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Unlabelled: The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS) patients during the disease onset predicts long term disability., Methods: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS) was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure., Results: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003)., Discussion: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

Background and Purpose: Epidemiologic studies of incidence and prevalence in Parkinson's Disease (PD) show highly variable results. Despite the large number of studies performed worldwide during the last decades, little is known about its prevalence in South America and no incidence studies have been performed. The goal of this study is to assess the incidence and prevalence of PD in a health maintenance organization from Buenos Aires City, the capital city of Argentina., Methods: The population were all members of the 'Plan de Salud, Hospital Italiano de Buenos Aires', a large prepaid health medical organization in Buenos Aires. From 1 January 2003 to 31 December 2008 patients diagnosed with PD according to Brain Bank of London diagnostic criteria were identified retrospectively. Incidence density was calculated with 95% confidence interval., Results: Hundred and forty thousand people were followed for a total of 754,082 person-years. A total of 239 incident cases of PD were identified. Crude incidence density was 31.2/100,000 person-years. Prevalence was 394/100,000 in the population older than 40 years. Male to female ratio was 1.31., Conclusions: This is the first study in South America that estimates the incidence of PD. Our results are consistent with other studies from other regions using similar methodologies., (© 2012 The Author(s). European Journal of Neurology © 2012 EFNS.)

Objective: To determine if the presence of oligoclonal bands (OB) at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB., Methods: Relapsing-remitting multiple sclerosis (RRMS) patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF) were included. SIENAX was used for total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV)., Results: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS), treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6) compared with 1.64 mm³ x 10(6) in the negative ones (p=0.02). GMV was 0.51 mm³ x 10(6) in positive IgG-OB compared with 0.62 mm³ x 10(6) in negative ones (p=0.002). No differences in WMV (p=0.09) were seen., Conclusions: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR) markers in early RRMS.

Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power., Methods: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome., Results: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001)., Conclusions: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.

The purpose of this study was to determine the value of spinal cord lesions as a predictive factor for conversion in clinically isolated syndrome (CIS) patients. Patients with CIS and without immunomodulatory treatment were prospectively included. Age at onset, sex, clinical syndrome at onset, oligoclonal bands, and presence, number and location of lesions on brain and spinal MRI were analyzed. Conversion to multiple sclerosis (MS) was the primary endpoint. Cox regression was used to compare outcomes between groups. A total of 75 patients were included: 53 (71%) women, mean age at onset 32.7 years (SD ± 7.5), mean follow-up time 72.5 months (SD ± 9; range 17-104 months). There were 11 (14.6%) patients with one focal spinal cord lesion, while 13 (17%) patients had two or more spinal cord lesions at the first scan during the onset of the disease. Of the 23 patients (30.6%) who converted to clinically definite MS (CDMS), 2 had a normal spinal cord MRI, 8 patients had one spinal cord lesion, and 13 had more than one lesion on MRI (p < 0.001). In multivariable analyses, one focal spinal cord lesion was significantly associated with increased risk of conversion to MS (p = 0.01, HR 3.5, CI 95% 2.1-6.9), while the presence of two or more focal spinal cord lesions was independently associated with a higher risk of conversion to MS (p < 0.001, HR 5.9, CI 95% 3.2-10.8). CIS patients with an abnormal baseline spinal cord MRI have a higher risk for developing clinically definite MS, independent of brain lesions as well as the presence of cerebrospinal fluid oligoclonal banding (OSF-OB) .

Introduction: Epidemiological studies on acute transverse myelitis (ATM) in South America are scarce. The aim of our study was to describe demographic, clinical and para-clinical features of patients with ATM in a health care organisation in Buenos Aires. A further objective was to determine the aetiologies of ATM., Methods: All patients diagnosed with ATM between June 1, 2002 and June 30, 2010 were retrospectively identified, using the Transverse Myelitis Consortium Working Group criteria., Results: A total of 40 patients diagnosed with ATM, (24 females, 60%) were included. The mean follow-up was 57 ± 8 months. The principal cause of myelitis found was ATM secondary to demyelinating disease (55%). Idiopathic ATM was diagnosed in 15 (37.5%) cases in the sample. The majority of patients had an extensive cord lesion (50%) detectable with spinal MRI., Conclusion: There are few epidemiological studies concerning ATM in Argentina, and we believe that it is important to be aware of the manner in which this condition manifests itself in this region. We would therefore be able to compare them with studies previously published in other countries., (Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

The objective of the present study was to perform a systematic review and a meta-analysis in order to determine the epidemiological profile of multiple sclerosis (MS) in Argentina. A systematic search was performed in electronic databases and lists of references, focused on epidemiological studies of MS in Argentina. Data obtained were analyzed with the StatsDirect software. A total of 275 studies were retrieved of which 15 included. The prevalence was described in 4 studies, most of them reported a prevalence of 17 cases per 100,000 inhabitants. The incidence, prospectively described in one hospital based study, was 1.76 cases per 100,000 persons-years. In this study, 65.5% of cases were relapsing-remitting MS, 21.5% secondary progressive, 10.6% primary progressive and 2.4 progressive with relapsing MS. Female/male ratio was 1.55. This study provided information regarding the epidemiological feature of MS in Argentina. Future researches will contribute to increase the number of recorded cases, and the knowledge on the behavior of this disease in the country.

Objectives: We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS)., Methods: The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation., Results: A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation., Conclusion: In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.

Background: A female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients was demonstrated in many countries around the world. So far, a direct comparison of sex ratio time-trends among MS populations from different geographical areas was not carried out., Objective: In this paper we assessed and compared sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas., Methods: Data of a cohort of 15,996 (F = 11,290; M = 4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from the international MSBase registry and the New Zealand MS database. Gender ratios were calculated by six decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the respective national registries of births., Results: Adjusted sex ratios showed a significant increase from the first to the last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the subgroups belonging to the areas between 83° N and 45° N (from 1.93 to 4.55; p<0.0001) and between 45° N to 35° N (from 1.46 to 2.30; p<0.05) latitude, while a sex ratio stability over time was found in the subgroup from areas between 12° S and 55° S latitude. The sex ratio increase mainly affected relapsing-remitting (RR) MS., Conclusions: Our results confirm a general sex ratio increase over time in RRMS and also demonstrate a latitudinal gradient of this increase. These findings add useful information for planning case-control studies aimed to explore sex-related factors responsible for MS development.

Introduction: Previous reports have shown that CD24 gene polymorphisms have an important role in the risk of development and progression of multiple sclerosis (MS)., Objective: To investigate the association between P226 polymorphisms (T/C), P1056 (A/G), P1527 (TG/del) and P1626 (A/G) of the CD24 gene and MS, comparing allele and genotype frequencies of patients versus controls., Materials and Methods: We analyzed DNA samples from 102 MS patients and from 205 unrelated healthy individuals. DNA was extracted from peripheral blood and polymorphic regions were amplified by nested PCR. Genotyping was performed by restriction fragments length polymorphisms. Time from disease onset to reach EDSS 6 and time to conversion to secondary progressive phase (SP) were used as variables of survival as well as percentage of patients that reached those endpoints. We used the log Rank test for data comparison (significant p≤0.05)., Results: We found no differences between cases and controls in frequency of polymorphisms at the CD24 gene. 44.6% of patients with the AA genotype (P1626) reached an EDSS 6 vs 16% of patients with other genotypes (p<0.001, HR 3.2, 95% CI 1.4 to 7.4). 45.8% of patients with the AA genotype reached SPMS vs 16.7% without this genotype (p<0.001, HR 3.4, 95% CI 1.5 to 7.8)., Conclusions: This study showed a strong association between the presence of AA genotype in the 1626 polymorphism of the CD24 gene and the risk of disease progression in MS patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The mechanisms of epigenetic regulation play an important role in the development and function of body systems. Failure in the maintenance of this regulation as well as environmental factors could contribute to the development of multiple diseases in genetically predisposed patients. Although the molecular mechanisms responsible for the etiology of most diseases are unknown, there is evidence of both genetic and environmental factors that could influence this development. Recent findings involve epigenetic mechanisms in the origin of various diseases. This review aims to describe in detail the mechanisms of epigenetic regulation and the known findings involving the dysfunction of these mechanisms as a possible cause of various diseases.

Introduction: previous reports have shown that in Dementia with Lewy body (DLB) and attention-deficit and hyperactivity disorder (ADHD) a hypodopaminergic and noradrenergic substrate seems to play a central role in developing the diseases. We investigated the hypothesis that attention deficit may precede DLB expressed as adult ADHD symptoms long before the clinical onset of dementia., Methods: patients with DLB, Alzheimer disease type (ADT) and controls were recruited from the membership of the Italian Hospital Medical Care Program in Argentina from 2000 to 2005. The DSM-IV criteria adapted for the identification of adult patients with ADHD and validated to Spanish Wender Utah Rating Scale were used to identify individuals with preceding ADHD symptoms during their adult life. Analysis of categorical variables was carried out using chi-square. Mann-Whitney test was used for continuous variables. Statistical significance was P < 0.05., Results: a total of 109 patients with DLB and 251 patients with ADT were matched by age, sex and year of education with 149 controls. The frequency of preceding ADHD symptoms in DLB cases was 47.8% in ADT 15.2% and 15.1% in the control group. The prevalence of ADHD symptoms in DLB cases was significantly higher compared with the control group (P ≤ 0.001, OR 5.1 95%CI 2.7-9.6) and also higher when compared with ADT (P ≤ 0.001, OR 4.9, 95%CI 2.8-8.4)., Conclusion: we found a higher risk of DLB in patients with preceding adult ADHD symptoms. To date, there is no clear explanation for the association found; however, further investigation will widen our understanding about both disorders.

Introduction: Previous reports have shown that brain atrophy appears early in the course of multiple sclerosis (MS). The aim of the present study was to evaluate whether brain atrophy already exists in clinically isolated syndrome (CIS) by comparing with a control sample., Methods: Patients with CIS were included prospectively from June 2008 to June 2009. A control group of healthy persons, matched by age and gender with CIS, was also included during the same period of time. An automated analysis tool, SIENAX, was used to obtain total brain volume (TBV), gray matter volume (GMV) and white matter volume (WMV). Mann-Whitney U test was used to analyze the data., Results: Twenty CIS patients and 30 healthy controls were included (8 vs. 17 females, p=0.11). Mean age for CIS was 35 ± 6 years vs. 34.4±5 in controls (p=0.61). Mean EDSS in CIS was 1.1 ± 0.5. Eighteen patients with CIS (90%) had abnormal baseline MRI. The TBV in CIS was 1.6.l ± 0.22.l × 106 vs.1.65 ± 0.15 × 106 in controls (p=0.005), the GMV in CIS was 0.58 ± 0.05 × 106 vs. 0.67 ± 0.03 × 106 in controls (p ≤ 0.001) and the WMV in CIS was 1 ± 0.1 × 106 vs. 1.12 ± 0.02 × 106 in controls (p=0.03)., Conclusions: This is the first study dealing with brain atrophy in a CIS sample from Latin America in which brain atrophy, mainly grey matter atrophy, was shown in early stages of the disease compared with healthy individuals.

Aim: To investigate the long-term impact of interferon-beta (IFNbeta) therapy on disease severity in relapsing-remitting multiple sclerosis (RRMS) patients., Patients and Methods: We included 210 patients with RRMS and indication for immunomodulatory treatment followed up at least for nine years. We compared between treated and untreated groups: time since the beginning of the disease to reach EDSS 6.0 and time to conversion to secondary progressive multiple sclerosis. Log-rank test was used to compare outcomes between groups, p < 0.05 were considered significant., Results: 160 patients were IFNbeta-treated, 50 untreated. The percentage of patients that converted to SPMS after 9 years of follow-up was 7.1% for treated vs. 21.7% for untreated (p = 0.022; RR = 0.32; 95% CI = 0.13-0.74). About 7.7% for IFNbeta-treated vs. 18.7% of untreated patients reached EDSS 6.0 after the period of follow-up (p = 0.032; RR = 0.4; 95% CI = 0.16-0.95). Mean time to reach EDSS 6.0 was 8.1 years for IFNbeta-treated vs. 5.8 years for untreated patients (p < 0.001)., Conclusion: Long term treatment with IFNbeta slows progression in MS measured by EDSS and time to conversion to secondary progressive multiple sclerosis.

Objective: The present study was undertaken to determine the incidence of MS in a health maintenance organization from Buenos Aires, the largest populated area in Argentina., Methods: Population was all members of a hospital-based health maintenance organization who were affiliated since January 1992 up to December 2007. Each person was followed contributing time at risk since January 1992 or enrollment date to the final date. Patients with definite diagnosis according to Poser's criteria were included. Incidence density was calculated with 95% confidence intervals., Results: A total of 145,000 patients were followed for a total of 1,021,515 person-years, of whom 18 developed the disease. Incidence density (ID): 1.76 /100 000 person-years (95% CI: 1.1-2.8/100,000 person-years)., Conclusion: The incidence density of 1.76 per 100,000 suggests a low-median risk area for MS. This study constitutes the first of its kind to cover data of MS incidence in Argentina.

Background: This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006643. DOI: 10.1002/14651858.CD006643.pub2).Therapeutic trials with ss-interferon in Multiple Sclerosis (MS) have mainly focused on remitting-relapsing multiple sclerosis (RRMS), demonstrating a reduction in relapse rate. However, there is not enough evidence about their efficacy in patients with primary progressive multiple sclerosis (PPMS)., Objectives: Identify and summarize the evidence that ss-interferon is beneficial and safe in patients with PPMS., Search Strategy: We searched the Cochrane MS Group Trials Register (May 2009); The Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library, (2009, Issue 2); MEDLINE (PubMed) (January 1966 to May 2009), EMBASE (January 1974 to May 2009); NICE (January 1999 to May 2009); LILACS (January 1986 to May 2009); Screening of reference lists of all primary studies found; Contact and inquiry of drug manufactures and multiple sclerosis experts., Selection Criteria: Randomized double or single blind, placebo-controlled trials of recombinant ss-interferon in patients with PPMS including trials of MS which report separate outcomes in subgroups of patients with PPMS., Data Collection and Analysis: Two reviewers independently extracted and assessed trials' quality according to the criteria outlined in The Cochrane Handbook., Main Results: Of 1777 potential studies evaluated, only two Randomized Control Trials (123 patients) were included. ss-interferon treatment compared to placebo did not show differences regarding the proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55 to1.43), and it was associated with a greater frequency of treatment-related adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI secondary outcome pre-specified in the protocol. This trial showed that at two years the numbers of active lesions on brain MRI scan in ss-interferon arm were significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI -2.15 to -0.45, P = 0.003); also, the number of participants with active lesions was significantly higher in placebo arm vs. ss-interferon arm at two years (RR 0.43, 95% CI 0.22 to 0.86, P = 0.02)., Authors' Conclusions: Limited data on the effect of ss-interferon treatment on PPMS exists. Only two single-centre placebo controlled trials of interferon beta have been done. Based on this review, the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients. However, the trial population was too small to allow definitive conclusions on the efficacy of ss-interferon therapy in PPMS patients. Larger research studies need to be done in patients with PPMS in order to clarify whether ss-interferon is effective in this population.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Most of autoimmune diseases arise by an abnormal activation of the inflammatory response against self-antigens (most of them unknown up to date) as a consequence of dysfunction in peripheral tolerance. Regulatory T-cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory conditions. Based on that knowledge, T-regulatory cells have emerged as a key component of the physiopathology of autoimmune diseases including MS. This review compiles the current knowledge on the role and function of T-regulatory cells in MS, the most prevalent CNS autoimmune disease in humans.

Zolpidem is a hypnotic drug used in sleep disorders. It binds selectively to alpha 1 subunit of the GABA A benzodiazepine receptor. Zolpidem reduces sleep latency, number of arousals and increases the total time of sleep. However, it is considered that it may increase phase 3 of non rapid eye movement sleep, where somnambulism can take place. Our aim is to report 8 cases of sleep related eating disorders associated with the use of this drug. We have evaluated the medical history of 8 patients who had received zolpidem for sleeping disorders and who have presented sleep related eating disorders. Eight patients (6 women, 2 men) aged between 32 to 72 years old, which received 10 mg of zolpidem/night except 1 that received 12.5 mg, were presented. They have referred strange eating behavior compatible to sleep related eating disorder. Symptoms appeared at a mean of 39.8 days after starting the medication. The numbers of nocturnal episodes recorded by the family or by the patient were 1 to 8 episodes of nocturnal eating per night. The morning after, patients found leftovers from the night before which they did not recall to have eaten. The remission was complete after discontinuing zolpidem. Zolpidem may induce sleep related eating disorder in about 1% of patients, although we consider there may be a subdiagnosis of this phenomenon. It will be important to bear in mind and look for this side effect because all the episodes could easily be controlled by withdrawing the drug.

The statistical concept of accuracy has never been applied to verify the history data collected on seizure disorders by open format interview. We compared patients'/witnesses' descriptions of epileptic seizures with videotaped seizure characteristics and analyzed the accuracy (ACC), sensitivity (SN), specificity (SP), false-positive rate (FPR), and false-negative rate (FNR) of various components of the semiology in patients with partial epilepsy. Language disturbances, complex automatisms, and autonomic signs have high ACC and intermediate FNRs. This means that these manifestations are most obvious to the witness/patient and, therefore, are memorized easily. Dystonic posturing and upper limb automatisms have the highest FNRs, leading to low ACC. These are very subtle signs, not vigorous enough to be paid attention to, but their predictive value in partial epilepsy syndromes is relatively high. We believe these signs need to be directly sought in the interview, because often the patient/witness pays limited attention to them.

Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever vaccine-associated neurotropic disease. This terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. The objective of this communication is to report a patient who received a YF vaccine in Argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. A 56-year-old man began with progressive paraparesia, urinary retention, and constipation 48 h previous to admission. The patient received YF vaccine 45 days prior to the onset of the symptoms. There was no history of other immunization or relevant condition. MR of the spine showed longitudinal intramedullary hyperintense signal (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests for other flavivirus were negative. A diagnosis of longitudinal myelitis without encephalitis associated with YF vaccine was performed and symptoms improved 5 days later. This is the first report dealing with longitudinal myelitis as a serious adverse event associated with YF vaccination in which confirmation of the presence of antibodies in CSF was found. To date, it is also the first report with serological confirmation in Argentina and in South America. We consider that the present investigation will raise awareness in the region in the reporting of adverse events related to YF vaccine and improve our knowledge of adverse reactions to the vaccine.

Background and Purpose: Increasing evidence links infections to atherosclerosis. Case-control and cohort studies have found that infections, especially respiratory and dental, are associated with coronary heart disease. However, data on the association of infections with cerebrovascular disease are limited, especially beyond Europe and the United States. We assessed the relationship between recent infections and atherothrombotic disease in a South American cohort., Methods: We conducted a case-control study of 105 cases and 354 control subjects in a Buenos Aires healthcare system matched by age (mean age, 73.2+/-12.3 and 72.9+/-12.8 years), sex, and major cardiovascular risk factors. Cases were patients hospitalized with atherothrombotic ischemic stroke from December 2006 to October 2007. Control subjects were randomly assigned from an electronic outpatient database. Data from the preceding year on inpatient and ambulatory respiratory, urinary and abdominal infections as well as peripheral white blood cell count were collected., Results: Infections were more frequent in cases than control subjects (29% versus 13%; OR, 2.6; 95% CI, 1.4 to 4.5; P=0.0004); however, this was driven by community-acquired respiratory tract infections (19% versus 6%; OR, 3.9; 95% CI, 1.9 to 8; P<0.001) because there were no differences between cases and control subjects for other types of infection. Respiratory tract infections were the most prevalent type of infection during the 3 months before an atherothrombotic ischemic event, occurring more in cases compared with control subjects (17% versus 4%; OR, 5; 95% CI, 2.2 to 11.3; P<0.001). In multivariable analysis adjusting for major vascular risk factors, history of respiratory infection in the prior year was associated more with cases than control subjects (OR, 4.9; 95% CI, 2.3 to 10.2;P<0.001). White blood cell count was slightly higher in cases versus control subjects (7602+/-2058 versus 7121.6+/-1947, P=0.01)., Conclusions: In this South American cohort, recent respiratory tract infections were significantly associated with atherothrombotic stroke, suggesting that prompt identification and treatment of individuals with or at risk for these infections may mitigate the burden from this type of stroke.

Background: The influence of pregnancy on Multiple Sclerosis (MS) has been extensively studied but such influence on Latin American women with MS has not been characterized. Our objective was to describe the course of pregnancy and birth outcome in Argentinean MS patients and the evolution of MS during pregnancy and after delivery., Method: We used a retrospective design in eight MS centers in Argentina and administered a survey to women with definite MS (Mc Donald) with pregnancies during or after MS onset. We contacted 355 women of which 81 met inclusion criteria. We recorded 141 pregnancies., Results: Involuntary abortion was observed in 16% of pregnancies (95% CI = 10-23). Thirty five women received immunomodulatory therapy (IMT) before 42 pregnancies. Twenty three (55%) out of 42 pregnancies were exposed to IMT. The mean time of IMT discontinuation before conception in 19 (45.2%) pregnancies without exposure, was 104 days (95% CI = 61.0-147.0). There were 103 deliveries: 79% full term. Birth defects were detected in 19% of pregnancies exposed to IMT (95% CI = 4-46) and in 2% of non-exposed (95% CI = 0.3-8.0). The mean relapse rate was: pre-pregnancy year: 0.22 (95% CI = 0.12-0.32); pregnancy: 0.31 in 1st (95% CI = 0.10-0.52), 0.19 (95% CI = 0.03-0.36) in 2nd, and 0.04 in 3rd trimester (95% CI = -0.04-0.12); 1st trimester post delivery: 0.82 (95% CI = 0.42-1.22)., Conclusion: We observed a higher rate of birth defects among infants exposed to immunomodulators in utero than those not exposed. The reduction in MS relapses during 2nd and 3rd trimester of pregnancy and its increase during postpartum is consistent with previous reports.

Background: The association of multiple sclerosis (MS) with HLA DR subtypes, and particularly human leukocyte antigen (HLA)-DRB1*15 has been a consistent finding across nearly all Caucasian MS populations. In South America, scarce data exist about this issue. As the complete characterization of the HLA association range around the world is important to understand the role of this locus in MS susceptibility, we analyzed the frequency of HLA-DRB1* allelic groups in an MS population in Argentina., Methods: HLA-DRB1 locus was genotyped using PCR and sequence-specific primer amplification in 61 MS patients born in Buenos Aires, Argentina and 1216 healthy controls. Allele frequencies were compared between groups., Results: The HLA-DRB1*15 allele frequency significantly differed between controls and patients (13.5% and 33.9% respectively, P < 0.001, OR 2.51, 95% CI: 1.7-3.0). The other allele frequencies did not show significant differences between patients and controls., Conclusions: The present HLA class II population study is in accordance with other Caucasian MS surveys which have found that HLA-DRB1*15 allele is strongly associated with MS disease. In Argentina, this is the first study performed to analyze the association of HLA-DRB1*15 and MS susceptibility in a Caucasian population and therefore contributes with new data to the immunogenomic global MS map.

Background: Scarce data exist about multiple sclerosis (MS) prevalence in South America. The objective of the study is to determine the prevalence of MS in a high populated area from Argentina (Greater Buenos Aires Metropolitan area) using the capture-recapture methodology., Methods: Greater Buenos Aires is the generic denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking July 1996 as the prevalence month. We used capture-recapture method to estimate the prevalence of MS cross matching registries from four MS Centers., Results: A total of 803 registries were obtained from the four lists. Log-linear model for capture-recapture method was used to analyze the data. The population of the area based on the 1990 census was 12,594,974; the number of MS cases estimated amongst sources interactions were between 1833 and 2359; the prevalence estimated ranged from 14 to 19.8 cases per 100,000 inhabitants., Conclusions: This is the first study to provide epidemiological data on the prevalence of MS in a large population in Argentina (Greater Buenos Aires Metropolitan area). Further epidemiological studies will clarify the true prevalence of MS in South America.

The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.

Background: Therapeutic trials with ss-interferon in Multiple Sclerosis (MS) have mainly focused on remitting-relapsing multiple sclerosis (RRMS), demonstrating a reduction in relapse rate. However, there is not enough evidence about their efficacy in patients with primary progressive multiple sclerosis (PPMS)., Objectives: Identify and summarize the evidence that ss-interferon is beneficial and safe in patients with PPMS., Search Strategy: We searched (until April 2008) the Cochrane MS Group Trials Register; The Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library, (2008, Issue 3,); MEDLINE (PubMed) (January 1966 to April 2008), EMBASE (January 1974 to April 2008); NICE (January 1999 to April 2008); LILACS (January 1986 to April 2008); Screening of reference lists of all primary studies found; Contact and inquiry of drug manufactures and multiple sclerosis experts., Selection Criteria: Randomized double or single blind, placebo-controlled trials of recombinant ss-interferon in patients with PPMS including trials of MS which report separate outcomes in subgroups of patients with PPMS., Data Collection and Analysis: Two reviewers independently extracted and assessed trials' quality according to the criteria outlined in The Cochrane Handbook., Main Results: Of 1280 potential studies evaluated, only two Randomized Control Trials (123 patients) were included. ss-interferon treatment compared to placebo did not show differences regarding the proportion of patients with progression of the disease (RR 0.89, 95% CI 0.55 to1.43), and it was associated with a greater frequency of treatment-related adverse events (RR 1.90, 95% CI 1.45-2.48). One of the trials evaluated the MRI secondary outcome pre-specified in the protocol. This trial showed that at two years the numbers of active lesions on brain MRI scan in ss-interferon arm were significantly lower than in placebo arm (weighted mean difference -1.3, 95% CI -2.15 to -0.45, P = 0.003); also, the number of participants with active lesions was significantly higher in placebo arm vs. ss-interferon arm at two years (RR 0.43, 95% CI 0.22 to 0.86, P = 0.02)., Authors' Conclusions: Limited data on the effect of ss-interferon treatment on PPMS exists. Only two single-centre placebo controlled trials of interferon beta have been done. Based on this review, the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients. However, the trial population was too small to allow definitive conclusions on the efficacy of ss-interferon therapy in PPMS patients. Larger research studies need to be done in patients with PPMS in order to clarify whether ss-interferon is effective in this population.

Hundreds of publications dealing with the prevalence of multiple sclerosis (MS) throughout the world exist, but little data have been published from South America. Epidemiological studies of MS vary according to environmental, racial and genetic factors; a better understanding of MS in South America would help us to elucidate the disease pattern in this population. The aim of this study is to review the evidence relevant to MS epidemiology in South America. We performed a systematic review of articles of MS epidemiology in South America, with special emphasis on those providing information on the incidence and prevalence of MS (population-based studies). Six papers provided information on MS epidemiology. One paper used the capture-recapture methodology, while the remainder employed traditional methods to collect the data. Population-based studies showed an MS prevalence rate ranging from 1.48 to 17 per 100 000 inhabitants. Available data suggest that the prevalence of MS is lower in South America than in developed countries. The reason for this observation is unknown. Some investigators suggest that certain environmental factors like sun exposure and vitamin D supplementation or the called 'hygiene hypothesis' may protect this population. Future studies will contribute to elucidate the etiology of that difference.

There are few studies reporting multiple sclerosis prevalence rates in the Buenos Aires region, Argentina (latitude 34 degrees S) (between 12-18.5/100 000 inhabitants), and no studies have been performed in the larger region between parallels 36 degrees and 55 degrees S. The aim of this study is to determine the prevalence rates and clinical features of multiple sclerosis in residents of the Argentine Patagonia. Four cities from the region were selected for this study, giving a sample population of 417 666 inhabitants (approximately 24% of the total Patagonia population). 1(st) March 2002 was determined as prevalence day. Patients were ascertained using multiple case-finding methods. The point prevalence rate was 17.2/100 000 (17.2 age-adjusted to the world population). Prevalence rates were higher for women than for men, 22.1 versus 12.2/100 000 inhabitants (21.4 versus 12.7 sex-adjusted to the world population). The study population was mainly of European descent and mestizoes. Clinical features were similar to those reported in other countries. This study shows that Argentine Patagonia is a medium-risk area with no south-north gradient between parallels 55 degrees and 36 degrees S. The Patagonia population shows recent internal migration that makes it difficult to determine whether the exposure to potential risk factors has been long enough to modify the disease incidence.

Background: Transesophageal echocardiography (TEE) constitutes a valuable tool in patients with stroke and cardiac embolization, but its indication is controversial in lacunar stroke. The purpose of this study was to assess the findings of TEE in lacunar stroke., Methods: Initial symptoms, brain computed tomography or magnetic resonance imaging, and TEE were performed for all patients with ischemic stroke admitted consecutively to our department of neurology. The subtype of ischemic stroke (lacunar v large-vessel stroke) was also reviewed., Results: In all, 124 patients with ischemic stroke were identified and lacunar syndrome occurred in 46. Major risk factor of embolization in patients with lacunar stroke and indication for anticoagulation were detected in 20% (9 of 46). We compared findings in both groups (lacunar v nonlacunar stroke) to evaluate the differences in the presence of major risk factor for embolization, Chi square = 0.07, P = .8 (odds ratio 95% CI = 0.35-2.18). Characteristics of the 9 patients with lacunar stroke and major risk of embolization show that history of lacunar ischemic stroke was present in all the patients of this group., Discussion: The results of the study suggest that TEE may be necessary to obtain a complete evaluation to optimize preventive treatment in patients with clinical and radiologic presentation that suggest lacunar infarct, particularly in cases with a history of ischemic stroke, in which a potential cardiac source of embolization may be detected.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

Introduction: Papillary fibroelastoma is the most common primary cardiac valvular tumor. Historically, papillary fibroelastoma was an incidental autopsy finding, deemed to have no clinical significance. More recently, reports of symptomatic cases of papillary fibroelastoma with complications such as myocardial infarction and stroke suggest it should be considered a potentially dangerous lesion. In this report, we describe the clinical and echocardiographic findings of 3 patients with cardiac papillary fibroelastoma who presented with cerebral vascular events., Objective: To describe the clinical and echocardiographic findings of 3 patients with cardiac papillary fibroelastoma (CPF) who presented cerebral vascular events., Methods: Describe the findings of 3 patients and review of the literature., Results: We report 3 cases with cerebral ischemic events associated with the presence of CPF that were confirmed by histopathological examination., Conclusions: Cardiogenic embolism is recognized increasingly as an important cause of stroke, accounting of 20% of ischemic strokes. Cardioembolic stroke is largely preventable. The likelihood of recurrence is relatively high for most cardioembolic sources and therefore secondary stroke prevention is fundamental. TEE allowed to characterize well-established sources of embolism, and it was the best diagnostic approach in our patients. Magnetic resonance imaging was used in 1 of these patients, while it confirmed the presumptive diagnosis of cardiac tumor. The first-choice treatment of symptomatic CPF is surgical excision which must be performed as early as possible to reduce the risk of early recurrences of embolic events. The use of TEE in the evaluation of cerebral vascular events is not routinely performed, this method must be considered in patients for whom the cause of cerebrovascular ischemia is unclear, after noninvasive neurovascular studies.

Introduction: Lumbar spinal stenosis is defined as a narrowing of the neural canal and foramina that result in compression of the lumbosacral nerve roots or cauda equina. Patients with lumbar spinal stenosis may present a variety of signs and symptoms. One such syndrome is neurogenic intermittent claudication, characterized by radicular symptoms exacerbated by walking or standing and relieved by rest. Infrequently, lumbar spinal stenosis produces a cauda equina compression, characterized by intermittent urinary or fecal incontinence, impotence and in rare cases priapism., Case Report: A 50 year-aged male, presented with spontaneous intermittent priapism and few months later weakness, numbness and pain of his legs provoked by bipedestation or physical exertion that completely disappeared by sitting or lying down. A computed tomographic scan showed a lumbar canal narrowing of L4 through L5. A diagnosis of neurogenic intermittent claudication with dysfunction of the cauda equina roots secondary to the presence of lumbar spinal stenosis was carried out. The symptoms completely resolved after descompressive lumbar laminectomy of L4 and L5., Conclusions: Causal interpretation of neurogenic intermittent claudication still remains obscure. An inadequate blood supply provoked by increased intra-raquid pressure among the roots may act as a dynamic factor. This mechanism could cause stagnant anoxia during the exercise resulting in clinical symptoms. Lumbar spinal stenosis should be kept in mind when autonomic features appear.

Old age groups have different risk profile and stroke features compared to younger groups. Our aim was to examine the risk factor profile and stroke subtype in patients older than 80 years with ischemic stroke. Data of 535 patients with ischemic stroke or transient ischemic attack (TIA) were prospectively recorded. Cardiovascular risk factors and stroke subtype in individuals aged 80 years or older were compared with patients under 80. Of 535 patients a total of 179 were over 80 years (33.5%). The mean age was 84.4 +/- 4.4 years (61.8%; 111 women). The most common risk factors included hypertension (82.7%) and hyperlipidemia (40.2%). Lacunar stroke was the most frequent subtype of stroke (41.7%). When the groups were compared, we observed the following risk factors more frequently in the group older than 80: female patients (P = <0.001), hypertension (OR = 1.62), atrial fibrillation (OR = 2.64); whereas diabetes (OR = 0.54), hyperlipidemia (OR = 0.57), smoking (OR = 0.17) and obesity (OR = 0.58) were more frequent in the group younger than 80. In the old group we found a high incidence of ischemic stroke in women. We also found a higher frequency of hypertension and atrial fibrillation. The available and future epidemiological data will provide a better knowledge about the effect of typical risk factors in old people.

Introduction: Multiple sclerosis (MS) is the most common primary demyelinating disease affecting the central nervous system. In recent years the development of new drugs that have been shown to modify the natural history of MS have had a substantial impact on the treatment of the disease., Aims: To harmonise and integrate the evidence available on optimising the treatment of patients with MS., Development: In order to fulfil our main aim, a group of experts from different Latin American countries drew up a list of statements related to the use of immunomodulatory agents in the different clinical forms of the disease and the strategies that should be considered in cases in which the therapeutic response was suboptimal. Each of the participants used a structured scale to express the extent to which he or she agreed or disagreed, and a consensus was considered to have been reached when acceptance of each of the statements was equal to or higher than 80%., Conclusions: These recommendations will provide neurologists with the tools needed to make decisions that optimise the treatment of MS patients.

Young and old age stroke groups have different vascular risk profiles for cerebral ischemic events. The objective of the study was to describe the risk factor profile and stroke subtype in this population of very elderly people. We included patients over 80 years old with diagnosis of ischemic stroke and transient ischemic attack registered between June 2003 and June 2006. We described the demographic data and subtype of ischemic stroke. Of 535 patients with cerebrovascular ischemic events, the final diagnosis was stroke in 366 cases and transient ischemic attack in 169. Of these patients 33.5% were over 80 years old (179). The mean age was 84.4 +/- 4.4 years. The most frequent risk factors were: hypertension 82.7%, dyslipemia 40.2% and atrial fibrillation 24.6%. Stroke subtype was: large artery disease 6%, cardioembolic stroke 19.7%, small artery disease 41.7%, and other causes 0.8%. Among traditional risk factors for stroke in our very elderly patients, the most significant were hypertension and dyslipemia. This agrees with previous epidemiological studies. The high incidence of small artery disease in our patients may be explained by the risk factor profile.

Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.

Observational cohort studies are a powerful tool to assess the long-term outcome in chronic diseases. This study design has been utilized in local and regional outcome studies in multiple sclerosis (MS) and has yielded invaluable epidemiological information. The World Wide Web now provides an excellent opportunity for an international, collaborative cohort study of MS outcomes. A web platform--MSBase--has been designed to collect prospective data on patients with MS. It is purely observational, enabling participating neurologists to contribute data on diagnosis, treatment and progress, to review anonymous aggregate data and to benchmark their patient population against other patient subsets or the entire dataset. MSBase facilitates collaborative research by allowing the online creation of investigator-initiated regional, national and international substudies. The registry aims to answer epidemiological questions that can only be addressed by prospective assessments of large patient cohorts. The registry is funded through the independent MSBase Foundation, and governed by an International Scientific Advisory Board. The MSBase Foundation commenced operations in July 2004 and since then, 22 neurologists from 11 countries have joined MSBase and are contributing 2400 patients to the total data pool.

The recent advances in assisted reproduction have made it possible to study and interfere in almost every step of the human reproductive process except for implantation. The most complex and important step remains in great part unknown. Implantation in human has proven to be less efficient compared with other species. However, in in vitro fertilization (IVF) patients, it has been evaluated to be even poorer. This paper highlights the factors related to infertile patients and IVF treatments that can affect implantation and implantation's clinical aspects related to these treatments: implantation failure and early pregnancy loss.

Current knowledge of stroke risk factors and epidemiology is based mostly on USA or European studies; scarce data have been published from developing countries. Because epidemiological and clinical characteristics in stroke vary according to regional factors, we need to know the peculiarities of stroke on this subcontinent. The purpose is to describe the clinical subtypes and risk factors in patients with ischemic stroke. We analyzed all consecutive ischemic stroke in patients admitted at Hospital Italiano of Buenos Aires, between June 1, 2003 and June 1, 2005. Among 395 ischemic stroke patients, the mean age was 71.36 years (+/- 13.82) and 55% were male. Ischemic stroke subtypes were as follows: 40% patients had lacunar, 20% atherosclerotic stroke, 10% cardioembolic infarction, and 5% other causes of stroke. Hypertension (76%), hyperlipemia (50%) and prior stroke (34%) were the most frequent risk factors. Most patients with cortical symptoms had significant large-artery atherosclerosis (> 70%). Stroke informations in developing countries is difficult to obtain. This could be the reason for the very few stroke registries in South America. Hypertension was the most frequent risk factor in our registry. The pattern of stroke subtypes seems to be different from that reported in other regions of the world, with a higher frequency of small-vessel disease.

Spontaneous intracranial hypotension is an infrequent clinical entity characterized by orthostatic headache, low cerebrospinal fluid pressure, and magnetic resonance imaging findings of diffuse pachymeningeal gadolinium enhancement without previous history of head trauma or lumbar puncture. A 24 year-old healthy woman was referred after having daily headaches for two weeks. She described a headache that occurred soon after assuming an upright position and disappeared after resuming a recumbent position. The cerebrospinal fluid showed pleocytosis primarily lymphocitic, raised protein content and an opening pressure of 20 mm H2O. Magnetic resonance imaging of the head showed diffuse pachymeningeal gadolinium enhancement. Radioisotope cisternography using 99mTc-DTPA confirmed the cerebrospinal fluid leak in the thoracic region. With conservative treatment the patient improved in a few days and the headache disappeared. Radiological findings, together with a compatible clinical condition, help to establish the diagnosis of spontaneous intracranial hypotension and avoid the use of unnecessary clinical investigations.

The primary objective in the management of a chronic disease is to maximise therapeutic effectiveness, according to the general consensus among specialists. Recent market research has confirmed that a treatment's effectiveness is the primary consideration for neurologists' choice of therapy for multiple sclerosis (MS). Of the available disease-modifying therapies, interferon (IFN) beta appears to be consistently more efficacious than glatiramer acetate. High doses of therapy, and frequent administration of IFN beta should be used to provide maximal effects. This has been supported by a recent Class I comparative trial of two commercial preparations of IFN beta-1a. Preliminary results indicated significantly greater efficacy for IFN beta-1a (Rebif, Serono) 44 microg administered subcutaneously three times weekly (t.i.w.), over IFN beta-1 (Avonex, Biogen) 30 microg administered intramuscularly once weekly IFN beta-1a, 44 microg t.i.w., provides maximal efficacy for patients with relapsing forms of MS.

Biotechnological research and a better understanding of the immunopathogenesis of multiple sclerosis (MS) have recently led to major breakthroughs in treatment. Different drugs that modify the disease process such as interferon beta 1a, interferon beta 1b and glatiramer acetate are now available. Decisions about initiation of therapy and choice of agent should be individualised based on the severity and activity of the disease, concomitant illnesses, adverse effects of the drugs, lifestyle issues, and patient preferences. These different drugs were tested in different clinical trials that used different designs, patient populations, endpoints and statistical analysis. Therefore, simple comparisons between them are hazardous. In this article, the pivotal clinical trials of beta interferons and glatiramer acetate in the treatment of MS are reviewed, and recommendations for their appropriate use are provided. Several ongoing and planned clinical trials in various stages of disease will help to define further the role of these agents in the treatment of multiple sclerosis.

We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.