Meng Zhu, Hong Bu, and Yu-lan Peng
Chen-Yu Ding, Han-Pei Cai, Hong-Liang Ge, Liang-Hong Yu, Yuan-Xiang Lin, and De-Zhi Kang
The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.
The authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.
Forty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).
The serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.
Ang Deng, Hong-Qi Zhang, Ming-Xing Tang, Shao-Hua Liu, Yu-Xiang Wang, and Qi-Le Gao
The objective of this study was to evaluate the clinical efficacy of posterior-only surgical correction of dystrophic scoliosis in patients with neurofibromatosis Type 1 (NF1) using a multiple anchor point method (MAPM).
From 2005 to 2014, 31 patients (mean age 13.5 years old, range 10–22 years old) suffering from dystrophic scoliosis associated with NF1 underwent posterior-only surgical correction using a MAPM. The apex of the deformity was thoracic (n = 25), thoracolumbar (n = 4), and lumbar (n = 2). The mean preoperative coronal Cobb angle was 69.1° (range 48.9°–91.4°). The mean Cobb angle on the side-bending radiograph of the convex side was 58.2° (range 40°–79.8°). The mean flexibility and apical vertebral rotation (AVR) were 15.6% (range 8.3%–28.2%) and 2.5° (range 2°–3°), respectively. The mean angle of sagittal kyphosis was 58.3° (range 34.1°–79.6°).
The mean follow-up period was 53 months (range 12–96 months). The mean postoperative coronal Cobb angle was 27.4° (range 16.3°–46.7°). Postoperatively, the mean AVR and angle of sagittal kyphosis were 1.2° (range 1°–2°) and 22.4° (range 4.2°–36.3°), respectively. All patients showed good correction of all indices postoperatively. The mean postoperative correction rate was 58.7% (range 46.3%–74.1%). At the final follow-up evaluation, the corrective loss rate of the Cobb angle was only 2.3%. Only 1 patient required revision surgery. No severe complications such as spinal cord, neural, or large vascular injury occurred during the operation.
Posterior-only surgical correction of dystrophic scoliosis in patients with NF1 using a MAPM could yield satisfactory clinical efficacy of correction and fusion.
Jian Ren, Tao Hong, Chuan He, Xiaoyu Li, Yongjie Ma, Jiaxing Yu, Feng Ling, and Hongqi Zhang
Optimal surgical strategies for intramedullary spinal cord cavernous malformations (ISCCMs) are not optimized and remain problematic. In this study the authors identify rational surgical strategies for ISCCMs and predictors of outcomes after resection.
A single-center study was performed with 219 consecutive surgically treated patients who presented from 2002 to 2017 and were analyzed retrospectively. The American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate neurological functions. Patient characteristics, surgical approaches, and immediate and long-term postoperative outcomes were identified.
The average ISCCM size was 10.5 mm. The spinal level affected was cervical in 24.8% of patients, thoracic in 73.4%, and lumbar in 1.8%. The locations of the lesions in the horizontal plane were 30.4% ventral, 41.6% dorsal, and 28.0% central. Of the 214 patients included in the cohort for operative evaluation, 62.6% had superficially located lesions, while 37.4% were embedded. Gross-total resection was achieved in 98.1% of patients. The immediate postoperative neurological condition worsened in 10.3% of the patients. Multivariate logistic regression identified mild preoperative function (p = 0.014, odds ratio [OR] 4.5, 95% confidence interval [CI] 1.4–14.8) and thoracolumbar-level lesions (p = 0.01, OR 15.7, 95% CI 1.9–130.2) as independent predictors of worsening. The mean follow-up duration in 187 patients was 45.9 months. Of these patients, 63.1% were stable, 33.2% improved, and 3.7% worsened. Favorable outcomes were observed in 86.1% of patients during long-term follow-up and were significantly associated with preoperative mild neurological and disability status (p = 0.000) and cervically located lesions (p = 0.009). The depths of the lesions were associated with worse long-term outcomes (p = 0.001), and performing myelotomy directly through a yellowish abnormal surface in moderate-depth lesions was an independent predictor of worsening (p = 0.023, OR 35.3, 95% CI 1.6–756.3).
Resection performed with an individualized surgical approach remains the primary therapeutic option in ISCCMs. Performing surgery in patients with mild symptoms at the thoracolumbar level and embedded located lesions requires more discretion.
John Spooner, Hong Yu, Chris Kao, Karl Sillay, and Peter Konrad
✓The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation.
This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patient's pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone.
The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.
Qing-Song Lin, Wei-Xiong Wang, Yuan-Xiang Lin, Zhang-Ya Lin, Liang-Hong Yu, Yin Kang, and De-Zhi Kang
Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.
Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction.
ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression.
ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.
Jian-tao Liang, Yu-hai Bao, Hong-qi Zhang, Li-rong Huo, Zhen-yu Wang, and Feng Ling
The authors conducted a study to assess the clinical pattern, radiological features, therapeutic strategies, and long-term outcomes in patients with intramedullary spinal cord cavernomas (ISCCs) based on a large case series.
This retrospective study identified 96 patients (60 males, 36 females) surgically (81 cases) or conservatively (15 cases) treated for ISCCs between May 1993 and November 2007. Each diagnosis was based on MR imaging and spinal angiography evidence. For all surgically treated patients, the diagnosis was verified pathologically. The neurological outcomes pre- and postoperatively, as well as long-term follow-up, were assessed using the Aminoff-Logue Disability Scale.
The mean age at the onset of symptoms was 34.5 years (range 9–80 years). Of the lesions, 68 (71%) were located in the thoracic spine, 25 (26%) in the cervical spine, and only 3 (3%) in the lumbar spine. The median symptom duration was 19.7 months. The clinical behavior of the lesion was a slow progression in 73 cases and an acute decline in 23 cases. Long-term follow-up data (mean 45.8 months, range 10–183 months) were available for 75 patients (64 surgical cases and 11 conservative cases). In the surgical group, a complete resection was achieved in 60 patients, and incomplete resection was detected in 4 patients after operation. At the end of the follow-up period in the operative group, 23 patients (36%) improved, 35 (55%) remained unchanged, and 6 (9%) worsened. In the nonoperative group, 5 patients improved, 6 patients remained unchanged, and none worsened.
For differential diagnosis, spinal angiography was necessary in some cases. For most symptomatic lesions, complete microsurgical resection of the symptomatic ISCC is safe and prevents rebleeding and further neurological deterioration. However, in patients whose lesions were small and located ventrally in the spinal cord, one can also opt for a rigorous follow-up, considering the high surgical risk.
Hong-Qi Zhang, Tong Chen, Shao-Shuai Wu, Liang-Hong Teng, Yong-Zhong Li, Li-Yong Sun, Zhi-Ping Zhang, De-Yu Guo, De-Hong Lu, and Feng Ling
The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM).
This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages.
Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons.
This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.
Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang, and Guo Zhong Li
Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke–related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke.
The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)–treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)–induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3′ untranslated region (3′UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase–9 [MMP-9], tumor necrosis factor–α [TNF-α], and interleukin-1β [IL-1β]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V–FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits.
JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3′UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1β). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit.
These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.
Joshua J. Loya, Stefan A. Mindea, Hong Yu, Chitra Venkatasubramanian, Steven D. Chang, and Terry C. Burns
Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension–associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.