Robert T. Geertman

The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration

Spinal cord oligodendrocytes originate in the ventricular zone and subsequently migrate to white matter, stop, proliferate, and differentiate. Here we demonstrate a role for the chemokine CXCL1 and its receptor CXCR2 in patterning the developing spinal cord. Signaling through CXCR2, CXCL1 inhibited oligodendrocyte precursor migration. The migrational arrest was rapid, reversible, concentration dependent, and reflected enhanced cell/substrate interactions. White matter expression of CXCL1 was temporo-spatially regulated. Developing CXCR2 null spinal cords contained reduced oligodendrocytes, abnormally concentrated at the periphery. In slice preparations, CXCL1 inhibited embryonic oligodendrocyte precursor migration, and widespread dispersal of postnatal precursors occurred in the absence of CXCR2 signaling. These data suggest that population of presumptive white matter by oligodendrocyte precursors is dependent on localized expression of CXCL1.

Lower Thoracic Spinal Cord Stimulation to Restore Cough in Patients With Spinal Cord Injury: Results of a National Institutes of Health–Sponsored Clinical Trial. Part I: Methodology and Effectiveness of Expiratory Muscle Activation

OBJECTIVE Evaluation of the capacity of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles and generate large airway pressures and high peak airflows characteristic of cough, in subjects with tetraplegia. DESIGN Clinical trial. SETTING Inpatient hospital setting for electrode insertion; outpatient setting for measurement of respiratory pressures; home setting for application of SCS. PARTICIPANTS Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury and weak cough. INTERVENTIONS A fully implantable electrical stimulation system was surgically placed in each subject. Partial hemilaminectomies were made to place single-disk electrodes in the epidural space at the T9, T11, and L1 spinal levels. A radiofrequency receiver was placed in a subcutaneous pocket over the anterior portion of the chest wall. Electrode wires were tunneled subcutaneously and connected to the receiver. Stimulation was applied by activating a small portable external stimulus controller box powered by a rechargeable battery to each electrode lead alone and in combination. MAIN OUTCOME MEASURES Peak airflow and airway pressure generation achieved with SCS. RESULTS Supramaximal SCS resulted in high peak airflow rates and large airway pressures during stimulation at each electrode lead. Maximum peak airflow rates and airway pressures were achieved with combined stimulation of any 2 leads. At total lung capacity, mean maximum peak airflow rates and airway pressure generation were 8.6+/-1.8 (mean +/- SE) L/s and 137+/-30 cmH2O (mean +/- SE), respectively. CONCLUSIONS Lower thoracic SCS results in near maximum activation of the expiratory muscles and the generation of high peak airflow rates and positive airway pressures in the range of those observed with maximum cough efforts in healthy persons.

Lower Thoracic Spinal Cord Stimulation to Restore Cough in Patients with Spinal Cord Injury: Results of a National Institutes of Health-Sponsored Clinical Trial. Part II: Clinical Outcomes

OBJECTIVE To evaluate the clinical effects of spinal cord stimulation (SCS) to restore cough in subjects with cervical spinal cord injury. DESIGN Clinical trial assessing the clinical outcomes and side effects associated with the cough system. SETTING Outpatient hospital or residence. PARTICIPANTS Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury. INTERVENTIONS SCS was performed at home by either the subjects themselves or caregivers on a chronic basis and as needed for secretion management. MAIN OUTCOME MEASURES Ease in raising secretions, requirement for trained caregiver support related to secretion management, and incidence of acute respiratory tract infections. RESULTS The degree of difficulty in raising secretions improved markedly, and the need for alternative methods of secretion removal was virtually eliminated. Subject life quality related to respiratory care improved, with subjects reporting greater control of breathing problems and enhanced mobility. The incidence of acute respiratory tract infections fell from 2.0+/-0.5 to 0.7+/-0.4 events/subject year (P<.01), and mean level of trained caregiver support related to secretion management measured over a 2-week period decreased from 16.9+/-7.9 to 2.1+/-1.6 and 0.4+/-0.3 times/wk (P<.01) at 28 and 40 weeks after implantation of the device, respectively. Three subjects developed mild hemodynamic effects that abated completely with continued SCS. Subjects experienced mild leg jerks during SCS, which were well tolerated. There were no instances of bowel or bladder leakage. CONCLUSIONS Restoration of cough via SCS is safe and efficacious. This method improves life quality and has the potential to reduce the morbidity and mortality associated with recurrent respiratory tract infections in this patient population.

Long-term follow-up of spinal cord stimulation to restore cough in subjects with spinal cord injury

Abstract Objective To determine the long-term effects of the cough stimulation system. Design Nonrandomized clinical trial of subjects using the study device well beyond the period of close follow-up. Setting Use of the study device in the home setting. Participants Subjects (N = 10) implanted with the device for a minimum of 2 years (mean 4.6 ± 0.6 years). Interventions Application of daily stimulation. Outcome measures Airway pressure generation and other clinical assessments including ease in raising secretions, life quality, caregiver support, and incidence of respiratory tract infections were measured at 1 year and mean 4.6 years after implantation. Results Each subject continued to use the device on a regular basis. During SCS, mean maximum airway pressures were 103.1 ± 20.4 and 107.7 ± 23.0 cmH2O at the 1-year and mean 4.6-year follow-up points, respectively (P < 0.05 compared with pre-implant and not significantly different (NS) compared with 1-year follow-up). Benchmarks related to ease in raising secretions and improvements in life quality related to respiratory care were maintained at the mean 4.6 year follow-up. The need for trained caregivers to provide other means of secretion management remained significantly below the pre-implant values (P < 0.05). The incidence of acute respiratory tract infections remained low at 0.2 ± 0.1 events/year, which is significantly below the pre-implant value of 1.4 ± 0.3 events/year (P < 0.05). Conclusion Subjects continued to use the system on a long-term basis beyond the period of close follow-up and to continued derive significant clinical benefits.

Duplication of the pituitary gland associated with multiple blastogenesis defects: Duplication of the pituitary gland (DPG)-plus syndrome. Case report and review of literature

Background: Duplication of the pituitary gland (DPG) is a rare craniofacial developmental anomaly occurring during blastogenesis with postulated etiology such as incomplete twinning, teratogens, median cleft face syndrome or splitting of the notochord. The complex craniocaudal spectrum of blastogenesis defects associated with DPG is examined with an illustrative case. Case Description: We report for the first time in the medical literature some unique associations with DPG, such as a clival encephalocele, third cerebral peduncle, duplicate odontoid process and a double tongue with independent volitional control. This patient also has the previously reported common associations such as duplicated sella, cleft palate, hypertelorism, callosal agenesis, hypothalamic enlargement, nasopharyngeal teratoma, fenestrated basilar artery and supernumerary teeth. This study also reviews 37 cases of DPG identified through MEDLINE literature search from 1880 to 2011. It provides a detailed analysis of the current case through physical examination and imaging. Conclusion: The authors propose that the developmental deformities associated with duplication of pituitary gland (DPG) occur as part of a developmental continuum, not as chance associations. Considering the fact that DPG is uniquely and certainly present throughout the spectrum of these blastogenesis defects, we suggest the term DPG-plus syndrome.

Extracranial ligation of ethmoidal arteries before resection of giant olfactory groove or planum sphenoidale meningiomas: 3 illustrative cases with a review of the literature on surgical techniques

OBJECT There are several surgical techniques for reducing blood loss-open surgical and endoscopic-prior to resection of giant anterior skull base meningiomas, especially when preoperative embolization is risky or not technically feasible. The authors present examples of an institutional experience using surgical ligation of the anterior and posterior ethmoidal arteries producing persistent tumor blush in partially embolized tumors. METHODS The authors identified 12 patients who underwent extracranial surgical ligation of ethmoidal arteries through either a transcaruncular or a Lynch approach. Of these, 3 patients had giant olfactory groove or planum sphenoidale meningiomas. After approval from the institution privacy officer, the authors studied the medical records and imaging data of these 3 patients, with special attention to surgical technique and outcome. The variations of ethmoidal artery foramina pertaining to this surgical approach were studied using preserved human skulls from the Hamann-Todd Osteological Collection at the Museum of Natural History, Cleveland, Ohio. RESULTS The extracranial ligation was performed successfully for control of the ethmoidal arteries prior to resection of hypervascular giant anterior skull base meningiomas. The surgical anatomy and landmarks for ethmoidal arteries were reviewed in anthropology specimens and available literature with reference to described surgical techniques. CONCLUSIONS Extracranial surgical ligation of anterior, and often posterior, ethmoidal arteries prior to resection of large olfactory groove or planum sphenoidale meningiomas provides a safe and feasible option for control of these vessels prior to either open or endoscopic resection of nonembolized or partially embolized tumors.

Holospinal epidural abscess of the spinal axis: two illustrative cases with review of treatment strategies and surgical techniques

Despite the increasing prevalence of spinal infections, the subcategory of holospinal epidural abscesses (HEAs) is extremely infrequent and requires unique management. Panspinal imaging (preferably MRI), modern aggressive antibiotic therapy, and prompt surgical intervention remain the standard of care for all spinal axis infections including HEAs; however, the surgical decision making on timing and extent of the procedure still remain ill defined for HEAs. Decompression including skip laminectomies or laminoplasties is described, with varied clinical outcomes. In this review the authors present the illustrative cases of 2 patients with HEAs who were treated using skip laminectomies and epidural catheter irrigation techniques. The discussion highlights different management strategies including the role of conservative (nonsurgical) management in these lesions, especially with an already identified pathogen and the absence of mass effect on MRI or significant neurological defects. Among fewer than 25 case reports of HEA published in the past 25 years, the most important aspect in deciding a role for surgery is the neurological examination. Nearly 20% were treated successfully with medical therapy alone if neurologically intact. None of the reported cases had an associated cranial infection with HEA, because the dural adhesion around the foramen magnum prevented rostral spread of infection. Traditionally a posterior approach to the epidural space with irrigation is performed, unless an extensive focal ventral collection is causing cord compression. Surgical intervention for HEA should be an adjuvant treatment strategy for all acutely deteriorating patients, whereas aspiration of other infected sites like a psoas abscess can determine an infective pathogen, and appropriate antibiotic treatment may avoid surgical intervention in the neurologically intact patient.

Minimally invasive method to activate the expiratory muscles to restore cough

Context: Spinal cord stimulation (SCS) via disc electrodes surgically placed via laminotomy incisions has been shown to restore an effective cough in subjects with spinal cord injury (SCI). The purpose of this study was to evaluate a new method of expiratory muscle activation utilizing spinal cord wire leads, which can be implanted with minimally invasive techniques. Methods: In a subject with SCI, parallel wire leads with two electrode contacts were inserted percutaneously through a needle, advanced to the T9, T11 spinal levels and connected to an implanted radiofrequency receiver. Stimulus parameters were set at values resulting in near maximum airway pressure generation (Paw) (40V, 50Hz, 0.2ms). Paw was measured at functional residual capacity (FRC) and total lung capacity (TLC) as an index of expiratory muscle strength. Results: Paw during spontaneous efforts was 20 cmH2O (8.6% predicted). Bipolar (T9-T11) SCS resulted in Paw of 84 and 103 cmH2O, at FRC and TLC respectively. Monopolar (T9 only) SCS resulted in Paw of 61 and 86 cmH2O, at FRC and TLC respectively. This subject experienced much greater ease in raising secretions with use of SCS and no longer required other methods of secretion management. Conclusion: SCS via wire leads, which can be implanted using minimally invasive techniques, may provide a new useful method to restore an effective cough and possibly reduce the morbidity and mortality associated with respiratory tract infections in patients with SCI.

Economic consequences of an implanted neuroprosthesis in subjects with spinal cord injury for restoration of an effective cough

Objective: To determine if an implanted neuroprosthesis for restoration of an effective cough is less costly than conventional methods of respiratory management. Methods: Nonrandomized clinical trial of participants (N = 14) with spinal cord injury (SCI) using the Cough Stimulator device in the inpatient hospital setting for Cough Stimulator implantation and outpatient hospital or residence for follow-up. A neuroprosthesis was implanted for restoration of an effective cough. The annual costs associated with respiratory management, without (pre implantation) and with (post implantation) the neuroprosthesis, were examined over a 4-year period. Results: The total cost related to implantation of the Cough Stimulator was

Ultrasound Guided Local Endovascular Coiling of an Iatrogenic Superficial Temporal Artery Pseudoaneurysm.

59,891, with no maintenance costs over subsequent years. The incidence of respiratory tract infections and the need for caregiver support fell significantly following implantation. The costs associated with respiratory tract infections fell significantly from a mean of