Modern endovascular treatments of occlusive pediatric acute ischemic strokes: case series and review of the literature.

PURPOSE: Literature on the endovascular treatment of occlusive acute ischemic stroke (AIS) in the pediatric population remains nebulous. Clinical trials evaluating the role of systemic and intra-arterial thrombolysis, and mechanical thrombectomy have been strictly isolated to the adult population and largely unknown in their safety and efficacy in the pediatric group. METHODS: The authors present a review of the literature and their own two cases of occlusive acute ischemic stroke in children younger than the age of 10 years who were treated with modern endovascular devices, specifically with stent retrievers, and discuss their clinical and technical considerations as well as their limitations. RESULTS: In both pediatric patients, a combination of stent retriever and Penumbra aspiration were used to achieve Thrombolysis In Cerebral Infarction (TICI) 2a or greater with reduction of overall stroke burden. A reduction of National Institutes of Health Stroke Scale (NIHSS) of 8 or greater was achieved at discharge. At 3-month follow-up, the patients had a NIHSS of 6 and 2, respectively. One patient continued to improve from NIHSS of 6 to 3 at 6 months. CONCLUSION: In carefully, selected pediatric patients, modern endovascular techniques may be used to treat occlusive pediatric AIS. However, larger clinical trials are needed to evaluate the overall safety and effectiveness.

Guillain-Barré syndrome after elective lateral lumbar interbody fusion.

Complications following lateral retroperitoneal transpsoas lumbar fusion (LLIF) surgery include femoral nerve apraxia, bowel/bladder injury, ureteral injury, and potentially, as illustrated in this case report, Guillain-Barré syndrome. Guillain-Barré syndrome (GBS) is an autoimmune inflammatory condition that typically presents after infection, or, less frequently, post-operatively. We report a case of GBS following elective lumbar fusion through the lateral retroperitoneal transpsoas approach (LLIF). A 56-year-old patient presented with left lower extremity (LLE) weakness on post-operative day 12. EMG showed bilateral upper extremity muscle recruitment, worse distally. Following a treatment with intravenous immunoglobulin (IVIG), the patient gradually improved, and her condition was favorable at 6-month post-operative follow-up. CSF analysis and EMG should be part of the workup for patients presenting with lower extremity neuropathy following LLIF.

National Rates, Reasons, and Risk Factors for 30- and 90-Day Readmission and Reoperation Among Patients Undergoing Anterior Cervical Discectomy and Fusion: An Analysis Using the Nationwide Readmissions Database.

STUDY DESIGN: Retrospective cohort study of the Nationwide Readmissions Database (NRD). OBJECTIVE: To determine causes of and independent risk factors for 30- and 90-day readmission in a cohort of anterior cervical discectomy and fusion (ACDF) patients. SUMMARY OF BACKGROUND DATA: Identifying populations at high-risk of 30-day readmission is a priority in healthcare reform so as to reduce cost and patient morbidity. However, among patients undergoing ACDF, nationally-representative data have been limited, and have seldom described 90-day readmissions, early reoperation, or socioeconomic influences. METHODS: We queried the NRD, which longitudinally tracks 49.3% of hospitalizations, for all adult patients undergoing ACDF. We calculated the rates of, and determined reasons for, readmission and reoperation at 30 and 90 days, and determined risk factors for readmission at each timepoint. RESULTS: We identified 50,126 patients between January and September 2014. Of these, 2294 (4.6%) and 4152 (8.3%) were readmitted within 30 and 90 days of discharge, respectively, and were most commonly readmitted for infections, medical complications, and dysphagia. The characteristics most strongly associated with readmission were Medicare or Medicaid insurance, length of stay greater than or equal to 4 days, three or more comorbidities, and non-routine discharge, whereas surgical factors (e.g., greater number of vertebrae fused) were more modest. By 30 and 90 days, 8.2% and 11.7% of readmitted patients underwent an additional spinal procedure, respectively. CONCLUSION: Our analysis uses the NRD to thoroughly characterize readmission in the general ACDF population. Readmissions are often delayed (after 30 days), strongly associated with insurance status, and many result in reoperation. Our results are crucial for risk-stratifying future ACDF patients and developing interventions to reduce readmission.Level of Evidence: 3.

Targeting the mTOR pathway using novel ATP­competitive inhibitors, Torin1, Torin2 and XL388, in the treatment of glioblastoma.

Mechanistic target of rapamycin (mTOR), which functions via two multiprotein complexes termed mTORC1 and mTORC2, is positioned in the canonical phosphoinositide 3­kinase­related kinase (PI3K)/AKT (PI3K/AKT) pathways. These complexes exert their actions by regulating other important kinases, such as 40S ribosomal S6 kinases (S6K), eukaryotic translation initiation factor 4E (elF4E)­binding protein 1 (4E­BP1) and AKT, to control cell growth, proliferation, migration and survival in response to nutrients and growth factors. Glioblastoma (GB) is a devastating form of brain cancer, where the mTOR pathway is deregulated due to frequent upregulation of the Receptor Tyrosine Kinase/PI3K pathways and loss of the tumor suppressor phosphatase and tensin homologue (PTEN). Rapamycin and its analogs were less successful in clinical trials for patients with GB due to their incomplete inhibition of mTORC1 and the activation of mitogenic pathways via negative feedback loops. Here, the effects of selective ATP­competitive dual inhibitors of mTORC1 and mTORC2, Torin1, Torin2 and XL388, are reported. Torin2 exhibited concentration­dependent pharmacodynamic effects on inhibition of phosphorylation of the mTORC1 substrates S6KSer235/236 and 4E­BP1Thr37/46 as well as the mTORC2 substrate AKTSer473 resulting in suppression of tumor cell migration, proliferation and S­phase entry. Torin1 demonstrated similar effects, but only at higher doses. XL388 suppressed cell proliferation at a higher dose, but failed to inhibit cell migration. Treatment with Torin1 suppressed phosphorylation of proline rich AKT substrate of 40 kDa (PRAS40) at Threonine 246 (PRAS40Thr246) whereas Torin2 completely abolished it. XL388 treatment suppressed the phosphorylation of PRAS40Thr246 only at higher doses. Drug resistance analysis revealed that treatment of GB cells with XL388 rendered partial drug resistance, which was also seen to a lesser extent with rapamycin and Torin1 treatments. However, treatment with Torin2 completely eradicated the tumor cell population. These results strongly suggest that Torin2, compared to Torin1 or XL388, is more effective in suppressing mTORC1 and mTORC2, and therefore in the inhibition of the GB cell proliferation, dissemination and in overcoming resistance to therapy. These findings underscore the significance of Torin2 in the treatment of GB.

Laparoscopic intragastric removal of giant trichobezoar.

BACKGROUND AND OBJECTIVES: Gastric bezoars are a rare clinical entity, most commonly observed in patients with mental or emotional illness. Large bezoars can be difficult to remove laparoscopically without extending a port incision. METHODS: We report the case of a large symptomatic trichobezoar with Rapunzel syndrome that occurred in a 17-year-old girl who had trichotillomania. RESULTS: The bezoar was removed laparoscopically, in piecemeal fashion, through a gastrotomy port. This procedure did not require an extension of any incision, nor did it require the contents of the stomach to directly touch the incision, thereby reducing the risk of infection. The patient was discharged home, on the fourth postoperative day, free of any complications. CONCLUSION: This case illustrates the safety of the laparoscopic approach in the removal of large gastric bezoars. In considering use of this approach, the potentially long operative time must be weighed against the benefits of both minimal risk of infection and minimal incisions.

Epidermoid Cyst of the Lumbar Spine After Lumbar Puncture: A Clinical, Radiographic, and Pathologic Correlation.

BACKGROUND: Epidermoid cysts can rarely arise as a late complication of lumbar puncture. We describe a young man who had a remote history of a lumbar puncture and who was subsequently found to have a lumbar spinal epidermoid cyst on imaging, after presenting with lower extremity radicular pain. CASE DESCRIPTION: A 24-year-old man with a remote history of lumbar puncture presented with lower back pain and radicular leg pain which had been ongoing for over a year. Despite conservative management, the patient's symptoms progressed to worsening back pain and left L4 radiculopathy. Magnetic resonance imaging of the lumbar spine demonstrated a peripherally enhancing, intradural, extramedullary lesion at L4-5. Diffusion-weighted imaging revealed diffusion restriction within the lesion, characteristic of an epidermoid cyst. The patient underwent an L4-5 laminectomy for resection of the intradural tumor. The lesion was noted to contain pearly white granules consistent with the appearance of an epidermoid cyst. Histopathology confirmed the diagnosis. On follow-up examination, the patient demonstrated improvement of his back pain and resolution of radicular symptoms. CONCLUSIONS: Lumbar spinal epidermoid cysts may be either congenital or secondary to an iatrogenic cause. This patient had a remote history of lumbar puncture during workup for meningitis as a child. As a complication of a lumbar puncture, the formation of an epidermoid cyst can occur and is thought to be the result of implanted cutaneous tissue. This case provides a comprehensive illustration of the clinical, radiographic, intraoperative, and pathologic findings consistent with an iatrogenic epidermoid cyst.

A Novel Technique for Prevention of Subarachnoid-Pleural Fistula After Incidental Durotomy During Transthoracic Spinal Surgery.

BACKGROUND: Subarachnoid-pleural fistulas (SPFs) are rare but significant complications of transthoracic spinal surgery. Whether noted intraoperatively or in the postoperative period, SPF requires implementation of aggressive management, with consideration given to direct surgical repair. Additionally, the physical constraints of the thoracic cavity often hinder direct SPF repair. OBJECTIVE: To present a novel operative technique that can be used to easily and quickly address incidental durotomy incurred during transthoracic spinal surgery while working within the confines of the thorax. METHODS: Surgical hemostatic clips were used to affix a patch-graft of dural substitute to the parietal pleura surrounding the site of a transthoracic spinal decompression in which an incidental durotomy was incurred. The patch-graft was augmented with the application of biological glue and was successful in preventing symptomatic SPF. RESULTS: The use of surgical clips to affix a patch graft is a quick, easy, and effective means of addressing an incidental durotomy during thoracotomy and preventing SPF. The clip applier is significantly easier to maneuver within the narrow working channel of the thorax than are instruments used during direct repair. CONCLUSION: Preventing SPF can be challenging. The physical constraints of the thoracic cavity make water-tight repair difficult and time-consuming, particularly when the morphology of the dural tear prevents primary apposition of the defect. The authors present a novel technique of preventing development of SPF using hemostatic clips to simply and quickly affix suturable dural substitute to the parietal pleura overlying the site of an incidental durotomy.

Spontaneous Fusion of S2/S3 Spondyloptosis in an Adult.

BACKGROUND: Spondyloptosis is grade V on the Meyerding classification. Traumatic spondyloptosis can occur throughout the spinal column, particularly at junctional levels, and finding an ideal surgical strategy to address it remains a challenge for spinal surgeons. The sacrum is considered a united bone in adults, and sacral intersegmental spondyloptosis is extremely rare. CASE REPORT: Herein, we present an unusual case of S2/S3 spondyloptosis in a 27-year-old female patient with spontaneous solid fusion. CONCLUSIONS: This case demonstrates that similar distal sacral pathologies may be managed conservatively when there is no associated neurologic deficit, and the osteodiskoligamentous integrity of the lumbosacropelvic unit remains intact. Our report plus the very few published papers in the literature illustrate the natural history of uncomplicated traumatic spondyloptosis and support the role of in situ fusion and instrumentation as a reliable alternative to circumferential fusion in patients who cannot tolerate staged or prolonged operations.

Traumatic Lumbar Subdural Hematoma in the Absence of Intracranial Disease.

BACKGROUND: Traumatic spinal subdural hematoma is an exceedingly rare condition, with those occurring in the absence of intracranial disease being particularly uncommon. Only 13 such cases have been reported. Although theories exist to describe the pathophysiology of traumatic spinal subdural hematoma, the precise mechanism and guidelines for management remain unclear. CASE DESCRIPTION: This report describes a 37-year-old woman who suffered a traumatic assault who developed progressive low back pain with radicular symptoms 2 days after presentation. Magnetic resonance imaging revealed a lumbar subdural hematoma extending from L1 to L5. No intracranial disease was detected on imaging. CONCLUSIONS: Definitive guidelines for management of this condition are uncertain; however, successful use of conservative management, lumbar drainage, and surgical evacuation has been reported. This patient underwent a lumbar laminectomy with evacuation of the hematoma, resulting in immediate pain relief and resolution of symptoms within 1 week of the procedure.

Successful Treatment of Complex Regional Pain Syndrome with Pseudoaneurysm Excision and Median Nerve Neurolysis.

BACKGROUND: Complex regional pain syndrome (CRPS), formerly referred to as reflex sympathetic dystrophy, is a pain syndrome characterized by severe pain, altered autonomic and motor function, and trophic changes. CRPS is usually associated with soft tissue injury or trauma. It has also been described as a rare complication of arterial access for angiography secondary to pseudoaneurysm formation. CASE DESCRIPTION: A 73-year-old woman underwent catheterization of the left brachial artery for angiography of the celiac artery. The following day, the patient noticed numbness and severe pain in the median nerve distribution of the left upper extremity. Over the next 6 months, the patient developed CRPS in the left hand with pain and signs of autonomic dysfunction. Further work-up revealed the formation of a left brachial artery pseudoaneurysm with impingement on the median nerve. She underwent excision of the pseudoaneurysm with decompression and neurolysis of the left median nerve. Approximately 6 weeks after surgery, the patient had noticed significant improvement in autonomic symptoms. CONCLUSIONS: This case involves a unique presentation of CRPS caused by brachial artery angiography and pseudoaneurysm formation. In addition, the case demonstrates the efficacy of pseudoaneurysm excision and median nerve neurolysis in the treatment of CRPS as a rare complication of arterial angiography.

Rheumatoid Arthritis and the Cervical Spine: A Review on the Role of Surgery.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting a significant percentage of the population. The cervical spine is often affected in this disease and can present in the form of atlantoaxial instability (AAI), cranial settling (CS), or subaxial subluxation (SAS). Patients may present with symptoms and disability secondary to these entities but may also be neurologically intact. Cervical spine involvement in RA can pose a challenge to the clinician and the appropriate role of surgical intervention is controversial. The aim of this paper is to describe the pathology, pathophysiology, clinical manifestations, and diagnostic evaluation of rheumatoid arthritis in the cervical spine in order to provide a better understanding of the indications and options for surgery. Both the medical and surgical treatment options for RA have improved, so has the prognosis of the cervical spine disease. With the advent of disease modifying antirheumatic drugs (DMARDs), fewer patients are presenting with cervical spine manifestations of RA; however, those that do, now have improved surgical techniques available to them. We hope that, by reading this paper, the clinician is able to better evaluate patients with RA in the cervical spine and determine in which patients surgery is indicated.

Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes.

Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that functions via two multiprotein complexes, namely mTORC1 and mTORC2, each characterized by different binding partners that confer separate functions. mTORC1 function is tightly regulated by PI3-K/Akt and is sensitive to rapamycin. mTORC2 is sensitive to growth factors, not nutrients, and is associated with rapamycin-insensitivity. mTORC1 regulates protein synthesis and cell growth through downstream molecules: 4E-BP1 (also called EIF4E-BP1) and S6K. Also, mTORC2 is thought to modulate growth factor signaling by phosphorylating the C-terminal hydrophobic motif of some AGC kinases such as Akt and SGK. Recent evidence has suggested that mTORC2 may play an important role in maintenance of normal as well as cancer cells by virtue of its association with ribosomes, which may be involved in metabolic regulation of the cell. Rapamycin (sirolimus) and its analogs known as rapalogues, such as RAD001 (everolimus) and CCI-779 (temsirolimus), suppress mTOR activity through an allosteric mechanism that acts at a distance from the ATP-catalytic binding site, and are considered incomplete inhibitors. Moreover, these compounds suppress mTORC1-mediated S6K activation, thereby blocking a negative feedback loop, leading to activation of mitogenic pathways promoting cell survival and growth. Consequently, mTOR is a suitable target of therapy in cancer treatments. However, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. In recent years, new pharmacologic agents have been developed which can inhibit these complexes via ATP-binding mechanism, or dual inhibition of the canonical PI3-K/Akt/mTOR signaling pathway. These compounds include WYE-354, KU-003679, PI-103, Torin1, and Torin2, which can target both complexes or serve as a dual inhibitor for PI3-K/mTOR. This investigation describes the mechanism of action of pharmacological agents that effectively target mTORC1 and mTORC2 resulting in suppression of growth, proliferation, and migration of tumor and cancer stem cells.