Successful Endovascular Management of Massive Pansinus Thrombosis: Case Report and Review of Literature.

Cerebral sinus venous thrombosis (CSVT) is a recognized cause of childhood and neonatal stroke. More than 50% of neonates have a poor outcome, and mortality is high. Coma is a predictor of death in neonatal CSVT. We present the case of a 9-day-old infant, who presented in coma and was treated successfully with a combination of mechanical thrombectomy using the MindFrame System via the right jugular vein, local infusion of recombinant tissue plasminogen activator and abciximab, as well as anticoagulation. In this case, aggressive thrombectomy and thrombolysis achieved complete neurologic restoration safely and quickly.

Superoxide is involved in the central nervous system activation and sympathoexcitation of myocardial infarction-induced heart failure.

Increased angiotensin II signaling in the brain has been shown to play a critical role in the excessive sympathoexcitation and development of heart failure (HF) after myocardial infarction (MI). We have recently demonstrated that reactive oxygen species mediate the actions of angiotensin II in the brain. In this study, we tested the hypothesis that increased redox signaling in central cardiovascular control regions is a key mechanism in the neurocardiovascular dysregulation that follows MI. Ligation of the left coronary artery induced a large MI and subsequent HF in adult C57BL/6 mice, as demonstrated by cardiac hypertrophy, hydrothorax, and ascites. Immunohistochemical analysis of Fos, a marker of neuronal activation, revealed a significant increase in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 and 4 weeks after MI compared with sham mice. Intracerebroventricular injection of an adenoviral vector encoding superoxide dismutase (Ad-Cu/ZnSOD) caused a significant decrease in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 weeks after MI compared with mice receiving either saline or a control vector (Ad-LacZ). There was also a diminished role of sympathetic drive in post-MI mice treated centrally with Ad-Cu/ZnSOD, as demonstrated by significantly attenuated falls in heart rate and mean arterial pressure to the ganglionic blocker hexamethonium and decreased urinary norepinephrine levels in these mice compared with Ad-LacZ-treated MI mice. These results suggest that superoxide plays a key role in the central activation and sympathetic hyperactivity after MI in mice and that oxygen radicals in the brain may be important new targets for therapeutic treatment of heart failure.

Successful Treatment of a Three-Column Thoracic Extension Injury with Recumbency.

We report a unique instance of a 66-year-old male patient with an unstable three-column thoracic extension injury at the level of T4/5 who was treated with recumbency and bracing without surgery. A posterior long segment fixation was attempted three times on two separate occasions over the course of a week with failure due to difficulty in ventilating the patient during prone positioning, cardiopulmonary arrest, and hemodynamic instability during prone positioning for surgery. The decision then was to treat this fracture with recumbency. He was fitted with a thoracolumbosacral orthosis (TLSO), and was kept on bed rest for eight weeks. The patient's activity was advanced to head of bed for 45 degrees for four weeks and then to 90 degrees for four other weeks. At his 16th week visit, the patient was asymptomatic, and a computer tomography (CT) scan and magnetic resonance imaging (MRI) of the thoracic spine demonstrated evidence of osteophyte bridging and restoration of normal alignment. Three-column thoracic extension injuries can be successfully treated with recumbency in poor surgical candidates.

Acute Presentation of Lumbar Spinal Schwannoma Due to Torsion: A Case Report.

Although schwannomas are common spinal tumors with insidious presentations, acute neurological deterioration is an extremely rare manifestation that can occur in the setting of tumor torsion and infarction. The present case reports an unusual presentation of a spinal schwannoma that underwent torsion and infarction. A 65-year-old male presented initially with acute radicular pain progressing to cauda equina syndrome and confusion. MRI of the lumbar spine revealed an intradural extramedullary lesion at the level of L1/L2 measuring 1.1x0.9 cm. Intraoperatively, a reddish mass was seen caudally twisted around itself. Gross total resection was achieved with a final diagnosis of schwannoma with areas of infarction. At his six week follow up clinical visit, the patient was asymptomatic and his neurological exam was normal. The neurosurgeon should be aware of such atypical radiographic and clinical presentation amongst the spectrum of clinical manifestation of these nerve sheath tumors.

Targeted viral delivery of Cre recombinase induces conditional gene deletion in cardiovascular circuits of the mouse brain.

The Cre/loxP system has shown promise for investigating genes involved in nervous system function and pathology, although its application for studying central neural regulation of cardiovascular function and disease has not been explored. Here, we report for the first time that recombination of loxP-flanked genes can be achieved in discrete cardiovascular regulatory nuclei of adult mouse brain using targeted delivery of adenovirus (Ad) or feline immunodeficiency virus (FIV) bearing Cre recombinase (Ad-Cre, FIV-Cre). Single stereotaxic microinjections of Ad-Cre or FIV-Cre into specific nuclei along the subfornical organ-hypothalamic-hypophysial and brain stem-parabrachial axes resulted in robust and highly localized gene deletion as early as 7 days and for as long as 3 wk in a reporter mouse model in which Cre recombinase activates beta-galactosidase expression. An even greater selectivity in Cre-mediated gene deletion could be achieved in unique subpopulations of cells, such as vasopressin-synthesizing magnocellular neurons, by delivering Ad-Cre via retrograde transport. Moreover, Ad-Cre and FIV-Cre induced gene recombination in differential cell populations within these cardiovascular nuclei. FIV-Cre infection resulted in LacZ activation selectively in neurons, whereas both neuronal and glial cell types underwent gene recombination upon infection with Ad-Cre. These results establish the feasibility of using a combination of viral and Cre/loxP technologies to target specific cardiovascular nuclei in the brain for conditional gene modification and suggest the potential of this approach for determining the functional role of genes within these sites.

Effect of steerable cage placement during minimally invasive transforaminal lumbar interbody fusion on lumbar lordosis.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is commonly used for the treatment of a variety of degenerative spine disorders. Recently, steerable interbody cages have been developed which potentially allow for greater restoration of lumbar lordosis. Here we describe a technique and radiographic results following minimally invasive placement of steerable cages through a bilateral approach. A retrospective review was conducted of the charts and radiographs of 15 consecutive patients who underwent 19 levels of bilateral MIS-TLIF with the placement of steerable cages. These were compared to 10 patients who underwent 16 levels of unilateral MIS-TLIF with the placement of bullet cages. The average age, body mass index, distribution of the levels operated and follow-up were similar in both groups. The average height of the steerable cage placed was 10.9 mm compared to 8.5mm for bullet cages. The preoperative focal Cobb's angle per level was similar between both groups with a mean of -5.3 degrees for the steerable cage group and -4.8 degrees for the bullet cage group. There was a significant improvement in postoperative Cobb's angle after placement of a steerable cage with a mean of -13.7 (p<0.01) and this persisted at the last follow-up with -13 degrees (p<0.01). There was no significant change in Cobb's angle after bullet cage placement with -5.7 degrees postoperatively and a return to the baseline preoperative Cobb's angle of -4.8 at the last follow-up. Steerable cage placement for MIS-TLIF improves focal lordosis compared to bullet cage placement.

Intracranial glioblastoma with drop metastases to the spine after stereotactic biopsy.

BACKGROUND: Glioblastoma (GBM) is the most common primary intracranial tumor, but metastases are rarely reported. Previous reports have documented the occurrence of drop metastases to the spine. However, few of these reports have demonstrated the occurrence of spinal metastases after biopsy with stable intracranial disease. Here we present such a case. CASE DESCRIPTION: We present a case of GBM metastatic to the spinal cord after a stereotactic biopsy with stable intracranial disease. To our knowledge, this occurrence has only been reported in one previous case. CONCLUSION: We propose that traversing the lateral ventricle at the time of biopsy contributed to cerebrospinal fluid seeding with tumor cells and subsequent development of spinal disease.

Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 (-) after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a(-/-) mice and found reduced neurodegeneration after FPI. Both HCO3 (-) administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis.

OBJECT: Management of pediatric occipitocervical instability remains especially challenging. The off-label use of recombinant human bone morphogenetic protein (rhBMP)-2 for spinal fusion has increased with a well-documented increase in fusion rate in many case series. Unfortunately, recent reports have documented complications associated with rhBMP use in adult spinal fusions. Complications associated with the use of rhBMP in pediatric spinal surgery is less well understood. In this study the authors report on the fusion rate and complications associated with rhBMP in pediatric occipitocervical arthrodesis. METHODS: The authors reviewed the medical records of those patients 18 years old and younger who underwent dorsal occipitocervical fusion from January 2004 to December 2007 at the University of Iowa Hospitals and Clinics. Forty-eight patients were identified who received rhBMP-augmented fusion. The clinical outcome and complications of these fusions were analyzed. RESULTS: All 48 patients had fusion confirmed on lateral radiographs within 4-14 months with an average fusion time of 6.7 months. There were 6 complications, 5 of which included seroma formation. Two of 5 patients who developed postoperative seroma presented with symptoms suggesting brainstem compression and obstructive hydrocephalus requiring emergency reoperation. One patient developed heterotopic bone formation causing cervicomedullary compression requiring reoperation. CONCLUSIONS: The use of rhBMP to augment autograft in occipitocervical fusion allows for a high rate of successful arthrodesis, but is associated with potentially life-threatening complications in pediatric patients.

Minimally invasive surgery (endonasal) for anterior fossa and sellar tumors.

The primary goal of any surgical approach is to adequately visualize and treat the pathologic condition with minimal disruption to adjacent normal anatomy. The work of several researchers has revealed the promise of minimally invasive endonasal neurosurgery and paved the way for broader applications of the technology. This article discusses the current state of minimally invasive endonasal techniques to address the pathologic conditions of the anterior cranial fossa and parasellar region.

A "neurosurgical crisis" of sickle cell disease.

The occurrence of spontaneous acute epidural hematomas is rare in patients with sickle cell disease. The authors report the case of a patient with sickle cell anemia who presented with a sickle cell crisis that was complicated by the development of multiple acute epidural and subgaleal hematomas requiring surgical evacuation. Possible underlying mechanisms are discussed. Although rare, clinicians should be aware of this phenomenon as part of a spectrum of neurological complications in these patients.

Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction.

Dysregulation in central nervous system (CNS) signaling that results in chronic sympathetic hyperactivity is now recognized to play a critical role in the pathogenesis of heart failure (HF) following myocardial infarction (MI). We recently demonstrated that adenovirus-mediated gene transfer of cytoplasmic superoxide dismutase (Ad-Cu/ZnSOD) to forebrain circumventricular organs, unique sensory structures that lack a blood-brain barrier and link peripheral blood-borne signals to central nervous system cardiovascular circuits, inhibits both the MI-induced activation of these central signaling pathways and the accompanying sympathoexcitation. Here, we tested the hypothesis that this forebrain-targeted reduction in oxidative stress translates into amelioration of the post-MI decline in myocardial function and increase in mortality. Adult C57BL/6 mice underwent left coronary artery ligation or sham surgery along with forebrain-targeted gene transfer of Ad-Cu/ZnSOD or a control vector. The results demonstrate marked MI-induced increases in superoxide radical formation in one of these forebrain regions, the subfornical organ (SFO). Ad-Cu/ZnSOD targeted to this region abolished the increased superoxide levels and led to significantly improved myocardial function compared with control vector-treated mice. This was accompanied by diminished levels of cardiomyocyte apoptosis in the Ad-Cu/ZnSOD but not the control vector-treated group. These effects of superoxide scavenging with Ad-Cu/ZnSOD in the forebrain paralleled increased post-MI survival rates compared with controls. This suggests that oxidative stress in the SFO plays a critical role in the deterioration of cardiac function following MI and underscores the promise of CNS-targeted antioxidant therapy for the treatment of MI-induced HF.

Sequence, expression and evolutionary relationships of carbamoyl phosphate synthetase I in the toad Xenopus laevis.

The sequence of carbamoyl phosphate synthetase I (CPSase I) cDNA and expression of the enzyme in liver of the toad Xenopus laevis are reported. CPSase I mRNA increases 6-fold when toads are exposed to high salinity for extended periods of time. The deduced 1,494-amino acid sequence of the CPSase I is homologous to other CPSases and reveals a domain structure and conserved amino acids common to other CPSases. A serine residue (S287) is present where there is a cysteine residue required for glutamine-dependent activity in CPSase Types III and II (Type I CPSases utilize only ammonia as nitrogen-donating substrate). A sequence of DNA 964 bases upstream from the ATG start codon for the CPSase I gene is also reported. Phylogenetic analysis for 30 CPSase isoforms, including X. laevis CPSase I, across a wide spectrum of phyla is reported and discussed. The results are consistent with the views that eukaryotic CPSase II as a multifunctional complex evolved from prokaryotic CPSase II and that CPSase I in terrestrial vertebrates and CPSase III in fishes arose from eukaryotic CPSase II by independent events after the divergence of plants in eukaryotic evolution.

Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats.

Accumulating data support the hypothesis that reactive oxygen species (ROS) play a critical role in the vascular complications observed in diabetes. However, the mechanisms of ROS-mediated vascular complications in diabetes are not clear. We tested the hypothesis that ROS-mediated increase in proapoptotic factor Bax expression leads to medial smooth muscle cell (SMC) apoptosis that is associated with neointima formation. We used a fructose-rich diet for 4 wk to model Type 2 diabetes in rats. SOD mimetic membrane-permeable 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol, 1 mM) was administered in drinking water to scavenge superoxide starting 1 day before surgery and continued during the duration of the experiment. Vascular injury resulted in a significant increase in medial SMC apoptosis that was associated with neointima formation. The number of medial SMC positive for Bax immunostaining significantly increased in injured arteries compared with uninjured arteries. Superoxide scavenging by Tempol treatment inhibited both the Bax-positive index as well as the apoptotic index of medial SMC in response to vascular injury. Tempol treatment inhibited apoptotic loss of medial SMC, thus increasing their density in the injured arteries. These alterations in the media were associated with a marked decrease in neointima formation in injured arteries. We conclude that Bax expression may play an important role in vascular SMC apoptosis and, finally, that this regulatory mechanism is redox sensitive.

Selective gene transfer to key cardiovascular regions of the brain: comparison of two viral vector systems.

The systemic renin-angiotensin system (RAS) plays a critical role in cardiovascular (CV) homeostasis. All components of the RAS are also known to be produced cell-specifically within specific brain regions, although the role of the brain RAS relative to the systemic RAS has remained a puzzle due to the difficulty of dissecting these two systems. Selectively targeting these regions with genes that modify the RAS could help unravel this puzzle. We compared the ability of adenovirus (Ad) and lentivirus (feline immunodeficiency virus, FIV) vectors to mediate gene delivery in vivo to the supraoptic nucleus (SON) and subfornical organ (SFO), two important CV control regions known to express the various RAS genes. SON or SFO of adult C57BL/6 mice (n=37) were stereotaxically injected with replication-deficient recombinant Ad or FIV harboring a beta-galactosidase (beta-gal) reporter gene. At 1, 3, or 8 weeks post-injection, brain sections were processed for beta-Gal activity, double immunofluorescence to verify cell-type specificity of viral transduction, or immunohistochemical detection of inflammatory mediators. Our results demonstrate that: (1) murine SFO and SON can be selectively targeted for gene transfer in vivo;(2) FIV mediated neuron-specific gene delivery, whereas Ad transduced both neuronal and glial cell types in SFO and SON; (3) Ad injected into the SON transduced neurons within the SFO through retrograde transport, whereas FIV did not; (4) beta-gal activity remained stable for 3 weeks but then declined by 8 weeks with Ad, while minimal decline occurred with FIV; (5) FIV did not cause inflammatory responses, whereas infiltrate was detectable in Ad-injected SFO and SON. These vectors are potentially important tools for dissecting the cell- and site-specific components of the brain RAS and other important CV regulatory systems within this circuitry, and may have therapeutic applications for centrally mediated CV diseases.