A novel SCNN1G mutation in a PHA I infant patient correlates with nephropathy.

Systematic form of pseudohypoaldosteronism Type I (PHA I) is a rare recessive homozygous inherited syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. It is caused by mutations in one of the genes encoding the α, ß and γ subunits of epithelial sodium channels (ENaC). In this study, we performed whole exome sequencing on an infant patient with PHA I as well as nephropathy. The result presented a novel homozygous six-base deletion in the γ subunit encoding gene SCNN1G. Then we correlated the mutant to kidney damage, along with transcriptional alterations of genes involved in inflammation, oxidative stress and apoptosis, via in vitro and in vivo tests. In addition, it was demonstrated that the SCNN1G defects triggered programmed cell death via inhibiting miR-21 and upregulating PTEN, which then orchestrated the key downstream regulators, including Bcl2, Bax2, and cleaved Caspse-3 in a way that favors cell apoptosis. The study enhances our understanding of the pathophysiology of the disorder of PHA I and the mechanisms of renal damage induced by the novel defect.

[Diagnosis and surgical treatment of tight carotid stenosis].

OBJECTIVE: To explore the specialty of diagnosis and surgery of tight carotid stenosis. METHOD: From January 2000 to December 2009, 53 patients with tight carotid stenosis (> 95%) were operated on. All 53 patients had tight carotid stenosis more than 95% on one side in whom 28 had contralateral carotid stenosis or occlusion. The clinical and imaging data as well as surgical outcomes of the patients were retrospectively analyzed. RESULTS: Forty-five patients had postoperatively done well without any complications. There were 3 cases of hemodynamic instability and one case of cardiac ischemia which resolved in one to two days. One patient developed mild hoarseness. One complicated with bacteremia due to deep vein catheter insertion. Two patients experienced brain hemorrhage. None of this series occurred perioperative brain ischemia. CONCLUSIONS: Tight carotid stenosis indicates a need for expeditious carotid endarterectomy with very low rates of brain ischemia. Intraoperative shunting is seldom necessary. Postoperative hyperperfusion syndrome and brain hemorrhage should be worried. Micro-endarterectomy can effectively prevent from restenosis.

[The strategy of management for bilateral carotid atherosclerotic stenosis].

OBJECTIVE: To evaluate the indication, time and strategy of surgery for patients with bilateral carotid atherosclerotic stenosis. METHODS: Seventy-four patients with bilateral carotid atherosclecrotic stenosis were admitted to our hospital from February 1987 to December 2007. In 34 patients who presented with unilateral symptoms and underwent ipsilateral carotid endarterectomy (CEA), contralateral CEA or carotid artery stenting (CAS) was performed in 8 because of severe stenosis (> 70%) or unstable plaque. Thirty-eight patients presented with bilateral symptoms. Among them, 15 underwent CEA on both sides, 3 were performed CEA on one side and CAS on the other side, while 20 underwent unilateral CEA only. In 2 asymptomatic patients, CEA was also performed. RESULTS: Ninety-three cases of CEA were performed in 74 patients. Sixty-eight patients were uneventful after operation. Neurological deficits deteriorated in 2 patients. Four patients developed cardiac ischemia, cerebral hemorrhage and hoarseness respectively. Sixty-seven patients were followed-up for 4.9 years. No cerebral ischemia relevant to operated carotid artery developed in 63 patients. CONCLUSIONS: If the indication is obvious, CEA should be performed no matter how contralateral carotid artery is. The strategy of therapy is individual. Whether using shunt depends on intra-operative monitoring.

Image-guided endoscopic surgery for spontaneous supratentorial intracerebral hematoma.

OBJECTIVE Endoscopic removal of intracerebral hematomas is becoming increasingly common, but there is no standard technique. The authors explored the use of a simple image-guided endoscopic method for removal of spontaneous supratentorial hematomas. METHODS Virtual reality technology based on a hospital picture archiving and communications systems (PACS) was used in 3D hematoma visualization and surgical planning. Augmented reality based on an Android smartphone app, Sina neurosurgical assist, allowed a projection of the hematoma to be seen on the patient's scalp to facilitate selection of the best trajectory to the center of the hematoma. A obturator and transparent sheath were used to establish a working channel, and an endoscope and a metal suction apparatus were used to remove the hematoma. RESULTS A total of 25 patients were included in the study, including 18 with putamen hemorrhages and 7 with lobar cerebral hemorrhages. Virtual reality combined with augmented reality helped in achieving the desired position with the obturator and sheath. The median time from the initial surgical incision to completion of closure was 50 minutes (range 40-70 minutes). The actual endoscopic operating time was 30 (range 15-50) minutes. The median blood loss was 80 (range 40-150) ml. No patient experienced postoperative rebleeding. The average hematoma evacuation rate was 97%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 6.7 ± 3.2; 1 week after hematoma evacuation the mean GCS score had improved to 11.9 ± 3.1 (p < 0.01). CONCLUSIONS Virtual reality using hospital PACS and augmented reality with a smartphone app helped precisely localize hematomas and plan the appropriate endoscopic approach. A transparent sheath helped establish a surgical channel, and an endoscope enabled observation of the hematoma's location to achieve satisfactory hematoma removal.

Impact of Virtual and Augmented Reality Based on Intraoperative Magnetic Resonance Imaging and Functional Neuronavigation in Glioma Surgery Involving Eloquent Areas.

BACKGROUND: The utility of virtual and augmented reality based on functional neuronavigation and intraoperative magnetic resonance imaging (MRI) for glioma surgery has not been previously investigated. METHODS: The study population consisted of 79 glioma patients and 55 control subjects. Preoperatively, the lesion and related eloquent structures were visualized by diffusion tensor tractography and blood oxygen level-dependent functional MRI. Intraoperatively, microscope-based functional neuronavigation was used to integrate the reconstructed eloquent structure and the real head and brain, which enabled safe resection of the lesion. Intraoperative MRI was used to verify brain shift during the surgical process and provided quality control during surgery. The control group underwent surgery guided by anatomic neuronavigation. RESULTS: Virtual and augmented reality protocols based on functional neuronavigation and intraoperative MRI provided useful information for performing tailored and optimized surgery. Complete resection was achieved in 55 of 79 (69.6%) glioma patients and 20 of 55 (36.4%) control subjects, with average resection rates of 95.2% ± 8.5% and 84.9% ± 15.7%, respectively. Both the complete resection rate and average extent of resection differed significantly between the 2 groups (P < 0.01). Postoperatively, the rate of preservation of neural functions (motor, visual field, and language) was lower in controls than in glioma patients at 2 weeks and 3 months (P < 0.01). CONCLUSION: Combining virtual and augmented reality based on functional neuronavigation and intraoperative MRI can facilitate resection of gliomas involving eloquent areas.

A portion of inhibitory neurons in human temporal lobe epilepsy are functionally upregulated: an endogenous mechanism for seizure termination.

MAIN PROBLEM: Epilepsy is one of the more common neurological disorders. The medication is often ineffective to the patients suffering from intractable temporal lobe epilepsy (TLE). As their seizures are usually self-terminated, the elucidation of the mechanism underlying endogenous seizure termination will help to find a new strategy for epilepsy treatment. We aim to examine the role of inhibitory interneurons in endogenous seizure termination in TLE patients. METHODS: Whole-cell recordings were conducted on inhibitory interneurons in seizure-onset cortices of intractable TLE patients and the temporal lobe cortices of nonseizure individuals. The intrinsic property of the inhibitory interneurons and the strength of their GABAergic synaptic outputs were measured. The quantitative data were introduced into the computer-simulated neuronal networks to figure out a role of these inhibitory units in the seizure termination. RESULTS: In addition to functional downregulation, a portion of inhibitory interneurons in seizure-onset cortices were upregulated in encoding the spikes and controlling their postsynaptic neurons. A patch-like upregulation of inhibitory neurons in the local network facilitated seizure termination. The upregulations of both inhibitory neurons and their output synapses synergistically shortened seizure duration, attenuated seizure strength, and terminated seizure propagation. CONCLUSION: Automatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.

Rosai-Dorfman disease: a retrospective analysis of 13 cases.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, histiocytic proliferative disorder, the infrequent occurrence of which limits in-depth studies. Consequently, many characteristics of this disease remain unknown, restricting early diagnosis and proper treatment. METHODS: In this study, the literature was reviewed and a retrospective analysis of the medical records of 13 patients with RDD conducted to investigate the demographic data, clinical data, laboratory and imaging results, treatment, and prognosis of this disease. RESULTS: Of the 13 cases in our sample, 10 (77%) were purely extranodal RDD, 2 (15%) were both nodal and extranodal, and 1 (8%) was purely nodal. The locations of the 10 purely extranodal RDD lesions included the central nervous system (n = 6, 60%), nasal cavity and paranasal sinuses (n = 3, 30%), and the cutis (n = 1, 10%). The locations of the central nervous system-related RDD lesions included the cerebral subdura (n = 2, 29%), the sellar region (n = 3, 14%), the cerebral parenchyma (n = 1, 14%) and the spinal subdura (n = 1, 14%). Ten patients (77%) had stable conditions, 3 (23%) experienced recurrence, and 2 (15%) experienced recurrence and lesion metastasis. CONCLUSIONS: RDD is rare, requiring knowledge of its clinical manifestations for a rapid and correct diagnosis. In light of the possibility of recurrence and lesion metastasis, long-term follow-up is needed. Treatment is still controversial. Future efforts should be directed at investigating the etiology and postoperative treatment for relapsing cases or those with subresected lesions.