Pre‑ and intra‑operative prognostic factors of facial nerve function in cerebellopontine angle surgery

Acord transformatiu CRUE-CSICPurpose: The study assesses whether pre- and intraoperative factors linked to electromyography and direct electrical stimulation (DES) of facial nerve can predict facial nerve function in the short- (12 days) and long-term (1 year) after cerebellopontine angle (CPA) tumor resection. Methods: 157 patients who underwent surgical resection of CPA tumors with facial nerve monitoring. Pre-operative factors (age, tumor size, pure tone average), surgical time and intra-operative parameters regarding facial function, minimum stimulation threshold (MST), compound muscle action potential (CMAP) and the diference between proximal and distal CMAP (DPDC) were evaluated. Results: A correlation between tumor size, MST, CMAP and facial function in both short and long term was found. A higher grade of immediate facial paralysis corresponded to a higher risk of poor outcome after one year. A postoperative House-Brackmann (HB) score of V or VI was correlated with poor outcome in 88.8% and 93.8% of cases. A risk of HB 3 or more, in the long term, was correlated with a tumor size of 20.2 mm. Using an MST of 0.1 mA, for long-term predictions, sensitivity and specifcity were 0.62 (95% CI 0.46-0.75) and 0.73 (95% CI 0.61-0.82), respectively. With a CMAP cut-of<200 µV, for long-term prediction, sensitivity was 0.73 (95% CI 0.53-0.87) and specifcity 0.73 (95% CI 0.55-0.85). Conclusion: The assessment based on the cut-ofs described increases the ability to predict facial function. Improving predictive accuracy enables surgeons to address patients' expectations and to establish an intervention timeline for planning facial reanimation

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans

Hair cell (HC) loss by epithelial extrusion has been described to occur in the rodent vestibular system during chronic 3,3'-iminodipropionitrile (IDPN) ototoxicity. This is preceded by dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. Here, we evaluated whether these phenomena have wider significance. First, we studied rats receiving seven different doses of streptomycin, ranging from 100 to 800 mg/kg/day, for 3 to 8 weeks. Streptomycin caused loss of vestibular function associated with partial loss of HCI and decreased expression of contactin-associated protein (CASPR1), denoting calyceal junction dismantlement, in the calyces encasing the surviving HCI. Additional molecular and ultrastructural data supported the conclusion that HC-calyx detachment precede HCI loss by extrusion. Animals allowed to survive after the treatment showed functional recuperation and rebuilding of the calyceal junction. Second, we evaluated human sensory epithelia obtained during therapeutic labyrinthectomies and trans-labyrinthine tumour excisions. Some samples showed abnormal CASPR1 label strongly suggestive of calyceal junction dismantlement. Therefore, reversible dismantlement of the vestibular calyceal junction may be a common response triggered by chronic stress, including ototoxic stress, before HCI loss. This may partly explain clinical observations of reversion in function loss after aminoglycoside exposure

Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb

Background: A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Case presentation: Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inactivating hit. In addition, a distinct NF2 point mutation in each tumor was identified, representing independent second hits. In accordance with these results, no deletions or point mutations in the SMARCB1 gene were identified. None of the mutations were present in the blood. Two of the patient's children inherited chromosome 22 deleted in schwannomas of the mother, but in its wild type form. Conclusions: These results conclusively confirm the segmental mosaic NF2 nature of the clinical phenotype presented

Caracterización de la hipoacusia en la enfermedad de Paget

Introducción y objetivos: La enfermedad ósea de Paget (EOP) puede cursar con hipoacusia. Con el objetivo de cuantificar, caracterizar, determinar los factores de riesgo de hipoacusia y analizar las posibles relaciones de la hipoacusia con los hallazgos tomográficos en un grupo de pacientes con EOP, se realiza el presente estudio. Métodos: Se realizó un estudio observacional, transversal del tipo casos y controles que incluyó una cohorte de 76 sujetos con diagnóstico de enfermedad ósea de Paget (EOP) en el grupo caso y un grupo control de 134 sujetos. Se analiza la información clínica, demográfica, audiométrica y radiológica, mediante una TC de hueso temporal, de los sujetos incluidos. Resultados: El análisis comparativo entre el grupo de sujetos con EOP y el grupo control determinó que el grupo caso presentaban un umbral medio auditivo mayor (39,51 dB) que en el grupo control (37,28 dB) (p=0,069) y que presentaba hipoacusia transmisiva con mayor frecuencia (22,76%) que el grupo control (12,05%) (p=0,0062). El análisis de los factores de riesgo de hipoacusia determinó que la afectación craneal en la gammagrafía ósea, la edad y la HTA entre otros, constituían factores de riesgo de mayor pérdida auditiva en EOP. El estudio tomográfico constató que los pacientes con EOP presentaban una menor densidad ósea en unidades Hounsfield (UH) en el peñasco del temporal respecto al grupo control. Así mismo se pudo observar que la densidad ósea en la cápsula ótica en pacientes con EOP se correlacionaba con el umbral auditivo tanto de vía aérea como de vía ósea (p<0,05) y que la presencia de un gap en la audiometría se correlacionaba con la afectación por hueso pagético del temporal. Conclusiones: - El 63,45% de los sujetos con enfermedad ósea de Paget (EOP) padecen hipoacusia, con un umbral auditivo medio de 39,51dB. - Los sujetos con enfermedad ósea de Paget (EOP) presentaron una pérdida auditiva más severa y con mayor frecuencia de tipo transmisivo que el grupo control. - Los sujetos con afectación de la calota craneal por EOP presentaron mayor pérdida auditiva que los sujetos sin afectación craneal. La afectación de la calota craneal por la EOP y la edad constituyeron factores de riesgo de hipoacusia. - En los sujetos con EOP el umbral auditivo tanto de vía aérea como ósea se relaciona con la disminución de densidad en la cápsula ótica.Introduction and objectives: Paget’s disease of bone (PDB) may lead to hearing loss. The present study is conducted with the aim of measuring, characterizing, determining the risk factors for hearing loss and analyse the possible relation of hearing loss with tomography findings in a group of subjects with PDB. Methods: An observational, transversal, case-control study was conducted, a cohort of 76 subjects diagnosed of Paget’s disease of bone (PDB) in the case group and a control group of 134 subjects were included. Clinical, demographic, audiometric and tomographic data (by means of a CT scan study) were analysed. Results: The comparative analysis between the subjects in the PDB group and the control group found that the case group showed higher hearing thresholds (39,51dB) comparing with the control group (37,28 dB) (p=0,069) and presented a greater rate of conductive hearing loss (22,76%) than the control group (12,05%) (p=0,0062). The study of risk factors for hearing loss found that skull involvement in bone scintigraphy, age and high blood pressure were risk factors for higher hearing impairment in PDB. The CT scan data showed that subjects in the PDB group had lower temporal bone density (Hounsfield Units, HU) comparing with the control group. It was also found that the otic capsule bone density in the PDB group correlated with both the air and bone conduction hearing thresholds (p<0,05) and that the finding of an air-bone gap in the audiogram correlated with Paget’s disease temporal bone involvement. Conclusions: − The 63,45% of subjects with Paget’s disease of bone (PDB) suffer hearing loss with a hearing threshold of 39,51dB on average. − The subjects with PDB showed a deeper hearing loss and a higher proportion of conductive type than the control group. − The patients with PDB and skull involvement presented a more severe hearing loss compared with the subjects without skull involvement. Skull involvement and age were found to be risk factors for hearing loss. − In the PDB group both the air and bone conduction hearing thresholds correlated with the otic capsule bone density

Caracterización de la hipoacusia en la enfermedad de Paget /

Introducción y objetivos: La enfermedad ósea de Paget (EOP) puede cursar con hipoacusia. Con el objetivo de cuantificar, caracterizar, determinar los factores de riesgo de hipoacusia y analizar las posibles relaciones de la hipoacusia con los hallazgos tomográficos en un grupo de pacientes con EOP, se realiza el presente estudio. Métodos: Se realizó un estudio observacional, transversal del tipo casos y controles que incluyó una cohorte de 76 sujetos con diagnóstico de enfermedad ósea de Paget (EOP) en el grupo caso y un grupo control de 134 sujetos. Se analiza la información clínica, demográfica, audiométrica y radiológica, mediante una TC de hueso temporal, de los sujetos incluidos. Resultados: El análisis comparativo entre el grupo de sujetos con EOP y el grupo control determinó que el grupo caso presentaban un umbral medio auditivo mayor (39,51 dB) que en el grupo control (37,28 dB) (p=0,069) y que presentaba hipoacusia transmisiva con mayor frecuencia (22,76%) que el grupo control (12,05%) (p=0,0062). El análisis de los factores de riesgo de hipoacusia determinó que la afectación craneal en la gammagrafía ósea, la edad y la HTA entre otros, constituían factores de riesgo de mayor pérdida auditiva en EOP. El estudio tomográfico constató que los pacientes con EOP presentaban una menor densidad ósea en unidades Hounsfield (UH) en el peñasco del temporal respecto al grupo control. Así mismo se pudo observar que la densidad ósea en la cápsula ótica en pacientes con EOP se correlacionaba con el umbral auditivo tanto de vía aérea como de vía ósea (p 0,05) y que la presencia de un gap en la audiometría se correlacionaba con la afectación por hueso pagético del temporal. Conclusiones: -El 63,45% de los sujetos con enfermedad ósea de Paget (EOP) padecen hipoacusia, con un umbral auditivo medio de 39,51dB. -Los sujetos con enfermedad ósea de Paget (EOP) presentaron una pérdida auditiva más severa y con mayor frecuencia de tipo transmisivo que el grupo control. -Los sujetos con afectación de la calota craneal por EOP presentaron mayor pérdida auditiva que los sujetos sin afectación craneal. La afectación de la calota craneal por la EOP y la edad constituyeron factores de riesgo de hipoacusia. -En los sujetos con EOP el umbral auditivo tanto de vía aérea como ósea se relaciona con la disminución de densidad en la cápsula ótica.Introduction and objectives: Paget's disease of bone (PDB) may lead to hearing loss. The present study is conducted with the aim of measuring, characterizing, determining the risk factors for hearing loss and analyse the possible relation of hearing loss with tomography findings in a group of subjects with PDB. Methods: An observational, transversal, case-control study was conducted, a cohort of 76 subjects diagnosed of Paget's disease of bone (PDB) in the case group and a control group of 134 subjects were included. Clinical, demographic, audiometric and tomographic data (by means of a CT scan study) were analysed. Results: The comparative analysis between the subjects in the PDB group and the control group found that the case group showed higher hearing thresholds (39,51dB) comparing with the control group (37,28 dB) (p=0,069) and presented a greater rate of conductive hearing loss (22,76%) than the control group (12,05%) (p=0,0062). The study of risk factors for hearing loss found that skull involvement in bone scintigraphy, age and high blood pressure were risk factors for higher hearing impairment in PDB. The CT scan data showed that subjects in the PDB group had lower temporal bone density (Hounsfield Units, HU) comparing with the control group. It was also found that the otic capsule bone density in the PDB group correlated with both the air and bone conduction hearing thresholds (p 0,05) and that the finding of an air-bone gap in the audiogram correlated with Paget's disease temporal bone involvement. Conclusions: − The 63,45% of subjects with Paget's disease of bone (PDB) suffer hearing loss with a hearing threshold of 39,51dB on average. − The subjects with PDB showed a deeper hearing loss and a higher proportion of conductive type than the control group. − The patients with PDB and skull involvement presented a more severe hearing loss compared with the subjects without skull involvement. Skull involvement and age were found to be risk factors for hearing loss. − In the PDB group both the air and bone conduction hearing thresholds correlated with the otic capsule bone density

Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb

Background: A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Case presentation: Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inactivating hit. In addition, a distinct NF2 point mutation in each tumor was identified, representing independent second hits. In accordance with these results, no deletions or point mutations in the SMARCB1 gene were identified. None of the mutations were present in the blood. Two of the patient's children inherited chromosome 22 deleted in schwannomas of the mother, but in its wild type form. Conclusions: These results conclusively confirm the segmental mosaic NF2 nature of the clinical phenotype presented