Hot cross bun sign in JC-Virus Granule cell neuronopathy in HIV infected patient - a case report.

BACKGROUND: John Cunningham virus related granule cell neuronopathy (JCV-GCN) is a rare manifestation of the reactivation of infection of the cerebellar granule cells by the JCV, mostly in immunocompromised individuals. The "hot cross bun" (HCB) sign is a cruciform hyperintensity seen in the midpons on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences on magnetic resonance imaging (MRI) of the brain. An index sub-Saharan Africa report of a case of JCV-GCN with HCB sign follows. CASE PRESENTATION: A 27-year-old HIV positive female with JCV-GCN was re-evaluated for chronic ataxia complicated by subacute progressive horizontal diplopia. Cerebrospinal fluid (CSF) had trace Mycobacterium tuberculosis (MTB) detected by GeneXpert Mycobacterium Tuberculosis/Rifampicin resistance (MTB/RIF) assay test. Brain MRI revealed diffuse severe cerebellar atrophy with a hot cross bun sign and patchy enhancement contiguous to the cerebellar dentate nuclei bilaterally. She continued Highly Active Antiretroviral Therapy (HAART) pending CSF HIV viral load counts and started standard brain TB local treatment regimen protocols with progressive improvement in limb ataxia. CONCLUSIONS: In conclusion, finding of the HCB sign may be indicative of and aid diagnosis of JCV-GCN in the right clinical context. This could be an important neuroimaging marker in this context, that may radiologically be more evident in later stages of the condition.

Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient.

This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab's potential for severe infectious complications, despite its promise in treating RRMM.

Inflammatory progressive multifocal leukoencephalopathy with human T-cell lymphotropic virus-1 coinfection.

A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild dysarthria and ataxia. Brain MRI revealed asymmetric T2-hyperintense lesions in the cerebral white matter, cerebellum and brainstem. A small amount of JC virus (JCV) genome in cerebrospinal fluid was detected by PCR and cerebellar biopsy demonstrated JCV-DNA presence. Pathological findings showed demyelinating lesions and glial cells with mildly enlarged nuclei, accompanied by T-lymphocytes, neutrophils and plasma cell infiltration. The CD4+/CD8+ratio was 0.83. High-dose corticosteroid therapy was effective for inflammatory PML lesions, and the administration of mefloquine combined with mirtazapine led to favourable outcome. The encephalitis in this case is considered to have occurred secondarily to JCV infection in the presence of HTLV-1 infection. Therefore, it is crucial to investigate the presence of HTLV-1 in order to understand the aetiology of this brain inflammation.

High-throughput drug screen identifies calcium and calmodulin inhibitors that reduce JCPyV infection.

JC polyomavirus (JCPyV) is a nonenveloped, double-stranded DNA virus that infects the majority of the population. Immunocompetent individuals harbor infection in their kidneys, while severe immunosuppression can result in JCPyV spread to the brain, causing the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Due to a lack of approved therapies to treat JCPyV and PML, the disease results in rapid deterioration, and is often fatal. In order to identify potential antiviral treatments for JCPyV, a high-throughput, large-scale drug screen was performed using the National Institutes of Health Clinical Collection (NCC). Drugs from the NCC were tested for inhibitory effects on JCPyV infection, and drugs from various classes that reduced JCPyV infection were identified, including receptor agonists and antagonists, calcium signaling modulators, and enzyme inhibitors. Given the role of calcium signaling in viral infection including Merkel cell polyomavirus and simian virus 40 polyomavirus (SV40), calcium signaling inhibitors were further explored for the capacity to impact JCPyV infection. Calcium and calmodulin inhibitors trifluoperazine (TFP), W-7, tetrandrine, and nifedipine reduced JCPyV infection, and TFP specifically reduced viral internalization. Additionally, TFP and W-7 reduced infection by BK polyomavirus, SV40, and SARS-CoV-2. These results highlight specific inhibitors, some FDA-approved, for the possible treatment and prevention of JCPyV and several other viruses, and further illuminate the calcium and calmodulin pathway as a potential target for antiviral drug development.

18F-THK5351 Positron Emission Tomography Clearly Depicted Progressive Multifocal Leukoencephalopathy after Mantle Cell Lymphoma Treatment.

An 84-year-old Japanese woman presented with left hemiplegia 8 months after completing chemotherapy for mantle cell lymphoma. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion extending from the right parietal lobe to the left parietal lobe. Compared with these MRI results, 18F-THK5351 PET revealed more extensive accumulation. A brain biopsy showed progressive multifocal leukoencephalopathy (PML). Immunohistochemistry and John Cunningham virus (JCV) DNA-polymerase chain reaction indicated JCV infection. Therefore, a diagnosis of PML was made. 18F-THK5351 PET, indicative of activated astrocytes, clearly depicted PML lesions composed of reactive and atypical astrocytes. 18F-THK5351 PET may capture fresh progressive PML lesions better than MRI.

Leucoencefalopatía multifocal progresiva en el curso de terapia combinada con bendamustina y rituximab / Progressive multifocal leukoencephalopathy in the course of combined therapy with bendamustine and rituximab

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Eficacia de mefloquina y mirtazapina sobre la leucoencefalopatía multifocal progresiva en un paciente con linfoma T periférico / Efficacy of mefloquine and mirtazapine on progressive multifocal leukoencephalopathy in a patient with peripheral T-cell lymphoma

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Estudio retrospectivo de la eficacia y seguridad del natalizumab en el tratamiento de la esclerosis múltiple en Portugal / The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study

Introducción. Los estudios han demostrado que el natalizumab constituye un tratamiento eficaz contra la esclerosis múltiple remitente recurrente (EMRR). Hasta la fecha, no había datos de pacientes portugueses. Objetivo. Determinar la eficacia y la seguridad del natalizumab en pacientes con EMRR atendidos en la práctica clínica ordinaria en Portugal. Pacientes y métodos. Los datos clínicos de adultos con EMRR tratados con natalizumab en centros especializados de neurología en Portugal se introdujeron de forma retrospectiva en una base de datos para llevar a cabo un análisis entre octubre de 2010 y febrero de 2012. Se analizó el cambio en la tasa anualizada de brotes (TAB), en las puntuaciones de la escala ampliada de discapacidad (EDSS) y en el estado de discapacidad. Resultados. Se admitió un total de 383 pacientes atendidos en 20 centros. Antes de iniciar el tratamiento con natalizumab, la mediana inicial de la EDSS era de 4,0 y la TAB media, de 1,64. La mayor parte de los pacientes ya había recibido tratamiento contra la esclerosis múltiple (93,0%). La duración media del tratamiento con natalizumab era de 12 meses. El tratamiento propicio reducciones significativas (p < 0,001) de los valores iniciales de la TAB media y de las puntuaciones EDSS en los tratados con el anticuerpo durante ≥ 12 meses (n = 288) y durante ≥ 24 meses (n = 160). El natalizumab resulto mas eficaz en los pacientes que presentaban un menor grado de discapacidad (EDSS < 3,0) y en los que no habían recibido ningún tratamiento modificador de la enfermedad. Se notificaron dos casos de leuco encefalopatía multifocal progresiva. No hubo efectos adversos inesperados. Conclusión. El natalizumab presenta una tolerabilidad satisfactoria y se muestra eficaz en la reducción de las recidivas y la estabilización de la EMRR en el marco de la practica clínica ordinaria en Portugal. Conserva su eficacia con el tratamiento continuado y podría ser eficaz especialmente en los pacientes con menos discapacidad y en aquellos que no han recibido ningún tratamiento modificador de la enfermedad hasta el momento (AU)

Introduction. Studies have shown that natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). To date, no data are available in Portuguese patients. Aim. To determine the efficacy and safety of natalizumab in patients with RRMS in routine clinical practice in Portugal. Patients and methods. Clinical data for adult patients with RRMS treated with natalizumab at specialist neurology centres in Portugal were entered retrospectively into a database for analysis between October 2010 and February 2012. Changes in annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores and disability status were analysed. Results. A total of 383 patients from 20 centres were included. Prior to starting natalizumab, the baseline median EDSS score was 4 and the mean ARR was 1.64. Most patients had previously received multiple sclerosis treatment (93.0%). Median natalizumab treatment duration was 12 months. Natalizumab treatment was associated with significant (p < 0.001) reductions from baseline in the mean ARR and EDSS scores in patients treated with natalizumab for ≥ 12 months (n = 288) and for ≥ 24 months (n = 160). Natalizumab was more effective in patients with less disability (EDSS < 3) and in those who had not previously received disease-modifying treatments. Two cases of progressive multifocal leukoencephalopathy were reported. No new unexpected adverse events occurred. Conclusion. Natalizumab is well tolerated, and is effective in reducing relapse rate and stabilising disease in patients with RRMS in the clinical practice setting in Portugal. Its efficacy persists with continued treatment, and it may be particularly effective in patients with less disability and without prior disease modifying therapy (AU)

Natalizumab y leucoencefalopatía multifocal progresiva: adecuación a las recomendaciones del Ministerio de Sanidad de España / Natalizumab and progressive multifocal leukoencephalopathy: in compliance with the recommendations of the Spanish Ministry of Health

Introducción y Objetivo: Valorar el seguimiento de las recomendaciones emitidas por el ministerio de sanidad dirigidas a minimizar el riesgo de aparación de Leucoencefalopatía Multifocal Progresiva (LMP) asociada al tratamiento con natalizumab por parte de los profesionales sanitarios de nuestro centro. Material y método: Revisión del 100% de pacientes diagnosticados de Esclerosis Múltiple a tratamiento con natalizumab (septiembre 2008-junio 2013). Resultados: 34 pacientes. La duración de tratamiento fue inferior a 1 año en 10 pacientes, entre 1 y 2 años para 11 pacientes y superior a 2 años en 13 pacientes. Se encuentran 24 resultados de serología VJC: positiva 14 y negativa10. Ningún paciente había recibido inmunosupresores y en el 100% de ellos se realizaron resonancias. Fueron informados acerca del riesgo de desarrollar LMP 18 pacientes, 10 con serología VJC positiva llevando 7 de ellos más de dos años a tratamiento con natalizumab. Discusión: Los facultativos se ajustan a las recomendaciones en la gran mayoría de los pacientes sin embargo, la información previa al inicio de tratamiento y una vez alcanzados los 2 años no se realiza de manera extendida. Sería adecuado realizar una estratificación de riesgo en función de presencia o ausencia de determinados factores que permitiría una selección segura y eficaz de la terapia para EM más adecuada para cada paciente

Introduction and Objective: To judge the follow-up of the recommendations made by the Ministry of Health. These recommendations are aimed at minimizing the risk of Progressive Multifocal Leukoencephalopathy (PML) occurrence, which is associated with natalizumab treatments provided by the neurologists of our centre. Methods: Check-up of 100% of the patients diagnosed with multiple sclerosis being treated with natalizumab (September 2008-June 2013). Results: During the study period 34 patients received at least one dose of natalizumab. The duration of the treatment was less than one year for 10 patients between 1 and 2 years for 11 patients, and more than 2 years for 13 patients. 24 results of JCV serology were found, 14 of which were positive and 10, negative. No patient had been given immunosuppressant drugs and resonance tests were done on 100% of them. 18 patients were informed at the risk of developing PML, among whom ten had positive JCV serology. Seven of them, had been treated with natalizumab for more than two years. Discussion: Doctors are following the recommendations with the vast majority of patients. Nevertheless, the information that precedes the treatment and once that the second year of it is reached is not generally provided. Due to the fact that there are currently no tools to predict an individual’s risk of developing PML, it would be appropriate to carry out a risk stratification based on the presence or absence of certain factors that would allow a safe and effective choice of the most appropriate multiple sclerosis therapy for each patient

Progressive multifocal leukoencephalopathy: new concepts / Leucoencefalopatia multifocal progressiva: novos conceitos

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the CNS caused by reactivation of JC virus (JCV) in a setting of cellular immunosuppression. Originally, PML was observed in patients with advanced HIV infection, lymphoproliferative disorders and transplant recipients. However, the widespread use of HIV antiretroviral drugs and the new selective immunomodulatory and immunosuppressive medications, such as Rituximab and Natalizumab, has recently modified the epidemiology, clinical presentation and prognosis of PML. Herein, we discuss the new concepts on PML, emphasizing the recent modification in the epidemiology; the impact of new immunomodulatory treatments in the disease, PML-IRIS (Immune reconstitution inflammatory síndrome), new treatment strategies and other JCV related CNS diseases.

A leucoencefalopatia multifocal progressiva (LMP) é uma doença desmielinizante do sistema nervoso central (SNC) causada pela reativação do vírus JC (JCV) em um ambiente de imunossupressão celular. Originalmente, LMP foi descrita em pacientes com infecção avançada pelo HIV, doenças linfoproliferativas e transplantados. No entanto, a utilização generalizada de anti-retrovirais para a infecção pelo HIV e novos imunomoduladores seletivos e imunossupressores, como Rituximab e Natalizumab, modificaram recentemente a epidemiologia, apresentação clínica e prognóstico da LMP. Neste artigo, vamos discutir os novos conceitos sobre LMP, enfatizando a recente modificação na epidemiologia, o impacto de novos tratamentos imunomoduladores na doença, síndrome inflamatória da reconstituição imune, novas estratégias de tratamento e outras doenças relacionadas ao JCV no SNC.

Tratamiento conjunto con mirtazapina y terapia antiretroviral para la leucoencefalopatía multifocal progresiva asociada a infección por VIH-1: presentación de un caso clínico y revisión de la literatura / Mirtazapine and antiretroviral therapy in the treatment of progressive multifocal leukoencephalopathy associated with HIV-1 infection: report of a case and review of literature

We report a 43 years old HIV-1 infected male who developed a severe subacute neurological damage because of a progressive multifocal leukoencephalopathy confirmed by PCR for JC virus. The patient was treated with antiretroviral therapy in adequate doses for CNS penetration and mirtazapine, an antidepressant inhibitor of serotonin receptors. His evolution during one year follow up has been favorable in both, clinically and images.

Se presenta el caso clínico de un paciente de sexo masculino, de 43 años portador de VIH que desarrolló un grave daño neurológico subagudo debido a una leucoencefalopatía multifocal progresiva diagnosticada mediante reacción de polimerasa en cadena de virus JC. El paciente fue tratado con terapia anti-retroviral de penetración eficiente al SNC y con mirtazapina, un antidepresivo inhibidor de los receptores de serotonina. Su evolución durante un año de seguimiento ha sido favorable tanto del punto de vista clínico como de imágenes.

Tratamiento anestésico de un paciente diagnosticado de CADASIL (arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía) / Anesthetic management of a patient diagnosed with CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy)

CADASIL (arteriopatía cerebral autosómica dominante, con infartos subcorticales y leucoencefalopatía) es una enfermedad hereditaria poco frecuente que puede tener implicaciones anestesiológicas, escasamente comunicadas. Presentamos el caso de un varón, previamente diagnosticado de CADASIL, que había sufrido un accidente cerebrovascular isquémico, con resonancia magnética compatible con leucoencefalopatía, y estaba muy limitado para las actividades diarias, con demencia, alteraciones del comportamiento, apatía e incontinencia urinaria. Entre sus antecedentes familiares, había varios parientes con síntomas psiquiátricos y accidentes cerebrovasculares, como su padre, dos hermanos y una hermana. Programado para artrodesis de la rodilla izquierda por complicaciones infecciosas tras cirugía de prótesis de rodilla, estaba tomando clopidogrel, que había suspendido 7 días antes. Se empleó anestesia combinada epidural-subaracnoidea y sedación intraoperatoria con midazolam, así como analgesia multimodal en el postoperatorio que incluyó analgesia epidural. No hubo incidencias notables. La anestesia y la analgesia epidurales permitieron mantener la estabilidad hemodinámica para una perfusión cerebral adecuada, clave para no empeorar los efectos de la arteriopatía crónica en la CADASIL(AU)

CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) is an infrequent inherited disease that could have anesthetic implications. However these have rarely been reported. We present a male patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, and sustained dementia, mood alterations, apathy, and urine incontinence. He had familial antecedents of psychiatric symptoms and ischemic stroke events in several relatives including his father, two brothers and one sister. He was scheduled for arthrodesis of the left knee because of multiple infectious complications of prosthetic knee surgery. He was under clopidogrel treatment which was withdrawn seven days before surgery. The procedure was performed under combined spinal-epidural anesthesia, intraoperative sedation with midazolam, and postoperative multimodal analgesia including epidural patient controlled analgesia. The perioperative management was uneventful and we outline the adequacy of managing these patients under regional anesthesia and analgesia, as these permit to maintain hemodynamic stability leading to adequate cerebral perfusion, key to avoid an increase in the effects of the chronic arteriopathy patients with CADASIL sustain(AU)

Natalizumab para la esclerosis múltiple remitente-recurrente / Natalizumab for relapsing-remitting multiple sclerosis

Introducción: Natalizumab es un anticuerpo monoclonal inhibidor de la migración leucocitaria a través de la barrera hematoencefálica, autorizado para el tratamiento de la esclerosis múltiple remitente-recurrente. Objetivo: Realizar una revisión y actualización de los aspectos farmacológicos y terapéuticos de natalizumab, con especial énfasis en los datos de eficacia, efectividad y seguridad publicados más recientemente. Desarrollo: Varios ensayos clínicos aleatorizados en pacientes con formas recurrentes de esclerosis múltiple han demostrado que natalizumab reduce considerablemente la actividad clínica y radiológica de la enfermedad. El análisis post hoc de ensayos clínicos fase III y los resultados de estudios observacionales postautorización indican que natalizumab incrementa significativamente la proporción de pacientes con respuesta clínica y radiológica completa, y que es eficaz en aquellos con formas muy activas de esclerosis múltiple y con respuesta subóptima a otras terapias. Al igual que otros anticuerpos monoclonales, natalizumab puede causar reacciones de hipersensibilidad, siendo graves en el 1% de los pacientes. Otros efectos adversos de natalizumab son en general leves o poco frecuentes. No obstante, se han detectado varios casos de leucoencefalopatía multifocal progresiva en pacientes tratados con natalizumab en monoterapia. El riesgo de esta grave complicación parece incrementarse con el número de dosis recibidas. Conclusión: Natalizumab ha demostrado una relación beneficio-riesgo favorable en el tratamiento de la esclerosis múltiple remitente-recurrente. El riesgo potencial de leucoencefalopatía multifocal progresiva, sin embargo, obliga a la selección cuidadosa de los pacientes y a seguir protocolos de actuación específicos durante su administración (AU)

Introduction: Natalizumab is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier and has been approved for the treatment of relapsing-remitting multiple sclerosis. Objective: To provide a review and update of the pharmacological and therapeutic characteristics of natalizumab, with special emphasis on the most recently published data on the efficacy, effectiveness and safety of this drug. Development: Several randomized clinical trials in patients with relapsing forms of multiple sclerosis have demonstrated that natalizumab substantially reduces clinical and radiological disease activity. Post hoc analysis of phase III clinical trials and the results of post-approval observational studies indicate that natalizumab significantly increases the proportion of patients with complete clinical and radiological response and is effective in patients with highly active forms of multiple sclerosis and suboptimal response to other treatments. Like other monoclonal antibodies, natalizumab can cause hypersensitivity reactions, which are severe in 1% of patients. Other adverse effects are generally mild or infrequent. Nevertheless, several cases of progressive multifocal leukoencephalopathy have been detected in patients treated with natalizumab monotherapy. The risk of this severe complication seems to increase with the number of doses administered. Conclusion: Natalizumab has a favorable risk-benefit ratio in the treatment of relapsing -remitting multiple sclerosis. However, because of the potential risk of progressive multifocal leukoencephalopathy, patients must be carefully selected and specific protocols must be followed during the drug's administration (AU)

Natalizumab en el tratamiento de la esclerosis múltiple / Natalizumab in the treatment of multiple sclerosis

Revisar y actualizar la información sobre el mecanismo de acción del natalizumab y su eficacia en el tratamientode la esclerosis múltiple (EM). Desarrollo. El natalizumab, un anticuerpo humanizado monoclonal frente a la integrina alfa-4, se une a su receptor en la superficie de los linfocitos e impide la transmigración de éstos a las zonas inflamadasdel tejido cerebral. Además, parece que el natalizumab disminuye la activación de los linfocitos T que ocurre tras su infiltración en el parénquima cerebral y puede contribuir a la apoptosis de los linfocitos T en estos tejidos. Se han llevado a cabo dosgrandes ensayos clínicos multicéntricos de dos años de duración (AFFIRM y SENTINEL), que demuestran una eficacia superior a la conocida hasta ahora en la prevención de las recaídas y de la progresión de la EM. El natalizumab redujo la frecuencia anual de las recaídas en un 68 y 54% en estos ensayos respectivamente (p < 0,001). Además, también disminuyó significativamenteel riesgo de progresión de la discapacidad en un 42 y un 24%, respectivamente. Según los resultados del estudioAFFIRM, los acontecimientos adversos que fueron significativamente más frecuentes en el grupo tratado con natalizumab que en el grupo placebo fueron la fatiga (27 frente a 21%) y las reacciones alérgicas (9 frente a 4%). La incidencia de reaccionesde hipersensibilidad graves descritas como anafilácticas o anafilactoides fue baja (< 1%) y respondieron adecuadamente al tratamiento habitual. En el estudio SENTINEL se diagnosticaron dos casos de leucoencefalopatía multifocal progresiva(LMP), uno de ellos mortal, en el grupo tratado con natalizumab asociado a interferón beta-1a. Conclusiones. El natalizumab ha demostrado reducir el riesgo de progresión sostenida de discapacidad y la frecuencia de recaídas clínicamente detectadas en pacientes con EM remitente recurrente. A pesar de su bajo riesgo de producción de reacciones adversas, debe vigilarse alos pacientes tratados con natalizumab a intervalos regulares para detectar cualquier aparición o empeoramiento de signos o síntomas neurológicos que pudieran ser indicativos de LMP, y su empleo debe restringirse a las indicaciones aprobadas

To review and update the mechanism of action of natalizumab and its efficacy in the treatment of multiplesclerosis (MS). Development. Natalizumab, an anti-alfa-4 integrin monoclonal humanized antibody, binds to lymphocyte surface receptors to prevent transmigration of lymphocytes to areas of inflammation into the brain tissue. Furthermore, natalizumab appears to reduce T-cell activation following their infiltration of the brain parenchyma and may contribute toT-cell apoptosis in these tissues. Two large two-year, multicenter phase III trials (AFFIRM and SENTINEL) have been completed and demonstrate previously unseen efficacy in preventing MS relapses and disease progression. Natalizumabreduced the rate of clinical relapse at one year by 68 and 54% respectively in these trials (p < 0.001). Moreover, natalizumab reduced significantly the risk of sustained progression of disability by 42 and 24% respectively. Based on results from theAFFIRM study, the adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 vs. 21%) and allergic reaction (9 vs. 4%). There was a low incidence (< 1%) of serious systemic hypersensitivityreactions described as anaphylactoid or anaphylactic, and they appear to be effectively managed by post-treatment observation and by timely and appropriate medical treatment. In the SENTINEL study, two cases of progressive multifocal leukoencephalopathy (PML), one of which was fatal, were diagnosed in natalizumab plus interferon beta-1a treated patients.Conclusions. Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing MS. In spite of their low risk of adverse reactions, patients must be monitored at regular intervals for any newor worsening neurological symptoms or signs that may be suggestive of PML, and natalizumab use must be restricted to the indicated patients

Enfermedad de Crohn / Crohn’s disease

Dos temas fueron los que más interés suscitaron en la presente edición de la DDW: el perfil de seguridad del tratamiento actual y los resultados obtenidos por nuevos fármacos, que conocemos como «terapia biológica». En relación al primero, cabe destacar la ausencia de nuevos casos de leucoencefalopatía multifocal progresiva en un estudio que incluyó 3.500 pacientes tratados con natalizumab, el registro americano TREAT que, con un seguimiento de más de 15.000 pacientes-año, demuestra que la toma de esteroides (pero no de azatioprina o infliximab) se asocia a una mayor frecuencia de infecciones graves y de mortalidad y, finalmente, 2 estudios que describen una mayor frecuencia de anomalías en la citología cervical en las mujeres tratadas con inmunosupresores. En relación con la terapia biológica, se presentaron diversos estudios que sugieren que certolizumab, adalimumab y visilizumab, entre otros nuevos fármacos, pueden ser útiles en el tratamiento de la enfermedad de Crohn (AU)

At the last congress of the American Gastroenterological Association: Digestive Diseases Week, two topics aroused the greatest interest: the safety profile of current treatments and the results obtained by new drugs, known as biological therapy. Among safety data, notable were the absence of new cases of progressive multifocal leukoencephalopathy in a study that included 3500 patients treated with natalizumab; the American registry TREAT which, with a follow-up of more than 15,000 patients/year, shows that taking steroids (but not azathioprine or infliximab) is associated with a greater frequency of severe infections and mortality; finally, two studies report a greater frequency of anomalous findings in cervical cytology in women treated with immunosuppressive drugs. Several studies on biological therapy suggest that certolizumab, adalimumab and visilizumab, among other new drugs, could be useful in the treatment of Crohn’s disease (AU)