Molecular characterization of congenital myasthenic syndromes in Spain.

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

[Diagnostic, prognostic and therapeutic implications of transcranial color-coded duplex sonography in acute ischemic stroke: TIBI and COGIF scores validation]. / Implicaciones diagnosticas, pronosticas y terapeuticas del duplex color transcraneal en el ictus isquemico agudo: validacion de los grados TIBI y COGIF.

AIM: To describe the information provided by transcranial color-coded duplex (TCCD) sonography for therapeutic decision-making in patients with acute ischemic stroke and to analyze the relationship between TCCD findings and the severity and prognosis of stroke. PATIENTS AND METHODS: TCCD performed within the six first hours after an acute ischemic stroke were analyzed in our institution. The presence of an arterial occlusion and its location were collected using TIBI (Thrombolysis in Brain Ischemia) and COGIF (Consensus on Grading Intracranial Flow Obstruction) criteria. Arterial recanalization within 24 hours after stroke was determined using TIBI and COGIF criteria. Favorable functional outcome was defined as a modified Rankin scale from 0 to 2 at three months. RESULTS: TCCD was performed in 104 patients, 85 were treated with intravenous thrombolysis. Arterial occlusion was detected in 79.8% of patients. The detection of arterial occlusion with TCCD allowed the selection for endovascular treatment in 23.1% of patients. Arterial occlusion was associated with a higher severity of stroke. Recanalization was detected in 44.1% using TIBI and 45.8% according to COGIF criteria. 80.8% of recanalized patients and only 39.5% of not recanalized had a favorable functional outcome at three months. Recanalization rate depended on the location of arterial occlusion. CONCLUSION: TCCD is a useful technique for the detection and location of arterial occlusion. It provides valuable prognostic information and allows selecting patients for endovascular recanalizing therapies. TIBI and COGIF scores provide a comparable information.

TITLE: Implicaciones diagnosticas, pronosticas y terapeuticas del duplex color transcraneal en el ictus isquemico agudo: validacion de los grados TIBI y COGIF.Objetivo. Describir la informacion aportada por el duplex color transcraneal (DCTC) en pacientes con ictus isquemico agudo, analizando la relacion entre los hallazgos del DCTC, la gravedad y el pronostico, asi como su utilidad en la toma de decisiones terapeuticas. Pacientes y metodos. Analizamos los DCTC realizados a pacientes con ictus agudo de menos de seis horas de evolucion. Recogimos la existencia de oclusion arterial empleando las clasificaciones TIBI (Thrombolysis in Brain Ischemia) y COGIF (Consensus on Grading Intracranial Flow Obstruction). Determinamos la recanalizacion arterial a las 24 horas del ictus empleando criterios TIBI y COGIF. Consideramos buena evolucion funcional puntuaciones en la escala de Rankin de 0 a 2 a los tres meses. Resultados. Realizamos DCTC en 104 pacientes, 85 tratados con trombolisis intravenosa. Objetivamos oclusion arterial en el 79,8%. La deteccion de una oclusion arterial mediante DCTC permitio indicar tratamiento endovascular en el 23,1% de los pacientes. La presencia de oclusion arterial se asocio a mayor gravedad del ictus. Detectamos recanalizacion arterial en el 44,1% segun los criterios TIBI y en el 45,8% segun los criterios COGIF. El 80,8% de los pacientes que recanalizaron y solo el 39,5% de los que no recanalizaron obtuvieron una buena evolucion funcional a los tres meses. La recanalizacion dependio de la localizacion de la oclusion arterial. Conclusiones. El DCTC es util para deteccion y localizacion de oclusion arterial, aporta informacion pronostica valiosa y permite seleccionar pacientes para el empleo de terapias endovasculares. La informacion aportada por las clasificaciones TIBI y COGIF es equiparable.

Use of cell-based assays in myasthenia gravis and other antibody-mediated diseases.

The increasing demand on diagnostic assays that are sensitive and specific for pathogenic antibodies, and the interest in identifying new antigens, prompted the development of cell-based assays for the detection of autoantibodies in myasthenia gravis and other autoimmune disorders. Cell-based assays were initially used to show that clustering the AChR improved the positivity in myasthenia gravis, and similar assays have now been applied to detection of antibodies to neuromuscular junction candidate proteins such as LRP4 and agrin. In addition cell-based assays have been used in the routine detection of antibodies to proteins expressed on the surface of neurons (NMDAR, LGI1, CASPR2, AMPAR, GABA-A/B, GlyR, and DPPX) and glia (AQP4, MOG). Here, we summarize the findings in myasthenia and discuss the advantages, disadvantages and controversial issues of using cell-based assays in the detection of these antibodies, and their relevance to the testing of preclinical models of disease.

Spontaneous spinal epidural haematoma: a retrospective study of a series of 13 cases.

INTRODUCTION: Spontaneous spinal epidural haematoma (SSEH) has an estimated incidence of one per million inhabitants. It is classified as spontaneous when no identifiable cause can be linked to its onset. OBJECTIVE: To describe a sample of patients with SSEH and analyse variables related to its functional prognosis. PATIENTS AND METHODS: Retrospective study carried out in patients diagnosed with SSEH between 2001 and 2013 in our hospital. RESULTS: We included 13 subjects (7 men) with a mean age of 71 years. Of the total, 62% had hypertension and 54% were treated with oral anticoagulants; of the latter, 57% had an International Normalised Ratio above 3. The most frequent manifestation was spinal column pain (85%). Nearly all subjects presented an associated neurological deficit, whether sensory-motor (70%), pure motor (15%), or pure sensory (7%). Five patients underwent surgical treatment and 8 had conservative treatment. After one year, 3 of the patients treated surgically and 4 of those on conservative treatment had a score of 2 or lower on the modified Rankin Scale. Poorer prognosis was observed in patients with anticoagulant therapy, large haematomas, location in the lumbar region, and more pronounced motor disability at onset. CONCLUSIONS: Old age, hypertension, and anticoagulant therapy are the main risk factors for SSEH. The typical presentation consists of back pain with subsequent motor deficit. In patients with established motor symptoms, surgical treatment within the first 24hours seems to be the best option.

Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study.

INTRODUCTION: Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. METHODS: We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañón, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. RESULTS: The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. CONCLUSIONS: Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments.

[Aetiological classification of ischaemic strokes: comparison of the new A-S-C-O classification and the classification by the Spanish Society of Neurology's Cerebrovascular Disease Study Group]. / Clasificación etiológica del ictus isquémico: comparación entre la nueva clasificación A-S-C-O y la clasificación del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

INTRODUCTION: The A-S-C-O classification may be better than other methods for classifying ischaemic stroke by aetiology. Our aims are to describe A-S-C-O phenotype distribution (A: atherosclerosis, S: small vessel disease, C: cardiac source, O: other causes; 1: potential cause, 2: causality uncertain, 3: unlikely to be a direct cause although disease is present) and compare them to the Spanish Society of Neurology's Cerebrovascular Disease Study Group (GEECV/SEN) classification. We will also find the degree of concordance between these classification methods and determine whether using the A-S-C-O classification delivers a smaller percentage of strokes of undetermined cause. METHODS: We analysed those patients with ischaemic stroke admitted to our stroke unit in 2010 with strokes that were classified according to GEECV/SEN and A-S-C-O criteria. RESULTS: The study included 496 patients. The percentages of strokes caused by atherosclerosis and small vessel disease according to GEECV/SEN criteria were higher than the percentages for potential atherosclerotic stroke (A1) (14.1 vs. 11.9%; P=.16) and potential small vessel stroke (S1) (14.3 vs. 3%; P<.001). Cardioembolic stroke (C1) was more frequent (22.2 vs. 31%; P<.001). No differences between unusual cause of stroke and other potential causes (O1) were observed. Some degree of atherosclerosis was present in 53.5% of patients (A1, A2, or A3); 65.5% showed markers of small vessel disease (S1, S2, or S3), and 74.9% showed signs of cardioembolism (C1, C2, or C3). Fewer patients in the group without scores of 1 or 2 for any of the A-S-C-O phenotypes were identified as having a stroke of undetermined cause (46.6 vs. 29.2%; P<.001). The agreement between the 2 classifications ranged from κ<0.2 (small vessel and S1) to κ>0.8 (unusual causes and O1). CONCLUSION: Our results show that GEECV/SEN and A-S-C-O classifications are neither fully comparable nor consistent. Using the A-S-C-O classification provided additional information on co-morbidities and delivered a smaller percentage of strokes classified as having an undetermined cause.