions in pain, edema and inflammation, cell proliferation, and even apoptosis. The outcomes of photobiomodulation include the regeneration of cells, the stimulation of the growth of Schwann cells, a reduction in spasticity, functional improvements, a reduction in nitric oxide levels, and the upregulation of the cytokine IL10, demonstrating that this therapeutic modality can offer neuroprotection., Methods: A randomized, controlled, double-blind, clinical trial is proposed. The patients will be divided into 6 groups. Groups 1 and 2 will receive sham and active photobiomodulation in the sublingual region, respectively. Groups 3 and 4 will receive sham and active photobiomodulation along the spinal cord, respectively. Group 5 will receive placebo treatment with photobiomodulation on the skin in the region of the radial artery with a specific bracelet. Group 6 will be treated with photobiomodulation on the skin in the region of the radial artery., Discussion: Treatment for MS is directed at the immune response and slowing the progression of the disease. This is one of the first clinical trials involving photobiomodulation in the sublingual region and along the spinal cord, which could help establish a promising new form of nonpharmacological treatment for autoimmune diseases. This is one of the first clinical trials with sublingual photobiomodulation and along the spinal cord that could help establish a new form of promising treatment of the disease associated with pharmacological treatment.

Background Brain volume assessment has become an important outcome within research and treatment of multiple sclerosis (MS). MSmetrix (Icometrix) has been developed specifically for patients with MS. The original healthy, 'normal' population used for determination of the acceptable brain volume data consisted mainly of Europeans. Methods In the present study, results from 295 completely normal magnetic resonance imaging scans from Brazilian subjects were plotted against the original results in MSmetrix. Results With regard to whole brain volume, only 2% of the healthy adult subjects from Brazil were below the 5th percentile of the graph, and for grey matter volume, only 3% of the subjects were below the 5th percentile of MSmetrix standards. Conclusion MSmetrix may be used across different populations.

Alexithymia is a personality trait characterized by difficulties identifying and describing feelings. Some researchers describe high levels of alexithymia among patients with multiple sclerosis (MS) but literature data on this subject are scarce., Objective: The objective of the present study was to characterize findings of alexithymia in patients with MS., Methods: This cross-sectional case-control study included 180 patients with MS and a matched control group. Data for patients with MS included disease duration, number of demyelinating relapses and degree of neurological disability, as assessed by the Expanded Disability Scale Score (EDSS). In addition, the Hospital Anxiety and Depression (HAD) scale and the Toronto Alexithymia Scale (TAS) were used., Results: There were 126 women and 54 men in each group, with median age of 37 years and median education of 16 years. Patients with MS had higher degrees of depression (p<0.01), anxiety (p=0.01) and alexithymia (p<0.01) than did control subjects. For individuals with MS, depressive traits (p<0.01), anxious traits (p=0.03), higher age (p=0.02), lower education level (p=0.02), higher degree of disability (p<0.01) and not being actively employed (p=0.03) were associated with higher rates of alexithymia., Conclusion: Alexithymia was a relevant finding in patients with MS., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

Augusta Marie Déjerine-Klumpke (1859-1927) was a formidable neurologist, neuroanatomist and researcher in France. One of the first women to be accepted for medical internship, externship and research in Paris, Augusta made her name studying and teaching anatomy, histology and dissection, attending clinical activities in neurology, obstetrics, pediatrics and neurologic trauma, performing necropsies, and writing scientific papers and book chapters. Her main research in neurology awarded her an eponym for the avulsion of the lowest root of the brachial plexus (Klumpke's palsy). Married to her professor, the remarkable Dr. Joseph Jules Déjerine, Augusta continued her career and became the first female president of the French Society of Neurology.

Background: Chronic demyelinating diseases of the central nervous system (CNS) are autoimmune conditions that, although rarely fatal, may lead to severe disability. Among these diseases, Multiple Sclerosis (MS) and neuromyelitis optica (NMO) are particularly important and subject of worldwide research. MS and NMO are chronic types of CNS disease, with recurrent episodes of demyelination. For many years, these two conditions were considered to be only one, but lately it is known that they have different epidemiological, physiopathological and prognostic characteristics. The present study aims at reviewing the specificities of MS and NMO affecting patients before they complete 18 years of age., Methods: Literature review on data about MS and NMO in patients below the age of 18 years., Results: There are no clinical trials for any drug used to treat MS and NMO in children or adolescents. Data are mainly on anedoctal cases, case series and recommendations from experts. At present, there is no evidence-based treatment to be recommended for patients with MS and NMO before the age of 18 years., Conclusion: Despite being a particularly vulnerable population for severe disability in the future, there are no evidence-based guidelines for the treatment of MS and NMO in children and adolescents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals., Methods: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase., Results: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%)., Conclusions: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.

Background: Fingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to "sphingosine-1-phosphate"(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P 1 receptors. The aim of the present study was to assess whether the degree of lymphopenia was correlated to the positive treatment response of RRMS patients with fingolimod., Methods: Data was sourced from the MSBase Registry. Patients were divided into two groups, according to the lymphocyte count on peripheral blood examination. Annualized Relapse Rate (ARR), time to first relapse and time to six-month confirmed disability progression were compared between groups., Results: Group one consisted of 202 patients who reached 750 lymphocytes/mm 3 during treatment while the comparison group two included 101 patients who never reached less than 1000 lymphocytes/mm 3 in peripheral blood during the observation period. There were no differences between groups in ARR, time to first relapse or time to six-month confirmed disability progression., Conclusion: The degree of lymphopenia in peripheral blood was not associated to the positive treatment response of fingolimod in RRMS patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Fingolimod was the first oral medication approved for management of multiple sclerosis and is currently used by tens of thousands patients worldwide. Fingolimod acts via the sphingosine 1-phosphate (S1P) receptor, maintaining peripheral lymphocytes entrapped in the lymph nodes. In consequence, there is a reduction in the infiltration of aggressive lymphocytes into the central nervous system. The drug is safe and effective, and its first hours of use are associated with related to S1P receptors in the heart. This side effect is well known by all doctors prescribing fingolimod. However, the drug has other potential adverse events that, although relatively rare, require awareness from the neurologist. Among these there are infections (herpes simplex, herpes zoster, Cryptococcus, Epstein-Barr virus, hepatitis, Molluscum Contagiosum, and leishmaniosis), lung and thyroid complications, refractory headaches, encephalopathy, vasculopathy, tumefactive lesions in magnetic resonance imaging and ophthalmological disorders. The present review lists the non-cardiologic adverse events that all neurologists prescribing fingolimod should be aware of.

Mary Broadfoot Walker was a Scottish physician who, in 1935, described in great detail the effect of an anticholinesterase drug (physostigmine) on the signs and symptoms of myasthenia gravis. An original five-minutes movie is available online and the skepticism of her contemporary British medical doctors is understandable when the drastic effect of the treatment is shown in this movie. What Mary Walker taught us, more than eight decades ago, about myasthenia gravis continues to be the basis of a pharmacological diagnostic test and treatment of this disease.

[Purpose] Present study aimed to evaluate the relationship between sleep bruxism and headache in school children. [Subjects and Methods] This study was conducted with 103 children aged 3-6 years. The exclusion criteria were early tooth loss, dental appliance was used, physical or psychological limitations, chronic disease and continuous medication. Sleep bruxism was diagnosed based on an indication by parents of the occurrence of teeth clenching/grinding and incisor/occlusal tooth wear, following the criteria of the American Academy of Sleep Medicine. Sleep quality was evaluated by a questionnarie, detailing the child's sleep characteristics. [Results] Forty-nine children (47.6%) were diagnosed with sleep bruxism. Those with sleep bruxism were 3.25-fold more likely to present headache. Children whose parents were separated had a significantly greater frequency of sleep bruxism and primary headache. The relative risk of exhibiting primary headache was 13.1 among children with sleep bruxism whose parents were separated. [Conclusion] Children with SB demonstrated a greater risk of having primary headache and those whose parents were separated had a greater chance of having headache. Only sleep bruxism was associated with headache, clenching the teeth during waking hours was not correlated with primary headache.

Brain volume measurements are becoming an important tool for assessing success in controlling multiple sclerosis (MS) activity. MSmetrix (icometrix) is an easy-to-use platform, specific for MS magnetic resonance imaging (MRI) of the brain. It provides data on total brain volume, grey matter volume and lesion load volume. The objective of the present study was to assess whether disability and the number of relapses during the previous year correlated with brain volume measurements from MSmetrix. Data on 185 icometrix reports from patients with MS were used to evaluate the potential correlation between brain volume measurements and clinical parameters. There was a significant correlation between higher disability and decreased brain volume (total and grey matter). Increased lesion load in the brain and higher number of relapses in the previous year were also independently correlated with decreased brain tissue volume and with increased disability. This is the first study with real-world data to show that icometrix is a relevant tool for the study of brain volume loss in MS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The treatment of multiple sclerosis (MS) has quickly evolved from a time when controlling clinical relapses would suffice, to the present day, when complete disease control is expected. Measurement of brain volume is still at an early stage to be indicative of therapeutic decisions in MS., Methods: This paper provides a critical review of potential biases and artifacts in brain measurement in the follow-up of patients with MS., Results: Clinical conditions (such as hydration or ovulation), time of the day, type of magnetic resonance machine (manufacturer and potency), brain volume artifacts and different platforms for volumetric assessment of the brain can induce variations that exceed the acceptable physiological rate of annual loss of brain volume., Conclusion: Although potentially extremely valuable, brain volume measurement still has to be regarded with caution in MS.

Objectives: The aim of this study is to investigate whether patients with multiple sclerosis (MS) have more orofacial dysfunctions than the general population, using the Nordic Orofacial Test-Screening (NOT-S)., Materials and Methods: The NOT-S instrument was applied in 34 patients with MS, who went to the MS Reference Center, Universidade Metropolitana de Santos and 34 healthy patients, matched for gender and age. NOT-S results were compared between patients with MS and control subjects. Disability and disease duration were assessed among the patients, in order to establish whether these parameters might affect the results from NOT-S., Results: There was no significant difference in orofacial function between patients with MS and control subjects. There was no statistically significant correlation between disability and NOT-S or between disease duration and NOT-S. However, the correlation between disease duration and the degree of disability was statistically significant, thus suggesting that the results are in accordance with what would be expected regarding MS., Conclusions: These results indicate that there was no correlation between orofacial dysfunction and MS, although there were some differences in the affected domains., Clinical Relevance: This study points out the orofacial dysfunctions which health professionals should be aware in this population.

Objective: Multiple sclerosis (MS) is a chronic neuroimmunological disease that mainly affects young adults and leads to neurological disabilities. Depression, anxiety, cognitive dysfunction, and other psychiatric conditions have often been reported in patients with MS. Other, subtler aspects of psychosocial conditions in MS have been studied, but there is a paucity of papers on the subject. Remarkable degrees of aggression have been described in up to a quarter of patients with MS, but few studies have targeted this outcome in the psychopathological assessment on patients. The objective of the present study was to assess aggressiveness in patients with MS and compare with matched control subjects., Method: The present study included a group of 24 patients and 24 healthy controls matched for gender, age, and socioeconomic level. Patients with moderate or severe disability, anxiety, or depression were excluded. A validated tool was used for assessment of aggressive trait., Results: Aggressive traits were studied in patients and matched controls, and the results point to a very low level of aggressive tendency in patients with MS, in comparison with controls., Conclusion: The results from the present study do not confirm findings from other authors who had observed high levels of aggressive behavior in patients with MS. The authors are aware that exclusion of patients with moderate or severe disability, anxiety, or depression might have influenced the results., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Methods: Series of cases collected from Brazilian centers., Results: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset., Conclusion: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

Objective: Vitamin D has taken center stage in research and treatment of multiple sclerosis (MS). The objective of the present study was to assess the serum vitamin D levels of a large population of patients with MS and controls living in a restricted tropical area., Methods: Data from 535 patients with MS and 350 control subjects were obtained from 14 cities around the Tropic of Capricorn., Results: The mean serum 25-OH vitamin D level was 26.07 ± 10.27 ng/mL for the control subjects, and 28.03 ± 12.19 ng/mL for patients with MS. No correlation was observed between vitamin D levels and the disability of patients over the disease duration., Conclusion: At least for the region around the Tropic of Capricorn, serum levels of vitamin D typically are within the range of 20 to 30 ng/mL for controls and patients with MS.

Objective: To assess the prevalence of headache in post-menopausal women., Methods: Women attending gynecology outpatient services in the coastal region of the state of Sao Paulo, Brazil were invited to participate in this study. Only those with non-surgical menopause and no hormone replacement therapy were included. Prevalence and characterization of headaches were assessed, as well as the burden of migraine, traits of anxiety and depression, and menopausal symptomatology., Results: One hundred and three women were included in the study. Migraine affected 14.7% of them. Some previous type of headache was reported by 86.2% of the women, most of whom improved during menopause but still presented with headache attacks. There was a correlation between higher migraine disability and depressive traits., Conclusions: Many women believe that their headaches, particularly migraine, will end after menopause. This is, unfortunately, not the case for many of them.

Methods: This is a single center, cross-sectional study, of 34 patients with MS and 34 matched control subjects. A specific questionnaire (empathy quotient) was used., Results: Patients with MS showed significantly lower levels of empathy. This finding was not correlated with disease duration, degree of disability, drugs for treating MS or lesion load on resonance magnetic imaging., Conclusion: Decreased empathy is a frequent condition in patients with MS and should be addressed in order to diminish the psychosocial burden of this neurological disease.

Objective: To assess the relationship between states of anger and stroke., Methods: Systematic review of the literature., Results: In total, 21 papers were selected for the systematic review of data published on the subject of anger and stroke. A state of anger may be a risk factor for stroke, as well as a consequence of brain lesions affecting specific areas that are caused by a stroke. Scales to assess anger varied among authors. There was no consensus regarding the area of brain lesions that might lead to a state of anger. Although some authors agreed that lesions on the right side led to angrier behaviour, others found that lesions on the left side were more relevant to anger. Likewise, there was no consensus regarding the prevalence of anger pre or post-stroke. Some authors did not even find that these two conditions were related., Conclusion: Although most authors have accepted that there is a relationship between anger and stroke, studies with uniform methodology need to be conducted if this association is to be properly evaluated and understood.

Objective: The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients' satisfaction with the treatment must be taken into consideration., Methods: Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs., Results: One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability., Conclusion: Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

Objective: To assess safety of the switch between natalizumab and fingolimod without a washout period., Methods: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed., Results: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported., Conclusion: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

Retinoic acid (RA) is a potent regulator of gene transcription via its activation of a set of nuclear receptors controlling transcriptional activation. Precise maintenance of where and when RA is generated is essential and achieved by local expression of synthetic and catabolic enzymes. The catabolic enzymes Cyp26a1 and Cyp26b1 have been studied in detail in the embryo, where they limit gradients of RA that form patterns of gene expression, crucial for morphogenesis. This paracrine role of RA has been assumed to occur in most tissues and that the RA synthetic enzymes release RA at a site distant from the catabolic enzymes. In contrast to the embryonic CNS, relatively little is known about RA metabolism in the adult brain. This study investigated the distribution of Cyp26a1 and Cyp26b1 transcripts in the rat brain, identifying several novel regions of expression, including the cerebral cortex for both enzymes and striatum for Cyp26b1. In vivo use of a new and potent inhibitor of the Cyp26 enzymes, ser 2-7, demonstrated a function for endogenous Cyp26 in the brain and that hippocampal RA levels can be raised by ser 2-7, altering the effect of RA on differential patterning of cell proliferation in the hippocampal region of neurogenesis, the subgranular zone. The expression of CYP26A1 and CYP26B1 was also investigated in the adult human brain and colocalization of CYP26A1 and the RA synthetic enzyme RALDH2 indicated a different, autocrine role for RA in human hippocampal neurons. Studies with the SH-SY5Y human neuroblastoma cell line implied that the co-expression of RA synthetic and catabolic enzymes maintains retinoid homeostasis within neurons. This presents a novel view of RA in human neurons as part of an autocrine, intracellular signaling system.

Background: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS)., Objective: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group., Methods: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine., Results: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients., Conclusion: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Unlabelled: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities., Methods: Retrospective data on patients with arterial dissection related to sports and recreation., Results: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature., Conclusion: Arterial dissection may be a complication from practicing sports.

Background: Multiple sclerosis (MS) is a central nervous system disease associated with irreversible progression of disability, which imposes a substantial socioeconomic onus. The objective of this study was to determine the economic impact of multiple sclerosis from the Brazilian household and healthcare system perspectives. Secondary objectives were to assess the impact of fatigue on daily living and health-related quality of life (HRQL) of MS patients., Methods: This is a cross-sectional study in which Brazilian eligible patients attending eight major MS specialized sites answered an interview capturing data on demographics, disease characteristics and severity, comorbidities, resource utilization, fatigue, utilities and health-related quality of life from November/2011 to May/2012 . Costs were assessed considering a prevalence-based approach within 1 year of resource consumption and were estimated by multiplying the amount used by the corresponding unit cost. Patients were classified as having mild, moderate or severe disability according to the Expanded Disability Status Scale (EDSS)., Results: In total, 210 patients who met eligibility criteria were included, 40 % had mild, 43 % moderate and 16 % severe disability; disability level was missing for 1 %. The average total direct cost per year was USD 19,012.32 (SD = 10,465.96), and no statistically significant differences were not observed according to MS disability level (p = 0.398). The use of disease modifying therapies (DMTs) corresponded to the majority of direct expenditures, especially among those patients with lower levels of disability, representing around 90 % of total costs for mild and moderate MS patients. It was also observed that expenses with medical (except DMTs) and non-medical resources are higher among patients with more severe disease. Worsening disability also had an important influence on health-related quality of life and self-perceived impact of fatigue on daily living., Conclusion: Our data demonstrates the significant economic impact of MS on both Brazilian household and health system, in terms of DMTs and other disease management costs. When patients move upwards on the disease severity scale, costs with health resources other than drugs are significantly increased.

Dengue fever is the most prevalent mosquito-borne viral illness in humans. There may be different clinical manifestations of the disease, from mild symptoms to hemorrhagic forms of dengue fever and even neurological complications of this viral infection. Blood cells are usually affected, and thrombocytopenia is the hallmark of the disease. This paper presents 15 cases of dengue fever in patients with multiple sclerosis (MS) taking fingolimod or natalizumab. There were no complications of dengue fever or worse outcomes of MS in these patients, and only four of them needed short-term treatment withdrawal due to lymphopenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose Recent papers suggest that patients with multiple sclerosis (MS) are prone to alcohol misuse. This may be due to the combination of a lifelong and disabling disease with a psychiatric profile typical of MS. The objective of the present study was to assess these findings in a culturally different population of patients with MS.Method The present case-control transversal study assessed 168 patients with MS and 168 control subjects from Brazil.Results There were no evidence that patients with MS drank more alcohol or, smoked more than did controls. In fact, control subjects had a significantly higher alcohol consumption. The only trait associated to higher alcohol consumption was anxiety, both for patients and controls.Conclusion Unlike previous reports in the literature, patients with MS in our study did not drink or smoked more than a control population.