Hemophilia and non-accidental head trauma in two siblings: lessons and legal implications.

Non-accidental head trauma (NAHT) is a common cause of traumatic brain injury in childhood, origin of profound and disabling neurological sequalae, and in the most disgraceful cases, ultimately death.Subdural hematoma (SDH) is the most common intracranial finding in NAHT. On the other hand, congenital bleeding disorders are a minor but a significant cause of ICH in the neonate and toddler. Not uncommonly, intracranial bleeding is the first sign of a severe inherited coagulation disorder. In the presence of an unexpected intracranial bleeding after a minor trauma or without a clear history of the related events, physicians and caregivers may be confronted to the dilemma of a possible child abuse. It must be bear in mind that physical abuse and bleeding disorders can co-exist in the same child.We report here the case of two siblings in whom a diagnosis of hemophilia coexisted with the presumption of a non-accidental head trauma. Child abuses were inflicted in both children with a spare time of 2 years. A diagnosis of mild hemophilia was prompted in the first sibling after initial NAHT, while inflicted trauma was evident in the second sibling after neuroimaging findings and concomitant lesions. Lessons from this case in co-existing bleeding disorders and inflicted trauma and legal implications derived will be discussed thereafter.The possibility of a bleeding disorder should be considered in all children presenting with unexplained bleeding at a critical site in the setting of suspected physical maltreatment, particularly intracranial hemorrhage (ICH).

Megalencephaly-capillary malformation syndrome and associated hydrocephalus: treatment options and revision of the literature.

PURPOSE: We describe our series of 4 patients with megalencephaly-capillary malformation syndrome (MCAP) and review the literature in order to assess the optimal treatment for the associated hydrocephalus. METHODS: We review our institutional series of hydrocephalus associated with MCAP and review the literature, analyzing the causes that could originate the hydrocephalus and the different types of treatments proposed for them. RESULTS: Of our patients treated with ventriculoperitoneal (VP) shunt, one suffered a surgical revision of the shunt and died due to a cranial trauma unrelated to her syndrome or the previous shunt surgery, and the other did not undergo surgical revisions until the end of her follow-up. Our patients treated with endoscopic third ventriculostomy (ETV) have improved their symptomatology and have not suffered of any complications related to the hydrocephalus after the ETV surgery. CONCLUSIONS: We update the treatment of MCAP-associated hydrocephalus and propose ETV as a valid treatment, as it seems a safe procedure with a low rate of complications.

Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life.

INTRODUCTION: Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. METHODS: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients' medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. RESULTS: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. CONCLUSIONS: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life.

Mild clinical and biochemical phenotype in two patients with PMM2-CDG (congenital disorder of glycosylation Ia).

Phosphomannomutase 2 deficiency (PMM2-CDG) patients may present as mild phenotypes, with the cerebellum frequently involved. In those cases, false-negative results in screening may occur when applying conventional biochemical procedures. Our aim was to report two patients with a diagnosis of PMM2-CDG presenting with mild clinical phenotype. Patient 1-at 9 months of age, she presented with just psychomotor delay, tremor, hypotonia, and slight lipodystrophy. Patient 2-she presented at 8 months of age with psychomotor delay, hand stereotypes, hypotonia, convergent bilateral strabismus, and tremor but no lipodystrophy. Routine biochemical parameters including blood count, clotting factors, proteins, and thyroid hormone were normal in both cases. Cranial MRI evidenced mild cerebellar atrophy with moderate vermis hypoplasia. In case 1, sialotransferrin pattern showed very slightly increased disialotransferrin with no asialotransferrin, and in case 2, the transferrin pattern was impaired in the first study but nearly normal in the second. Nevertheless, in all the samples, quantification of the patterns obtained by capillary zone electrophoresis analysis gave results out of the control range. High residual PMM2 activity was observed in both cases and the genetic analysis showed that patient 1 was heterozygous for c.722G>C (p.C241S) and c.368G>A (p.R123Q) mutations, and patient 2 showed the c.722G>C and the c.470T>C (p.F157S) mutations in the PMM2 gene. We would like to stress the importance of the use of sensitive semiquantitative methods of screening for CDG in order to achieve early identification of patients with mild phenotypes. Intentional tremor was an atypical but remarkable clinical feature in both cases, and the global cerebellar atrophy with vermis hypoplasia reinforced the early clinical suspicion of a PMM2-CDG disease.

Granulosa cell tumor and endometrial cancer: a case report and review of the literature.

Granulosa cell tumors (GCTs) of the ovary are an uncommon type of ovarian cancer, representing only 2-5%. Frequently, their tumoral cells present some features of normal granulosa cells, like hormonal production. As a consequence, this neoplasia can be diagnosed either by common ovarian cancer symptoms or endometrial pathologies due to an estrogenic effect. Symptoms caused by estrogen production can also give rise to different clinical manifestations depending on whether they appear in postmenopausal or young women. In the case we present below, a patient was referred for presenting postmenopausal bleeding of one year's duration. Once endometrial cancer was diagnosed and subsequently staged, an ovarian mass was detected. We report an atypical case of ovarian cancer with the aim of reviewing the clinical features of GCT, as well as its prognosis, treatment and follow-up recommendations, according to the available literature.

Gliomatosis cerebri and Rasmussen's encephalitis: Two different entities causing refractory epilepsy. Comparison through two clinical cases.

BACKGROUND AND IMPORTANCE: Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. CLINICAL PRESENTATION: We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. CONCLUSION: The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system.

BACKGROUND: The SLC39A14, SLC30A10 and SLC39A8 are considered to be key genes involved in manganese (Mn) homeostasis in humans. Mn levels in plasma and urine are useful tools for early recognition of these disorders. We aimed to explore further biomarkers of Mn deposition in the central nervous system in two siblings presenting with acute dystonia and hypermanganesemia due to mutations in SLC39A14. These biomarkers may help clinicians to establish faster and accurate diagnosis and to monitor disease progression after chelation therapy is administered. RESULTS: A customized gene panel for movement disorders revealed a novel missense variant (c.311G > T; p.Ser104Ile) in SLC39A14 gene in two siblings presenting at the age of 10 months with acute dystonia and motor regression. Mn concentrations were analyzed using inductively coupled mass spectrometry in plasma and cerebrospinal fluid, disclosing elevated Mn levels in the index case compared to control patients. Surprisingly, Mn values were 3-fold higher in CSF than in plasma. We quantified the pallidal index, defined as the ratio between the signal intensity in the globus pallidus and the subcortical frontal white matter in axial T1-weighted MRI, and found significantly higher values in the SLC39A14 patient than in controls. These values increased over a period of 10 years, suggesting the relentless pallidal accumulation of Mn. Following genetic confirmation, a trial with the Mn chelator Na2CaEDTA led to a reduction in plasma Mn, zinc and selenium levels. However, parents reported worsening of cervical dystonia, irritability and sleep difficulties and chelation therapy was discontinued. CONCLUSIONS: Our study expands the very few descriptions of patients with SLC39A14 mutations. We report for the first time the elevation of Mn in CSF of SLC39A14 mutated patients, supporting the hypothesis that brain is an important organ of Mn deposition in SLC39A14-related disease. The pallidal index is an indirect and non-invasive method that can be used to rate disease progression on follow-up MRIs. Finally, we propose that patients with inherited defects of manganese transport should be initially treated with low doses of Na2CaEDTA followed by gradual dose escalation, together with a close monitoring of blood trace elements in order to avoid side effects.

[Hydrocephalus due to hyperplasia of the choroid plexuses in a patient with trisomy 9 mosaicism. A real diagnostic and therapeutic challenge]. / Hidrocefalia por hiperplasia de plexos coroideos en un paciente con mosaicismo de trisomia 9. Un verdadero reto diagnostico y terapeutico.

INTRODUCTION: Trisomy 9 is an unusual chromosome abnormality in live-born patients, which is frequently accompanied by functional and structural anomalies of the central nervous system. Among many other alterations, several studies have been published in the English-speaking literature that show an association between chromosome 9 abnormality and pathologies affecting the choroid plexuses. CASE REPORT: We report the case of a 4-month-old male with trisomy 9 mosaicism associated to hydrocephalus secondary to choroid plexus hyperplasia, who was referred due to a clinical picture of intracranial hypertension. The cerebrospinal fluid (CSF) drainage procedure that was initially chosen caused massive ascites due to an excessive production of CSF, and led to a cascade of multiple surgical interventions, which included endoscopic and drainage procedures. CONCLUSIONS: This is another example of an association between choroid plexus pathologies and chromosome 9 abnormality. Due to its scarce incidence, diagnosis of hydrocephalus secondary to plexus hyperplasia is difficult, as is selecting its most suitable treatment. In this type of hydrocephalus there is a double pathophysiological mechanism, which involves an increase in CSF production and a decrease in its reabsorption. Despite taking these considerations into account, the treatment of hydrocephalus secondary to plexus hyperplasia is a real challenge that usually leads to multiple surgical interventions ranging from plexectomy or coagulation of the choroid plexuses to the implantation of CSF drainage devices.

TITLE: Hidrocefalia por hiperplasia de plexos coroideos en un paciente con mosaicismo de trisomia 9. Un verdadero reto diagnostico y terapeutico.Introduccion. La trisomia 9 es una cromosomopatia inusual en pacientes nacidos vivos, que frecuentemente se acompaña de anomalias funcionales y estructurales del sistema nervioso central. Entre otras muchas alteraciones, varios trabajos en la bibliografia anglosajona demuestran una asociacion entre cromosomopatia 9 y patologia de los plexos coroideos. Caso clinico. Varon de 4 meses de vida con mosaicismo de trisomia 9 asociado a hidrocefalia secundaria a hiperplasia de los plexos coroideos, que fue remitido por clinica de hipertension intracraneal. El procedimiento derivativo de liquido cefalorraquideo por el que optamos inicialmente provoco una ascitis masiva debida a la produccion desmesurada de liquido cefalorraquideo, y desemboco en una cascada de multiples intervenciones quirurgicas, entre las que se incluyeron procedimientos endoscopicos y derivativos. Conclusiones. Se trata de un ejemplo mas de asociacion entre patologia de los plexos coroideos y cromosomopatia 9. Debido a su escasa incidencia, es dificil establecer el diagnostico de hidrocefalia secundaria a hiperplasia de los plexos y, por tanto, el tratamiento mas adecuado. En este tipo de hidrocefalia existe un doble mecanismo fisiopatologico, que implica un aumento de produccion de liquido cefalorraquideo y una disminucion de su reabsorcion. A pesar de tener en cuenta dicha consideracion, el tratamiento de la hidrocefalia secundaria a hiperplasia de los plexos supone un verdadero reto que habitualmente pasa por multiples procedimientos quirurgicos, desde la plexectomia o coagulacion de los plexos coroideos hasta la implantacion de dispositivos de derivacion de liquido cefalorraquideo.

Outbreak of brainstem encephalitis associated with enterovirus-A71 in Catalonia, Spain (2016): a clinical observational study in a children's reference centre in Catalonia.

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.

Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism.

Patients with acute venous thromboembolism have an increased risk for occult malignancy. Limited screening for these malignancies has become common practice but little is known about its usefulness. This is a prospective cohort follow-up study in consecutive patients with acute venous thromboembolism. All patients underwent a routine clinical evaluation for malignancy, if negative, followed by a limited diagnostic work-up consisting of abdominal and pelvic ultrasound and laboratory markers for malignancy. Clinical follow-up was conducted to detect screening failures. The routine clinical evaluation was performed in 864 patients and revealed malignancy in 34 (3.9%) of them. Among the remaining 830 patients the limited diagnostic work-up revealed 13 further malignancies. During follow-up, cancer became symptomatic in 14 patients who were negative for cancer at screening (sensitivity of limited diagnostic work-up, 48.1%). Malignancies that were identified by the limited diagnostic work-up were early stage in 61% of cases vs. 14% in cases occurring during follow-up. Most patients with occult cancer had idiopathic venous thromboembolism and were older than 70 years. A limited diagnostic work-up for occult cancer in patients with venous thromboembolism has the capacity to identify approximately one-half of the malignancies. Identified malignancies were predominantly in an early stage.

Prospective study on the usefulness of lung scan in patients with deep vein thrombosis of the lower limbs.

BACKGROUND: Asymptomatic pulmonary embolism (PE) is a common finding in patients with deep venous thrombosis (DVT) of the lower limbs, but the usefulness of seeking for silent PE in patients with acute DVT has not been evaluated. PATIENTS AND METHODS: This was a prospective study involving consecutive patients with acute symptomatic proximal DVT (confirmed by objective methods) and no clinical suspicion of PE. All patients underwent chest X-ray, ventilation-perfusion lung scan and arterial blood gases on admission, and received anticoagulant therapy. Those with scintigraphic evidence of PE underwent repeated lung scan and blood gases 7 days later. The aim of the study was to assess how many patients with silent PE develop symptoms while on heparin therapy, and in how many of them such symptoms are due to recurrent PE. RESULTS: 946 consecutive patients with acute, proximal DVT had no contraindications to full-dose anticoagulant therapy. Baseline lung scan revealed high-probability defects (silent PE) in 200 (21%). Seven of these 200 patients had symptomatic recurrences during the 7-day study period, and an inferior vena cava filter was inserted. Besides, 6 patients developed PE symptoms, but no new perfusion defects were found on repeated scan. They switched to coumarin therapy, and they did not develop any further complications. CONCLUSIONS: Lung scan in patients with symptomatic DVT and no clinical suspicion of PE may be useful, since some patients with silent PE may develop symptoms while on heparin therapy. Without a baseline scintigraphy all these patients would have been considered to have recurrent PE, and vena cava interruption could have been performed.

[Endovascular resolution of iliac artery pseudoaneurysm in a transplanted patient]. / Tratamiento endovascular de un pseudoaneurisma de arteria ilíaca primitiva postrasplante renal.

A 58-year-old patient with end-stage idiopatic renal disease underwent kidney transplantation from a cadaveric donor. Approximately one year after the transplant he complained of abdominal pain and presented a pulsating mass in his right pelvic region. Dupplex study and arteriography were performed and showed a large pseudoaneurysm arising from the right common iliac artery. We report the case in which a covered stent placement and an embolization of the right internal iliac artery solved the problem with successful clinical and radiological results.

[Angioplasty for intracranial internal carotid artery stenosis]. / Angioplastia de arteria carótida interna intracraneal.

INTRODUCTION: Percutaneous transluminal angioplastia has in recent years become an alternative to surgery and increasingly used for revascularization of the extracranial arteries in patients with cerebral ischemia. However, intracranial angioplasty is a technique which is still not widely used since it is technically more difficult and until now endoprotheses (stents) have not been available specifically designed for intracranial territory. CLINICAL CASE: A 73 year old patient with extensive extracranial and intracranial atheromatous lesions, multiple vascular risk factors and cardiac ischemia which contraindicated surgical treatment which was treated consecutively by angioplasty and angioplasty with implantation of stents in both carotid bifurcations. Subsequently, he was treated by angioplasty for a stenosing lesion of 90% of the right carotid siphon with clinical and hemodynamic repercussions. Following the procedure, which was well-tolerated by the patient, there was clinical and angiographic improvement and return to normal of the hemodynamic parameters measured by transcranial Doppler. CONCLUSIONS: Angioplasty is a technique which may be used in intracranial stenosing atheromatous lesions. Even without perfect angiographic correction, adequate blood flow is established in the hemodynamically affected lesions. As far as we know this is the first case of intracranial angioplasty of a lesion of the carotid siphon reported in Spain.

[Ischemic brain lesions following carotid revascularisation procedures: a comparative study using diffusion-weighted magnetic resonance imaging]. / Lesiones cerebrales isquémicas tras procedimientos de revascularización carotídea: estudio comparativo con resonancia magnética por difusión.

INTRODUCTION: The risk of cerebral embolism following angioplasty-stent placement (AGP) is higher than that observed after a carotid endarterectomy (CE) using transcranial Doppler ultrasonography. Nevertheless, no studies have been conducted to compare the two revascularisation procedures with the latest neuroimaging techniques. AIMS: To analyse the presence and repercussion of acute cerebral ischemia detected by diffusion-weighted magnetic resonance imaging (DMR) following carotid revascularisation procedures. PATIENTS AND METHODS: Our prospective study included a sample of 20 consecutive patients with atherosclerotic stroke and symptomatic carotid stenosis > 70% according to NASCET criteria and treated by CE (n = 10) or AGP (n = 10). Patients were submitted to a DMR during the 48 hours prior to revascularisation and another within the 72 hours following the intervention in order to evaluate the existence of new acute cerebral ischemic lesions. Patients were explored by a neurologist before and after the intervention. RESULTS: DMR allowed new areas of cerebral ischemia to be detected in 10% of the CE and in 40% of the AGP patients. 50% of the post-AGP ischemic lesions were multiple and 10% of the lesions in each therapeutic group presented some clinical correlation in the form of transient neurological focal signs. No significant differences were observed with respect to the pattern of risk of complications between the two therapeutic groups and no factors associated to a higher risk of new ischemic lesions were detected by DMR in patients submitted to AGP. CONCLUSIONS: Carotid AGP is linked to a higher frequency of new ischemic lesions in the brain than in the case of CE. Nevertheless, these ischemic lesions detected by DMR are usually silent. Symptomatic complications were similar in the two procedures.

Balloon catheter sphincteroplasty and biliary stone expulsion into the duodenum in patients with an indwelling T tube.

BACKGROUND: To present an alternate approach for treating residual biliary stones in patients with indwelling T tube that uses the immature tract created by the T tube to carry out both sphincteroplasty and expulsion of the calculi with the same angioplasty balloon catheter. METHODS: This technique was performed in five patients. Access to the bile duct was through an 8-Fr T tube. First a guidewire was inserted and advanced beyond the obstructing stone to the duodenal lumen. The T tube was removed over the guidewire, and a balloon catheter was introduced. Sphincteroplasty was carried out. Then the balloon was deflated and retracted to a position proximal to the stone. It was then reinflated and used to push the stone, expelling it into the duodenum. RESULTS: In all cases, all biliary stones were expelled without pain, in a single session, and with no immediate complications. All patients showed rapid clinical and analytic improvement. During clinical and echographic follow-up of 2-22 months (mean = 12.4 months), there were no complications or relapses. CONCLUSIONS: Our limited experience indicates that sphincteroplasty and expulsion of biliary stones with angioplasty balloon catheters through the T tube immature tract is a simple, safe, low-cost technique that gives good results.

Systemic to pulmonary fistulas in Hodgkin's disease.

Systemic to pulmonary fistula is an unusual entity and its association with hematological diseases like Hodgkin's is extremely rare. We present a case of a 26-year-old woman with a thoracic mass and large arteriovenous fistula. The diagnosis of Hodgkin's disease, nodular sclerosis, was obtained by a biopsy of the supraclavicular lymph node. We achieved an excellent response after combined treatment with chemotherapy, radiotherapy and arterial embolization with complete disappearance of the mass.