Neuropatía periférica como forma de presentación de poliangeítis microscópica / Peripheral neuropathy as a first sign of microscopic polyangiitis

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Influencia del polimorfismo del gen de la APOE en la respuesta al tratamiento con interferón beta en esclerosis múltiple / Influence of APOE gene polymorphisms on interferon-beta treatment response in multiple sclerosis

Objetivos: Los ensayos clínicos llevados a cabo con el interferón beta (INFB) en esclerosis múltiple remitente recidivante (EMRR) han mostrado que reducen la tasa de brotes. Sin embargo, no todos los pacientes responden a este tratamiento, si bien aún no hay un absoluto consenso a propósito de la definición de respuesta al tratamiento. Las razones para este fracaso terapéutico no son conocidas, y probablemente hay factores genéticos implicados, como se ha mostrado con los polimorfismos de los genes que codifican la interleuquina 10 o el interferón gamma. El papel del gen de la apolipoproteína E (APOE) en la EM ha sido investigado en los últimos años y no parece aumentar el riesgo de aparición de la enfermedad ni influir en su severidad. Variaciones en este gen influyen en la respuesta al tratamiento con inhibidores de la colinesterasa en la enfermedad de Alzheimer o a las estatinas en la hipercolesterolemia. Esto podría tener implicaciones futuras en la EM. Material y métodos: Hemos revisado retrospectivamente 38 pacientes diagnosticados de EMRR (32 mujeres y 6 varones) tratados con INFB durante al menos dos años. Los criterios para llevar a cabo el tratamiento eran uniformes de acuerdo con las indicaciones del Comité asesor para el tratamiento de la EM. Recogimos datos acerca de la edad y tiempo de evolución de la enfermedad. Al cabo de dos años del inicio del tratamiento los pacientes fueron clasificados como respondedores o no-respondedores de acuerdo con los criterios clínicos disponibles, basados en la presencia de brotes, evolución de la discapacidad, o ambos. El genotipo APOE se determinó de muestras sanguíneas utilizando métodos validados de reacción en cadena de la polimerasa. Se estudió la correlación entre la condición de respondedor o no respondedor y la presencia de los alelos E2 o E4. Resultados: Veinte pacientes (52,6%) recibían INFB1b subcutáneo (Betaferón®), 13 (34,2%) INFB1a intramuscular (Avonex®) y 5 (13,2%) INFB1a subcutáneo (Rebif®) (AU)

Objective: Clinical trials with interferon beta in relapsing remitting multiple sclerosis (RRMS) have demonstrated a reduction in the relapse rate. Nevertheless, not all patients respond tothis treatment, although there is no consensus regarding the definition of response to therapy. The reasons for this failure are not known but genetic factors probably influence this, as hasbeen previously shown with Interleukin 10 or Interferon gamma polymorphisms.The role of apolipoprotein E (APOE) gene in MS has been investigated and does not appear to increase risk for MS or influence disease severity. Interestingly APOE variation influencesresponse to cholinesterase inhibitor treatment in Alzheimer disease or to statins in hypercholesterolemia.This might have future implications for MS. Material and methods: We retrospectively reviewed 38 RRMS patients (32 females and 6 males) treated with interferon beta (INFbeta) over at least two years. Criteria for treatment were uniform accordingly to an ‘‘Advisory Committee for the Treatment of Multiple Sclerosis’’. We collected data variables including age, age of onset, clinical type or diseaseduration. Patients were classified, two years after the start of treatment, as responders and nonrespondersbased upon clinical criteria available in the literature, which rely on the presenceof relapses, increase of disability, or both. APOE genotype was determined from blood samples using validated polymerase chain reaction methods. Correlation between patient respondingstatus with allele E2 or E4 was tested.Results: A total of 20 patients (52.6%) received subcutaneous INFbeta1b (Betaferón®), 13 (34.2%) INFbeta1a intramuscular (Avonex®), and 5 (13.2%) subcutaneous INFbeta1a (Rebif®). We found 2 patients (5.2%) heterozygous for the E2 allele and 9 (23.7%) for the E4 allele. Nopatient was homozygous for E2 or E4 (AU)

Serum uric acid levels in multiple sclerosis patients inversely correlate with disability.

Uric acid (UA) is an endogenous antioxidant. Some studies have described that multiple sclerosis (MS) patients have lower serum UA levels than controls, although it has not been established whether UA is primarily deficient, or secondarily reduced due to its scavenging activity. UA has also been proposed as an indicator of disease activity. We, retrospectively, reviewed 478 serum UA levels obtained in 94 MS patients. Ninety samples were collected during a relapse. Correlation between UA levels obtained during a relapse or in a relapse-free period, and comparison between UA and expanded disability status scale (EDSS) score was tested using a two-tailed Student's t test and Spearman correlation coefficients test. UA levels were significantly lower when measured during a relapse (n 90) than in a remission period (n 368) (r -0.16, p 0.003) UA levels measured outside a relapse inversely correlated with EDSS score (r -0.15, p 0.001). Lower uric acid levels in MS patients are associated with clinical relapse. This is the first description of an inverse correlation of serum UA levels with disability as assessed by EDSS score.

Influence of APOE gene polymorphisms on interferon-beta treatment response in multiple sclerosis.

OBJECTIVE: Clinical trials with interferon beta in relapsing remitting multiple sclerosis (RRMS) have demonstrated a reduction in the relapse rate. Nevertheless, not all patients respond to this treatment, although there is no consensus regarding the definition of response to therapy. The reasons for this failure are not known but genetic factors probably influence this, as has been previously shown with Interleukin 10 or Interferon gamma polymorphisms. The role of apolipoprotein E (APOE) gene in MS has been investigated and does not appear to increase risk for MS or influence disease severity. Interestingly APOE variation influences response to cholinesterase inhibitor treatment in Alzheimer disease or to statins in hypercholesterolemia. This might have future implications for MS. MATERIAL AND METHODS: We retrospectively reviewed 38 RRMS patients (32 females and 6 males) treated with interferon beta (INFbeta) over at least two years. Criteria for treatment were uniform accordingly to an "Advisory Committee for the Treatment of Multiple Sclerosis". We collected data variables including age, age of onset, clinical type or disease duration. Patients were classified, two years after the start of treatment, as responders and non-responders based upon clinical criteria available in the literature, which rely on the presence of relapses, increase of disability, or both. APOE genotype was determined from blood samples using validated polymerase chain reaction methods. Correlation between patient responding status with allele E2 or E4 was tested. RESULTS: A total of 20 patients (52.6%) received subcutaneous INFbeta1b (Betaferón(®)), 13 (34.2%) INFbeta1a intramuscular (Avonex(®)), and 5 (13.2%) subcutaneous INFbeta1a (Rebif(®)). We found 2 patients (5.2%) heterozygous for the E2 allele and 9 (23.7%) for the E4 allele. No patient was homozygous for E2 or E4. Comparison of patients with and without E2 or E4 allele showed no significant differences in any of the ten therapy response variables assessed. CONCLUSION: Findings of a recent meta-analysis have not supported a role for APOE in MS susceptibility or severity. We have not found, in our data, any influence of this gene in the RRMS response to INFbeta. However, larger series would be required to validate these results.

Patrones estacionales de nacimiento en esclerosis múltiple / Seasonal birth patterns in multiple sclerosis

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Hematomas cerebrales espontáneos múltiples. Descripción de una serie y revisión de la bibliografía / Multiple spontaneous cerebral haemorrahges. Descriptión of a series and review of the literature

Resumen. Introducción. La aparición simultánea de hemorragias cerebrales en diferentes territorios arteriales ocurre en el 2-3% de los accidentes cerebrovasculares. Diversos factores de riesgo se han asociado con la presentación de múltiples hemorragias cerebrales, pero ninguno ha sido confirmado. Presentamos los síntomas clínicos, las manifestaciones radiológicas y la evolución clínica de siete casos admitidos en nuestro centro durante los últimos nueve años, así como los distintos factores etiológicos. Pacientes y métodos. Se revisaron retrospectivamente los pacientes con un episodio de accidente cerebrovascular agudo ingresados en nuestro servicio durante el período comprendido entre enero de 1998 y febrero de 2007. Se excluyó a los pacientes con historia de traumatismo cerebral o infartos hemorrágicos. Se analizaron la edad, los factores de riesgo, la presentación clínica, el número y localización de los hematomas y su evolución. Resultados. Presentamos 7 casos (5 hombres y 2 mujeres). La edad media fue de 78 años. Las manifestaciones clínicas más frecuentes fueron la disminución del nivel de conciencia y la pérdida de fuerza. El total de hematomas fue de 20, de los cuales 19 (95%) eran supratentoriales, y 15 (75%), lobares. En un paciente la hemorragia se extendió al sistema ventricular. Tres pacientes (43%) tuvieron historia de hipertensión, un caso se asoció con la toma de anticoagulación oral (14%) y otro con discrasias sanguíneas (14%). Tres pacientes fallecieron (43%). Conclusión. Nuestra serie de pacientes con múltiples hemorragias cerebrales, respecto a los síntomas, los hallazgos radiológicos y la evolución es similar a otras previamente descritas, pero nuestros pacientes son mayores. La avanzada edad y la localización de los hematomas sugieren que la angiopatía amiloidea puede ser un importante factor de riesgo para presentar hemorragias cerebrales múltiples (AU)

Summary. Introduction. The simultaneous occurrence of intracerebral haemorraghes in different arterial territories is an clinical event that develops in 2% to 3% of hemorrhagic strokes. Multiple risk factors have been associated with multiple intracerebral haemorraghes, but none of them are clearly defined. We reported clinical features, radiological findings, and outcome of 7 patients admitted to our department during last nine years and the diverse etiologic factors are discussed. Patients and methods.We retrospectively reviewed all patients with acute stroke admitted to our department during the period January 1998-February 2007. Patients with a history of traumatic brain injury or suspected hemorrhagic infarctions were excluded. We collected data concerning age, risk factors, clinical features, number and location of haematomas and outcome. Results. We studied 7 patients (5 males and 2 females) Mean age was 78. The most common clinical manifestations were decreased alertness and weakness. Total number of haematomas was 20, 19 (95%) supratentorial and 15 (75%) in lobar area. One patient haemorrhage extended into the ventricular system. Three patients (43%) had hipertensive history, and in only one case was associated with oral anticoagulant (14%) and one blood dyscrasia (14%). Three patients died (43%). Conclusion. In our series of patients with multiple intracerebral haemorraghes, clinical and radiological findings and outcome were comparable to others previously described, but our patients were older. The advanced age and lobar localization suggest amyloid angiopathy is an important risk factor to multiple intracerebral haemorraghes (AU)

[Multiple spontaneous cerebral haemorrhages. Description of a series and review of the literature]. / Hematomas cerebrales espontáneos múltiples. Descripción de una serie y revisión de la bibliografía.

INTRODUCTION: The simultaneous occurrence of intracerebral haemorraghes in different arterial territories is an clinical event that develops in 2% to 3% of hemorrhagic strokes. Multiple risk factors have been associated with multiple intracerebral haemorraghes, but none of them are clearly defined. We reported clinical features, radiological findings, and outcome of 7 patients admitted to our department during last nine years and the diverse etiologic factors are discussed. PATIENTS AND METHODS: We retrospectively reviewed all patients with acute stroke admitted to our department during the period January 1998-February 2007. Patients with a history of traumatic brain injury or suspected hemorrhagic infarctions were excluded. We collected data concerning age, risk factors, clinical features, number and location of haematomas and outcome. RESULTS: We studied 7 patients (5 males and 2 females) Mean age was 78. The most common clinical manifestations were decreased alertness and weakness. Total number of haematomas was 20, 19 (95%) supratentorial and 15 (75%) in lobar area. One patient haemorrhage extended into the ventricular system. Three patients (43%) had hipertensive history, and in only one case was associated with oral anticoagulant (14%) and one blood dyscrasia (14%). Three patients died (43%). CONCLUSION: In our series of patients with multiple intracerebral haemorraghes, clinical and radiological findings and outcome were comparable to others previously described, but our patients were older. The advanced age and lobar localization suggest amyloid angiopathy is an important risk factor to multiple intracerebral haemorraghes.

Representación de la cefalea numular en una consulta general de neurología / No disponible

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Afectación trigeminal en el SUNCT / Trigeminal involvement in SUNCT syndrome

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Variation of serum uric acid levels in multiple sclerosis during relapses and immunomodulatory treatment.

Uric acid (UA), a product of purine metabolism, may be an antioxidant, perhaps acting as a scavenger of peroxynitrite. Patients with gout have a reduced incidence of multiple sclerosis (MS). A number of studies found that patients with MS have low serum levels of UA, although it has not been established whether this represents a primary deficit or a secondary effect. UA has also been proposed as a marker of disease activity and response to immunosuppressive or immunomodulatory treatment. We retrospectively reviewed 83 relapsing-remitting or secondary progressive MS patients (64 females and 19 males) followed in our Neurology Unit. We collected data concerning demographic variables as age and sex, and clinical variables as age of onset, clinical type, disease duration, EDSS score and total number of relapses. We considered UA levels in three different situations: during a relapse, during remission period and during remission period under immunomodulatory treatment [Interferon Beta 1a i.m. (Avonex; Biogen Idec Inc., Cambridge, MA, USA), Interferon Beta 1a s.c. (Rebif; Serono Europe Limited, London, UK), Interferon Beta 1b (Betaferon; Bayer Schering Pharma AG, Berlin, Germany) or Glatiramer Acetate (Copaxone; TEVA Neuroscience LLC, Kansas City, MO, USA)]. A Wilcoxon matched pairs test was carried out to determine differences between groups. A P-value less than 0.05 was considered statistically significant. In 33 patients, we were able to compare at least one UA value obtained during a relapse with at least one when remission without treatment. Mean serum UA levels were significantly lower when measured during a relapse (r: 0.39, P: 0.024). In 27 cases, we compared at least one remission value without treatment with at least one obtained during remission and immunomodulatory treatment. Mean serum UA levels significantly increased when determined during Interferon Beta or Glatiramer Acetate therapy (r: 0.84, P < 0.001). Although we do not know exactly whether and how UA is involved in MS pathogenesis, our data suggest that UA might reflect disease activity or treatment response in MS.

Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score.

OBJECTIVES: During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual variation in the clinical course of MS, there is no consensus method for measuring progression using single assessments of disability. Recently, Multiple Sclerosis Severity Score (MSSS) method has been proposed for comparing disease progression using single data. We evaluate in our population if there is any correlation between APOE genotype and severity according to MSSS. METHODS: We studied 82 patients followed up in our Neurology Unit throughout the year 2005, diagnosed with MS, and with disease duration of at least 2 years. We collected data concerning demographic and clinical variables including age of onset, disease duration, Expanded Disability Status Scale (EDSS) score and the total number of relapses. When reached, we determined the latency to EDSS scores of 4.0 and 6.0. We calculated progression index (PI) and relapse rate (RR). We ascertained MSSS for our patients in the global MSSS table. RESULTS: We found four patients heterozygous for the E2 allele and 16 for the E4 allele. No patient was homozygous for E2 or E4. RR (P = 0.017 with 95% CI: 0.005-0.57) and PI (P = 0.016 with 95% CI: 0.004-0.38) were significantly lower in E4 carriers. MSSS scores were not associated with carriership of E2 or E4. CONCLUSION: Our results show no effect of the APOE genotype on the severity of MS measured by MSSS, as a recently published meta-analysis has noticed. So, our data do not support a role for APOE in MS severity, in spite of the seeming influence shown using other measures such as PI. MSSS is probably the best method to measure severity with a single measure of disability and should be used more frequently when performing genetic research.

Mielinolisis central pontina tras síndrome neuroléptico maligno / Central pontine myelinolysis after malignant neuroleptic syndrome

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[Cavernous sinus syndrome: an initial expression of a breast carcinoma]. / Síndrome del seno cavernoso como manifestación inicial de una neoplasia mamaria.

Cavernous sinus syndrome (CSS) may be caused by a wide range of pathological process among we include metastatic disease. A case of a woman whose breast neoplasm was initially expressed by a CSS is discussed in this article. We describe a 64-year-old woman with several weeks progressive course of pain and numbness in her left-side facies and occasional diplopia. Neurological examination showed left ptosis, limitation of elevation of left eye and abducens nerve palsy as well as hypoesthesia in the frontal and maxillary regions of her left-side facies. Brain magnetic resonance imaging (MRI) scan revealed the presence of a mass in the orbit and left cavernous sinus. General examination disclosed a sclerotic and retractile lesion in her left breast which involved the nipple suggesting breast carcinoma metastases. The patient underwent a breast fine-needle aspiration biopsy which established the presence of an infiltrating breast carcinoma. This case shows the importance role of the general physical examination to determine the etiology of the CSS. It is necessary and fundamental to perform it on each patient not only to orientate further investigations but also to avoid more invasive diagnostic procedures.

Síndrome del seno cavernoso como manifestación inicial de una neoplasia mamaria / Cavernous sinus syndrome: an initial expression of a breast carcinoma

El síndrome del seno cavernoso (SSC) puede ser causado por una gran variedad de procesos patológicos, entre los que se incluye la enfermedad metastásica. Discutimos aquí el caso de una mujer cuya neoplasia mamaria se inició con un SSC. Se trata de una mujer de 64 años que consultó por cuadro progresivo de dolor y parestesias en región facial izquierda y diplopía ocasional de varias semanas de evolución. En la exploración neurológica se objetivó ptosis palpebral izquierda, incapacidad para elevar y abducir el ojo izquierdo, así como hipoestesia tactoalgésica en el territorio frontal y maxilar superior de la hemicara izquierda. La tomografía computarizada y la resonancia magnética cerebrales detectaron la presencia de una masa localizada en la órbita y seno cavernoso izquierdos. La exploración general puso de manifiesto una lesión esclerosa, retráctil, en mama izquierda que englobaba el pezón, sugiriendo metástasis de una posible neoplasia mamaria. El estudio anatomopatológico de la muestra obtenida por punción aspiración con aguja fina reveló un carcinoma infiltrante de mama. Este caso ilustra la relevancia de la exploración física completa en el establecimiento de la etiología del SSC. Su realización de forma sistemática es necesaria y fundamental para, por una parte, orientar los posibles exámenes complementarios y, por otra, evitar procedimientos diagnósticos más invasivos

Cavernous sinus syndrome (CSS) may be caused by a wide range of pathological process among we include metastatic disease. A case of a woman whose breast neoplasm was initially expressed by a CSS is discussed in this article. We describe a 64-year-old woman with several weeks progressive course of pain and numbness in her left-side facies and occasional diplopia. Neurological examination showed left ptosis, limitation of elevation of left eye and abducens nerve palsy as well as hypoesthesia in the frontal and maxillary regions of her left-side facies. Brain magnetic resonance imaging (MRI) scan revealed the presence of a mass in the orbit and left cavernous sinus. General examination disclosed a sclerotic and retractile lesion in her left breast which involved the nipple suggesting breast carcinoma metastases. The patient underwent a breast fineneedle aspiration biopsy which established the presence of an infiltrating breast carcinoma. This case shows the importance role of the general physical examination to determine the etiology of the CSS. It is necessary and fundamental to perform it on each patient not only to orientate further investigations but also to avoid more invasive diagnostic procedures