Búsqueda de variantes del gen LRP4 en mujeres con alta masa ósea y en pacientes con malformación de Chiari tipo I / Search for variants of the LRP4 gene in women with high bone mass and in patients with Chiari type I malformation

Objetivo: LRP4 es un facilitador esencial en la inhibición específica de esclerostina de la vía canónica de Wnt. Mutaciones en LRP4 se han asociado a diversas patologías entre las cuales se incluyen la patología de crecimiento óseo, esclerosteosis y la malformación de Chiari tipo I (MCI). Material y métodos: Se ha re-secuenciado el gen LRP4 en dos pequeñas cohortes de pacientes con el fenotipo de alta masa ósea (HBM) y con MCI con el objetivo de encontrar variantes causales. Resultados: Entre las mutaciones encontradas destacamos: 1) una mutación de cambio de sentido (missense) en un paciente con MCI, que no cosegrega con el fenotipo en la familia; 2) una mutación intrónica no descrita previamente (c.3364+16A>C) en una mujer con HBM; y 3) una mutación intrónica en una mujer con HBM cuya frecuencia en población control europea es muy baja. Conclusión: Aunque no hemos encontrado variantes en LRP4 que expliquen el fenotipo HBM o MCI en los pacientes estudiados, animamos a otros investigadores a que analicen el gen LRP4 en sus pacientes ya que es un buen candidato funcional de ambos fenotipos. (AU)

Objetive: LRP4 is an essential facilitator in sclerostin-specific inhibition of the canonical Wnt pathway. Mutations in LRP4 have been associated with various conditions, including bone growth disease, sclerosteosis, and Chiari type I malformation (CMI). Material and methods: The LRP4 has been re-sequenced in two patient cohorts with high bone mass phenotype (HBM) and with CMI aimed at finding causal variants. Results: Among the mutations found, we would highlight: 1) a missense mutation in a patient with CMI, which does not co-segregate with the phenotype in the family; 2) a previously undescribed intronic mutation (c.3364+16A>C) in a woman with HBM; and 3) an intronic mutation in a woman with HBM with a very low frequency in the European control population. Conclusion: Although we have not found variants in LRP4 to explain the HBM or CMI phenotype in the patients studied, we encourage other researchers to analyze the LRP4 gene in their patients as it is a good functional candidate for both phenotypes. (AU)

Malformación de Chiari tipo I tratada con descompresión de la fosa posteriorapoyada por ultrasonido intraoperatorio / Management of Chiari type I malformation with posterior fossa craniectomy decompression supported by intraoperative ultrasound

Objetivo: Describir la utilidad intraoperatoria de la ultrasonografía en la descompresión de fosa posterior en la cirugía de la malformación de Chiari tipo I. Caso clínico: Paciente masculino, de 11 años de edad, que acudió a consulta de Neurocirugía en el Hospital Pediátrico Universitario de Holguín “Octavio de la Concepción de la Pedraja”, acompañado de sus padres, quienes refirieron que hacía aproximadamente cuatro meses había tenido pérdida de la conciencia aguda, y, luego, comenzó con cefaleas occipitales opresivas. Dos meses después del iniciode las primeras manifestaciones, presentó movimientos involuntarios en las piernas, y dificultad para la deglución de los alimentos sólidos. Al examen físico se constató: fasciculaciones en la lengua, dismetría bilateral a predominio derecho, disdiadococinesia, Romberg con lateralización a la derecha, reflejos osteotendinosos aumentados a predominio crural, con clonus rotuliano derecho y tobillo izquierdo, Babinski derecho. En la resonancia magnética de cráneo se observó descenso de lasamígdalas cerebelosas, a través del agujero magno, y se diagnosticó malformación de Chiari tipo I. Sele realizó tratamiento quirúrgico: descompresión de la fosa posterior mediante craniectomía sin duroplastia, apoyado por ultrasonido intraoperatorio. El paciente evolucionó favorablemente.Conclusiones: El ultrasonido intraoperatorio proporcionó información sobre la circulación del líquidocefalorraquídeo (LCR) a través de la unión craneoespinal. Con este resultado el equipo quirúrgico no tuvo que realizar la apertura dural y el paciente presentó una evolución satisfactoria(AU)

Objective: To describe the intraoperative utility of ultrasonography in decompressing the posterior fossa in the Chiari type I malformation surgeryCase report: An 11-year old male patient went to the neurosurgery service at Octavio de la Concepción de la Pedraja University Pediatric Hospital in Holguín accompanied by his parents. They reported that approximately four months ago the child had lost acute consciousness, and he began withoppressive occipital headaches. Two months after the beginning of the first manifestations, he had involuntary movements in the legs, and difficulty swallowing solid foods. The physical examination showed fasciculations in the tongue, bilateral dysmetry at right predominance, dysdiadocokinesia,Romberg with lateralization to the right, osteotendinous reflexes increased to crural predominance, with right patellar clone and left ankle, right Babinski. Magnetic resonance imaging of the skullshowed a decrease in cerebellar tonsils, through the great hole, and Chiari type I malformation was diagnosed. He underwent surgical treatment, decompression of the posterior fossa by craniectomy without duroplasty, supported by intraoperative ultrasound. The patient evolved favorably.Conclusions: Intraoperative ultrasound provided information on cerebrospinal fluid (CSF) circulation through the cranioespinal junction, which allowed the surgical team not to perform the dural opening and the patient had a satisfactory evolution(AU)

Audio-vestibular signs and symptoms in Chiari malformation type i. Case series and literature review.

INTRODUCTION: Chiari malformation is an alteration of the base of the skull with herniation through the foramen magnum of the brain stem and cerebellum. Although the most common presentation is occipital headache, the association of audio-vestibular symptoms is not rare. The aim of our study was to describe audio-vestibular signs and symptoms in Chiari malformation type i (CM-I). MATERIALS AND METHODS: We performed a retrospective observational study of patients referred to our unit during the last 5 years. We also carried out a literature review of audio-vestibular signs and symptoms in this disease. RESULTS: There were 9 patients (2 males and 7 females), with an average age of 42.8 years. Five patients presented a Ménière-like syndrome; 2 cases, a recurrent vertigo with peripheral features; one patient showed a sudden hearing loss; and one case suffered a sensorineural hearing loss with early childhood onset. The most common audio-vestibular symptom indicated in the literature in patients with CM-I is unsteadiness (49%), followed by dizziness (18%), nystagmus (15%) and hearing loss (15%). Nystagmus is frequently horizontal (74%) or down-beating (18%). Other audio-vestibular signs and symptoms are tinnitus (11%), aural fullness (10%) and hyperacusis (1%). Occipital headache that increases with Valsalva manoeuvres and hand paresthesias are very suggestive symptoms. CONCLUSIONS: The appearance of audio-vestibular manifestations in CM-I makes it common to refer these patients to neurotologists. Unsteadiness, vertiginous syndromes and sensorineural hearing loss are frequent. Nystagmus, especially horizontal and down-beating, is not rare. It is important for neurotologists to familiarise themselves with CM-I symptoms to be able to consider it in differential diagnosis.

Sleep disturbance: a forgotten syndrome in patients with Chiari I malformation.

INTRODUCTION: Chiari type I malformation (CM-I) is characterised by caudal ectopia of the cerebellar tonsils through the foramen magnum. This is associated with brain stem, high spinal cord, and cranial nerve compression phenomena. The most frequent symptoms are occipital headaches and dizziness. Less well-known symptoms are sleep disorders and nocturnal respiratory abnormalities. SOURCES: MEDLINE and information from patients evaluated at the Neurosurgery and Clinical Neurophysiology Departments at Hospital Universitario Vall d'Hebron. DEVELOPMENT: Review article based on data obtained from MEDLINE articles since 1966, using combinations of the following keywords: «Chiari malformation¼ or «Arnold-Chiari malformation¼ and «sleep apnea¼ or «sleep disorders¼. CONCLUSIONS: CM-I patients show a higher prevalence of sleep disorders than that observed in the general population. Some studies report a 50% prevalence of sleep apnea-hypopnea syndrome (SAHS), probably associated with sudden death in some cases. These results support analysing sleep respiratory parameters in theses patients. Identifying SAHS symptoms may help optimise treatment, thereby improving quality of life and prognosis.

Síndrome de Marcapaso en paciente con Síndrome de QT Prolongado / Pacemaker syndrome in long QT syndrome patient

El síndrome de marcapasos es generado por la desincronización de la actividad auricular con la ventricular durante el marcapaso ventricular VVI en pacientes portadores de enfermedad del nodo. La enfermedad evoluciona de meses hasta varios años después del implante del marcapaso, siendo más frecuente en pacientes adultos mayores. El único tratamiento es el implante de un electrodo auricular para una estimulación aurículo ventricular sincrónica. Se presenta el caso de una paciente diagnosticada con enfermedad del nodo sinusal asociada a un QT prolongado, a la cual se le implantó un marcapaso VVIR, luego de algunos meses comenzó a presentar síntomas de insuficiencia cardiaca,a los 3 años del implante presento un episodio sincopal,en cuya evaluación con Holter ECG se registró un episodio de una taquicardia ventricular no sostenida observándose la presencia de ondas P retrogradas tras cada estimulación ventricular con marcapasos. Se consideró la probabilidad de un síncope arrítmico, que se manejó con Amiodarona. Se diagnosticó síndrome de marcapaso, realizando un mejoramiento del marcapaso por un equipo bicameral, con lo cual todos los síntomas de insuficiencia cardiaca desaparecieron. No se repitió el evento sincopal y desde la época la paciente se maneja en una capacidad funcional normal.

Pacemaker syndrome is an entity generated by a desynchronization between the auricular and ventricular activity during the paced ventricleVVI in patients with node disease.This syndrome can develop in moths even years after the pacemaker implant, being more frequent in elderly patients. The only treatment is to implant an auricular electrode for a synchronic atrioventricular stimulation. It presents the case of a patient diagnosed with a sinus node disease associated to long QT, for this reason it was implanted a pacemaker VVIR, few months later the patient started to have symptoms of heart failure, three years after that presented a syncope episodes showed in a Holter ECG study that reported unsustainable ventricular tachycardia episode and retrograde P waves after every ventricular stimulation sent by the pacemaker. The probability of an arrhythmic syncope was considered treated with Amiodarona. Pacemaker syndrome was diagnosed, making an improvement by a dual chamber pacemaker and all symptoms of heart failure disappeared. Syncopal event was not repeated and from the time the patient is operated on a normal functional capacity.

Siringomielia asociado a Malformación de Chiari tipo I / Associated syringomyelia Chiari Malformation type I

La Siringomielia asociada a Malformación de Chiari tipo I, se refiere a una cavidad formada en la médula espinal debido a la obstrucción del canal medular por el desplazamiento de las amígdalas cerebelosas hacia el agujero magno, manifestándose entre los 25-40 años, con cuadros progresivos de dorsalgias, cervicalgias, dolor de extremidades uni-bilateral, pérdida de sensibilidad; dependiendo del tamaño de la cavidad, la medula espinal puede comprimirse y generar la lesión irreversible de la médula espinal. Se presenta un caso clínico de Siringomielia asociada a Malformación de Chiari tipo I; que presentó cuadro clínico de larga data previa a su diagnóstico; caracterizado por dorsalgias recurrentes que fueron tratadas con diclofenaco y complejo B, pensando en problema muscular. Se le diagnostica por resonancia magnética (RM), y el tratamiento fue la descompresión de fosa posterior; un año después de su tratamiento quirúrgico se le realiza una RM de control donde hay ausencia de la Siringomielia.

Syringomyelia associated with Chiari I malformation, refers to a cavity in the spinal cord because obstruction of the spinal canal by the displacement of the cerebellar tonsils into the magnum foramen, manifested during 25-40 years, with progressive frames of back pain, cervical pain, uni-bilateral limb pain, loss of sensitivity, depending on the size of the cavity, can compress the spinal cord and generate irreversible injury of the spinal cord. It is reports a case of syringomyelia associated with Chiari I malformation that presents longstanding clinical disorder prior to the diagnosis, characterized by recurrent back pain treated just with diclofenac and B complex, thinking as a in muscle problem. Diagnosed by magnetic resonance imaging (MRI), and the treatment was a posterior fossa decompression; a year after the surgery treatment a second control MRI scan was performed with absent of syringomyelia.