Manifestaciones clínicas atípicas como forma de presentación de la esclerosis múltiple / Atypical clinical manifestations as a form of presentation in multiple sclerosis

Resumen Las manifestaciones clínicas atípicas al inicio de la esclerosis múltiple (EM) son poco frecuentes y sugieren la posibilidad de un diagnóstico alternativo. El objetivo fue describir las características clínicas en la EM con síntomas atípicos al inicio, y estimar la sensibilidad, especificidad y valor predictivo posi tivo (VPP) para el diagnóstico de EM. Se trata de un análisis retrospectivo de historias clínicas. Se registraron los siguientes datos: pacientes con diagnóstico de EM acorde a los criterios diagnósticos correspondientes, tipo de síntoma de inicio, tiempo hasta la segunda recaída, presencia de bandas oligoclonales en el líquido cefalorraquídeo (LCR) y de banderas rojas radiológicas en la Resonancia Magnética de encéfalo (RMN). Se realizó un análisis descriptivo e inferencial utilizando la prueba de chi cuadrado y se calcularon la sensibilidad, la especificidad y el VPP. Seiscientos dos pacientes tuvieron un diagnóstico final de EM, de los cuales 22 (3.7%) tuvieron una presentación clínica atípica. El 54.5% eran mujeres. La edad promedio fue de 29 años (DE ± 11.7). El síntoma atípico más frecuente fue parálisis facial periférica aislada (6/22). El VPP para el inicio atípico fue de 6.1%; p < 0001. La sensibilidad y especificidad de estos síntomas al diagnóstico de EM fueron del 3.7% y 19%, respectivamente. En nuestra cohorte, demostramos que la presencia de síntomas atípicos como presentación de la EM es poco frecuente. Es mandatorio la exclusión de otras enfermedades, teniendo en cuenta su baja sensibilidad, especificidad y VPP.

Abstract The atypical clinical features in multiple sclerosis (MS) have been rarely reported and suggest the possibility of an alternative diagnosis. The aim was to describe the clinical and demographic characteristics of MS patients who debuted with atypical symptoms and to estimate the sensitivity, specificity and positive predictive value (PPV) for MS diagnosis. A retrospective analysis of clinical records was performed. The following data were recorded: patients with MS diagnosis according to current diagnostic criteria at the time of diagnosis, type of symptom at the onset, time to second relapse, presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and radiological red flags on MRI. A descriptive and inferential analysis was performed using the chi square test, and sensitivity, specificity and PPV were calculated. Six hundred two patients were diagnosed with MS, of which 22 (3.65%) had an atypical clinical presentation. 54.5% were women. The mean age was 29 years (SD ± 11.7). The most common atypical symptom was peripheral facial palsy (27%). The PPV for atypical onset was 6.14%; p < 0.001. Sensitivity and specificity of these symptoms to MS diagnosis were 3.65% and 19%, respectively. In our research, the presence of atypical symptoms at the onset of MS was very low. Other diseases must be excluded, taking into account their low sensitivity, specificity and PPV.

Work status and cognitive performance in patients with relapsing remitting multiple sclerosis

La discapacidad física y el curso de la enfermedad son fuertes predictores del estatus laboral en los pacientes con Esclerosis Múltiple (EM). Sin embargo, la cognición no tiene el mismo grado de evidencia. Este estudio plantea el objetivo de investigar la relación entre la situación laboral y el rendimiento cognitivo en la EM. Se recogieron los datos de 61 pacientes con EM de curso recurrente-remitente (EMRR) que fueron a atenderse en un hospital público entre abril de 2014 y abril de 2015. El 29.5% estaban desempleados, el 54.1% estaban empleados y el 10.4% eran estudiantes o amas de casa. Se implementaron como test neuropsicológicos la Batería Neuropsicológica Breve para Esclerosis Múltiple y el test Símbolo-Dígito. Además se administraron la Escala de Estatus de Discapacidad Expandida y el Inventario de Depresión de Beck II. La evaluación se realizó de forma individual en dos sesiones, una con el neurólogo y otra con el neuropsicólogo en un consultorio privado. Las diferencias no fueron significativas en edad y años de instrucción entre los pacientes con y sin empleo. En cambio, los pacientes desempleados tenían un puntaje más bajo en el Símbolo-Dígito, así como la Escala de Estatus de Discapacidad Expandida y un Inventario de Depresión de Beck más altos que aquellos con trabajos. Los pacientes con EMRR que estaban desempleados tenían un peor desempeño en la velocidad de procesamiento de la información, más depresión y discapacidad física que aquellos que conservan sus trabajos.

Employment is a very important aspect of a person's life, and that is why any health-related factor that can interfere in such activity must be identified. The reality of a Latin American country is different and should be approached as a separate object of study. Many factors that contribute to a patient losing the job can be identified in time in order to be reversed or compensated. Thus, identifying the vulnerability profile of the patients with multiple sclerosis (MS) who are at risk of losing their jobs is an important task for researchers. Physical disability and disease course are both strong predictors of work status in MS patients, however, cognition and affective variables do not have the same degree of evidence. This study raises the aim of investigating the relationship between employment status and cognitive performance in MS. With this knowledge, it would be possible to design a neuropsychological rehabilitation plan for patients, which focuses on compensating and recovering from cognitive impairment, as well as on serving as orientation for the person who is at risk of losing their job. A group difference design was used. The sample units were selected through a non-probability accidental sampling. We collected the data of 61 patients with relapsing-remitting MS (RRMS) who had attended consultation between April 2014 and April 2015, in a public hospital. 29.5% were unemployed; 54.1% were employed; and 10.4% were students or housewives. The Brief Repeatable Battery of Neuropsychology Tests adapted for Argentine population; Symbol Digit Modalities Test (SDMT), Expanded Disability Status Scale (EDSS) and Beck Depression Inventory-II (BDI-II), were administered individually in two sessions, one with a neurologist and one with the neuropsychologist in a private consulting room. Age and years of instruction differences between patients with and without employment were not significant. There were 60.8% of patients with cognitive impairment. Among them, 38.7% were unemployed. The relationship between cognitive deterioration and work status was not significant, X² = .404, df = 1, p = .371. When comparing the groups in the cognitive battery, a meaningful difference in cognitive performance was observed between the subjects who had a job with those who were unemployed in SDMT (t = -2.421, df = 49, p = .019); performance being higher among the former. No other cognitive score showed significant results. Unemployed patients had higher EDSS and depression, than those with jobs. The cognitive tests administered, together with the BDI-II and EDSS, were included in the binary logistic regression analysis. The second model retained the SDMT and the BDI-II; both tests were ableto correctly classify almost 80% of the cases. Also, both SDMT (ß = .080, p = .014) and BDI-II (ß = -.098, p = .022) shown significant effects on work status. This study is one of the first attempts in Argentina to analyze the possible determinants of unemployment, which is extremely important in the context of a lack of determining literature about the issue in Latin America. According to results, patients with RRMS who are unemployed have worse performance in speed of information processing, more depression and physical disability than those who retain their jobs. Results are in line with previous studies, although in the present research a cognitive variable showed a greater negative influence on employment status over motor difficulties or physical disability. Clinicians would be able to identify patients whose profile shows a higher tendency towards work life decline, so that they can receive early treatment and delay that progression. It is suggested the realization of a multicentric Latin American study, blind to the patients labor status, with the aim of broadening the results by improving the study methodology.

Everything you always wanted to know about sex and Neurology: neurological disability and sexuality / Todo lo que siempre quiso saber sobre sexo y Neurologia pero nunca se atrevió a preguntar: estudio sobre discapacidad neurologica y sexualidad

ABSTRACT Chronic neurological disorders generate disabilities affecting multiple aspects of life, including sexuality. Objective To describe the presence of sexual dysfunction and comorbidities in a population with chronic neurological disorders. To analyze the relationship between disability and sexual dysfunction. Methods A cross-sectional case-control study was carried out. Patients with amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's disease (PD), and stroke of at least one year since the onset of symptoms were included, and compared with controls with no neurological disease, matched by age and sex. Results We included 71 participants: 29 controls, with a mean age of 49.4 years, and 42 patients with a mean age of 53.8 years. Sexual dysfunction was present in 22.5% of the controls and 77.5% of the patients. A statistically significant relationship between sexual dysfunction and disability was found in the logistic regression analysis (OR = 20.38, 95%CI: 2.5 -165.86). Conclusions Disability proved to be the main variable related to the presence of sexual dysfunction. Patients with ALS had the worst rates of sexual dysfunction. Patients with MS were similar to the control group. As for the PD group, no patient had normal sexuality. Finally, in stroke patients, the presence of comorbidities and their treatment may have negatively influenced sexuality. These findings showed that patients with chronic neurological diseases have sexual dysfunction and underscore the need for neurologists to know and address this problem.

RESUMO Las enfermedades neurológicas crónicas generan discapacidad afectando múltiples aspectos de la vida, incluida la sexual. Objetivo Describir en una población con enfermedades neurológicas crónicas la presencia de disfunción sexual y posibles comorbilidades acompañantes. Analizar la relación entre discapacidad y disfunción sexual. Métodos Se realizó un estudio transversal de tipo casos y controles. Se incluyeron pacientes con Esclerosis Lateral Amiotrófica (ELA), Esclerosis Múltiple (EM), enfermedad de Parkinson (EP) y secuelados por enfermedad cerebrovascular (sACV) de al menos un año de evolución, controlando con sujetos sin enfermedad neurológica pareados por edad y sexo. Resultados Se incluyeron 71 sujetos: 29 controles, con una edad media 49,4 años y 42 casos con una edad media de 53,8 años. Presentaron disfunción sexual el 22,5% de los controles y el 77,5% de los casos. En el análisis por regresión logística se encontró una relación estadísticamente significativamente entre disfunción sexual y discapacidad. (OR = 20.38, IC95%: 2.5-165.86). Conclusiones La discapacidad demostró ser la principal variable relacionada con la presencia de disfunción sexual. Los enfermos con ELA fueron los que peores índices de disfunción sexual presentaron. Los pacientes con EM se comportaron de forma similar al grupo control. En cuanto al grupo de EP todos los pacientes tuvieron algún trastorno en su sexualidad. Por último, en sACV la presencia de comorbilidades y su tratamiento podrían influir negativamente en la sexualidad. Estos hallazgos evidencian que la disfunción sexual está presente en los pacientes con enfermedades neurológicas crónicas y confirma la necesidad de conocer este problema por parte de los neurólogos.

Prospective memory in patients with relapsing remitting Multiple Sclerosis

La Memoria Prospectiva (MP) es un conjunto de habilidades cognitivas que permite recordar y realizar acciones planeadas o intenciones demoradas. El objetivo de este estudio fue investigar la MP en pacientes con Esclerosis Múltiple Recaídas y Remisiones (EMRR) con dos pruebas experimentales que evalúan distintos aspectos de la MP. Se evaluaron 36 pacientes con EMRR y un grupo control de 35 voluntarios sanos (GC), apareados por edad y escolaridad. Se administró una batería de tests neuropsicológicos que incluye dos técnicas que evalúan la MP: El Cóndor y el Test de Memoria Prospectiva de Tareas Múltiples (MTPM). Los pacientes obtuvieron un puntaje más bajo que el GC (en puntaje total de El Cóndor, p = .007, d = 0.7). En el MTPM, el GC obtuvo significativamente más puntos en la Fase de Formación de la intención (p = .027, d = .5). El 63% de los pacientes versus el 88.5% del GC, autoiniciaron la intención (p = .014). Los pacientes que obtuvieron mejor puntaje en Formación, autoiniciaron más la acción proyectada (p = .012). La educación, la duración de la enfermedad y la depresión correlacionaron leve y significativamente con el Cóndor y el MTPM. La discapacidad física se relacionó sólo con la capacidad de autoiniciar del MTPM. Se concluye que la MP parece estar afectada negativamente en pacientes con EMRR. Se encontró un deterioro de la planificación y la autoiniciación de la intención. La autoniciación fue influenciada por la calidad de la planificación. Los resultados destacan la necesidad de evaluar objetivamente la MP en pacientes con EMRR para poder detectar cualquier alteración en las etapas iniciales de la enfermedad y comenzar una rehabilitación apropiada.

Prospective Memory (PM) is a set of cognitive abilities that allow us to remember to perform planned actions or delayed intentions. It requires the recall of the content of the planned task in the form of an intention to be able to execute it at the appropriate moment. Previous studies have yielded conflicting results as some show that MS patients have difficulty in remembering the content of intentions and others in the process of self-initiation of delayed intentions. Moreover, the relationship between PM and clinical variables also remains unclear. The aim of this study was to investigate PM in Relapsing-Remitting Multiple Sclerosis (RRMS) with two experimental tests that evaluate different aspects of the MP. Another aim of the current study was to analyse the relationship between PM and demographic variables and clinical variables. 36 outpatients with a diagnosis of RRMS attending to two centers specialized in multiple sclerosis clinics, were recruited. Thirty five healthy volunteers formed the contrast group (CG), matched for age, gender and education with the MS patients. A neuropsychological test battery that included two techniques for measuring PM was administered. The Condor Test consists of reading a text whilst simultaneously executing many actions. In the Multitask Prospective Memory (MTPM), the participant must remember to initiate a complex intention, which was previously planned. The test yields formation scores of the intention, initiation, plan retention capacity and finally two execution scores. A depression scale (Beck Depression Inventory, BDI-II) was administered and physical disability was revealed using the Expanded Disability Status Scale. In the RRMS group, the majority of patients (80.6%) had none or minimal signs of depression according to BDI-II classification criteria. Seventy five % of patients were in full- or half-time employment, 13.9% were unemployed or in occasional employment and 11.1% were house wives or retired on grounds of age. With respect to cognitive performance 47.2% of MS patients presented cognitive impairment. RRMS patients and the CG did not differ significantly on age and years of formal education. Groups showed no significant differences in distribution of Gender. Patients scored significantly lower than the CG on the Condor's total score, p = .007, d = .7. On the MTPM, the CG obtained significantly more points for intention formation than patients, p = .027, d = .5. Sixty-three percent of patients versus 88.5% of the CG self-initiated the intention, p = .014. Patients who obtained a higher score on Formation, self-initiated more often, p = .012. Education, disease progression and depression measure with the Beck Depression Inventory, significantly and mildly correlated with the Condor and the MTPM. Physical disability was only associated with the intention planning phase of MTPM. PM appears to be impaired in patients with RRMS. A deficit was found in planning and self-initiation of planned actions. Self-initiation was influenced by planning quality. Education, disease progression and depression were shown to influence recall and execution of future intentions. Physical disability was only associated with the intention planning phase. Some previous studies have not found a significant relationship between physical disability and cognitive measures. This study suggests that PM can be affected in patients with a low level of physical impairment. Results highlight the need for objective assessment of PM in RRMS patients to be able to detect any disorder in the initial stages of the disease and start appropriate rehabilitation. Amongst the limitations of this study, the observational, non-blind design must be acknowledged, as well as the small sample size. Also, the instruments used to assess PM are relatively new and studies of their psychometric properties are lacking. Nevertheless, the use of an instrument like The Condor is notable, given that it was developed for local population.

El test El Cóndor como medida de memoria prospectiva en esclerosis múltiple recaídas y remisiones / The Condor as a measure of prospective memory in relapsing-remitting multiple sclerosis

Introducción: Los déficits cognitivos muestran una prevalencia del 43 en Esclerosis Múltiple (EM) en nuestro país. Influyen de manera discapacitante sobre la calidad de vida, en particular en las actividades sociales y laborales. Un nuevo paradigma de estudio es la Memoria Prospectiva (MP), definida como la habilidad para recordar intenciones demoradas. Objetivo: Analizar el rendimiento de MP en pacientes con EM y su relación con otras variables cognitivas y con la discapacidad física. Metodología: Fueron evaluados 15 pacientes con EM Recaídas y Remisiones y 15 voluntarios sanos con una batería de test neuropsicológicos compuesta por El Cóndor como medida de MP y otros test de memoria, atención y funciones ejecutivas. Los pacientes fueron evaluados además con dos medidas de discapacidad. Resultados: Se hallaron diferencias significativas en el puntaje total de El Cóndor a favor del grupo control. Se hallaron correlaciones significativas entre la MP y planificación, velocidad de procesamiento y memoria de trabajo. No se encontraron correlaciones entre MP y discapacidad. Conclusiones: Los pacientes con EM poseen bajo rendimiento en MP. La MP se asocia con medidas de memoria de trabajo, fluencia verbal y velocidad de procesamiento pero no con discapacidad.

Is tumor necrosis factor - 376a promoter polymorphism associated with susceptibility to multiple sclerosis? / ¿El polimorfismo-376A del promotor del gen del factor de necrosis tumoral se asocia con una mayor susceptibilidad a padecer esclerosis múltiple?

A single nucleotide polymorphism (SNP) at position -376 of the tumor necrosis factor α gene (TNFA) has been associated with susceptibility to multiple sclerosis (MS) in Spain. However, no association was found in populations from the USA and The Netherlands. Here we investigate the association between the TNFA - 376A SNP and MS susceptibility in Argentinean patients with MS. The A/G genotype was found in 4.4% of patients (n=90) and in 4.8% of healthy individuals (n=84; p=0.92; odds ratio=0.93; confidence interval: 0.23- 3.84). Thus, no significant differences in genotype and allele frequencies were found between healthy individuals and patients with MS in Argentina.

Un polimorfismo de nucleótido único (SNP, por sus iniciales en inglés) en la posición -376 del gen codificante del factor de necrosis tumoral α (TNFA) ha sido asociado en España con un mayor riesgo a padecer esclerosis múltiple (EM). Sin embargo, esta asociación no fue encontrada en estudios hechos en poblaciones provenientes de los EE.UU. y Holanda. Aquí investigamos la asociación entre el SNP TNFA -376A y el desarrollo de EM en una población de pacientes argentinos con EM. El genotipo A/G fue encontrado en 4.4% de los pacientes (n=90) y en 4.8% de los controles sanos (n=84; p=0.92; odds ratio=0.93; intervalo de confianza: 0.23-3.84). En consecuencia, no encontramos diferencias en las frecuencias alélicas y genotípicas entre los sujetos enfermos y los controles sanos en Argentina.

Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case report

La polineuropatía crónica inflamatoria desmielinizante (PCID) es una neuropatía inmuno-mediada, que presenta un curso clínico primariamente progresivo o en forma de recaídas. Las manifestaciones sensoriales pueden ser su unica forma de expresión clínica. El tratamiento con interferon beta 1a (IFN beta 1a) ha sido ensayado en varias oportunidades, con diferentes respuestas terapéuticas, en pacientes refractarios a las terapias inmunomoduladoras convencionales. Nosotros comunicamos un paciente con una forma ataxica recurrente de PCID, que no respondió al tratamiento con inmunoglobulina endovenosa. Posteriormente fue tratado con IFN beta 1 a por tres años. Durante el período de seguimiento no mostró nuevas recaídas y su cuadro neurológico se estabilizó.

Further studies on HTLV-I associated myelopathy in Argentina

We report 10 HTLV-I virus seropositive subjects, eight of them with HTLV-I associated myelopathy (HAM), two of them also infected with HIV as well as two asymptomatic HTLV-I+ relatives of two unrelated patients. HTLV-I is endemic in several tropical areas, where it causes different neurological diseases. Only few patients have been reported in our country since 1994. We studied 8 patients, who fulfilled the clinical criteria for chronic spastic paraplegia, and 2 other non-symptomatic HTLV-I seropositive relatives, with electromyography (EMG), motor and sensory conduction velocities (NCV), somatosensory, visual and brainstem auditory evoked potentials (SSEP, VEP and BAEP), Magnetic Resonance Images (MRI) and cerobrospinal fluid (CSF) analysis. The latter was carried out only in seven symptomatic patients. In every case positive ELISA tests for HTLV-I/II were confirmed by Western Blot. The two asymptomatic persons were clinically and electromyographically assessed, one of them was also submitted to SSEPs studies. Three patients were males. Patient's ages ranged from 5 to 65 years old. All symptomatic patients showed muscular weakness, spasticity with pyramidal signs and sphincter disturbances. Five of them had paresthesias and 2 had burning pain on their feet. The EMGS and the NCVs were normal in 7 patients and in the 2 asymptomatic ones. SSEPs, obtained by stimulating the posterior tibial nerves, were impaired in 7 patients and in the asymptomatic person who received the procedure. The 7 symptomatic patients who underwnt lumbar puncture had positive tests for HTLV-I in CSF, 3 out of these 7 patients had also high protein levels and 4 had increased number of lymphocytes. In 2 patients intrathecal IgG production could also be demonstrated. MRI were normal in 7 patients and in the 2 asymptomatics, the exception being a female who had bilateral hypertense lesions in cerebral white matter in T2. In conclusion, tropical spastic paraparesis is apparently a rare disorder in Argentina. However, some cases have been reported recently. Most probably, its prevalence is currently underestimated. Its diagnosis should be considered in every patient with progressive spastic paraplegia.