The cranial base synchondroses,comprised of opposite-facing bidirectional chondrocyte layers,drive anteroposterior cranial base growth.In humans,RUNX2 haploinsufficiency causes cleidocranial dysplasia associated with ...The cranial base synchondroses,comprised of opposite-facing bidirectional chondrocyte layers,drive anteroposterior cranial base growth.In humans,RUNX2 haploinsufficiency causes cleidocranial dysplasia associated with deficient midfacial growth.However,how RUNX2 regulates chondrocytes in the cranial base synchondroses remains unknown.To address this,we inactivated Runx2 in postnatal synchondrosis chondrocytes using a tamoxifen-inducible Fgfr3-creER(Fgfr3-Runx2cKO)mouse model.Fgfr3-Runx2cKO mice displayed skeletal dwarfism and reduced anteroposterior cranial base growth associated with premature synchondrosis ossification due to impaired chondrocyte proliferation,accelerated hypertrophy,apoptosis,and osteoclast-mediated cartilage resorption.Lineage tracing reveals that Runx2-deficient Fgfr3+cells failed to differentiate into osteoblasts.Notably,Runx2-deficient chondrocytes showed an elevated level of FGFR3 and its downstream signaling components,pERK1/2 and SOX9,suggesting that RUNX2 downregulates FGFR3 in the synchondrosis.This study unveils a new role of Runx2 in cranial base chondrocytes,identifying a possible RUNX2-FGFR3-MAPK-SOX9 signaling axis that may control cranial base growth.展开更多
The extremely complex anatomic relationships among bone, tumor, blood vessels and cranial nervesremains a big challenge for cranial base tumor surgery. Therefore, a good understanding of the patient specific anatomy a...The extremely complex anatomic relationships among bone, tumor, blood vessels and cranial nervesremains a big challenge for cranial base tumor surgery. Therefore, a good understanding of the patient specific anatomy and a preoperative planning are helpful and crucial for the neurosurgeons. Three dimensional （3-D） visualization of various imaging techniques have been widely explored to enhance the comprehension of volumetric data for surgical planning.展开更多
Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immun...Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.展开更多
Objectives/Hypothesis: The introduction of intranasal pedicled flaps has reduced the incidence of postoperative cerebrospinal fluid (CSF) leaks to less than 5%. Nevertheless, in malignant tumors those flaps are not al...Objectives/Hypothesis: The introduction of intranasal pedicled flaps has reduced the incidence of postoperative cerebrospinal fluid (CSF) leaks to less than 5%. Nevertheless, in malignant tumors those flaps are not always available because of nasal septum invasion. Minimally invasive pericranial flaps (PCF) are associated with minimal adverse effects and good cosmetic appearance. In spite of that, there are only a few reports of this reconstructive technic limited to short surgical series and radio-anatomical analysis. Clinical results of a surgical cohort are presented. Study Design: Cohort prospective study. Methods: Clinical data, including age, gender, stage, histopathological findings, rate of complications and appearance of PCF at fifth day and two months postoperative were recorded. Postoperative morbidities were recorded as wound abnormalities, nasosinusal, orbital and central nervous system complications. Chi-squared test was used to correlate qualitative variables and Student-t-test to correlated qualitative and quantitative variables. Items were considered statistically significant with a p value of less than 0.05 (confidence Interval of 95%). Results: Thirty patients (18 males and 12 females) were registered. Mean age was 51.5 years ± 23.0 and range between 20 and 71 years. Most common histologic subtypes were adenocarcinoma, epidermoid carcinoma and squamous cell carcinoma. Complete resection of the tumor was achieved in all patients including surgical margins. Length of the PCF varies between 9.9 cm and 13.9 cm with a mean of 11.8 cm. There was an association between length of the flaps and the covering structure with the nose apex relation. None patient experienced postoperative cerebrospinal fluid (CSF) leak, frontal sinusitis or other complications. Conclusions: Minimally invasive PCF constitute a good and inexpensive reconstructive option in patients with malignant anterior cranial base tumors in whose nasoseptal flap was not a feasible option.展开更多
Here we report a patient with uncontrolled diabetes, who presented with giddiness and fall due to an episode of seizure. On evaluation with CT and MRI scans, he was found to have pan sinusitis with erosions of the sku...Here we report a patient with uncontrolled diabetes, who presented with giddiness and fall due to an episode of seizure. On evaluation with CT and MRI scans, he was found to have pan sinusitis with erosions of the skull base in the floor of sphenoid near lateral recess. PET-CT showed evidence of increased metabolism. He was operated upon by functional endoscopic sinus surgery and debridement of lesion near skull base. The histopathological examination revealed evidence of inflammation with no granulomas or fungal elements or tubercle bacilli. No organisms were grown in microbiological cultures. He started on empirical antibiotics for 3 months and showed improvement. We are reporting this case due to rarity to skull base osteomyelitis.展开更多
基金National Institutes of Health grant F30DE030675(S.A.H.)National Institutes of Health grant T32DE007057(S.A.H.)+7 种基金University of Michigan Rackham Graduate School Pre-Candidate Research Grant(S.A.H.)University of Michigan Rackham Graduate School Candidate Research Grant(S.A.H.)National Institutes of Health grant R35DE034348(N.O.)National Institutes of Health grant R01DE026666(N.O.)National Institutes of Health grant R01DE030630(N.O.)National Institutes of Health grant R01DE029465(R.T.F.)Department of Defense grant W81XWH2010571(R.T.F.)National Institutes of Health grant P30 AR069620(The Michigan Integrative Musculoskeletal.Health Core Center).
文摘The cranial base synchondroses,comprised of opposite-facing bidirectional chondrocyte layers,drive anteroposterior cranial base growth.In humans,RUNX2 haploinsufficiency causes cleidocranial dysplasia associated with deficient midfacial growth.However,how RUNX2 regulates chondrocytes in the cranial base synchondroses remains unknown.To address this,we inactivated Runx2 in postnatal synchondrosis chondrocytes using a tamoxifen-inducible Fgfr3-creER(Fgfr3-Runx2cKO)mouse model.Fgfr3-Runx2cKO mice displayed skeletal dwarfism and reduced anteroposterior cranial base growth associated with premature synchondrosis ossification due to impaired chondrocyte proliferation,accelerated hypertrophy,apoptosis,and osteoclast-mediated cartilage resorption.Lineage tracing reveals that Runx2-deficient Fgfr3+cells failed to differentiate into osteoblasts.Notably,Runx2-deficient chondrocytes showed an elevated level of FGFR3 and its downstream signaling components,pERK1/2 and SOX9,suggesting that RUNX2 downregulates FGFR3 in the synchondrosis.This study unveils a new role of Runx2 in cranial base chondrocytes,identifying a possible RUNX2-FGFR3-MAPK-SOX9 signaling axis that may control cranial base growth.
文摘The extremely complex anatomic relationships among bone, tumor, blood vessels and cranial nervesremains a big challenge for cranial base tumor surgery. Therefore, a good understanding of the patient specific anatomy and a preoperative planning are helpful and crucial for the neurosurgeons. Three dimensional （3-D） visualization of various imaging techniques have been widely explored to enhance the comprehension of volumetric data for surgical planning.
文摘Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.
文摘Objectives/Hypothesis: The introduction of intranasal pedicled flaps has reduced the incidence of postoperative cerebrospinal fluid (CSF) leaks to less than 5%. Nevertheless, in malignant tumors those flaps are not always available because of nasal septum invasion. Minimally invasive pericranial flaps (PCF) are associated with minimal adverse effects and good cosmetic appearance. In spite of that, there are only a few reports of this reconstructive technic limited to short surgical series and radio-anatomical analysis. Clinical results of a surgical cohort are presented. Study Design: Cohort prospective study. Methods: Clinical data, including age, gender, stage, histopathological findings, rate of complications and appearance of PCF at fifth day and two months postoperative were recorded. Postoperative morbidities were recorded as wound abnormalities, nasosinusal, orbital and central nervous system complications. Chi-squared test was used to correlate qualitative variables and Student-t-test to correlated qualitative and quantitative variables. Items were considered statistically significant with a p value of less than 0.05 (confidence Interval of 95%). Results: Thirty patients (18 males and 12 females) were registered. Mean age was 51.5 years ± 23.0 and range between 20 and 71 years. Most common histologic subtypes were adenocarcinoma, epidermoid carcinoma and squamous cell carcinoma. Complete resection of the tumor was achieved in all patients including surgical margins. Length of the PCF varies between 9.9 cm and 13.9 cm with a mean of 11.8 cm. There was an association between length of the flaps and the covering structure with the nose apex relation. None patient experienced postoperative cerebrospinal fluid (CSF) leak, frontal sinusitis or other complications. Conclusions: Minimally invasive PCF constitute a good and inexpensive reconstructive option in patients with malignant anterior cranial base tumors in whose nasoseptal flap was not a feasible option.
文摘Here we report a patient with uncontrolled diabetes, who presented with giddiness and fall due to an episode of seizure. On evaluation with CT and MRI scans, he was found to have pan sinusitis with erosions of the skull base in the floor of sphenoid near lateral recess. PET-CT showed evidence of increased metabolism. He was operated upon by functional endoscopic sinus surgery and debridement of lesion near skull base. The histopathological examination revealed evidence of inflammation with no granulomas or fungal elements or tubercle bacilli. No organisms were grown in microbiological cultures. He started on empirical antibiotics for 3 months and showed improvement. We are reporting this case due to rarity to skull base osteomyelitis.
