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OBJECTIVESpontaneous spinal CSF leaks are caused by abnormalities of the spinal dura mater. Although most cases are treated conservatively or with an epidural blood patch, some intractable cases require neurosurgical treatment. However, previous reports are limited to a small number of cases. Preoperative detection and localization of spinal dural defects are difficult, and surgical repair of these defects is technically challenging. The authors present the anatomical characteristics of dural defects and surgical techniques in treating spontaneous CSF leaks.METHODSAmong the consecutive patients who were diagnosed with spontaneous CSF leaks at the authors’ institution between 2010 and 2020, those who required neurosurgical treatment were included in the study. All patients’ clinical information, radiological studies, surgical notes, and outcomes were reviewed retrospectively. Outcomes of two different procedures in repairing dural defects were compared.RESULTSAmong 77 patients diagnosed with spontaneous CSF leaks, 21 patients (15 men; mean age 57 years) underwent neurosurgery. Dural defects were detected by FIESTA MRI in 7 patients, by CT myelography in 12, by digital subtraction myelography in 1, and by dynamic CT myelography in 1. The spinal levels of the defects were localized at the cervicothoracic junction in 16 patients (76%) and thoracolumbar junction in 4 (19%). Intraoperative findings revealed that the dural defects were small, circumscribed longitudinal slits located at the ventral aspect of the dura mater. The median dural defect size was 5 × 2 mm. The presence of dural defects at the thoracolumbar junction was associated with manifestation of an altered mental status, which was an unusual manifestation of CSF leaks (p = 0.003). Eight patients were treated via the posterior transdural approach with watertight primary sutures of the ventral defects, and 13 were treated with muscle or fat grafting. Regardless of the two different procedures, postoperative MRI showed either complete disappearance or significant reduction of the extradural CSF collection. No patient experienced postoperative neurological deficits. Clinical symptoms improved or stabilized in 20 patients with a median follow-up of 12 months.CONCLUSIONSDural defects in spontaneous CSF leaks were small, circumscribed longitudinal slits located ventral to the spinal cord at either the cervicothoracic or thoracolumbar junction. Muscle/fat grafting may be an alternative treatment to watertight primary sutures of ventral dural defects with a good outcome.

OBJECTIVEAlthough the association between Chiari malformation (CM) and craniosynostosis is well recognized, management remains controversial. There are differences in the clinical course of CM in syndromic craniosynostosis (SC) patients and nonsyndromic craniosynostosis (NSC) patients. Still unclear is whether cranial expansion surgery, foramen magnum decompression (FMD), or both should be conducted and when the appropriate timing of surgery should be. Here, the authors retrospectively reviewed the clinical data at their institution to investigate the optimal management of CM associated with SC and NSC.METHODSThe authors retrospectively analyzed the clinical records of 163 children with craniosynostosis who underwent surgical treatment at the National Center for Child Health and Development between April 2002 and May 2018.RESULTSTwelve (10%) of 119 children with NSC and 14 (31.8%) of 44 children with SC were radiologically diagnosed with CM. The median age at which CM was radiologically diagnosed was 7 months. Of the 12 NSC patients with CM, 1 (8%) was symptomatic with gait disturbance. This patient underwent FMD following expansion surgery. Of the 14 SC patients with CM, 8 (57.1%) were symptomatic with central sleep apnea. For SC patients with symptomatic CM, cranial expansion surgery alone was conducted in 2 cases, FMD was conducted after cranial expansion in 4 cases, and FMD was conducted first and additional expansion surgery was then conducted in 2 cases. In all cases, symptoms of CM improved after completing this series of surgeries. Regarding patients with asymptomatic CM, cranial expansion surgery alone was performed, and none of the patients showed symptoms of CM thereafter in both SC and NSC cases.CONCLUSIONSMultiple surgeries tend to be necessary for symptomatic CM in both SC and NSC, while no patient with asymptomatic CM became symptomatic after cranial expansion surgery.

Large cell neuroendocrine carcinoma (LCNEC) is a highly malignant cancer originally found in lung in 1991. In extremely rare occasions, primary LCNEC is found in the mediastinum; approximately 40 of such cases have been reported. Due to the limited number of reported cases, a standardized treatment protocol has yet to be established. We report a case of a 66-year-old woman with primary mediastinal LCNEC who presented with superior vena cava syndrome. Emergent radiotherapy was performed, followed by systemic chemotherapy with cisplatin and etoposide, which resulted in a dramatic tumor reduction. This is the first report describing the achievement of a complete response after systemic chemotherapy in a patient with primary LCNEC.

Objective— APOA5 variants are strongly associated with hypertriglyceridemia, as well as increased risks of cardiovascular disease and acute pancreatitis. Hypertriglyceridemia in apo AV dysfunction often aggravates by environmental factors such as high-carbohydrate diets or aging. To date, the molecular mechanisms by which these environmental factors induce hypertriglyceridemia are poorly defined, leaving the high-risk hypertriglyceridemia condition undertreated. Previously, we reported that LXR (liver X receptor)-SREBP (sterol regulatory element-binding protein)-1c pathway regulates large-VLDL (very low-density lipoprotein) production induced by LXR agonist. However, the pathophysiological relevance of the finding remains unknown. Approach and Results— Here, we reconstitute the environment-induced hypertriglyceridemia phenotype of human APOA5 deficiency in Apoa5 −/− mice and delineate the role of SREBP-1c in vivo by generating Apoa5 −/− ;Srebp-1c −/− mice. The Apoa5 −/− mice, which showed moderate hypertriglyceridemia on a chow diet, developed severe hypertriglyceridemia on high-carbohydrate feeding or aging as seen in patients with human apo AV deficiency. These responses were nearly completely abolished in the Apoa5 −/− ;Srebp-1c −/− mice. Further mechanistic studies revealed that in response to these environmental factors, SREBP-1c was activated to increase triglyceride synthesis and to permit the incorporation of triglyceride into abnormally large-VLDL particles, which require apo AV for efficient clearance. Conclusions— Severe hypertriglyceridemia develops only when genetic factors (apo AV deficiency) and environmental effects (SREBP-1c activation) coexist. We demonstrate that the regulated production of large-sized VLDL particles via SREBP-1c determines plasma triglyceride levels in apo AV deficiency. Our findings explain the long-standing enigma of the late-onset hypertriglyceridemia phenotype of apo AV deficiency and suggest a new approach to treat hypertriglyceridemia by targeting genes that mediate environmental effects.

Background Although chronic subdural hematoma (CSDH) has a good prognosis after classical minimally-invasive drainage surgery, severe complications still occur at a substantial rate. Cerebral hyperperfusion syndrome (CHS), which is a common severe complication after carotid endarterectomy or carotid artery stenting for cervical carotid artery stenosis, is rare after drainage surgery for a CSDH. Case Description We describe the case of an 82-year-old woman who presented with ipsilesional symptoms including contralateral hemiparesis and dysarthria, progressively worsening consciousness, and status epilepticus after a burr hole drainage surgery for CSDH. Magnetic resonance fluid-attenuated inversion recovery imaging showed diffuse subcortical low intensity in the ipsilesional hemisphere almost simultaneously with the appearance of the symptoms. Arterial spin labeling magnetic resonance perfusion imaging showed the abnormal increase of cerebral blood flow in the hemisphere. Continuous propofol administration and blood pressure management improved the symptoms. Conclusions CHS can cause severe postoperative complications after drainage surgery for CSDH. Subcortical low-intensity fluid-attenuated inversion recovery imaging is a useful investigation for early detection of CHS in CSDH, and arterial spin labeling imaging is an effective minimally-invasive modality for confirming the diagnosis.

BACKGROUND Most cases of glioblastoma recur within one year even under the standard treatment of surgical resection, radiation therapy and chemotherapy. 60–70% of recurrences are local, and in rare cases of metastasis, most are within the CNS. Extradural metastasis is considered exceedingly rare. CASE REPORT We present a 21-year-old man post total resection of right parietal lobe glioblastoma, diagnosed with lumber metastasis. He originally presented with impaired consciousness and left hemiplegia at the age of 20 and underwent gross total resection of the tumor. Pathology was IDH wild type, H3F3A K34R/V wild-type glioblastoma. Radiotherapy and adjuvant temozolomide per the Stupp regimen as well as infusion of bevacizumab were conducted. 6 months after the resection of tumor, the patient presented with severe back pain. Radiographic studies showed an osteolytic mass on the first lumbar vertebrae, and needle biopsy was consistent with glioblastoma. Posterior spinal fusion, internal decompression and radiotherapy were conducted to relieve the pain. At 3 months after the diagnosis of lumbar metastasis, he is currently treated with temozolomide and bevacizumab, without the enlarging of the tumor. DISCUSSION As far as we investigated, there has been 30 cases of vertebral metastasis of glioblastoma reported in literature. Considering the biological obstacles that prevent glioblastomas from infiltrating outside of the CNS, it can be speculated that deposition of tumor cells into the blood stream or excision of the dura due to surgical interventions may attribute to extracranial metastasis. Due to the improvement of overall survival of glioblastoma, vertebral metastasis is suspected to be more common. Therefore, investigation of its risk factors and standardization of its treatment is necessary. CONCLUSION We reported a case of lumbar metastasis of glioblastoma. Extradural metastasis of glioblastoma must be included in differential diagnoses in treating patients with glioblastoma.

In response to hypoxic stress, hypoxia-inducible factor (HIF)-1α is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1α and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1α target genes. Interestingly, our results revealed that the downregulation of HIF-1α by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1α stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status. Cancer Res; 73(6); 1787–99. ©2012 AACR.