Michael T. Koltz

Serum S100β: A noninvasive marker of blood-brain barrier function and brain lesions

S100β protein is expressed constitutively by brain astrocytes. Elevated S100β levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100β also was shown to indicate blood‐brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100β reflect BBB dysfunction, parenchymal damage, or both.

Hyperextension cervical spine injuries and traumatic central cord syndrome

Traumatic central cord syndrome (TCCS), regardless of its biomechanics, is the most frequently encountered incomplete spinal cord injury. Patients with TCCS present with disproportionate weakness of the upper extremities, and variable sensory loss and bladder dysfunction. Fractures and/or subluxations, forced hyperextension, and herniated nucleus pulposus are the main pathogenetic mechanisms of TCCS. Nearly 50% of patients with TCCS suffer from congenital or degenerative spinal stenosis and sustained their injuries during hyperextension as originally described by Schneider in 1954. Immunohistochemical and imaging studies indicate mild to moderate insult to axons and their ensheathing myelin in the lateral funiculi culminating in cytoskeletal injury and impaired conduction. More than one-half of these patients enjoy spontaneous recovery of motor weakness; however, as time goes on, lack of manual dexterity, neuropathic pain, spasticity, bladder dysfunction, and imbalance of gait render their activities of daily living nearly impossible. Based on the current level of evidence, there is no clear indication of the timing of decompression for relief of sustained spinal cord compression in hyperextension injuries. Future research, taking advantage of validated digital imaging data such as maximum canal compromise, maximum spinal cord compression, and lesion length on the CT and MR images, as well as more sensitive measures of bladder and hand function, spasticity, and neuropathic pain may help tailor surgery for a specific group of these patients.

Long-term outcome of Gamma Knife stereotactic radiosurgery for arteriovenous malformations graded by the Spetzler-Martin classification

OBJECT The object of this study was to assess outcomes in patients with arteriovenous malformations (AVMs) treated by Gamma Knife stereotactic radiosurgery (SRS); lesions were stratified by size, symptomatology, and Spetzler-Martin (S-M) grade. METHODS The authors performed a retrospective analysis of 102 patients treated for an AVM with single-dose or staged-dose SRS between 1993 and 2004. Lesions were grouped by S-M grade, as hemorrhagic or nonhemorrhagic, and as small (< 3 cm) or large (≥ 3 cm). Outcomes included death, morbidity (new neurological deficit, new-onset seizure, or hemorrhage/rehemorrhage), nidus obliteration, and Karnofsky Performance Scale score. RESULTS The mean follow-up was 8.5 years (range 5-16 years). Overall nidus obliteration (achieved in 75% of patients) and morbidity (19%) correlated with lesion size and S-M grade. For S-M Grade I-III AVMs, nonhemorrhagic and hemorrhagic combined, treatment yielded obliteration rates of 100%, 89%, and 86%, respectively; high functional status (Karnofsky Performance Scale Score ≥ 80); and 1% mortality. For S-M Grade IV and V AVMs, outcomes were less favorable, with obliteration rates of 54% and 0%, respectively. The AVMs that were not obliterated had a mean reduction in nidus volume of 69% (range 35%-96%). On long-term follow-up, 10% of patients experienced hemorrhage/rehemorrhage (6% mortality rate), which correlated with lesion size and S-M grade; the mean interval to hemorrhage was 81 months. CONCLUSIONS For patients with S-M Grade I-III AVMs, SRS offers outcomes that are favorable and that, except for the timing of obliteration, appear to be comparable to surgical outcomes reported for the same S-M grades. Staged-dose SRS results in lesion obliteration in half of patients with S-M Grade IV lesions.

An analysis of deep vein thrombosis in 1277 consecutive neurosurgical patients undergoing routine weekly ultrasonography

OBJECT Patients requiring neurosurgical intervention are known to be at increased risk for deep vein thrombosis (DVT) and attendant morbidity and mortality. Pulmonary embolism (PE) is the most catastrophic sequela of DVT and is the direct cause of death in 16% of all in-hospital mortalities. Protocols for DVT screening and early detection, as well as treatment paradigms to prevent PE in the acute postoperative period, are needed in neurosurgery. The authors analyzed the effectiveness of weekly lower-extremity venous duplex ultrasonography (LEVDU) in patients requiring surgical intervention for cranial or spinal pathology for detection of DVT and prevention of PE. METHODS Data obtained in 1277 consecutive patients admitted to a major tertiary care center requiring neurosurgical intervention were retrospectively reviewed. All patients underwent admission (within 1 week of neurosurgical intervention) LEVDU as well as weekly LEVDU surveillance if the initial study was normal. Additional LEVDU was ordered in any patient in whom DVT was suspected on daily clinical physical examination or in patients in whom chest CT angiography confirmed a pulmonary embolus. An electronic database was created and statistical analyses performed. RESULTS The overall incidence of acute DVT was 2.8% (36 patients). Of these cases of DVT, a statistically significant greater number (86%) were discovered on admission (within 1-7 days after admission) screening LEVDU (p < 0.05), whereas fewer were documented 8-14 days after admission (2.8%) or after 14 days (11.2%) postadmission. Additionally, for acute DVT detection in the present population, there were no underlying statistically significant risk factors regarding baseline physical examination, age, ambulatory status, or type of surgery. The overall incidence of acute symptomatic PE was 0.3% and the mortality rate was 0%. CONCLUSIONS Performed within 1 week of admission in patients who will undergo neurosurgical intervention, LEVDU is effective in screening for acute DVT and initiating treatment to prevent PE, thereby decreasing the overall mortality rate. Routine LEVDU beyond this time point may not be needed to detect DVT and prevent PE unless a change in the patients physical examination status is detected.

The Protective Effect of Glibenclamide in a Model of Hemorrhagic Encephalopathy of Prematurity

We studied a model of hemorrhagic encephalopathy of prematurity (EP) that closely recapitulates findings in humans with hemorrhagic EP. This model involves tandem insults of 20 min intrauterine ischemia (IUI) plus an episode of elevated venous pressure induced by intraperitoneal glycerol on post-natal day (P) 0. We examined Sur1 expression, which is upregulated after focal ischemia but has not been studied after brief global ischemia including IUI. We found that 20 min IUI resulted in robust upregulation of Sur1 in periventricular microvessels and tissues. We studied tandem insult pups from untreated or vehicle-treated dams (TI-CTR), and tandem insult pups from dams administered a low-dose, non-hypoglycemogenic infusion of the Sur1 blocker, glibenclamide, for 1 week after IUI (TI-GLIB). Compared to pups from the TI-CTR group, pups from the TI-GLIB group had significantly fewer and less severe hemorrhages on P1, performed significantly better on the beam walk and accelerating Rotarod on P35 and in tests of thigmotaxis and rapid learning on P35–49, and had significantly greater body and brain weights at P52. We conclude that low-dose glibenclamide administered to the mother at the end of pregnancy protects pups subjected to IUI from post-natal events of elevated venous pressure and its consequences.

Sulfonylurea receptor 1 in the germinal matrix of premature infants

Germinal matrix (GM) hemorrhage (GMH) is a major cause of mortality and of life-long morbidity from cerebral palsy. GMH is typically preceded by hypoxic/ischemic events and is believed to arise from rupture of weakened veins in the GM. In the CNS, hypoxia/ischemia up-regulate sulfonylurea receptor 1 (SUR1)-regulated NCCa-ATP channels in microvascular endothelium, with channel activation by depletion of ATP being responsible for progressive secondary hemorrhage. We hypothesized that this channel might be up-regulated in the GM of preterm infants at risk for GMH. Here, we studied expression of the regulatory subunit of the channel, SUR1, and its transcriptional antecedent, hypoxia inducible factor 1 (HIF1), in postmortem tissues of premature infants who either were at risk for or who sustained GMH. We found regionally specific up-regulation of HIF1 and of SUR1 protein and mRNA in GM tissues, compared with remote cortical tissues. Up-regulation was prominent in most progenitor cells, whereas in veins, SUR1 was found predominantly in infants who had sustained GMH compared with those without hemorrhage. Our data suggest that the SUR1-regulated NCCa-ATP channel may be associated with GMH, and that pharmacological block of these channels could potentially reduce the incidence of this devastating complication of prematurity.

Comparison of neurologic and radiographic outcomes with Solitaire versus Merci/Penumbra systems for acute stroke intervention.

Background and Purpose. The Solitaire Flow Restoration was approved by the FDA in 2012 for mechanical thrombolysis of proximal occlusion of intracranial arteries. To compare the Solitaire FR device and the Merci/Penumbra (previously FDA approved) systems in terms of safety, clinical outcomes, and efficacy including radiographic brain parenchymal salvage. Methods. Thirty-one consecutive patients treated with the Solitaire and 20 patients with comparable baseline characteristics treated with Merci or Penumbra systems were included in the study. Primary outcome measures included recanalization rate and modified Rankin Scale score at followup. Secondary outcomes included length of procedure, incidence of symptomatic intracranial hemorrhage, 90-day mortality, and radiographic analysis of percentage area salvage. Results. Compared with the Merci/Penumbra group, the Solitaire group showed a statistically significant improvement in favorable outcomes (mRS ≤ 2) (69% versus 35%, P = 0.03) and symptomatic ICH rate (0 versus 15%, P = 0.05) with a trend towards higher recanalization rates (93.5% versus 75%, P = 0.096) and shorter length of procedure (58.5 min versus 70.8 min, P = 0.08). Radiographic comparison also showed a significantly larger area of salvage in the Solitaire group (81.9% versus 71.9%, P = 0.05). Conclusion. Our study suggests that the Solitaire system allows faster, safer, and more efficient thrombectomy than Merci or Penumbra systems.

Tandem insults of prenatal ischemia plus postnatal raised intrathoracic pressure in a novel rat model of encephalopathy of prematurity

OBJECT Encephalopathy of prematurity (EP) is common in preterm, low birth weight infants who require postnatal mechanical ventilation. The worst types of EP are the hemorrhagic forms, including choroid plexus, germinal matrix, periventricular, and intraventricular hemorrhages. Survivors exhibit life-long cognitive, behavioral, and motor abnormalities. Available preclinical models do not fully recapitulate the salient features of hemorrhagic EP encountered in humans. In this study, the authors evaluated a novel model using rats that featured tandem insults of transient prenatal intrauterine ischemia (IUI) plus transient postnatal raised intrathoracic pressure (RIP). METHODS Timed-pregnant Wistar rats were anesthetized and underwent laparotomy on embryonic Day 19. Intrauterine ischemia was induced by clamping the uterine and ovarian vasculature for 20 minutes. Natural birth occurred on embryonic Day 22. Six hours after birth, the pups were subjected to an episode of RIP, induced by injecting glycerol (50%, 13 μl/g intraperitoneally). Control groups included naive, sham surgery, and IUI alone. Pathological, histological, and behavioral analyses were performed on pups up to postnatal Day 52. RESULTS Compared with controls, pups subjected to IUI+RIP exhibited significant increases in postnatal mortality and hemorrhages in the choroid plexus, germinal matrix, and periventricular tissues as well as intraventricularly. On postnatal Days 35-52, they exhibited significant abnormalities involving complex vestibulomotor function and rapid spatial learning. On postnatal Day 52, the brain and body mass were significantly reduced. CONCLUSIONS Tandem insults of IUI plus postnatal RIP recapitulate many features of the hemorrhagic forms of EP found in humans, suggesting that these insults in combination may play important roles in pathogenesis.

C7 intralaminar screw placement, an alternative to lateral mass or pedicle fixation for treatment of cervical spondylytic myelopathy, kyphotic deformity, and trauma: A case report and technical note.

Background: The authors present a case to illustrate the necessity and technical feasibility of C7 laminar screw placement for treatment of sub-axial cervical spondylitic myelopathy. The indications for C7 lateral mass screw placement was required internal fixation, with small lateral masses (8 mm) and pedicles (4 mm). Case Description: A 67-year-old female with compressive myelopathy after a fall from standing is presented. Magnetic resonance (MR) imaging of the cervical spine showed severe C3-6 spondylosis with canal and foraminal compromise. Computed tomography of the cervical spine confirmed the MR imaging findings as well as showed suboptimal lateral mass and pedicles for screw placement. The patient underwent a C3-6 laminectomy, C3-6 lateral mass, and C7 laminar screw placement. Postoperatively, the patient recovered without complication. Conclusion: Internal fixation of the cervical spine after iatrogenic destabilization by decompression of neural elements secondary to advanced spondylosis can be technically challenging. Anatomical landmarks needed for safe placement of lateral mass or pedicle instrumentation are often distorted by the patients’ advanced pathology or Inherent biology. The C7 screw is a key structural element to a long construct and therefore necessitates large lateral masses or pedicles to safely place a functional screw. C7 laminar screws may be placed safely without fluoroscopic guidance when sufficient C7 lateral mass or pedicle screws are not possible or with undue risk.

Thoracic, Lumbar, and Sacral Pedicle Screw Placement Using Stryker-Ziehm Virtual Screw Technology and Navigated Stryker Cordless Driver 3: Technical Note

Object. Utilization of pedicle screws (PS) for spine stabilization is common in spinal surgery. With reliance on visual inspection of anatomical landmarks prior to screw placement, the free-hand technique requires a high level of surgeon skill and precision. Three-dimensional (3D), computer-assisted virtual neuronavigation improves the precision of PS placement and minimization steps. Methods. Twenty-three patients with degenerative, traumatic, or neoplastic pathologies received treatment via a novel three-step PS technique that utilizes a navigated power driver in combination with virtual screw technology. (1) Following visualization of neuroanatomy using intraoperative CT, a navigated 3-mm match stick drill bit was inserted at an anatomical entry point with a screen projection showing a virtual screw. (2) A Navigated Stryker Cordless Driver with an appropriate tap was used to access the vertebral body through a pedicle with a screen projection again showing a virtual screw. (3) A Navigated Stryker Cordless Driver with an actual screw was used with a screen projection showing the same virtual screw. One hundred and forty-four consecutive screws were inserted using this three-step, navigated driver, virtual screw technique. Results. Only 1 screw needed intraoperative revision after insertion using the three-step, navigated driver, virtual PS technique. This amounts to a 0.69% revision rate. One hundred percent of patients had intraoperative CT reconstructed images taken to confirm hardware placement. Conclusions. Pedicle screw placement utilizing the Stryker-Ziehm neuronavigation virtual screw technology with a three step, navigated power drill technique is safe and effective.