Non-inflammatory causes of emergency consultation in patients with multiple sclerosis.

OBJECTIVES: To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered. METHODS: We performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period. RESULTS: The study included 50 patients (33 were women; mean age 41.4 ±â€¯11.7 years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5). CONCLUSIONS: MS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients' symptoms.

Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish.

Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. We identify the Wnt signaling as a regulator of sphingolipid synthesis that mediates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid production. Sphingolipids determine the palmitoylation state of the Anthrax receptor, which then positions the mitotic spindle of dividing epiblast cells. Our data show how Wnt signaling mediates sphingolipid-dependent oriented division and how sphingolipids determine Anthrax receptor palmitoylation, which ultimately controls the activation of Diaphanous to mediate spindle rotation and oriented mitosis.

Anthrax toxin receptor 2a controls mitotic spindle positioning.

Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.

[Validation of supra-aortic trunks ultrasound in the diagnosis of atherosclerotic disease of the internal carotid artery. Comparison of the results with angiography]. / Validación del estudio ultrasonológico de troncos supraaórticos en el diagnóstico de la enfermedad aterosclerótica de la arteria carótida interna. Comparación de los resultados con los de angiografía.

INTRODUCTION: Arteriosclerosis of the extra-cranial arteries is believed to be responsible for almost one-third of all ischaemic strokes. The sound diagnosis of the degree of stenosis is essential in deciding the best therapeutic strategy. Although cerebral angiography is considered the reference technique, ultrasound study (UST) is a more readily available, non-invasive and well-established procedure for quantifying carotid stenosis. However, on being a dependent exploratory technique, it is recommended that each laboratory validates its results against angiography. OBJECTIVES: To establish the validity of the neuro-ultrasound study in our laboratory for use in the diagnosis of extracranial atheromatous disease, and determine its capacity to quantify the degree of stenosis in the internal carotid artery. MATERIAL AND METHODS: A retrospective study of patients with extracranial carotid atheromatous disease, in whom the diagnostic process was carried out with carotid ultrasound as well as supra-aortic trunk digital-subtraction angiography. RESULTS: A total of 254 carotids were evaluated and the degree of stenosis being classified into > 50%, 70-99% and 100%. The UST for the first group had a sensitivity (Se) of 97%, a specificity (Sp) of 90%, a positive predictive value (PPV) of 94.6% and a negative predictive value (NPV) of 94.2%. The second group had an Se of 96.4%, Sp 93%; PPV 94.4% and NPV 95.4%. The respective values for carotid occlusion were, 85%, 96.8%, 80% and 97.8%. CONCLUSIONS: Our data validates the ability of UST performed in our Laboratory to diagnose the degree of carotid stenosis.

[SUNCT syndrome and neoplasms in the central nervous system. A new association]. / Síndrome SUNCT y neoplasias en el sistema nervioso central. Una nueva asociación.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is a rare form of primary headache disorder, although secondary causes are well known. A growing number of cases have been described since its description in 1978 up to now. We report a new case in a 72 year old woman suffering SUNCT syndrome secondary to two ipsilateral intracranial lesions in the basal portion of the left frontal lobe of the sphenoid wing and the left pontocerebellar angle, suggestive of meningiomas. The patient was successfully treated with carbamazepine. We discuss the differential diagnosis with other very brief headaches associated with cranial autonomic features and the therapeutics possibilities. We review the secondary cases previously reported. The possible pathophysiological mechanism in this case is discussed.

Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development.

The basic helix-loop-helix transcription factor Twist regulates a series of distinct cell fate decisions within the Drosophila mesodermal lineage. These twist functions are reflected in its dynamic pattern of expression, which is characterized by initial uniform expression during mesoderm induction, followed by modulated expression at high and low levels in each mesodermal segment, and finally restricted expression in adult muscle progenitors. We show two distinct partner-dependent functions for Twist that are crucial for cell fate choice. We find that Twist can form homodimers and heterodimers with the Drosophila E protein homologue, Daughterless, in vitro. Using tethered dimers to assess directly the function of these two particular dimers in vivo, we show that Twist homodimers specify mesoderm and the subsequent allocation of mesodermal cells to the somatic muscle fate. Misexpression of Twist-tethered homodimers in the ectoderm or mesoderm leads to ectopic somatic muscle formation overriding other developmental cell fates. In addition, expression of tethered Twist homodimers in embryos null for twist can rescue mesoderm induction as well as somatic muscle development. Loss of function analyses, misexpression and dosage experiments, and biochemical studies indicate that heterodimers of Twist and Daughterless repress genes required for somatic myogenesis. We propose that these two opposing roles explain how modulated Twist levels promote the allocation of cells to the somatic muscle fate during the subdivision of the mesoderm. Moreover, this work provides a paradigm for understanding how the same protein controls a sequence of events within a single lineage.

The immunoglobulin-like protein Hibris functions as a dose-dependent regulator of myoblast fusion and is differentially controlled by Ras and Notch signaling.

Hibris (Hbs) is a transmembrane immunoglobulin-like protein that shows extensive homology to Drosophila Sticks and stones (Sns) and human kidney protein Nephrin. Hbs is expressed in embryonic visceral, somatic and pharyngeal mesoderm among other tissues. In the somatic mesoderm, Hbs is restricted to fusion competent myoblasts and is regulated by Notch and Ras signaling pathways. Embryos that lack or overexpress hbs show a partial block of myoblast fusion, followed by abnormal muscle morphogenesis. Abnormalities in visceral mesoderm are also observed. In vivo mapping of functional domains suggests that the intracellular domain mediates Hbs activity. Hbs and its paralog, Sns, co-localize at the cell membrane of fusion-competent myoblasts. The two proteins act antagonistically: loss of sns dominantly suppresses the hbs myoblast fusion and visceral mesoderm phenotypes, and enhances Hbs overexpression phenotypes. Data from a P-homed enhancer reporter into hbs and co-localization studies with Sns suggest that hbs is not continuously expressed in all fusion-competent myoblasts during the fusion process. We propose that the temporal pattern of hbs expression within fusion-competent myoblasts may reflect previously undescribed functional differences within this myoblast population.

[Cerebral infarction due to spontaneous dissection of the left common carotid artery]. / In process citation.

Spontaneous dissection of the extracranial cervicocephalic arteries occurs most often in the internal carotid artery or vertebral artery. Spontaneous dissection of a common carotid artery is rare, with only nine cases having been reported. A 43-year-old man was hospitalized for sudden onset of motor aphasia and right arm weakness due to spontaneous dissection of a left common carotid artery; no sign of aortic disection was evident on aortogram. The most common causes of dissection of the common carotid artery are the extension of an aortic dissection and the complication in an angiogram with direct puncture; spontaneous dissection being very rare. We review the previous literature on this topic.

[Motor neuron disease and HIV]. / Enfermedad de motoneurona e infección por VIH.

Motor-neuron disease, in particular its commonest form (lateral amyotrophic sclerosis) is a degenerative disease of unknown aetiology and inexorable course with an estimated incidence of 0.4-1.8 per 100,000 inhabitants. In recent years great efforts have been made to discover the aetiopathogenesis of this disorder, studying genetic, viral, endocrine, toxic factors, etc. We present the case of a 30 year old man who started to develop a clinical condition compatible with motor-neuron disease 18 months after diagnosis of HIV. An extensive differential diagnosis was considered in view of this past history. Complementary tests considered necessary for diagnosis of motor-neurone disease and for exclusion of other neurological conditions related to HIV were done. After 16 months of follow-up the condition has become a clear case of ELA type motor neurone disease with no further HIV-related pathology. We discuss questions concerning the aetiopathology of the disease, based on the currently accepted viral hypothesis and describe recent findings related to both.

[The association of the Eaton-Lambert myasthenic syndrome and subacute cerebellar degeneration of nonparaneoplastic origin]. / Asociación de síndrome miasteniforme de Eaton-Lambert y degeneración cerebelosa subaguda de origen no paraneoplásico.

A 52-year-old male with Eaton-Lambert syndrome associated to seven years subacute cerebellar degeneration of non paraneoplastic origin is presented. Immunosuppressive treatment with azathioprine allowed the neuromuscular symptoms to be controlled although no appreciable effects were observed in the cerebellar symptoms which remained stable.