Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases. / Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos.

INTRODUCTION: Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications. CASE REPORT: We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal. DISCUSSION AND CONCLUSIONS: This is a type of VPA-related encephalopathy, different from dose-dependent toxic encephalopathy, hyperammonaemic encephalopathy or encephalopathy related to liver failure. In children, it causes cognitive, motor, mood and behavioral deterioration, and may be accompanied by epileptic decompensation. Withdrawing the drug leads to complete clinical-radiological recovery, and reducing the dose leads to improvement.

TITLE: Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos.Introducción. La pseudoatrofia cerebral y cerebelosa es un efecto adverso infrecuente del ácido valproico (VPA) que debemos conocer por sus implicaciones diagnósticas y terapéuticas. Caso clínico. Presentamos tres casos de niños de entre 5 y 9 años, con epilepsia y resonancia magnética craneal previa normal, que llevaban el fármaco con dosis correctas. La pseudoatrofia se manifiesta de forma subaguda con síntomas e imagen de atrofia cerebral y/o cerebelosa, reversible tras la retirada del fármaco. Discusión y conclusiones. Se trata de un tipo de encefalopatía relacionada con VPA diferente a la encefalopatía tóxica dependiente de la dosis, la encefalopatía hiperamoniémica o la relacionada con fallo hepático. En niños, cursa con deterioro cognitivo, motor, anímico y conductual, y puede acompañarse de descompensación epiléptica. La retirada del fármaco conlleva una recuperación completa clinicorradiológica, y la disminución de dosis, una mejoría.

Pseudoatrofia cerebral y cerebelosa asociada a ácido valproico. Descripción de tres casos pediátricos / Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases

Introducción La pseudoatrofia cerebral y cerebelosa es un efecto adverso infrecuente del ácido valproico (VPA) que debemos conocer por sus implicaciones diagnósticas y terapéuticas. Caso clínico Presentamos tres casos de niños de entre 5 y 9 años, con epilepsia y resonancia magnética craneal previa normal, que llevaban el fármaco con dosis correctas. La pseudoatrofia se manifiesta de forma subaguda con síntomas e imagen de atrofia cerebral y/o cerebelosa, reversible tras la retirada del fármaco. Discusión y conclusiones. Se trata de un tipo de encefalopatía relacionada con VPA diferente a la encefalopatía tóxica dependiente de la dosis, la encefalopatía hiperamoniémica o la relacionada con fallo hepático. En niños, cursa con deterioro cognitivo, motor, anímico y conductual, y puede acompañarse de descompensación epiléptica. La retirada del fármaco conlleva una recuperación completa clinicorradiológica, y la disminución de dosis, una mejoría. (AU)

INTRODUCTION Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications. CASE REPORT We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal. Discussion and conclusions. This is a type of VPA-related encephalopathy, different from dose-dependent toxic encephalopathy, hyperammonaemic encephalopathy or encephalopathy related to liver failure. In children, it causes cognitive, motor, mood and behavioral deterioration, and may be accompanied by epileptic decompensation. Withdrawing the drug leads to complete clinical-radiological recovery, and reducing the dose leads to improvement. (AU)

[Variability of the clinical expression of KCNB1 encephalopathy]. / Variabilidad de la expresión clínica de la encefalopatía KCNB1.

INTRODUCTION: The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined. AIM: To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients. PATIENTS AND METHODS: Retrospective study of four patients from three families with KCNB1 encephalopathy, including an analysis of the clinical and electroencephalographic features of epilepsy, associated neurological manifestations and neurodevelopmental pattern. RESULTS: In two of them, the mutation in KCNB1 was de novo; the other two, who were sisters, inherited the variant from a parent with germline mosaicism. All had mild-to-moderate intellectual disability, two patients had autistic spectrum disorder and two had attention deficit hyperactivity disorder. Only case 2 displayed alterations in the MRI brain scan: progressive cortical atrophy. Three of them developed epilepsy (cases 1-3). Case 1: onset at 9.5 months with West syndrome that was well controlled with vigabatrine and zonisamide. Case 2: onset at 13 months with West syndrome, evolutionary development of polymorphic seizures (atonic, hypermotor, dysautonomic and tonic) that were refractory to 10 antiepileptic drugs and corticosteroids. Accompanied by a movement disorder characterised by ataxia, dyskinesias and tremor. Case 3: onset at 14.5 years with atonic seizures, multifocal EEG pattern and adequate control with levetiracetam. CONCLUSIONS: KCNB1 encephalopathy has a heterogeneous natural history, mainly with respect to epilepsy, ranging from patients with refractory epilepsy to patients without any epileptic seizures. All had neurodevelopmental disorders, such as intellectual disability or autism spectrum disorder, independent of epilepsy.

TITLE: Variabilidad de la expresión clínica de la encefalopatía KCNB1.Introducción. El gen KCNB1 codifica un canal de potasio dependiente del voltaje que regula corrientes transmembrana en las neuronas piramidales. Variantes en heterocigosis se han asociado recientemente con encefalopatías epilépticas de inicio precoz y discapacidad intelectual, pero su caracterización clínica no está completamente definida. Objetivo. Describir el espectro clínico asociado con variantes de KCNB1 en pacientes pediátricos. Pacientes y métodos. Estudio retrospectivo de cuatro pacientes procedentes de tres familias con encefalopatía KCNB1, analizando características clínicas y electroencefalográficas de la epilepsia, manifestaciones neurológicas asociadas y patrón de neurodesarrollo. Resultados. En dos, la mutación en KCNB1 fue de novo; las otras dos, hermanas, heredaron la variante de un progenitor con mosaicismo germinal. Todos presentaban discapacidad intelectual leve-moderada; dos pacientes, trastorno del espectro autista; y otros dos, trastorno por déficit de atención/hiperactividad. Sólo el caso 2 mostro´ alteraciones en la resonancia magnética cerebral: atrofia cortical evolutiva. Tres desarrollaron epilepsia (casos 1-3). Caso 1: inicio a los 9,5 meses con síndrome de West bien controlado con vigabatrina y zonisamida. Caso 2: inicio a los 13 meses con síndrome de West; desarrollo evolutivo de crisis polimorfas (atónicas, hipermotoras, disautonómicas y tónicas) refractarias a 10 fármacos antiepilépticos y corticoides. Asocio´ trastorno del movimiento caracterizado por ataxia, discinesias y temblor. Caso 3: inicio a los 14,5 años con crisis atónicas, patrón multifocal en el electroencefalograma y adecuado control con levetiracetam. Conclusiones. La encefalopatía KCNB1 presenta una evolución natural heterogénea, principalmente respecto a la epilepsia, y se observan desde pacientes con epilepsia refractaria hasta pacientes sin crisis epilépticas. Todos cursaron con alteraciones del neurodesarrollo, como discapacidad intelectual o trastorno del espectro autista, de forma independiente a la epilepsia.

Variabilidad de la expresión clínica de la encefalopatía KCNB1 / Variability of the clinical expression of KCNB1 encephalopathy

Introducción: El gen KCNB1 codifica un canal de potasio dependiente del voltaje que regula corrientes transmembrana en las neuronas piramidales. Variantes en heterocigosis se han asociado recientemente con encefalopatías epilépticas de inicio precoz y discapacidad intelectual, pero su caracterización clínica no está completamente definida.Objetivo: Describir el espectro clínico asociado con variantes de KCNB1 en pacientes pediátricos. Pacientes y métodos: Estudio retrospectivo de cuatro pacientes procedentes de tres familias con encefalopatía KCNB1, analizando características clínicas y electroencefalográficas de la epilepsia, manifestaciones neurológicas asociadas y patrón de neurodesarrollo. Resultados: En dos, la mutación en KCNB1 fue de novo; las otras dos, hermanas, heredaron la variante de un progenitor con mosaicismo germinal. Todos presentaban discapacidad intelectual leve-moderada; dos pacientes, trastorno del espectro autista; y otros dos, trastorno por déficit de atención/hiperactividad. Sólo el caso 2 mostro´ alteraciones en la resonancia magnética cerebral: atrofia cortical evolutiva. Tres desarrollaron epilepsia (casos 1-3). Caso 1: inicio a los 9,5 meses con síndrome de West bien controlado con vigabatrina y zonisamida. Caso 2: inicio a los 13 meses con síndrome de West; desarrollo evolutivo de crisis polimorfas (atónicas, hipermotoras, disautonómicas y tónicas) refractarias a 10 fármacos antiepilépticos y corticoides. Asocio´ trastorno del movimiento caracterizado por ataxia, discinesias y temblor. Caso 3: inicio a los 14,5 años con crisis atónicas, patrón multifocal en el electroencefalograma y adecuado control con levetiracetam. Conclusiones: La encefalopatía KCNB1 presenta una evolución natural heterogénea, principalmente respecto a la epilepsia, y se observan desde pacientes con epilepsia refractaria hasta pacientes sin crisis epilépticas...(AU)

Introduction: The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined. Aim: To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients. Patients and methods. Retrospective study of four patients from three families with KCNB1 encephalopathy, including an analysis of the clinical and electroencephalographic features of epilepsy, associated neurological manifestations and neurodevelopmental pattern. Results: In two of them, the mutation in KCNB1 was de novo; the other two, who were sisters, inherited the variant from a parent with germline mosaicism. All had mild-to-moderate intellectual disability, two patients had autistic spectrum disorder and two had attention deficit hyperactivity disorder. Only case 2 displayed alterations in the MRI brain scan: progressive cortical atrophy. Three of them developed epilepsy (cases 1-3). Case 1: onset at 9.5 months with West syndrome that was well controlled with vigabatrine and zonisamide. Case 2: onset at 13 months with West syndrome, evolutionary development of polymorphic seizures (atonic, hypermotor, dysautonomic and tonic) that were refractory to 10 antiepileptic drugs and corticosteroids. Accompanied by a movement disorder characterised by ataxia, dyskinesias and tremor. Case 3: onset at 14.5 years with atonic seizures, multifocal EEG pattern and adequate control with levetiracetam.Conclusions: KCNB1 encephalopathy has a heterogeneous natural history, mainly with respect to epilepsy, ranging from patients with refractory epilepsy to patients without any epileptic seizures. All had neurodevelopmental disorders, such as intellectual disability or autism spectrum disorder, independent of epilepsy.(AU)

Endometrial polyp or neoplasia? A case-control study in women with polyps at ultrasound.

OBJECTIVES: To identify factors associated with endometrial neoplasia in women diagnosed with endometrial polyp at transvaginal ultrasound. METHODS: Within a population of 1390 consecutive patients undergoing hysteroscopy following an ultrasonographic diagnosis of polyps, we compared the cases with a final diagnosis of endometrial neoplasia with controls with benign endometrial polyps. The controls were selected randomly in a ratio of 4 : 1 (controls : cases). Bivariate statistical analysis and multiple logistic regression were used to measure the association between various variables and endometrial neoplasia. RESULTS: Sixteen cases of endometrial neoplasia were compared to 64 controls with confirmed benign endometrial polyps. All cases of neoplasia were among symptomatic women, while 40.62% of women with benign polyps had been referred to hysteroscopy after a routine ultrasound and were asymptomatic. Women with endometrial neoplasia were significantly older (mean age 64.19 ± 9.382 vs. 52.03 ± 9.846 years; p < 0.001) and had a significantly greater body mass index (median 27.66 vs. 24.59 kg/m(2); p < 0.001). Other factors statistically associated with endometrial neoplasia were postmenopausal status and bleeding as a main symptom. At multivariate analysis with logistic regression, the only factors showing a statistically significant association with endometrial neoplasia were older age (odds ratio 1.102; 95% confidence interval 1.015-1.198) and bleeding (odds ratio 13.7; 95% confidence interval 1.486-126.278). CONCLUSION: When polyps are diagnosed at ultrasound, bleeding and an older age are independently associated with endometrial neoplasia. A significant proportion of asymptomatic women is referred to hysteroscopy because of a polyp seen at routine ultrasound, although malignancy is highly unlikely in these cases.

Malignant and premalignant changes in the endometrium of women with an ultrasound diagnosis of endometrial polyp.

The association between polyps and endometrial cancer is under debate. The main objectives of this study were to study the frequency and the characteristics of malignant and premalignant endometrial changes in women with endometrial polyp at ultrasound. The study population consisted of 1,390 consecutive patients that were referred to office hysteroscopy because of the ultrasonographic diagnosis of endometrial polyps. A total of 16 cases of endometrial neoplasia were diagnosed (1.15%). The frequencies of atypia and cancer in our population were 0.14% and 1.01%, respectively. All patients, except one, were postmenopausal (93.8%). All had undergone the initial ultrasonographic assessment because of symptoms (bleeding in the 93.8%). The neoplasia was not confined to the polyp in 75% of the cases. Nine cases had a lower risk disease (56.25%; atypical hyperplasia or endometrial cancer stage IA-G1,2), while seven had a higher risk cancer (43.75%; ≥ stage IA-G3). Patients with a higher risk disease were found to be significantly younger, and their polyps were smaller, albeit non-significantly. In spite of the common practice to refer all women with an ultrasound diagnosis of polyp to hysteroscopy, our data show how the prevalence of endometrial neoplasia in these patients is low (1.15%). Moreover, the malignancy is not confined to a polyp in most of the cases.

Dolor y medicina complementaria y acupuntura / Pain and complementary medicine and acupuncture

El objetivo de este artículo es entregar información documentada sobre la situación actual de la Medicina Complementaria y la Acupuntura en Chile, su definición, reglamentación, mecanismos de acción y evidencia. Busca orientar sobre el uso de estas herramientas terapéuticas que son cada vez más solicitadas en el país.

Corrección intrauterina de mielomeningocele: experiencia del programa de medicina y terapia fetal del Hospital Universitario Virgen del Rocío / Intrauterine myelomeningocele repair: Experience of the fetal medicine and therapy program of the Virgen de Rocío University Hospital

La forma más frecuente de espina bífida es el mielomeningocele, para el que no existe un tratamiento postnatal óptimo. Además del trastorno motor o sensitivo dependiente del nivel de la lesión, los niños suelen tener asociada la malformación de Arnold Chiari ii. El mielomeningocele presenta una alta mortalidad y puede acompañarse, hasta en el 80-90%, de hidrocefalia que es responsable de la gran afectación neurocognitiva, precisando de derivación para su supervivencia. La reparación intrauterina de malformaciones fetales mediante acceso abierto a través de histerotomía se ha convertido en una opción terapéutica gracias a la mejora de las técnicas quirúrgicas y anestésicas, y de la correspondiente instrumentación, que han convertido este tipo de intervenciones en una práctica relativamente frecuente. El tratamiento anestésico debe orientarse tanto a la madre como al feto, siendo importante mantener controlados los factores hemodinámicos que regulan el flujo placentario, la dinámica uterina, las pérdidas sanguíneas y el bienestar fetal. Dentro de nuestro Programa de Medicina y Terapia Fetal se han realizado 21 procedimientos de cirugía fetal abierta, 17 procedimientos EXIT y 4 procedimientos para la corrección intrauterina de mielomeningocele fetal. Describimos nuestra experiencia en la corrección intrauterina de mielomeningocele fetal mediante cirugía fetal abierta (AU)

The most frequent form of spina bifida is myelomeningocele. There is no optimal postnatal treatment for this defect. In addition to the motor or sensory deficits, which depend on the location of the lesion, the defect is usually associated with Chiari ii malformation in affected children. Myelomeningocele has high mortality and, in up to 80% to 90% of patients, can be accompanied by hydrocephalus, which causes severe neurocognitive impairment and requires the patient to be shunted for survival. Intrauterine repair of fetal malformations employing open access through hysterotomy has become a therapeutic option due to improved anesthetic and surgical techniques and instrumentation, which have allowed this type of intervention to become relatively frequent. Anesthetic treatment should focus on both the mother and fetus and the hemodynamic factors regulating placental flow, uterine dynamics, blood loss and fetal well-being must remain well-controlled. Within our Program for Fetal Medicine and Therapy, 21 open fetal interventions have been performed: 17 EXIT procedures and 4 procedures for the intrauterine correction of fetal myelomeningocele. We describe our experience of the intrauterine repair of fetal myelomeningocele through open fetal surgery (AU)

[Intrauterine myelomeningocele repair: experience of the fetal medicine and therapy program of the Virgen de Rocío University Hospital]. / Corrección intrauterina de mielomeningocele: experiencia del programa de medicina y terapia fetal del Hospital Universitario Virgen del Rocío.

The most frequent form of spina bifida is myelomeningocele. There is no optimal postnatal treatment for this defect. In addition to the motor or sensory deficits, which depend on the location of the lesion, the defect is usually associated with Chiari ii malformation in affected children. Myelomeningocele has high mortality and, in up to 80% to 90% of patients, can be accompanied by hydrocephalus, which causes severe neurocognitive impairment and requires the patient to be shunted for survival. Intrauterine repair of fetal malformations employing open access through hysterotomy has become a therapeutic option due to improved anesthetic and surgical techniques and instrumentation, which have allowed this type of intervention to become relatively frequent. Anesthetic treatment should focus on both the mother and fetus and the hemodynamic factors regulating placental flow, uterine dynamics, blood loss and fetal well-being must remain well-controlled. Within our Program for Fetal Medicine and Therapy, 21 open fetal interventions have been performed: 17 EXIT procedures and 4 procedures for the intrauterine correction of fetal myelomeningocele. We describe our experience of the intrauterine repair of fetal myelomeningocele through open fetal surgery.

mRNA expression of the putative antimetastatic gene BRMS1 and of apoptosis-related genes in breast cancer.

Breast cancer metastasis suppressor-1 (BRMS1) is a putative antimetastatic gene. However, results relating its expression to the prognosis of breast cancer are still controversial, and all studies carried out to date have failed to show a relationship between the expression of BRMS1 and axillary lymph node metastasis in breast cancer. It has been recently suggested that BRMS1 may exert its physiological role through the modulation of apoptosis. In order to test this hypothesis, we studied the expression of BRMS1 and genes known to be directly related with apoptosis in human breast carcinoma. The expression of mRNA corresponding to BRMS1, BCL2, BAX, CASP3 and the apoptosis-related X-chromosome RNA binding motif (RBM) genes (RBMX, RBM3, RBM10 small and large variant) was studied by means of differential RT-PCR in 94 samples obtained from previously untreated patients with breast carcinoma. A significant (p=0.03) inverse correlation between BRMS1 mRNA expression and expression of the mRNA corresponding to the large variant of the X-chromosome RBM10 gene was found. The degree of direct correlation with another member of the X-chromosome RBM gene family, RBMX, almost attained statistical significance (p=0.06). These results point towards a possible link between BRMS1 expression and apoptosis in human breast cancer through a relationship with the expression of genes belonging to the X-chromosome RBM family.

Periodontitis and osteoporosis: a systematic review.

BACKGROUND: Osteoporosis and periodontitis are frequent disorders that affect aging populations. It has been hypothesized that both conditions may be related. OBJECTIVE: To determine whether dental osteoporosis is a local manifestation of systemic bone loss having similar etiology and risk factors, or whether it is an independent process depending primarily on factors that cause periodontitis. METHODS: A systematic review of clinical trials assessing the relationship between osteoporosis and periodontitis was carried out. An electronic search was made based on Internet search engines, MEDLINE (from 1966 to December 2009) and the Cochrane Controlled Clinical Trials Register. RESULTS: A total of 145 studies dealing with the relationship osteoporosis-periodontitis were identified. Of them, 35 were considered suitable for selection. Studies on maxillary and/or mandible radiological findings have a positive correlation in the majority of the cases (18 positive vs. three negative), whereas the findings on clinical periodontal examination are inconclusive (six positive vs. five negative). There were ten studies in which a diagnosis of osteoporosis was made, based on the existence of non-traumatic fracture, while there were nine studies using radiographs for diagnosis, of which six studies were found to have a positive correlation. There was only one study based on a clinical periodontal examination that found a positive correlation. CONCLUSIONS: The majority of the studies suggested a relationship between osteoporosis and periodontitis. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully give an early warning for osteoporosis risk.

The value of hysteroscopic exploration for abnormal uterine bleeding.

STUDY OBJECTIVE: To determine sensitivity, specificity, positive predictive value, negative predictive value, and global diagnostic precision of hysteroscopic exploration in the diagnosis of endometrial hyperplasia and adenocarcinoma in women with abnormal uterine bleeding. DESIGN: Retrospective analysis. SETTING: University-affiliated hospital. PATIENTS: One thousand three hundred ninety-eight patients with abnormal uterine bleeding, 57.3% premenopausal and 42.6% postmenopausal. INTERVENTIONS: Diagnostic hysteroscopy and subsequent dilatation and curettage. MEASUREMENTS AND MAIN RESULTS: Endometrium was classified hysteroscopically as normal, atrophic, endometrial hyperplasia, and endometrial carcinoma. Histopathologic diagnosis was performed to determine the efficacy of hysteroscopy in diagnosing endometrial hyperplasia and adenocarcinoma. For endometrial hyperplasia in premenopausal women, sensitivity was 71.8%, specificity 96.4%, and global diagnostic precision 92.5%; in postmenopausal women, respective figures were 85. 1%, 100%, and 97.3%. For diagnosing adenocarcinoma in premenopausal patients, hysteroscopy was 100% sensitive, with specificity 99.4% and global diagnostic precision 99.5%; in postmenopausal women, respective figures were 100%, 99.4%, and 99.5%. CONCLUSIONS: In women with abnormal uterine bleeding, diagnostic hysteroscopy is a basic tool that allows precise diagnosis of endouterine lesions such as polyps and submucous myomas. It also is highly accurate for evaluating endometrial adenocarcinoma and hyperplasia.

Experience with epigastric free flap transfer in the rat: technique and results.

We have described the advantages and disadvantages of using the rat epigastric free flap as a means of studying transplantation phenomena. The study comprises 20 epigastric free flap autografts in rats. After 1 1/2 years of working on the model, we achieved a 75% success rate in the last 20 consecutive procedures. From our experience with this model, we feel that the rat epigastric flap has a place in the study of transplantation phenomena in the experimental laboratory. In addition, we feel that this is an excellent technical exercise for maintaining proficiency in performing microvascular anastomoses.