Differential diagnosis of multiple sclerosis in Latin America.

Improvement of multiple sclerosis (MS) diagnoses leads to earlier and correct disease management. The differential diagnostic workup for MS comprises a large variety of medical conditions. There are general guidelines and criteria for diagnosing MS worldwide, but awareness of regional differences needs to be kept in mind. Latin American patients who are screened for MS diagnoses may require an approach that is not exactly the same as that used for patients in North America, western Europe or Asia. In the present review, the conditions that are important for the differential diagnoses of MS in Latin America are reviewed. They include infections, metabolic diseases, nutritional deficits and other autoimmune conditions that physicians in charge of these patients need to be familiar with.

The expression and roles of Nde1 and Ndel1 in the adult mammalian central nervous system.

Mental and neurological illnesses affect one in four people. While genetic linkage analyses have shown an association of nuclear distribution factor E (NDE1, or NudE) and its ohnolog NDE-like 1 (NDEL1, or Nudel) with mental disorders, the cellular mechanisms remain unclear. In the present study, we have demonstrated that Nde1 and Ndel1 are differentially localised in the subventricular zone (SVZ) of the forebrain and the subgranular zone (SGZ) of the hippocampus, two regions where neurogenesis actively occurs in the adult brain. Nde1, but not Ndel1, is localized to putative SVZ stem cells, and to actively dividing progenitors of the SGZ. The influence of these proteins on neural stem cell differentiation was investigated by overexpression in a hippocampal neural stem cell line, HCN-A94. Increasing Nde1 expression in this neural stem cell line led to increased neuronal differentiation while decreasing levels of astroglial differentiation. In primary cultured neurons and astrocytes, Nde1 and Ndel1 were found to have different but comparable subcellular localizations. In addition, we have shown for the first time that Nde1 is heterogeneously distributed in cortical astrocytes of human brains. Our data indicate that Nde1 and Ndel1 have distinct but overlapping distribution patterns in mouse brain and cultured nerve cells. They may function differently and therefore their dosage changes may contribute to some aspects of mental disorders.

Towards establishing MS prevalence in Latin America and the Caribbean.

A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors' reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean.

What can we really tell women with multiple sclerosis regarding pregnancy? A systematic review and meta-analysis of the literature.

BACKGROUND: Although several papers report on pregnancy and multiple sclerosis (MS), no systematic review of the literature has been carried out. Neurologists and obstetricians need to have proper information to discuss with women presenting with MS who consider pregnancy. OBJECTIVES: Literature review and meta-analysis of data on pregnancy in women with MS. SEARCH STRATEGY: The present work followed the recommendations of the PRISMA Statement. Using the PICO framework, the authors independently searched for the terms 'pregnancy' OR 'gestation' OR 'pregnant' AND 'multiple sclerosis' OR 'MS' in the following databases: EMBASE/Excerpta Medica, Medline, Pubmed, Scopus, Index Medicus, Biomed Central, Ebsco Fulltext, LILACS, Scielo and the Cochrane Database of Systematic Reviews. SELECTION CRITERIA: only papers presenting original work with analysis of at least one of the outcomes among pregnant women with MS were included. DATA COLLECTION AND ANALYSIS: Two independent workers performed the literature review. All the authors selected and read the relevant papers. Two other authors summarised data for analysis. MAIN RESULTS: Twenty-two papers reporting on 13,144 women with MS and their pregnancies were analysed. A significant decrease in relapse rate was observed during pregnancy, followed by a significant increase after delivery. Miscarriages, low birthweight, prematurity, neonatal death and malformations were assessed among these women and their offspring. There seems to be a regional influence on the rates of caesarean sections and abortions among women with MS. Neonatal death and malformation rates did not seem to be particularly high. AUTHORS' CONCLUSIONS: The present work provides evidence-based data that can be discussed with women with MS and their relatives when pregnancy is considered by these families.

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.

Odors as triggering and worsening factors for migraine in men / Odores como fatores desencadeantes e de piora na enxaqueca de homens

OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48 percent), behind stressful situations (59 percent). Likewise, odors were the second most frequent worsening factor (73 percent), just behind excessive light (74 percent). Thirty-three individuals (33.4 percent) stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females.

OBJETIVO: Avaliar o papel dos odores como fatores desencadeantes e de piora da enxaqueca em homens. MÉTODO: Noventa e oito homens com enxaqueca na população geral foram avaliados individualmente por questionários. Os fatores ambientais relacionados à enxaqueca foram relatados, com foco especial no papel dos odores. RESULTADOS: Os odores foram o segundo fator mais frequente no desencadeamento de crise de enxaqueca (48 por cento), atrás das situações de estresse (59 por cento). Da mesma forma, os odores foram a segunda causa mais frequente de piora das crises (73 por cento), apenas atrás do excesso de luminosidade (74 por cento). Trinta e três indivíduos (33,4 por cento) relataram que os odores eram tanto fatores desencadeantes quanto fatores de piora de suas crises de enxaqueca. Perfume, fumaça de cigarro e produtos de limpeza foram os odores mais relatados como sendo relacionados a enxaqueca pelos homens. CONCLUSÃO: Este foi o primeiro estudo que avaliou o papel dos odores exclusivamente em homens com enxaqueca. Houve um alto índice de enxaqueca relacionada a odores, sugerindo que a educação dos pacientes poderia alertar fatores dependentes do gênero do paciente, uma vez que diferentes fatores desencadeantes e de piora das crises tem sido relatados por homens e mulheres.

Description and characteristics of 81 patients attending the Reference Center for Multiple Sclerosis of the coastal region of the state of São Paulo-Brazil

OBJECTIVE: To register multiple sclerosis (MS) patients residing in the coastal region of the State of São Paulo (CEREM Litoral Paulista). METHOD: Individual interviews with identified cases of MS. RESULTS: 81 individuals with diagnosis of MS agreed to come for registration (62 females [76.5%], 19 males [23.5%]). 65% of all patients were residents of the city of Santos. The mean age of these patients was 43 years (14 to 74 years), and the Expanded Disability Status Scale (EDSS) was < or = 5.5 in 76.5% of the cases. 82.7% of the assessed patients presented the relapsing/remitting form of MS. 81.5% of all patients were undergoing treatment with immunomodulators. CONCLUSION: Due to their clinical profile, patients seem to come to CEREM Litoral Paulista for prescription of immunomodulators. There is a clear need to identify other cases in the region and to allow other forms of treatment to be put into practice.

OBJETIVO: Registrar os pacientes portadores de esclerose múltipla (EM) residentes na região do litoral paulista (CEREM Litoral Paulista). MÉTODO: Entrevistas individuais com casos identificados de EM. RESULTADOS: 81 indivíduos com diagnóstico de EM (62 mulheres [76,5%] e 19 homens [23,5%]) concordaram em comparecer para registro no centro. 65% do grupo total de pacientes eram residentes da cidade de Santos. A idade média destes pacientes era 43 anos (14 a 74 anos), e o Expanded Disability Status Scale (EDSS) foi < 5,5 em 76,5% dos casos. 82,7% dos pacientes registrados apresentava a forma remitente-recorrente de EM. 81,5% de todos os pacientes estava recebendo tratamento com imunomoduladores. CONCLUSÃO: Pelo perfil clínico, os pacientes parecem vir ao CEREM Litoral Paulista para prescrição de imunomoduladores. Existe uma clara necessidade de identificar outros casos na região e permitir que outras formas de tratamento sejam implantadas.

Tolerability, adverse events and compliance to glatiramer acetate in 28 patients with multiple sclerosis using the drug continuously for at least six months

AIM: To assess tolerability, adverse events and compliance to treatment with glatiramer acetate in multiple sclerosis. METHOD: Review of patient records and individual interviews. RESULTS: 30 individuals residing in the coastal region of the State of São Paulo who had been in use of glatiramer acetate for at least 6 months were identified. From this group, 28 individuals came to regular consultations and were individually assessed, their complaints being noted down in confidential records. Ten patients reported systemic reactions to the drug. Four of them stopped the medication due to such reactions. Eight patients reported local reactions to the injections. Compliance with injections was achieved, although three patients reported forgetting the injection on a few days. CONCLUSION: We noticed a higher level of systemic adverse events in our patients than in reports in the literature.

OBJETIVO: Avaliar tolerância, eventos adversos e aderência ao tratamento com acetato de glatiramer em esclerose múltipla. MÉTODO:Revisão de prontuários de pacientes e entrevistas individuais. RESULTADOS: 30 indivíduos residentes na região do litoral do Estado de São Paulo, que fizeram tratamento com acetato de glatirâmer por pelo menos 6 meses foram identificados. Deste grupo, 28 indivíduos compareceram a consultas regulares e foram avaliados individualmente, sendo suas queixas anotadas em prontuário confidencial. Dez pacientes relataram reações sistêmicas à droga. Quatro deles suspenderam o tratamento devido às reações. Oito pacientes relataram reação local às injeções. Aderência às injeções foi obtida, embora três pacientes admitam ter esquecido a injeção alguns poucos dias. CONCLUSÃO: Observamos um índice maior de reações sistêmicas em nossos pacientes do que o relatado na literatura.

Efficacy and safety of metamizol vs. acetylsalicylic acid in patients with moderate episodic tension-type headache: a randomized, double-blind, placebo- and active-controlled, multicentre study.

We assessed the efficacy and safety of oral single doses of 0.5 and 1 g metamizol vs. 1 g acetylsalicylic acid (ASA) in 417 patients with moderate episodic tension-type headache included in a randomized, double-blind, placebo- and active-controlled, parallel, multicentre trial. Eligibility criteria included 18-65 years of age, history of at least two episodes of tension-type headache per month in the 3 months prior to enrollment, and successful previous pain relief with a non-opioid analgesic. Treatment arms were metamizol 0.5 g (n = 102), metamizol 1 g (n = 108), ASA 1 g (n = 102) and placebo (n = 105). The analgesic efficacy of 0.5 and 1 g metamizol vs. placebo was highly statistically significant (alpha: 0.025; one-sided) for sum of pain intensity differences, maximum pain intensity difference, number of patients with at least 50% pain reduction, time to 50% pain reduction, maximum pain relief and total pain relief. A trend towards an earlier onset of a more profound pain relief of 0.5 and 1 g metamizol over 1 g ASA was noticed. All medications including placebo were almost equally safe and well tolerated.

Low doses of gabapentin may be helpful in the management of chronic daily headache.

CONTEXT: The difficult management of chronic daily headache and the lack of clinical trials for this medical condition led the authors to perform this study. Gabapentin has been successfully used for a variety of chronic pain conditions and therefore may be of use in the treatment of chronic headache. OBJECTIVE: To assess the efficacy and safety of low doses of gabapentin in cases of chronic daily headache. DESIGN: Open-label study on a series of cases of chronic daily headache. PATIENTS: Twenty-one consecutive patients with primary headache lasting 4 or more hours a day, at least 15 days per month, were invited to participate in this open trial. They were treated with low doses of gabapentin for sufficient time to lead to a headache-free period of at least 7 consecutive days. A minimum of 1 follow-up visit and 1 phone call were made in the subsequent 6-9 months. MEASUREMENTS: A simple "Patient Impression of Change" was used to evaluate the results. Patients were also invited to compare this treatment to previous ones, whenever possible. RESULTS: The efficacy of the treatment with gabapentin was rated as "excellent" by 19% of the patients, "good" by 47.6%, "fair" by 19%, and "poor" by 14.4%. CONCLUSIONS: Despite the inherent limitations of such a small open trial, the authors concluded that ratings of excellent and good by two thirds of this population of patients with chronic daily headache should encourage the setup of a large double-blind, multicentric, placebo-controlled trial of low doses of gabapentin for chronic daily headache.

[Hemicrania continua] / Hemicrania Contínua.

OBJECTIVE: To report a case of Hemicrania Continua in a female aged 17, who presented this kind of headache for 9 years without diagnosis. Although this may be a relatively rare primary headache, the immediate response to clinical treatment with indomethacin justifies this entity be better known. METHODS: Case report of a female adolescent who had presented Hemicrania Continua for many years, without diagnosis and adequate treatment. Review of the relevant medical literature by means of Medline. RESULTS: Treatment with low doses of indomethacin caused complete cessation of the headache. CONCLUSION: Hemicrania Continua must be considered as a diagnostic possibility for patients who present continuous unilateral headache, without abnormalities in the clinical, neurologic and laboratorial examination, irrespective of the age the headache starts. This is the youngest patient reported to have Hemicrania continua and it was brought to discussion by a medical student, aware of this possible diagnosis.

Management of primary headache in emergency services of Santos and surrounding towns.

OBJECTIVES: Primary headaches are often seen by Clinicians on duty at Emergency Services. We have investigated the treatment of such patients by 43 medical doctors who have been working at Emergency Services in the city of Santos and surrounding towns for many years. RESULTS: We confirmed the high prevalence of primary headaches in Emergency Services. There seem to be diagnosis difficulties concerning differentiating attacks of migraine and tension type headache. We also observed that IV dipirone was the most frequently prescribed treatment for patients with primary headaches in this study. There is no protocol in the literature which recommends IV dipirone for the treatment of migraine attacks or other primary headaches. CONCLUSION: It would be advisable to perform controlled double blind studies in order to verify the advantages of IV dipirone in the treatment of intense attacks primary headaches. We concluded that headache management recycling programs could be of interest for doctors who regularly work at Emergency Services.

In vivo metabolism of alpha-tocopherol in lipoproteins and liver: studies on rabbits in response to acute cholesterol loading.

OBJECTIVE: To investigate the transport of alpha-tocopherol in lipoproteins of rabbits under normal diet and under acute loading of cholesterol. DESIGN: Two New Zealand White rabbits were fed 14C-alpha-tocopherol acetate in a single oral dose and the recovery of radiolabel in lipoproteins and plasma was monitored. Low density lipoprotein (LDL) from these animals was obtained and labeled with [3H] cholesteryl ester. Three other rabbits were injected with this double-labeled LDL in the native form; while three other animals received this LDL in the acetylated form. RESULTS: Plasma clearance, liver uptake and levels of radiolabel in high density lipoprotein (HDL) of animals injected with 14C[3H]acetyl LDL were significantly higher than those in animals injected with 14C[3H]native LDL. Larger particles of HDL, rich in apolipoprotein E (apoE) carried significantly higher levels of both labels in rabbits injected with acetylated LDL. CONCLUSION: These results provide evidence for in vivo mechanisms of "reverse alpha-tocopherol transport", analogous to "reverse cholesterol transport".

Neurologic manifestations of AIDS: a review of fifty cases in Santos, São Paulo, Brazil.

OBJECTIVE: To review the neurologic manifestations of AIDS in patients who were admitted to Hospital Guilherme Alvaro (HGA) due to any clinical manifestation of the disease. DESIGN: Case series. PATIENTS: All HIV+ patients admitted to the Faculty Hospital (HGA) between July 96 and April 97 were included in this review. RESULTS: From the 117 HIV+ patients admitted to hospitalization due to AIDS-related symptoms, 50 (42.7%) presented neurologic manifestations. The most prevalent of these was neurotoxoplasmosis (68%), but a variety of other neurologic diseases were observed. Only 36% of these 50 patients had neurological signs and symptoms as the main complaint for admission, 12% of the patients had at least complained of some neurologic dysfunction at the time of admission and 10% had no neurologic complaints at all. The remaining 42% (21 patients) only complained of neurologic manifestations of AIDS when specifically asked. CONCLUSIONS: The prevalence of neurologic manifestations of AIDS is very high in patients admitted to hospital. Even in the absence of neurologic-related complaints, these patients have to be carefully questioned and examined in the search for an underlying neurologic complication which may present high morbidity and mortality.

Hemicrania continua with onset at an early age.

The authors describe the case of an adolescent who had suffered from unilateral continuous headache since she was 8 years old. Treatment with indomethacin 50 mg/day promptly relieved the pain which had affected her for the previous 9 years. To the best of our knowledge, this is the earliest onset of hemicrania continua reported.

Reduction of migraine attacks during the use of warfarin.

Two recent reports on reduction of migraine attacks during treatment with vitamin K antagonists have caught my attention. Being a migraine sufferer myself, with considerable improvement of my headache during the use of warfarin, I became interested in the subject. Recently, a young man sought my advice for migraine attacks which had worsened after the withdrawal of warfarin. The previous reports on migraine and warfarin involved elderly patients. I report now on these two patients in their 30s, one of them being myself (case 1), who have experienced reduction of migraine attacks during the use of warfarin.