Reversal of delayed vasospasm by TS-011 in the dual hemorrhage dog model of subarachnoid hemorrhage.

PURPOSE: Arachidonic acid is avidly metabolized to a potent vasoconstrictor, 20-hydroxyeicosatetraenoic acid (20-HETE), in the cerebral circulation. 20-HETE has been reported to contribute to the acute fall in cerebral blood flow following subarachnoid hemorrhage (SAH), but its role in the development of delayed vasospasm is unknown. The present study examined whether delayed vasospasm is associated with elevations in 20-HETE in CSF in the dual hemorrhage model of SAH in dogs and if blockade of the synthesis of 20-HETE with N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. MATERIALS AND METHODS: Delayed vasospasm was induced in 22 adult beagle dogs by dual injection of blood (0.5 mL/kg) into the cisterna magna on days 1 and 4. Sequential samples of CSF were collected before intracisternal injections of blood on days 1 and 4 and after the development of delayed vasospasm on day 7. Sequential angiograms were obtained before and after intracisternal injection of blood on days 1 and 4 and before and 1 hour after administration of TS-011 (1 mg/kg IV) on day 7. RESULTS: The dogs consistently developed delayed vasospasm, and the diameter of the basilar artery fell to 68 +/- 3% (n = 15), 3 days after the second intracisternal injection of blood. The levels of 20-HETE in CSF increased from 4 +/- 2 to 39 +/- 16 pg/mL. In 9 dogs with delayed vasospasm, acute blockade of the synthesis of 20-HETE with TS011 (1 mg/kg IV) significantly increased the diameter of the basilar artery by 39%. Chronic administration of TS-011 (1 mg/kg per day) attenuated the development of delayed vasospasm, and the diameter of the basilar artery fell by 17 +/- 1% versus the 33 +/- 3% decrease in diameter seen in control animals 3 days following the second injection of blood into the cisterna magna. CONCLUSIONS: These results indicate that the development of delayed vasospasm in dogs is associated with an increase in 20-HETE levels in CSF, and acute blockade of the synthesis of 20-HETE with TS-011 reverses delayed vasospasm in this model.

Comparison of single-photon emission computed tomography with [123I]iodoamphetamine and xenon-enhanced computed tomography for assessing regional cerebral blood flow.

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.

Spinal cord evaluation by cortical evoked responses.

In ten monkeys, selective segmental lesions of the dorsal columns at the upper thoracic and middle cervical levels resulted in almost total attenuation of the cortical evoked potential responses to peripheral nerve stimulation. Conversely isolated segmental dorsal column preservation showed intact transmission of the evoked responses at rostral spinal cord, nucleus ventralis posterior lateralis, and cortical levels. Responses recorded from the intralaminar thalamic nuclei in the region of nucleus centrum medianum were unaffected by dorsal column ablation, but were markedly attenuated following bilateral ventral column ablation.

Single-voxel proton MR spectroscopy of nonneoplastic brain lesions suggestive of a neoplasm.

BACKGROUND AND PURPOSE: MR spectroscopy is used to characterize biochemical components of normal and abnormal brain tissue. We sought to evaluate common histologic findings in a diverse group of nonneoplastic diseases in patients with in vivo MR spectroscopic profiles suggestive of a CNS neoplasm. METHODS: During a 2-year period, 241 patients with suspected neoplastic CNS lesions detected on MR images were studied with MR spectroscopy. Of these, five patients with a nonneoplastic diagnosis were identified retrospectively; a sixth patient without tissue diagnosis was added. MR spectroscopic findings consistent with a neoplasm included elevated choline and decreased N-acetylaspartate and creatine, with or without detectable mobile lipid and lactate peaks. RESULTS: The histologic specimens in all five patients for whom tissue diagnoses were available showed significant WBC infiltrates, with both interstitial and perivascular accumulations of lymphocytes, macrophages, histiocytes, and (in one case) plasma cells. Reactive astrogliosis was also prominent in most tissue samples. This cellular immune response was an integral component of the underlying disorder in these patients, including fulminant demyelination in two patients, human herpesvirus 6 encephalitis in one patient, organizing hematoma from a small arteriovenous malformation in one patient, and inflammatory pseudotumor in one patient. Although no histologic data were available in the sixth patient, neoplasm was considered unlikely on the basis of ongoing clinical and neuroradiologic improvement without specific therapy. CONCLUSION: Nonneoplastic disease processes in the CNS may elicit a reactive proliferation of cellular elements of the immune system and of glial tissue that is associated with MR spectroscopic profiles indistinguishable from CNS neoplasms with current in vivo MR spectroscopic techniques. Such false-positive findings substantiate the need for histologic examination of tissue as the standard of reference for the diagnosis of intracranial mass lesions.

The biomechanics of spinal injuries.

This manuscript is directed to review the epidemiology of spinal trauma, the anatomy of the vertebral column, spinal ligaments, muscles, motion of the spine and spinal cord. Because little information is available on the material properties of ligaments and the components of the vertebral column, this material is also included. A review of the experimental spinal cord injury models is given because of the concerted interest in this area today. Laboratory studies conducted in animals to develop typical spinal cord injury models and the corresponding alterations in perfusion and metabolic pathways, forces, and changes in the evoked potentials are discussed. Light and electron microscopy evaluations of the spinal cord are also treated. Clinical classifications of spinal injuries, pathology, and typical examples of upper cervical injuries, atlanto-axial disc locations and fractures, lower cervical spine injuries, injuries to thoracolumbar column with mathematical models, and typical force levels are given. The final section, investigation examples, provides a review of typical spinal injuries associated with sports injuries, motorcycle helmets, industrial helmets, and swimming pools investigated in our laboratories and by those of others. With lumped parameter mathematical model which predicts cervical compression, force, the various energies encountered in a one-dimensional impact is given. Typical examples of studies conducted on football helmets, motorcycle helmets, and industrial helmets are also included. Because of the importance of crash dummies used in the analysis of spinal injuries, a separate appendix is included, as well as an appendix reviewing motorcycle standards which are often dispersed throughout the literature. Considerable emphasis is placed upon actual experimental values of force and energy measured in the living animal and the most recent studies conducted in the fresh human cadaver to delineate the biomechanical mechanisms of spinal injury.

Total stabilization of the cervical spine in patients with cervical spondylotic myelopathy.

Certain patients with cervical spondylotic myelopathy demonstrate instability in the upper cervical vertebral column associated with marked narrowing of the vertebral canal in the neighboring lower cervical segments. This combination of causative mechanisms creates difficulty in using routine surgical procedures, especially in elderly and severely debilitated patients. We present three cases that typify this situation and illustrate marked resolution of debilitating myelopathy through total posterior fusion of the cervical spine usually incorporating the occiput.

Radiological assessment of intrasellar prolactin-secreting tumors.

In this study, the value of high resolution computed tomography (CT) in defining prolactin-secreting intrasellar tumors was compared to the value of conventional hypocycloidal polytomography. In all cases, contrast-enhanced coronal CT images were capable of defining these tumors by the demonstration of abnormal dimensions, upward convexity, or regional low density areas in the pituitary gland. The focal regions of decreased density and contrast enhancement correlated consistently with the prolactin-secreting microadenoma location found during surgical removal. Polytomography was not as effective as CT in the diagnostic differentiation of these adenomas.

An experimental technique to induce and quantify complex cyclic forces to the lumbar spine.

The human spine is a complex, heterogeneous nonlinear and viscoelastic structure. In addition, in vivo loading is not uniaxial. Although many studies on the mechanical behavior of the spine under "pure" forces and single cycle load applications exist, little research is conducted with complex cyclic loads. In this study, we developed a technique to induce and quantify controlled complex physiological loads to the lumbar spinal column under cyclic (chronic) conditions. The methods described include specimen preparation and mounting to induce controlled complex loading (cyclic compression-flexion vector was chosen as an example), instrumentation, and biomechanical data to achieve the objectives. The results indicated that the specimen sustained the external load in a combined compression-flexion mechanism without considerable off-axis forces (lateral shears) and moments (lateral bending and torsion). By mounting the anchoring bolt in appropriate places (such as an anterolateral placement to induce compression-flexion-lateral bending), this technique can be used to apply and continuously quantify complex physiological acute or cyclic loads to describe the biomechanics of the spine. This procedure of inducing complex loads eliminates the difficulty in applying the principles of superposition, using the response from individual "pure" forces to account for the nonlinearity and viscoelasticity of the human lumbar spinal column.

Spontaneous reversal of internal carotid artery occlusion: case report.

Spontaneous dissection of the internal carotid arteries, including those dissections resulting in total occlusion, may be a spontaneously reversible process. A patient who had angiographic evidence of bilateral complete internal carotid artery occlusions of different ages of onset illustrates this process. This case suggests certain considerations regarding the pathogenesis of these dissections.

Superficial temporal-middle cerebral artery anastomosis associated with glioblastoma multiforme.

The authors report a case in which glioblastoma multiforme was intimately associated with a surgical anastomosis of the superficial temporal artery to a branch of the middle cerebral artery.

Spinal evoked potentials in the primate: neural substrate.

Summated responses evoked by peripheral nerve stimulation were recorded from electrodes located in the epidural and subdural spaces anterior and posterior to the monkey spinal cord. Segmental microsurgical resection of the dorsal columns both at the thoracic and cervical levels resulted in total obliteration of the response recorded rostral to these lesions. Isolated segmental dorsal column preservation did not significantly alter response latency or wave form recorded at the rostral electrodes. Bilateral cervical dorsolateral column resection also resulted in no discernible alterations of these responses. These data indicate that spinal evoked potentials recorded from levels rostral to their root entry zones arise almost exclusively from the dorsal columns.

Subarachnoid hemorrhage following chymopapain chemonucleolysis. Case report.

Subarachnoid hemorrhage is a frequent finding in patients who have incurred neurological complications following chymopapain chemonucleolysis, but the basis for this occurrence remains controversial. The authors report the clinical and postmortem findings in a 42-year-old man who died 5 days after chemonucleolysis at the L4-5 and L5-S1 disc spaces. The predominant histological abnormality was a severe inflammatory arteritis of a medium-sized artery at the upper cervical level with disruption of the vessel wall. The potential causative role of chymopapain in this situation and the correlation of a vascular basis for many of the complications found after inadvertent intrathecal chymopapain injector are discussed.

Mechanical and physiological effects of dentatotomy.

The role of the dentate ligaments in the pathogenesis of myelopathy secondary to disease conditions that alter the normal biomechanics of the spinal canal was studied in 14 dogs. The effects of posterior cord elevation on somatosensory evoked potentials (SSEP's) and tension requirements were compared before and after dentate ligaments section in acute experiments. At levels of posterior elevation usually within the confines of the canine canal, the dentate ligaments were the most significant element increasing tension requirements and SSEP alternations. Human cadaver studies also showed an approximate 50% reduction of force after dentatotomy. These findings suggests that after dentate ligaments section the applied tension is distributed over a longer segments of the cord with a reduction in tension and disruption of axonal conduction at the level at which the force was applied.

Effect of hypertension on small-vessel healing after microvascular anastomosis.

Artery-to-artery microvascular anastomosis (MVA) has become an established therapeutic alternative for patients with giant intracranial aneurysms and other forms of cerebrovascular disease. Many patients afflicted with cerebrovascular disease also suffer from hypertension. To evaluate the effect of hypertension on healing of small arteries following MVA, 36 spontaneously hypertensive rats were subjected to end-to-side MVA of their common carotid arteries. At specific times after surgery the rats were sacrificed; the anastomotic site was removed and examined with light microscopy and scanning electron microscopy. All MVA's were patent, and there was no evidence of thrombus formation or stenosis at the operative site in any group. Also, there was no difference between the spontaneously hypertensive rats and the control normotensive rat group in the rate of endothelial coverage of the MVA. The presence of hypertension appears to have no effect on healing of small arteries in the rat.

Biomechanics of sequential posterior lumbar surgical alterations.

Compromise of the functional integrity of the posterior lumbar ligaments and facet joints is a common occurrence after repeated lumbar operative procedures. To evaluate the biomechanical effects of sequential surgical alterations, this investigation analyzed bilateral facetectomies (medial, total, and total with posterior ligament section) in three segments of human cadaveric lumbar spines under increasing compression-flexion. These iatrogenic alterations, designed to replicate common methods of surgical exposure, were created at the lower intervertebral joint (L4-5) while the upper joint (L3-4) remained intact. Overall strength characteristics in the physiological range of 400 N and 600 N demonstrated significant differences (p less than 0.05) in applied compressions for all preparations compared to the intact specimen. Comparison of sequential surgeries, however, did not demonstrate this tendency. Significant changes in the movement of the spinous processes at the upper (unaltered) level occurred only after posterior ligament section, whereas the lower (altered) level showed markedly increasing distraction of both the facets and the spinous processes with sequential operations. Sectioning of the supraspinous/interspinous ligament and associated fascial attachments resulted in a marked transfer of motion to the altered level. This was manifested by the increased anterior displacement of the centrode at the lower level associated with probable posterior migration of the centrode at the upper level. These data suggest that the effects of progressive surgical alterations of the lumbar facet joints are controllable in a preparation undergoing acute compression-flexion loads until the supraspinous/interspinous ligaments, with associated residual tendinous, midline muscle, and fascial attachments, are violated.

Effects of vertebral column distraction in the monkey.

Experiments were performed to assess the effects of vertebral column distraction on evoked potential responses from multiple recording sites along the conducting pathway in the monkey, and on concurrent blood flows, measured with the radioactive microsphere technique, along the axis of the central nervous system. Linear distractive loads were applied until the amplitude of the evoked response was significantly reduced. In four monkeys, the loads (100 to 150 lb) were sustained, whereas in two monkeys the forces (80 to 110 lb) were relaxed. The earliest response changes were most marked in recordings dependent upon the integrity of the upper cervical dorsal columns or brain stem-lemniscal pathway. The responses returned to control levels with load relaxation, but maintenance of the tractive load produced generalized and progressive response attenuation. At selected periods of significant changes in the evoked potential response, blood flow remained stable except for the late onset of regional ischemia in the middle cervical through upper thoracic spinal cord levels in the animals undergoing sustained loads. These findings indicate that brain-stem or spinal cord dysfunction occurring with both acute and gradual elongation of the spinal canal are the result of excess tensile stress acting on fiber tracts, and the delayed onset of spinal cord ischemia is the probable result of a similar mechanical process acting upon intrinsic spinal cord blood vessels.

Distraction rod stabilization in the treatment of metastatic carcinoma.

Stabilization of the spinal column with Harrington distraction rods and acrylic fusion was the primary form of treatment in a select group of patients with metastatic carcinoma of the spinal column. Clinical criteria included patients in poor general medical condition with intractable pain originating from metastatic tumor involvement in the ventral components of the thoracic or upper lumbar spinal column and minimal evidence or absence of spinal cord compression. After stabilization, pain relief was almost total and sustained, and neurological status generally remained unchanged from preoperative findings without any evidence of improvement of preexisting abnormalities or occasions of rapid neurological deterioration. This form of spinal stabilization may offer significant relief of debilitating pain, lessen the risk of pathological fracture-dislocation of the thoracic or upper lumbar vertebral column, and reduction in the local compressive effects on the spinal cord caused by ventrally situated metastatic tumor.

Syringomyelia after removal of benign spinal extramedullary neoplasms.

STUDY DESIGN: This is a case report. OBJECTIVES: Two patients with noncommunicating syringomyelia manifesting symptoms years after the uneventful excision of a benign intradural extramedullary neoplasms are presented. SUMMARY OF BACKGROUND DATA: The association of noncommunicating syringomyelia with benign extramedullary neoplasms as a coexistent or delayed process is a rare event. The pathogenesis of such spinal cord cavitation after tumor removal and the relationship with therapeutic intervention is not well defined. METHODS: The delayed occurrence of neurologic impairment emphasizes the need for considering development of syringomyelia rather than tumor recurrence. RESULTS: The effects of chronic spinal cord compression in the thoracic region may be accelerated by adverse stresses acting on the spinal cord associated with tethering of the spinal cord. CONCLUSION: In defining the pathogenesis of this form of spinal cord cavitation, these cases suggest that therapeutic approaches directed at resolving the process should not only include lyses of adhesions, but shunting procedures, which appear to be most efficacious when these procedures are performed at or cephalad to the level of original tumor removal.

Biomechanical alterations induced by multilevel cervical laminectomy.

STUDY DESIGN: The biomechanical responses of the cervical spine undergoing a combined loading vector within the physiologic range and after multilevel laminectomy were evaluated. The experimental conditions were designed to more closely replicate the typical clinical situation than accomplished by previous studies. OBJECTIVE: To determine the biomechanical alterations induced by multilevel cervical spine laminectomy using an in vitro model. SUMMARY OF BACKGROUND DATA: The few previous laboratory studies concerned with the effects of cervical laminectomy have generally indicated a lack of significant change in strength or flexibility induced by the procedure. These studies have been limited by a variety of factors, including the use of pure loads under low physiologic loading conditions, restriction of the laminectomy to one or two segments, and the evaluation of a small number of specimens. METHODS: Twelve fresh human cadaver cervical spine segments from C2-T1 were used. A custom-designed fixture was attached to the proximal end of the specimen to apply a flexion-compression load. Retroreflective targets were positioned in bony landmarks for localized temporal kinematics of the entire cervical column. Testing was performed before (intact) and after a three-level (C4-C6) laminectomy, and data regarding the force, displacement, and kinematics at every level of the column were obtained. RESULTS: The mean stiffness of the intact cervical column was significantly greater (P < 0.05) than the mean stiffness for the laminectomized specimen. Sagittal rotation angle had significant (P < 0.05) differences between intact (3.6 degrees) and laminectomy (8.0 degrees). Laminectomized specimens consistently responded with higher rotations compared with the intact specimen at every cervical spine level. CONCLUSION: Multilevel cervical laminectomy induces significant increases in total column flexibility associated with increased segmental flexural sagittal rotations. These motion changes were generalized with a tendency to show the greatest change at the lower level of laminectomy. Such biomechanical changes may constitute part of the underlying basis for failure of laminectomy to offer sustained good therapeutic results of the myelopathy associated with cervical stenosis and cervical spondyloarthropathy.

Whiplash syndrome: kinematic factors influencing pain patterns.

STUDY DESIGN: The overall, local, and segmental kinematic responses of intact human cadaver head-neck complexes undergoing an inertia-type rear-end impact were quantified. High-speed, high-resolution digital video data of individual facet joint motions during the event were statistically evaluated. OBJECTIVES: To deduce the potential for various vertebral column components to be exposed to adverse strains that could result in their participation as pain generators, and to evaluate the abnormal motions that occur during this traumatic event. SUMMARY OF BACKGROUND DATA: The vertebral column is known to incur a nonphysiologic curvature during the application of an inertial-type rear-end impact. No previous studies, however, have quantified the local component motions (facet joint compression and sliding) that occur as a result of rear-impact loading. METHODS: Intact human cadaver head-neck complexes underwent inertia-type rear-end impact with predominant moments in the sagittal plane. High-resolution digital video was used to track the motions of individual facet joints during the event. Localized angular motion changes at each vertebral segment were analyzed to quantify the abnormal curvature changes. Facet joint motions were analyzed statistically to obtain differences between anterior and posterior strains. RESULTS: The spine initially assumed an S-curve, with the upper spinal levels in flexion and the lower spinal levels in extension. The upper C-spine flexion occurred early in the event (approximately 60 ms) during the time the head maintained its static inertia. The lower cervical spine facet joints demonstrated statistically greater compressive motions in the dorsal aspect than in the ventral aspect, whereas the sliding anteroposterior motions were the same. CONCLUSIONS: The nonphysiologic kinematic responses during a whiplash impact may induce stresses in certain upper cervical neural structures or lower facet joints, resulting in possible compromise sufficient to elicit either neuropathic or nociceptive pain. These dynamic alterations of the upper level (occiput to C2) could impart potentially adverse forces to related neural structures, with subsequent development of a neuropathic pain process. The pinching of the lower facet joints may lead to potential for local tissue injury and nociceptive pain.