Direct convective delivery of macromolecules to peripheral nerves

1998 ◽  
Vol 89 (4) ◽  
pp. 610-615 ◽  
Author(s):  
Russell R. Lonser ◽  
Robert J. Weil ◽  
Paul F. Morrison ◽  
Lance S. Governale ◽  
Edward H. Oldfield
Keyword(s):  
Mr Imaging ◽  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Volume Of Distribution ◽  
Neurological Deficits ◽  
Outer Diameter ◽  
Content Type ◽  
Peripheral Nerve Lesions ◽  
New Treatments ◽  
Fine Print

Object. Although many macromolecules have treatment potential for peripheral nerve disease, clinical use of these agents has been restricted because of limitations of delivery including systemic toxicity, heterogeneous dispersion, and inadequate distribution. In an effort to overcome these obstacles, the authors examined the use of convection to deliver and distribute macromolecules into peripheral nerves. Methods. For convective delivery, the authors used a gas-tight, noncompliant system that provided continuous flow through a small silica cannula (inner diameter 100 µm, outer diameter 170 µm) inserted into a peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and 80 µl) of 14C-labeled (nine nerves) or gadolinium-labeled (two nerves) albumin were infused unilaterally or bilaterally into the tibial nerves of six primates (Macaca mulatta) at 0.5 µl/minute. The volume of distribution (Vd), percentage recovery, and delivery homogeneity were determined using quantitative autoradiography, an imaging program developed by the National Institutes of Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K) analysis. One animal that was infused bilaterally with gadolinium-bound albumin (40 µl to each nerve) underwent MR imaging and was observed for 16 weeks after infusion. The Vd increased with the Vi in a logarithmic fashion. The mean Vd/Vi ratio over all Vi was 3.7 ± 0.8 (mean ± standard deviation). The concentration across the perfused region was homogeneous (K = −1.07). The infusate, which was limited circumferentially by the epineurium, followed the parallel arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm). Recovery of radioactivity was 75.8 ± 9%. No neurological deficits arose from infusion. Conclusions. Convective delivery of macromolecules to peripheral nerves is safe and reliable. It overcomes obstacles associated with current delivery methods and allows selective regional delivery of putative therapeutic agents to long sections of nerve. This technique should permit the development of new treatments for numerous types of peripheral nerve lesions.

A fatal, chronically growing basilar artery: a new type of dissecting aneurysm

1996 ◽  
Vol 84 (6) ◽  
pp. 962-971 ◽  
Author(s):  
Tohru Mizutani
Keyword(s):  
Mr Imaging ◽  
Basilar Artery ◽  
Dissecting Aneurysm ◽  
Neurological Deficits ◽  
Vertebrobasilar Insufficiency ◽  
Content Type ◽  
Asymptomatic Patients ◽  
Basilar Arteries ◽  
Fine Print

✓ A long-term follow-up study (minimum duration 2 years) was made of 13 patients with tortuous dilated basilar arteries. Of these, five patients had symptoms related to the presence of such arteries. Symptoms present at a very early stage included vertebrobasilar insufficiency in two patients, brainstem infarction in two patients, and left hemifacial spasm in one patient. Initial magnetic resonance (MR) imaging in serial slices of basilar arteries obtained from the five symptomatic patients showed an intimal flap or a subadventitial hematoma, both of which are characteristic of a dissecting aneurysm. In contrast, the basilar arteries in the eight asymptomatic patients did not show particular findings and they remained clinically and radiologically silent during the follow-up period. All of the lesions in the five symptomatic patients gradually grew to fantastic sizes, with progressive deterioration of the related clinical symptoms. Dilation of the basilar artery was consistent with hemorrhage into the “pseudolumen” within the laminated thrombus, which was confirmed by MR imaging studies. Of the five symptomatic patients studied, two died of fatal subarachnoid hemorrhage (SAH) and two of brainstem compression; the fifth patient remains alive without neurological deficits. In the three patients who underwent autopsy, a definite macroscopic double lumen was observed in both the proximal and distal ends of the aneurysms within the layer of the thickening intima. Microscopically, multiple mural dissections, fragmentation of internal elastic lamina (IEL), and degeneration of media were diffusely observed in the remarkably extended wall of the aneurysms. The substantial mechanism of pathogenesis and enlargement in the symptomatic, highly tortuous dilated artery might initially be macroscopic dissection within a thickening intima and subsequent repetitive hemorrhaging within a laminated thrombus in the pseudolumen combined with microscopic multiple mural dissections on the basis of a weakened IEL. The authors note and caution that symptomatic, tortuous dilated basilar arteries cannot be overlooked because they include a group of malignant arteries that may grow rapidly, resulting in a fatal course.

Intramedullary ependymoma of the spinal cord

1990 ◽  
Vol 72 (4) ◽  
pp. 523-532 ◽  
Author(s):  
Paul C. McCormick ◽  
Roland Torres ◽  
Kalmon D. Post ◽  
Bennett M. Stein
Keyword(s):  
Spinal Cord ◽  
Mr Imaging ◽  
Tumor Recurrence ◽  
Neurological Deficits ◽  
Functional Improvement ◽  
Consecutive Series ◽  
Intramedullary Spinal Cord ◽  
Content Type ◽  
Fine Print

✓ A consecutive series of 23 patients underwent operative removal of an intramedullary spinal cord ependymoma between January, 1976, and September, 1988. Thirteen women and 10 men between the age of 19 and 70 years experienced symptoms for a mean of 34 months preceding initial diagnosis. Eight patients had undergone treatment prior to tumor recurrence and referral. Mild neurological deficits were present in 22 patients on initial examination. The location of the tumors was predominantly cervical or cervicothoracic. Radiological evaluation revealed a wide spinal cord in all cases. Magnetic resonance (MR) imaging was the single most important radiological procedure. At operation, a complete removal was achieved in all patients. No patient received postoperative radiation therapy. Histological examination revealed a benign ependymoma in all cases. The follow-up period ranged from 6 to 159 months (mean 62 months) with seven patients followed for a minimum of 10 years after surgery. Fourteen patients underwent postoperative MR imaging at intervals ranging from 8 months to 10 years postoperatively. No patient has been lost to follow-up review and there were no deaths. No patient showed definite clinical or radiological evidence of tumor recurrence during the follow-up period. Recent neurological evaluation revealed functional improvement from initial preoperative clinical status in eight patients, no significant change in 12 patients, and deterioration in three patients. The data support the belief that long-term disease-free control of intramedullary spinal ependymomas with acceptable morbidity may be achieved utilizing microsurgical removal alone.

Vertebral artery injury in C1–2 transarticular screw fixation: results of a survey of the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves

1998 ◽  
Vol 88 (4) ◽  
pp. 634-640 ◽  
Author(s):  
Neill M. Wright ◽  
Carl Lauryssen
Keyword(s):  
Vertebral Artery ◽  
Neurological Deficit ◽  
Peripheral Nerves ◽  
Balloon Occlusion ◽  
Neurological Deficits ◽  
Transarticular Screw ◽  
Content Type ◽  
Iatrogenic Complications ◽  
Number Of Patients ◽  
Fine Print

Object. The 847 active members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Disorders of the Spine and Peripheral Nerves were surveyed to quantitate the risk of vertebral artery (VA) injury during C1–2 transarticular screw placement. Methods. This retrospective study elicited the number of patients treated with transarticular screws, the number of screws placed, the incidence of VA injury and subsequent neurological deficit, and the management of known or suspected VA injury. Two hundred thirteen (25.1%) of the 847 surgeons responded. One hundred one respondents (47.4%) had placed a total of 2492 C1–2 transarticular screws in 1318 patients. Thirty-one patients (2.4%) had known VA injuries and an additional 23 patients (1.7%) were suspected of having injuries. However, only two (3.7%) of the 54 patients with known or suspected VA injuries exhibited subsequent neurological deficits and only one (1.9%) died of bilateral VA injury. Other iatrogenic complications included dural tears, screw fractures, screw breakout, fusion failure, infection, and suboccipital numbness. Conclusions. Including both known and suspected cases, the risk of VA injury was 4.1% per patient or 2.2% per screw inserted. The risk of neurological deficit from VA injury was 0.2% per patient or 0.1% per screw, and the mortality rate was 0.1%. The choice of management of intraoperative VA injuries was evenly divided between placing the patient under observation and initiating immediate postoperative angiography with possible balloon occlusion.

Thermographic presentation of cutaneous sensory and vasomotor activity in the injured peripheral nerve

1985 ◽  
Vol 62 (5) ◽  
pp. 711-715 ◽  
Author(s):  
Kathleen L. Brelsford ◽  
Sumio Uematsu
Keyword(s):  
Elevated Temperature ◽  
Peripheral Nerve ◽  
Local Anesthesia ◽  
Peripheral Nerves ◽  
Peroneal Nerve ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Content Type ◽  
Vasomotor Activity ◽  
Fine Print

✓ Impaired function of cutaneous segments of monkey peripheral nerves experimentally blocked by lidocaine anesthesia was clearly visualized by means of elevated temperature measurements obtained on computerized color telethermography. Mean temperature elevations in the segments of anesthetized primate nerves were 2.40°C at the ulnar segment 17 minutes after nerve block, and 1.20°C at the peroneal nerve at 20 minutes. The vasomotor activity of specific nerves, recorded after local anesthesia and displayed by color telethermographic imaging, corresponded to the distribution of sensory segments identified by more cumbersome means. Telethermography is therefore shown to be a useful tool, both qualitatively and quantitatively, in mapping cutaneous distribution of peripheral nerves and for evaluation of peripheral nerve injuries.

Risk of early closed reduction in cervical spine subluxation injuries

1999 ◽  
Vol 90 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Gerald A. Grant ◽  
Sohail K. Mirza ◽  
Jens R. Chapman ◽  
H. Richard Winn ◽  
David W. Newell ◽  
...  
Keyword(s):  
Cervical Spine ◽  
Mr Imaging ◽  
Disc Herniation ◽  
Closed Reduction ◽  
Spinal Cord Injuries ◽  
Spinal Injury ◽  
Neurological Deterioration ◽  
Neurological Deficits ◽  
Content Type ◽  
Fine Print

Object. The authors retrospectively reviewed 121 patients with traumatic cervical spine injuries to determine the risk of neurological deterioration following early closed reduction. Methods. After excluding minor fractures and injuries without subluxation, the medical records and imaging studies (computerized tomography and magnetic resonance [MR] images) of 82 patients with bilateral and unilateral locked facet dislocations, burst fractures, extension injuries, or miscellaneous cervical fractures with subluxation were reviewed. Disc injury was defined on MR imaging as the presence of herniation or disruption: a herniation was described as deforming the thecal sac or nerve roots, and a disruption was defined as a disc with high T2-weighted signal characteristics in a widened disc space. Fifty-eight percent of patients presented with complete or incomplete spinal cord injuries. Thirteen percent of patients presented with a cervical radiculopathy, 22% were intact, and 9% had only transient neurological deficits in the field. Early, rapid closed reduction, using serial plain radiographs or fluoroscopy and Gardner—Wells craniocervical traction, was achieved in 97.6% of patients. In two patients (2.4%) closed reduction failed and they underwent emergency open surgical reduction. The average time to achieve closed reduction was 2.1 ± 0.24 hours (standard error of the mean). The incidence of disc herniation and disruption in the 80 patients who underwent postreduction MR imaging was 22% and 24%, respectively. However, the presence of disc herniation or disruption did not affect the degree of neurological recovery, as measured by American Spinal Injury Association motor score and the Frankel scale following early closed reduction. Only one (1.3%) of 80 patients deteriorated, but that occurred more than 6 hours following closed reduction. Conclusions. Although disc herniation and disruption can occur following all types of traumatic cervical fracture subluxations, the incidence of neurological deterioration following closed reduction in these patients is rare. The authors recommend early closed reduction in patients presenting with significant motor deficits without prior MR imaging.

Stereotactic radiosurgery of cavernous malformations

2000 ◽  
Vol 93 (6) ◽  
pp. 987-991 ◽  
Author(s):  
Bruce E. Pollock ◽  
Yolanda I. Garces ◽  
Scott L. Stafford ◽  
Robert L. Foote ◽  
Paula J. Schomberg ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Mr Imaging ◽  
Stereotactic Radiosurgery ◽  
Lesion Size ◽  
Neurological Deficits ◽  
Morbidity Rate ◽  
Cavernous Malformations ◽  
Content Type ◽  
Latency Interval ◽  
Fine Print

Object. The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years.Methods. Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months.The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long—repetition time MR imaging performed a median of 8 months (range 5–16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02).Conclusions. It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.

Computerized tomography of peripheral nerve lesions

1983 ◽  
Vol 59 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Stephen K. Powers ◽  
David Norman ◽  
Michael S. B. Edwards
Keyword(s):  
Peripheral Nerve ◽  
Computerized Tomography ◽  
Anatomical Location ◽  
Nerve Lesion ◽  
Peripheral Nerve Lesion ◽  
Nerve Lesions ◽  
Content Type ◽  
Peripheral Nerve Lesions ◽  
Relationship Of ◽  
Fine Print

✓ Nine patients with a peripheral nerve lesion (six intrinsic and three extrinsic) were evaluated with computerized tomography (CT). In all but one instance, the CT scans gave useful information regarding the anatomical location, size, and relationship of the lesion to surrounding structures. These cases illustrate the usefulness of CT as a diagnostic tool in the evaluation of peripheral nerve lesions.

A novel dynamic model for experimental spinal cord compression

2005 ◽  
Vol 2 (4) ◽  
pp. 466-471 ◽  
Author(s):  
Gerhard Marquardt ◽  
Matthias Setzer ◽  
Alf Theisen ◽  
Edgar Dettmann ◽  
Volker Seifert
Keyword(s):  
Spinal Cord ◽  
Mr Imaging ◽  
Dynamic Model ◽  
Dura Mater ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Neurological Deficits ◽  
Content Type ◽  
Interlaminar Approach ◽  
Fine Print

Object. The goal of this study was to develop a novel dynamic model for experimental spinal cord compression that closely approximates neoplastic epidural compression of the spinal cord in humans. Methods. In 30 New Zealand white rabbits, the thoracic spine was exposed via a posterior approach. On each side of one vertebral lamina a small hole was drilled caudal to the articular process. A silicone band was passed through these holes, forming a loop. The spinal dura mater was exposed via an interlaminar approach. The loop was brought into contact with the dura mater and fixed in its position encircling 270° of the circumference of the spinal cord. Thereafter, the loop was gradually tightened at set times by pulling at the ends of the band and fixing them again in their new position. The spinal cord was thus increasingly compressed in a circular and dynamic manner. Neurological deficits of various degrees were created in all animals in the compression group, and the compressive effect of the loop was reliably demonstrated on MR imaging. After decompression of the spinal cord, the neurological deficits were reversible in the majority of animals, and MR imaging revealed either no signal changes or only circumscribed ones within the cord. In contrast, MR images obtained in animals that did not recover revealed the occurrence of extensive chronic myelopathy. Conclusions. This novel model features reproducibility of paresis and neurological recovery. It is a dynamic model simulating circular tumor growth and is characterized by its easy, straightforward, and cost-saving applicability.

Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion

2002 ◽  
Vol 97 (4) ◽  
pp. 905-913 ◽  
Author(s):  
Russell R. Lonser ◽  
Stuart Walbridge ◽  
Kayhan Garmestani ◽  
John A. Butman ◽  
Hugh A. Walters ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Histological Analysis ◽  
Volume Of Distribution ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Large Molecular Weight ◽  
Fine Print

Object. Intrinsic disease processes of the brainstem (gliomas, neurodegenerative disease, and others) have remained difficult or impossible to treat effectively because of limited drug penetration across the blood—brainstem barrier with conventional delivery methods. The authors used convection-enhanced delivery (CED) of a macromolecular tracer visible on magnetic resonance (MR) imaging to examine the utility of CED for safe perfusion of the brainstem. Methods. Three primates (Macaca mulatta) underwent CED of various volumes of infusion ([Vis]; 85, 110, and 120 µl) of Gd-bound albumin (72 kD) in the pontine region of the brainstem during serial MR imaging. Infusate volume of distribution (Vd), homogeneity, and anatomical distribution were visualized and quantified using MR imaging. Neurological function was observed and recorded up to 35 days postinfusion. Histological analysis was performed in all animals. Large regions of the pons and midbrain were successfully and safely perfused with the macromolecular protein. The Vd was linearly proportional to the Vi (R2 = 0.94), with a Vd/Vi ratio of 8.7 ± 1.2 (mean ± standard deviation). Furthermore, the concentration across the perfused region was homogeneous. The Vd increased slightly at 24 hours after completion of the infusion, and remained larger until the intensity of infusion faded (by Day 7). No animal exhibited a neurological deficit after infusion. Histological analysis revealed normal tissue architecture and minimal gliosis that was limited to the region immediately surrounding the cannula track. Conclusions. First, CED can be used to perfuse the brainstem safely and effectively with macromolecules. Second, a large-molecular-weight imaging tracer can be used successfully to deliver, monitor in vivo, and control the distribution of small- and large-molecular-weight putative therapeutic agents for treatment of intrinsic brainstem processes.

Magnetic resonance imaging correlation in pediatric spinal cord injury without radiographic abnormality

2002 ◽  
Vol 97 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Amos O. Dare ◽  
Mark S. Dias ◽  
Veetai Li
Keyword(s):  
Magnetic Resonance Imaging ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Neurological Deficits ◽  
Resonance Imaging ◽  
Content Type ◽  
Cord Injury ◽  
Frankel Grade ◽  
Fine Print

Object. The authors conducted a study to determine correlations between clinical syndromes and early magnetic resonance (MR) imaging—documented findings in children with spinal cord injury without radiographic abnormality (SCIWORA). Methods. The authors retrospectively reviewed the records obtained in 20 patients who presented with SCIWORA to the Children's Hospital of Buffalo between 1992 and 1999. Initial neurological syndromes, subsequent hospital course and outcome, and early MR imaging findings obtained using conventional sequences on a 1.5-tesla unit were recorded. Neurological syndromes on presentation were complete (Frankel Grade A) in two patients (10%), severe partial (Frankel Grade C) in one patient (5%), and mild partial (Frankel Grade D) in 17 patients (85%). Partial neurological deficits resolved in 14 (78%) of 18 patients within 72 hours and lasted more than 72 hours in four patients (22%). Magnetic resonance imaging was performed in both patients presenting with complete injuries and in 17 of 18 patients presenting with partial neurological deficits. The studies were obtained within 24 hours in 17 patients (85%). Neuroimaging revealed spinal cord swelling at the cervical level in one of the children with complete injury and cord edema with associated hemorrhage at cervical and thoracic levels in the other. Neural and extraneural elements were shown to be normal in all 17 patients with partial injuries who underwent MR imaging, including in the four patients with partial motor deficits lasting more than 72 hours. Conclusions. In this series, the predominant neurological presentation of SCIWORA was a mild, partial syndrome that resolved within 72 hours. Magnetic resonance imaging revealed abnormal features only in those patients with complete neurological deficits. These findings suggest that in the acute setting conventional MR imaging sequences may lack the sensitivity to demonstrate neural and extraneural abnormalities associated with partial or temporary neurological deficits of SCIWORA, even when those deficits persist beyond 72 hours.

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