Hipertensión pulmonar: uno entre un millón / Pulmonary hypertension: one in a million

Introducción. La hipertensión pulmonar en pediatríasuele presentarse con una clínica inespecífica que hace difícilsu sospecha diagnóstica, siendo hasta en el 30% de los casosde etiología multifactorial.Caso clínico. Presentamos el caso de una lactante de2 meses de edad que comienza con clínica inespecífica(vómitos, rechazo de tomas, irritabilidad), presentando unempeoramiento progresivo que termina en varias paradascardiorrespiratorias abortadas. En el estudio diagnósticoúnicamente se encuentra una hipertensión pulmonar grave que no responde a tratamiento vasodilatador agresivo.Además, muestra hiperecogenicidad periventricular condesarrollo de edema cerebral progresivo, que termina conla vida de la paciente. El estudio metabólico muestra elevación de glicina en líquidos biológicos; y el estudio genético confirma una variante patogénica en homocigosis en elgen NFU1 (NM_001002755.3:c.622G>T, p.Gly208Cys), por loque se diagnostica de síndrome de disfunción mitocondrialmúltiple tipo 1.Conclusiones. El síndrome de disfunción mitocondrialmúltiple tipo 1 es una enfermedad autosómica recesiva conuna prevalencia <1/1.000.000, que afecta al metabolismomitocondrial por alteración del gen NFU1. La clínica comienza en las primeras etapas de la vida por síntomas inespecíficos, neurológicos e hipertensión pulmonar, con un cursomortal a los pocos meses de edad. Destaca un aumento deglicina y lactato en líquidos biológicos; una leucoencefalopatía periventricular con degeneración quística, cavitacionesy/o necrosis. El diagnóstico de las enfermedades metabólicasprecisa de una alta sospecha clínica. El curso rápidamenteprogresivo y refractario al tratamiento de una hipertensiónpulmonar que asocia clínica encefalopática, debe hacernossospechar una alteración en el metabolismo mitocondrial. (AU)

Introduction. Pulmonary hypertension in children usually presents with non-specific symptoms that makes thesuspicion difficult, being up to 30% of cases of multifactorialetiology.Clinical case. We present the case of a 2-month-old infantwho began with nonspecific symptoms, presenting a progressive worsening that results in aborted cardiorespiratoryarrest. The diagnostic work-up only shows a severe pulmonary hypertension that does not respond to aggressivevasodilator therapy. In addition, the patient has periventricular hyperechogenicity with progressive cerebral edema,causing the patient’s death. The metabolic study shows elevation of glycine in biological fluids; and the genetic study confirmed a homozygous pathogenic variant in the NFU1gene (NM_001002755.3:c.622G>T, p.Gly208Cys), leading tothe diagnosis of type 1 multiple mitochondrial dysfunctionsyndrome.Conclusion. Multiple mitochondrial dysfunction syndrome type 1 is an autosomal recessive disease with a prevalence <1/1,000,000, which affects mitochondrial metabolismdue to alterations in the NFU1 gene. The clinic begins in theearly stages of life presenting with nonspecific symptoms,neurological symptoms and pulmonary hypertension; witha fatal course in all cases. An increase in glycine and lactate in biological fluids is characteristic; it is also typical tofind a periventricular leukoencephalopathy with chemicaldegeneration, cavitations and/or necrosis. The diagnosisof metabolic disorders requires a high clinical suspicion. Asevere pulmonary hypertension associated with encephalopathy should lead us to suspect an alteration in mitochondrial metabolism (AU)

Analysis of the effectiveness of the prophylaxis of vestibular migraine depending on the diagnostic category and the prescribed drug.

INTRODUCTION: Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking. OBJECTIVE: To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis. MATERIAL AND METHODS: This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared. RESULTS: 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them. CONCLUSION: The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Probable benign paroxysmal positional vertigo, spontaneously resolved: Incidence in medical practice, patients' characteristics and the natural course.

BACKGROUND: Probable benign paroxysmal positional vertigo, spontaneously resolved (pBPPVsr), is a variant of benign paroxysmal positional vertigo (BPPV) in which there is no observable nystagmus and no vertigo with any positional maneuver. OBJECTIVES: To calculate the incidence pBPPVsr, compare the characteristics of the patients with pBPPVsr and BPPV not spontaneously resolved and describe the spontaneous resolution in the natural course of BPPV. METHODS: Multicenter prospective descriptive study. During a one-year period, all patients with suspected BPPV that presented to the Neurotology Units of five participating centers were recruited. The incidence of pBPPVsr was calculated as a percentage of the total number of patients with BPPV. The prevalence of several variables was compared between pBPPVsr and BPPV not spontaneously resolved. The timing of spontaneous resolution was estimated using Kaplan-Meier curves. RESULTS: 457 patients met the inclusion criteria. The incidence of pBPPVsr was 33.5%. It was significantly higher in males, in patients with normal bone mass and in patients who were not taking sulpiride. A rate of 18% of spontaneous resolution after the first month and 51% after the first year was found. This percentage did not change in a significant way after this moment. The curves for males, patients under 50 and patients with normal blood pressure decreased significantly faster. CONCLUSIONS: In our serie, BPPV spontaneously resolved in half of the patients with BPPV during the first year. This seemed to occur more commonly in males and could have been hindered by sulpiride intake, osteoporosis, advanced age and high blood pressure.

Healing criteria: How should an episode of benign paroxistic positional vertigo of posterior semicircular canal's resolution be defined? Prospective observational study.

OBJECTIVES: To compare the outcome of the Epley maneuver (EM) in benign paroxysmal positional vertigo of the posterior canal (CSP-BPPV) depending on the definition used for recovery. DESIGN: Multicenter observational prospective study. SETTING: Otoneurology Units of 5 tertiary reference hospitals. PARTICIPANTS: All patients presenting with unilateral CSP-BPPV assisted for 1-year period. EXCLUSION CRITERIA: Spontaneous nystagmus, positive McClure-Pagnini maneuver, positive bilateral Dix-Hallpike maneuver (DHM), positive DHM for vertigo but negative for nystagmus and atypical nystagmus. MAIN OUTCOME MEASURES: Response to EM was measured after 7 days in 3 different outcomes: disappearance of nystagmus during the DHM in the follow-up visit, disappearance of vertigo during the DHM and general status (GS) during daily life activities. RESULTS: 264 patients were recruited (68 male/166 female, mean age 62 years). After the EM, nystagmus disappeared in 67% of them, vertigo in 54% and 36% were asymptomatic in their daily life. These outcomes were strongly correlated, but they were not concordant in a clinically significant group of cases; only the 26% of patients met all of them. The healing process follows the next sequence: negativization of positional nystagmus, then disappearance of positional vertigo and, finally, the improvement of GS during daily life activities. CONCLUSION: Nowadays, healing criteria for the resolution of an PSC-BPPV episode have not been specifically defined yet. Provided that other otoneurological disorders have been ruled out, the next resolution criterion is proposed: absence of nystagmus and specifically during control DHM and disappearance of symptoms during daily life activities.

Analysis of risk factors influencing the outcome of the Epley maneuver.

Benign paroxysmal positional vertigo (BPPV) is the most frequent type of vertigo. The treatment of canalithiasis of the posterior semicircular canal consists in performing a particle-repositioning maneuver, such as the Epley maneuver (EM). However, the EM is not effective in all cases. The objective of this study is to identify risk factors, which predict the EM failure, among the clinical variables recorded in anamnesis and patient examination. This is an observational prospective multicentric study. All patients presenting with BPPV were recruited and applied the EM and appointed for a follow-up visit 7 days later. The following variables were recorded: sex, age, arterial hypertension, diabetes, hyperlipidemia, smoking habit, alcohol consumption, migraine, osteoporosis, diseases of the inner ear, previous ipsilateral BPPV, previous traumatic brain injury, previous sudden head deceleration, time of evolution, sulpiride or betahistine treatment, experienced symptoms, outcome of the Halmagyi maneuver, laterality, cephalic hyperextension of the neck, intensity of nystagmus, intensity of vertigo, duration of nystagmus, occurrence of orthotropic nystagmus, symptoms immediately after the EM, postural restrictions, and symptoms 7 days after the EM. Significant differences in the rate of loss of nystagmus were found for six variables: hyperlipidemia, previous ipsilateral BPPV, intensity of nystagmus, duration of nystagmus, post-maneuver sweating, and subjective status. The most useful significant variables in the clinical practice to predict the success of the EM are previous BPPV and intensity of nystagmus. In the other significant variables, no physiopathological hypothesis can be formulated or differences between groups are too small.

Retinoic Acid Modulates PTGDR Promoter Activity.

BACKGROUND AND OBJECTIVE: Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was to analyze the effect of RA on the activation of the promoter region of the PTGDR gene. METHODS: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG, and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. RESULTS: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. CONCLUSIONS: RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients.

Retinoic acid modulates PTGDR promoter activity

Background and Objective: Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was o analyze the effect of RA on the activation of the promoter region of the PTGDR gene. Methods: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG , and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. Results: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. Conclusions: RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients (AU)

Introducción y Objetivo: La vitamina A se ha relacionado con el desarrollo de las enfermedades alérgicas, si bien su papel no se comprende en su totalidad. El ácido retinoico, un metabolito de la vitamina A, se ha asociado previamente con la ruta de las prostaglandinas. Además, PTGDR, uno de los receptores de PGD2, se ha propuesto como un gen candidato en la alergia y el asma. Considerando el papel de PTGDR en la alergia, el objetivo de este estudio fue analizar el efecto del ácido retinoico sobre la activación de la región promotora del gen PTGDR. Métodos: Se utilizó la línea celular A549 de epitelio de pulmón. Las células fueron transfectadas con cuatro combinaciones de las variantes génicas de PTGDR y fueron estimuladas con ácido retinoico todo-trans (ATRA). Los ensayos de Luciferasa se llevaron a cabo mediante el sistema Dual Luciferase Reporter System. Se realizaron análisis de RT-qPCR para medir la expresión basal de PTGDR, CYP26A1, RARA, RARB, RARG y RXRA de los cultivos de A549 tras el tratamiento con ATRA. Se realizaron también análisis bioinformáticos. Resultados: Se encontraron diferencias significativas en la actividad promotora entre las variantes haplotípicas tras la transfección en la línea celular A549. Tras el tratamiento con ATRA se detectó un incremento de la expresión de CYP26A1 (12 veces) y RARB (4 veces). El ácido retinoico activó la actividad promotora de PTGDR en las células transfectadas (p<0,001). Se identificaron secuencias de Elementos de Respuesta a Ácido Retinoico (RARE) in silico en la región promotora de PTGDR. Conclusiones: El ácido retinoico modula la actividad promotora de PTGDR . Esto podría explicar las diferencias en los efectos del ácido retinoico y en las respuestas a los nuevos tratamientos de la enfermedad alérgica basados en la modulación del receptor PTGDR (AU)

Neuropatía multifocal motora y síndrome de Lewis-Sumner. A propósito de un caso / Multifocal motor neuropathy and the Lewis-Sumner syndrome. A case report

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Coste del infarto cerebral en su fase aguda / The cost of cerebral infarct in the acute phase

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Dependencia de opiáceos con patologíaafectiva asociada / Opioid dependence with associate mood disorders

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[Multifocal polyneuropathy with persistent conduction blockage. A new subset of chronic inflammatory polyneuropathies]. / Polineuropatía multifocal con bloqueos de conducción persistentes. Un nuevo subgrupo dentro de las polineuropatías inflamatorias crónicas.

Recently a subset of chronic demyelinating inflammatory polyneuropathies with asymmetrical involvement limited to upper limbs, at least at the onset, resembling a multifocal mononeuropathy has been described. Electrodiagnostic testing disclosed multifocal CB outside the common entrapment sites has been described. We report a 55 years old man with a 4 years history of paresis, numbness, fasciculations, myokymia, cramps and mild amyotrophy. Electrophysiological evaluation showed proximal multifocal conduction block and abundant spontaneous activity as fasciculations, myokymia and scarce denervation activity. The importance of taking into account this entity in the differential diagnosis of patients with suspected mononeuritis multiplex or motoneuron disease is emphasized. The nosologic place of this entity is also discussed.