Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement.

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.

An incidental finding in newborn screening leading to the diagnosis of a patient with ECHS1 mutations.

Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters, as well as in valine metabolism. ECHS1 deficiency has multiple manifestations, including Leigh syndrome early at birth or in childhood with poor prognosis, to cutis laxa, exercise-induced dystonia and congenital lactic acidosis. Here we describe the case of a newborn with mutations in ECHS1 that caught our attention after the incidental finding of 3-hydroxy-butyryl\3-hydroxy-isobutyryl\malonylcarnitine (C4OH\C3DC) and tiglylcarnitine (C5:1) on blood spot in the newborn screening (NBS) program. Diagnosis was suspected based on the analysis of organic acids on dried urine spot. A moderate increase of 2-methyl-2,3-dihydroxybutyric acid, was detected, which is a known marker of this disease. Exome analysis showed c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene. The child was therefore admitted to the hospital. Initial examination showed little response to auditory stimuli and mild hypertonia of the extremities. Clinical deterioration was evident at 4 months of age, including neurological and cardiac involvement, and the patient died at 5 months of age. This case illustrates how an incidental detection in the NBS Program can lead to the diagnosis ECHS1 deficiency. Although it is a severe disease, with no treatment available, early detection would allow adequate genetic counseling avoiding the odyssey that suffered most of these families.

Brain iron accumulation in a blood donor family with restless legs syndrome. / Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.

INTRODUCTION: The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency -which suggests disturbed iron homeostasis- remains to be elucidated. CASE REPORTS: We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload. CONCLUSION: The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS.

TITLE: Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.Introduccion. La fisiopatologia del sindrome de piernas inquietas (SPI) es compleja. El mecanismo a traves del cual la ferropenia favorece el desarrollo del SPI no esta esclarecido, aunque se sugiere la presencia de una alteracion en la homeostasis cerebral del hierro. Casos clinicos. Se presentan los hallazgos inusuales en una familia de donantes de sangre con SPI. Tres miembros de la misma familia fueron diagnosticados de SPI, cumpliendo los criterios definidos por el grupo internacional para el estudio del SPI (International Restless Legs Syndrome Study Group). Todos eran donantes de sangre habituales (rango de donacion: 10-40 años) y los sintomas de SPI tenian un curso de 3-5 años. La exploracion general y neurologica fue normal en todos los casos, asi como los electromiogramas. El estudio fenotipico y genotipico descarto la presencia de hemocromatosis y otras causas geneticas de sobrecarga cerebral de hierro. Los estudios polisomnograficos mostraron sueño nocturno perturbado, con reduccion de su eficiencia, y un aumento del indice de movimientos periodicos de las piernas. La resonancia magnetica craneal evidencio un aumento de los depositos cerebrales de hierro en los ganglios basales, la sustancia negra, el nucleo rojo y los dentados. Conclusion. Este aumento patologico de los depositos cerebrales de hierro sugiere la presencia de un complejo trastorno del metabolismo cerebral del hierro en nuestros pacientes. Futuros estudios deben confirmar estos hallazgos y profundizar en el estudio de su relacion con la fisiopatologia del SPI.

Predictive value of magnetic resonance for identifying neurovascular compressions in trigeminal neuralgia. / Valor predictivo de la resonancia magnética para la identificación de compresiones neurovasculares en la neuralgia del trigémino.

INTRODUCTION: Microvascular decompression (MVD) is accepted as the only aetiological surgical treatment for refractory classic trigeminal neuralgia (TN). There is therefore increasing interest in establishing the diagnostic and prognostic value of identifying neurovascular compressions (NVC) using preoperative high-resolution three-dimensional magnetic resonance (MRI) in patients with classic TN who are candidates for surgery. METHODS: This observational study includes a series of 74 consecutive patients with classic TN treated with MVD. All patients underwent a preoperative three-dimensional high-resolution MRI with DRIVE sequences to diagnose presence of NVC, as well as the degree, cause, and location of compressions. MRI results were analysed by doctors blinded to surgical findings and subsequently compared to those findings. After a minimum follow-up time of six months, we assessed the surgical outcome and graded it on the Barrow Neurological Institute pain intensity score (BNI score). The prognostic value of the preoperative MRI was estimated using binary logistic regression. RESULTS: Preoperative DRIVE MRI sequences showed a sensitivity of 95% and a specificity of 87%, with a 98% positive predictive value and a 70% negative predictive value. Moreover, Cohen's kappa (CK) indicated a good level of agreement between radiological and surgical findings regarding presence of NVC (CK 0.75), type of compression (CK 0.74) and the site of compression (CK 0.72), with only moderate agreement as to the degree of compression (CK 0.48). After a mean follow-up of 29 months (range 6-100 months), 81% of the patients reported pain control with or without medication (BNI score i-iiiI). Patients with an excellent surgical outcome, i.e. without pain and off medication (BNI score i), made up 66% of the total at the end of follow-up. Univariate analysis using binary logistic regression showed that a diagnosis of NVC on the preoperative MRI was a favorable prognostic factor that significantly increased the odds of obtaining an excellent outcome (OR 0.17, 95% CI 0.04-0.72; P=.02) or an acceptable outcome (OR 0.16, 95% CI 0.04-0.68; P=.01) after MVD. CONCLUSIONS: DRIVE MRI shows high sensitivity and specificity for diagnosing NVC in patients with refractory classic TN and who are candidates for MVD. The finding of NVC on preoperative MRI is a good prognostic factor for long-term pain relief with MVD.

Características de las pacientes portadoras de aneurisma de aorta abdominal / Characteristics of patients carriers of aorta abdominal aneurysm

Se realiza un estudio retrospectivo de las características de las pacientes de sexo femenino portadoras de aneurismas de aorta abdominal, distribuyendo las pacientes en tres grupos de tratamiento quirúrgico electivo, urgente y no tratadas. Se consideran factores de riesgo y otras características del aneurisma. Se analizan estos factores y se hacen consideraciones en relación con la información aportada en la bibliografía

A retrospective study of the characteristics of female patients with abdominal aortic aneurysms was carried out, distributing the patients in three groups of elective, urgent and untreated surgical treatment. They are considered risk factors and other features of the aneurysm. These factors are analysed, and considerations are made in relation to the information provided in the bibliography

A counterfactual impact evaluation of a bilingual program on students' grade point average at a spanish university.

This observational study intends to estimate the causal effects of an English as a Medium of Instruction (EMI) program (as predictor) on students Grade Point Average (GPA) (as outcome) at a particular University in Spain by using a Counterfactual Impact Evaluation (CIE). The need to address the crucial question of causal inferences in EMI programs to produce credible evidences of successful interventions contrasts, however, with the absence of experimental or quasi-experimental research and evaluation designs in the field. CIE approach is emerging as a methodologically viable solution to bridge that gap. The program evaluated here consisted in delivering an EMI program in a Primary Education Teacher Training Degree group. After achieving balance on the observed covariates and recreating a situation that would have been expected in a randomized experiment, three matching approaches such as genetic matching, nearest neighbor matching and Coarsened Exact Matching were used to analyze observational data from a total of 1288 undergraduate students, including both treatment and control group. Results show unfavorable effects of the bilingual group treatment condition. Potential interpretations and recommendations are provided in order to strengthen future causal evidences of bilingual education programs' effectiveness in Higher Education.

Neurologic emergencies in HIV-negative immunosuppressed patients. / Urgencias neurológicas en el paciente inmunosuprimido no VIH.

HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management.

Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum.

The analysis of acylcarnitines (AC) in plasma/serum is established as a useful test for the biochemical diagnosis and the monitoring of treatment of organic acidurias and fatty acid oxidation defects. External quality assurance (EQA) for qualitative and quantitative AC is offered by ERNDIM and CDC in dried blood spots but not in plasma/serum samples. A pilot interlaboratory comparison between 14 European laboratories was performed over 3 years using serum/plasma samples from patients with an established diagnosis of an organic aciduria or fatty acid oxidation defect. Twenty-three different samples with a short clinical description were circulated. Participants were asked to specify the method used to analyze diagnostic AC, to give quantitative data for diagnostic AC with the corresponding reference values, possible diagnosis, and advice for further investigations.Although the reference and pathological concentrations of AC varied among laboratories, elevated marker AC for propionic acidemia, isovaleric acidemia, medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and multiple acyl-CoA dehydrogenase deficiencies were correctly identified by all participants allowing the diagnosis of these diseases. Conversely, the increased concentrations of dicarboxylic AC were not always identified, and therefore the correct diagnosis was not reach by some participants, as exemplified in cases of malonic aciduria and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Misinterpretation occurred in those laboratories that used multiple-reaction monitoring acquisition mode, did not derivatize, or did not separate isomers. However, some of these laboratories suggested further analyses to clarify the diagnosis.This pilot experience highlights the importance of an EQA scheme for AC in plasma.

Development and validation of an open source quantification tool for DSC-MRI studies.

MOTIVATION: This work presents the development of an open source tool for the quantification of dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies. The development of this tool is motivated by the lack of open source tools implemented on open platforms to allow external developers to implement their own quantification methods easily and without the need of paying for a development license. MATERIALS AND METHODS: This quantification tool was developed as a plugin for the ImageJ image analysis platform using the Java programming language. A modular approach was used in the implementation of the components, in such a way that the addition of new methods can be done without breaking any of the existing functionalities. For the validation process, images from seven patients with brain tumors were acquired and quantified with the presented tool and with a widely used clinical software package. The resulting perfusion parameters were then compared. RESULTS: Perfusion parameters and the corresponding parametric images were obtained. When no gamma-fitting is used, an excellent agreement with the tool used as a gold-standard was obtained (R(2)>0.8 and values are within 95% CI limits in Bland-Altman plots). CONCLUSION: An open source tool that performs quantification of perfusion studies using magnetic resonance imaging has been developed and validated using a clinical software package. It works as an ImageJ plugin and the source code has been published with an open source license.

Prevalence of pain and relative diagnostic performance of screening tools for neuropathic pain in cancer patients: A cross-sectional study.

BACKGROUND: Neuropathic pain can be overlooked in cancer patients. The advent of screening tools can help in recognizing it. However, little is known about their relative diagnostic performance and factors that affect it. This study evaluated the prevalence of neuropathic pain using several diagnostic strategies in cancer patients undergoing chemotherapy. METHODS: Patients attending the Oncology Unit of the investigators' site to continue their chemotherapy schedule were systematically screened for this cross-sectional study. Before starting chemotherapy drugs, pain specialists made a clinical diagnosis of neuropathic pain (either disease related, treatment related or comorbid) and medical oncologists administered three validated screening tools. Their relative diagnostic performance and the impact of some pain features on it were analysed using multivariate statistical methods. RESULTS: From a total of 358 patients, 194 (54.2%) suffered from pain and 73 (20.4%) had a clinical diagnosis of pure neuropathic or mixed pain. Among the screening tools, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was more specific (93.4%), although less sensitive (68.1%) than the Douleur Neuropathique in 4 Questions (DN4) (sensitivity: 87.5%, specificity: 88.4%). Interestingly, the specificities of these two instruments did not differ in patients with mild pain, while the DN4 remained to be more sensitive than the LANSS regardless of pain severity. CONCLUSIONS: Neuropathic pain is common in cancer patients undergoing chemotherapy. The DN4 might be of great help for the early detection of patients at risk because of incipient chemotherapy-related neuropathies and the LANSS to rule out neuropathic pain in patients with complex pain conditions.

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation.

Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18 months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).

Reliability and accuracy of quantitative sensory testing for oxaliplatin-induced neurotoxicity.

OBJECTIVES: Thermal quantitative sensory testing (QST) is a non-invasive procedure helpful in the assessment of the function of small Aδ and C nerve sensory fibres. Oxaliplatin (OXA) is an effective chemotherapeutic agent, but is frequently associated with neurotoxic dose-limiting side effects. This controlled clinical trial evaluated the reliability and accuracy of thermal QST for assessing the OXA-induced acute neuropathic syndrome, whose clinical hallmark is cold-triggered painful paraesthesia. MATERIALS & METHODS: A testing protocol with the Thermal Sensory Analyzer (Medoc) was carried out in 20 colorectal cancer patients during the initial four cycles of OXA-based chemotherapy and in 20 age- and sex-matched healthy volunteers. Testing was carried out on the hands and included the determination of thermal detection and pain thresholds and the intensity of pain evoked by cold stimuli. Calculations were made of: coefficients of test-retest and inter-rater reliability, indices of responsiveness and parameters that quantify diagnostic accuracy. RESULTS: Thermal thresholds showed moderate to good reliability (ρ ≥ 0.383), but were not consistently responsive to the effects of chemotherapy (cold pain thresholds decreased in both groups, although almost twice in patients compared to healthy volunteers). Conversely, the intensity of pain evoked by suprathreshold cold stimuli was reliable (ρ ≥ 0.822), responsive (detected changes over time) and discriminated between patients and healthy volunteers (area under the ROC curve = 0.700). CONCLUSIONS: The procedure was reliable and accurate to evaluate cold hyperalgesia resulting from OXA administration. The data provided may be used to define efficacy endpoints for future clinical trials of therapies for OXA-induced neuropathies and calculate appropriate sample sizes.

Clinical and biochemical outcome after hydroxocobalamin dose escalation in a series of patients with cobalamin C deficiency.

BACKGROUND: CblC deficiency produces a combination of methylmalonic aciduria (MMA) and homocystinuria (HCU), and is the most common error of cobalamin metabolism. Patients present a wide spectrum of symptoms, ranging from early severe multisystemic forms, to milder late-onset phenotypes. Cognitive and visual impairment are nearly constant. Hydroxocobalamin (OHCbl), betaine, folinic acid, levocarnitine and eventually dietary protein restriction are the main therapeutic approaches. Although early introduction of OHCbl is crucial, no standardized protocols regarding dose adaptation exist. No reports on long-term outcomes after high doses of this vitamin have been published. METHODS: In this study five patients with CblC deficiency (early severe forms) were treated with high doses of OHCbl for 18 to 30months. Clinical examinations, neurological assessment, and biochemical studies (plasma total homocysteine (tHcy), amino acids, hydroxocobalamin, and methylmalonic acid in urine) were periodically performed. RESULTS: Variable clinical and biochemical outcomes were observed in patients treated with high doses of OHCbl. The best biochemical response was observed in those children with the worse metabolic control. By contrast, those patients with a concentration of tHcy around 50µmol/l or less showed only minor changes. Clinically, a considerable improvement was observed in those patients with severe problems in communication, expressive language and behavior. CONCLUSIONS: According to our study, high OHCbl doses in CblC deficiency could have a greater benefit in those children with a prior history of suboptimal metabolic control, and also in those with severe neurological phenotypes. More specifically, we observed improvements in communication skills and behavior. These results should encourage further prospective trials to determine the optimal OHCbl regimen and to generate protocols and guidelines in this rare disorder.

Experiencia preliminar en el tratamiento combinado de metástasis vertebrales mediante radiofrecuencia y cifoplastia en sesión única / No disponible

Objetivos: Describir nuestra experiencia preliminar en el tratamiento de metástasis vertebrales mediante radiofrecuencia y cifoplastia combinadas en sesión única. Material y métodos: Se trataron cuatro pacientes con metástasis vertebral única confirmada histológicamente (mama, próstata, pulmón y mieloma en D12, L1, L5 y D12, respectivamente). La indicación en todos los casos fue el dolor con una mala respuesta al tratamiento médico habitual. Todos los pacientes presentaban dolor en el rango 6-7 de la escala visual analógica (EVA). En dos casos existía lesión lítica del muro posterior. Tras la obtención del consentimiento informado se realizó el procedimiento bajo sedación e infiltración anestésica local. Se efectuó abordaje transpedicular bilateral con sistemas de punción ósea 11G. Se insertaron de forma coaxial dos agujas de radiofrecuencia para efectuar un ciclo de ablación por cada pedículo. Durante el ciclo de ablación la punta del dispositivo correspondiente se situó en la unión del tercio medio con el tercio anterior del cuerpo vertebral, empleando la segunda aguja como sensor térmico, con su extremo a la altura del muro posterior. La duración de cada ciclo de ablación fue de 8 minutos, alcanzando temperaturas intratumorales de 70-80 ºC. A continuación se realizó cifoplastia transpedicular. Resultados: No se registraron complicaciones intra-periprocedimiento, con alta domiciliaria en las 24 horas siguientes. En todos los pacientes hubo una mejoría inmediata del dolor tras el procedimiento (con dolor de intensidad 1-2 de la EVA). En tres pacientes se retiró progresivamente la medicación analgésica, sin evidencia en ninguno de ellos de progresión local de la enfermedad ni recurrencia-aumento del dolor en el seguimiento (dolor de intensidad 1 de la EVA en un seguimiento en el rango de 8-14 meses). En un paciente no se pudo efectuar seguimiento clínico-radiológico posterior al alta. Conclusión: El empleo de radiofrecuencia asociada a cifoplastia en la enfermedad metastásica vertebral puede contribuir al manejo del dolor refractario al tratamiento médico y al control local de la enfermedad (AU)

Objectives: Describe our preliminary experience in the treatment of vertebral metastases by radiofrequency and Kyphoplasty combined in one single session. Material and methods: Four patients with histologically confirmed single spinal metastasis (breast, prostate, lung and myeloma in L1, L5, D12, D12, respectively) were treated. The indication in all cases was pain with a poor response to medical treatment. All patients had pain in the range 6-7 visual analogue scale (VAS). In two cases there was a lytic lesion of the spinal posterior wall. After obtaining informed consent, and under sedation and local anesthetic the procedure took place. The transpedicular approach took place with a 11 G bone puncture system. Two radiofrequency needles were coaxially inserted to carry out an ablation cycle through each pedicle. During the ablation cycle the tip of the ablation neddle stood between the anterior and middle third of the vertebral body, while the second needle was used as thermal sensor with its end to the height of the vertebral posterior wall. The duration of each cycle of ablation was 8 minutes reaching intratumoral temperatures of 70-80 °C. Transpedicular Kyphoplasty was performed subsequently. Results: No complications were reported during or after the procedure and patients were discharged in the first 24 hours. There was an immediate improvement in pain after the procedure (with a VAS 1-2 intensity pain) in all patients. During follow up, analgesic medication was withdrawn in three patients, and there was no evidence of disease progression or recurrence of pain (pain intensity 1 (VAS) in a follow-up in the range of 8-14 months). Clinical and radiological follow-up after discharge could not be performed on a patient. Conclusion: The use of radio-frequency associated with Kyphoplasty in vertebral metastatic disease can contribute to the management of refractory pain to medical treatment (AU)

Analysis of coenzyme Q(10) in lymphocytes by HPLC-MS/MS.

Coenzyme Q(10) (CoQ(10)) deficiency syndromes are potentially treatable disorders. Skeletal muscle is the most widely accepted tissue for their study, but sampling is an invasive procedure. Cultured skin fibroblasts seem to improve the biochemical diagnosis, but their growth requires a certain period of time. Our aim was to set up a minimally invasive, fast and reliable analytical procedure to measure CoQ(10) in lymphocytes, to prevent any delay in diagnosing primary CoQ(10) deficiency. HPLC-MS/MS analysis of CoQ(10) showed high sensitivity and specificity. The reference range was established in apparently healthy volunteers (n=33); the mean of CoQ(10) in lymphocytes was 107nmol/g protein (95% confidence interval: 105-120) and 2.0nmol/UCS (95% confidence interval: 2.06-2.46). Therefore, the range was narrower when normalized to units of citrate synthase (UCS) than when normalized to grams of protein. The method was linear from 0.01 to 1µM with a good precision and sensitivity (limit of quantification 0.01µM). Intra-assay and inter-assay coefficients of variation were lower than 13%. Recovery was higher than 95%. In our hands, lymphocytes seem to be a reliable matrix as they reflect intracellular content of CoQ(10). In addition, they can be obtained by a minimally invasive procedure (venipuncture).

Estudio de la perfusión cerebral mediante técnicas de susceptibilidad magnética: técnica y aplicaciones / Studying cerebral perfusion using magnetic susceptibility techniques: technique and applications

Las técnicas de perfusión por resonancia magnética (PRM) permiten la valoración de la microvasculatura cerebral mediante los cambios de señal debidos al paso intravascular de un trazador. La técnica más empleada se basa en la susceptibilidad magnética del gadolinio en secuencias T2* y los parámetros más comúnmente valorados son: el volumen sanguíneo cerebral, el flujo sanguíneo cerebral y el tiempo de tránsito medio. En los estudios de PRM deben considerarse diversos aspectos técnicos como la secuencia empleada, la dosis o la velocidad de inyección del contraste. También debe valorarse la existencia de fuentes de error como las debidas a la fuga de contraste por alteración en la permeabilidad de la barrera hematoencefálica. Las aplicaciones clínicas más extendidas de la PRM incluyen la determinación del grado de agresividad de gliomas, la diferenciación de algunos tipos histológicos tumorales o de lesiones pseudotumorales y la valoración del área de penumbra en la isquemia aguda (AU)

Perfusion MRI makes it possible to evaluate the cerebral microvasculature through changes in signal due to a tracer passing through blood vessels. The most commonly used technique is based on the magnetic susceptibility of gadolinium in T2*-weighted sequences, and the most commonly evaluated parameters are cerebral blood volume, cerebral blood flow, and mean transit time. Diverse technical aspects, like the sequence used, and the dose and speed of contrast material injection, must be taken into account in perfusion MRI studies. It is also essential to consider possible sources of error like contrast material leaks due to changes in the permeability of the blood-brain barrier. The most widely used clinical applications of perfusion MRI include the determination of the degree of aggressiveness of gliomas, the differentiation of some histological types of tumors or pseudotumors, and the evaluation of the penumbral area in acute ischemia (AU)

¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso / Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case

Introducción: La falta de criterios homogéneos aceptados para la definición de algunas de las patologías desmielinizantes dificulta la caracterización diagnóstica limitando la reproducibilidad de los resultados y las recomendaciones terapéuticas. Especialmente controvertidas son las formas de encefalomielitis recurrentes (EAD-RR) y otras formas infrecuentes de neuromielitis óptica (NMO).Objetivo: Describimos la evolución clínico-radiológica de un caso de EAD-RR del adulto versus NMO, seguida durante 9 años. Paciente y métodos: La paciente debutó con síntomas severos de rombencefalomielitis y la resonancia magnética (RM) craneal y medular mostraron lesiones extensas, con captación de gadolinio en el tronco encefálico y de la médula, acorde con los síntomas clínicos de la paciente. Se excluyó etiología infecciosa, el índice IgG fue normal y fueron negativos los anticuerpos para NMO. Tras tratamiento con corticoides por vía intravenosa y plasmaféresis la recuperación del episodio fue excelente. Durante el seguimiento ha presentado 7 recurrencias, preferentemente medulares, con buena recuperación, que reproducen con severidad variable los mismos síntomas. Desde el inicio ha recibido tratamiento inmunosupresor. Conclusiones: Nuestro caso comparte características clínicas con EAD-RR y NMO e ilustra que, pese a los criterios vigentes, la caracterización diagnóstica de estas entidades no es fácil (AU)

Introduction: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. Objective:To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. Patient and methods: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning.Conclusions: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria (AU)

[Studying cerebral perfusion using magnetic susceptibility techniques: technique and applications]. / Estudio de la perfusión cerebral mediante técnicas de susceptibilidad magnética: técnica y aplicaciones.

Perfusion MRI makes it possible to evaluate the cerebral microvasculature through changes in signal due to a tracer passing through blood vessels. The most commonly used technique is based on the magnetic susceptibility of gadolinium in T2*-weighted sequences, and the most commonly evaluated parameters are cerebral blood volume, cerebral blood flow, and mean transit time. Diverse technical aspects, like the sequence used, and the dose and speed of contrast material injection, must be taken into account in perfusion MRI studies. It is also essential to consider possible sources of error like contrast material leaks due to changes in the permeability of the blood-brain barrier. The most widely used clinical applications of perfusion MRI include the determination of the degree of aggressiveness of gliomas, the differentiation of some histological types of tumors or pseudotumors, and the evaluation of the penumbral area in acute ischemia.

[Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case]. / ¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso.

INTRODUCTION: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. OBJECTIVE: To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. PATIENT AND METHODS: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning. CONCLUSIONS: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria.