Manifestaciones no infecciosas del síndrome variable común de inmunodeficiencia. Asociación con los inmunofenotipos de la enfermedad.

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2017/2018Background. Common variable immunodeficiency includes a heterogeneous group of clinical conditions. In this disease, a variable degree of B cell dysfunction and alterations of cellular immunity cause severe infection s. Beyond infections, these patients develop several non - infectious manifestations that frequently determine their clinical course. We aimed to analyze immunophenotypic markers of non - infectious manifestations in common variable immunodeficiency. Methods. We reviewed clinical histories of 40 patients fulfilling criteria of common variable immunodeficiency. The frequency of non - infectious manifestations was analyzed after grouping the patients according to immunophenotypic characteristics. Results. Granulom a ( p =0.021) and autoimmune thrombocytopenia ( p =0.028) were associated to Paris Class MB0 (42.9% and 57.1% respectively). When grouping by Freiburg criteria, both splenomegaly ( p =0.002) and thrombocytopenia ( p =0.02) showed significant differences, with grea ter prevalence in group Ia (77.8 and 55.6% respectively). EuroClass classification also produced significant differences in adenopathy ( p =0,025), splenomegaly (p=0.001) and thrombocytopenia (p<0.001), with a greater incidence in the group SmB - CD21low (66.7 %, 88.9% and 88.9%). When considering the levels of naïve CD4 T cells (CD45RA+), significant differences were found in the frequency of adenopathy ( p =0.01), splenomegaly ( p =0.014), thrombocytopenia ( p =0.014) and interstitial lung disease ( p =0.011), with a higher freq uency in patients showing lower levels (88.9%, 66.7%, 66.7% and 50% respectively). Conclusion. In CVID, immunophenotipic grouping of patients is a useful tool to predict the probability of non - infectious manifestations. Level of naïve CD4 T cell s is an important prognostic factor in CVID.4 RESUMEN Antecedentes. El síndrome variable común de inmunodeficiencia incluye un grupo muy heterogéneo de manifestaciones. Se caracteriza por presentar diversas alteraciones en las células B y en l a inmunidad celular, que producen infecciones graves. Junto con la inmunodeficiencia aparecen importantes manifestaciones no infecciosas, que pueden condicionar el pronóstico. Nuestro objetivo es estudiar estas manifestaciones buscando asociaciones con los distintos inmunofenotipos de la enfermedad. Métodos. Se analizaron las historias clínicas de 40 pacientes con criterios de síndrome variable común de inmunodeficiencia. Se agrupó a los pacientes según las clasificaciones inmunofenotípicas propuestas y se realizó un análisis de asociación con las manifestaciones no infecciosas. Resultados. La clasificación de Paris mostró diferencias entre inmunofenotipos para granulomas ( p= 0.021) y trombocitopenia ( p =0.028), con mayor frecuencia en el grupo MB0 (42.9% y 57.1%). La agrupación según Freiburg mostró diferencias significativas para esplenomegalia ( p =0.002) y trombocitopenia ( p =0.02), con mayor proporción en Ia (77 .8% y 55. 6%). EuroClass mostró diferencias en adenopatías ( p =0.025), esplenomegalia ( p =0.001) y trombocitopenia ( p <0.001) con mayor incidencia en SmB - CD21low (66.7%, 88.9% y 88.9%). La agrupación según niveles de células T CD4 vírgenes (CD45RA+) mostró diferencias en adenopatías ( p =0.01), esplenomegalia ( p =0.014), trombocitopenia ( p =0.014) y enfermed ad pulmonar intersticial ( p =0.011), más frecuentes en el grupo I (88.9%, 66.7%, 66.7% y 50% respectivamente) Conclusión. La clasificación inmunofenotípica proporciona información muy valiosa para predecir la aparición de manifestaciones no infecciosas. La determinación de células T CD4 vírgenes es un factor con gran rentabilidad pronóstic

Assessing suicidal risk with antiepileptic drugs

Recently, the US Food and Drug Administration issued an alert about an increased risk for suicidality during treatment with antiepileptic drugs (AEDs) for different indications, including epilepsy. We discuss the issue of suicide in epilepsy with special attention to AEDs and the assessment of suicide in people with epilepsy. It has been suggested that early medical treatment with AEDs might potentially reduce suicide risk of people with epilepsy, but it is of great importance that the choice of drug is tailored to the mental state of the patient. The issue of suicidality in epilepsy is likely to represent an example of how the underdiagnosis of psychiatric symptoms, the lack of input from professionals (eg, psychologists, social workers, and psychiatrists), and the delay in an optimized AED therapy may worsen the prognosis of the condition with the occurrence of severe complications such as suicide

The interictal dysphoric disorder of epilepsy: Legend or reality?

For a long time, the relationships between epilepsy and mood disorders captured the attention of clinicians and neuroscientists. The existence of a peculiar clinical presentation for mood disorders in epilepsy has been a matter of debate since the early reports of Kraepelin and Bleuler. The interictal dysphoric disorder (IDD) represents the modern reinterpretation of such early observations. This paper reviews current research on this topic discussing clinical implications, phenomenological observations, and directions for future research

The pharmacological management of psychiatric comorbidities in patients with epilepsy.

Psychiatric disorders represent a frequent comorbidity in patients with epilepsy affecting quality of life, morbidity and mortality. Evidence-based data on the management of these conditions are limited but a number of recommendations are now available to guide clinical practice. The present paper reviews the pharmacological treatment of psychiatric problems in epilepsy with special attention to data coming from randomised controlled trials (RCTs), pharmacological interactions with AEDs and the issue of seizure worsening during treatment with psychotropic drugs. Epidemiologically or clinically relevant psychiatric conditions are discussed namely mood and anxiety disorders, psychoses and attention deficit hyperactivity disorder

Epilepsy and Psychiatric Comorbidities: Drug Selection.

Purpose of review The pharmacological treatment of patients with epilepsy and psychiatric comorbidities may sometimes represent a therapeutic challenge. This review is focused on the pharmacological management of patients with epilepsy and psychiatric problems in terms of rationalization of the antiepileptic drug (AED) treatment and the pharmacological management of the most clinically relevant psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and attention deficit hyperactivity disorder (ADHD). Recent findings Up to 8% of patients with drug-resistant epilepsy develop treatment-emergent psychiatric adverse events of AED regardless of the mechanism of action of the drug and this is usually related to an underlying predisposition given by the previous psychiatric history and the involvement of mesolimbic structures. Careful history taking, periodic screening for mood and anxiety disorders, low starting doses, and slow titration schedules can reduce the possibility of AED-related problems. A pragmatic checklist for the pharmacological management of patients with epilepsy and psychiatric disorders is presented. Summary patients should be informed of potential behavioral effects of AEDs but no drugs should be excluded a priori. Any psychiatric comorbidity should be addressed in the appropriate setting and full remission and recovery should always represent the first goal of any therapeutic intervention. Neurologists should be aware of the side effects of major psychotropic drug classes in order to fully counsel their patients and other health professionals involved

The interplay of chemical structure, physical properties, and structural design as a tool to modulate the properties of melanins within mesopores

The design of modern devices that can fulfil the requirements for sustainability and renewable energy applications calls for both new materials and a better understanding of the mixing of existing materials. Among those, surely organic–inorganic hybrids are gaining increasing attention due to the wide possibility to tailor their properties by accurate structural design and materials choice. In this work, we’ll describe the tight interplay between porous Si and two melanic polymers permeating the pores. Melanins are a class of biopolymers, known to cause pigmentation in many living species, that shows very interesting potential applications in a wide variety of fields. Given the complexity of the polymerization process beyond the formation and structure, the full understanding of the melanins’ properties remains a challenging task. In this study, the use of a melanin/porous Si hybrid as a tool to characterize the polymer’s properties within mesopores gives new insights into the conduction mechanisms of melanins. We demonstrate the dramatic effect induced on these mechanisms in a confined environment by the presence of a thick interface. In previous studies, we already showed that the interactions at the interface between porous Si and eumelanin play a key role in determining the final properties of composite materials. Here, thanks to a careful monitoring of the photoconductivity properties of porous Si filled with melanins obtained by ammonia-induced solid-state polymerization (AISSP) of 5,6-dihydroxyindole (DHI) or 1,8-dihydroxynaphthalene (DHN), we investigate the effect of wet, dry, and vacuum cycles of storage from the freshly prepared samples to months-old samples. A computational study on the mobility of water molecules within a melanin polymer is also presented to complete the understanding of the experimental data. Our results demonstrate that: (a) the hydration-dependent behavior of melanins is recovered in large pores (≈ 60 nm diameter) while is almost absent in thinner pores (≈ 20 nm diameter); (b) DHN-melanin materials can generate higher photocurrents and proved to be stable for several weeks and more sensitive to the wet/dry variations

Different attachment styles correlate with mood disorders in adults with epilepsy or migraine.

PURPOSE: Interpersonal relationships are viewed as important contexts within which psychopathology emerges and persists or desists. Attachment theory describes the dynamics of long-term relationships between humans especially in families and lifelong friendships. The present study was aimed at investigating attachment styles in adult patients with epilepsy as compared to subjects with migraine and their potential correlates with a history of mood disorders. METHODS: A consecutive sample of 219 adult outpatients with epilepsy (117) or migraine (102) was assessed with the Attachment Style Questionnaire (ASQ). RESULTS: Patients with epilepsy and a lifetime history of mood disorders presented elevated scores for Need for approval (p<0.001) and Preoccupation with relationships (p<0.001). Age correlated with the Relationships as secondary (r=0.322; p<0.001) and Need for approval (r=0.217; p=0.019) subscales while age at onset correlated only with Relationships as secondary (r=0.225; p=0.015). Seizure-free patients presented lower scores for Need for approval (p=0.003). Patients with migraine and a lifetime history of mood disorders presented lower scores in Confidence (p=0.002) and higher scores in Discomfort with closeness (p=0.026). CONCLUSIONS: An anxious-preoccupied attachment correlated with mood disorders in epilepsy while it was an avoidant pattern in migraine. Our results bring further data on the role of psychological variables in mood disorders in epilepsy. Further studies will allow early identification of patients at risk and the development of preventive strategies