Assessment of Lactate Production and Proteoglycans Synthesis by the Intact and Degenerated Intervertebral Disc Cells under the Influence of Activated Macrophages: an In Vitro Study.

The effects of proinflammatory cytokines on the secretion of glycosaminoglycans and lactate production by normal and degenerated intervertebral disk cells were studied on the model of their co-culturing with activated macrophage-like cells. It was found that proinflammatory cytokines produced a direct effect on intervertebral disk cells in a 3D culture reducing the rate of glycolysis and synthetic activity of both normal and degenerated cells of annulus fibrosus and nucleus pulposus, which is an important factor in progression of intervertebral disk degeneration.

Development of an In Vitro Model of Inflammatory Cytokine Influences on Intervertebral Disk Cells in 3D Cell Culture Using Activated Macrophage-Like THP-1 Cells.

We developed a new model for evaluation of the influence of proinflammatory cytokines on intervertebral disc cells in a 3D culture based on co-culturing of these cells with activated macrophage-like THP-1 cells. The levels of TNFα, IL-1ß, IL-6, IL-8, IL-10, and IL-12p70 production were assessed by flow cytofluorometry using microspheres. Considerable differences in the level of spontaneous cytokine secretion by normal and degenerated intervertebral disc cells were revealed. A significant increase in the level of IL-1ß and IL-8 was observed during co-culturing, which confirms consistency of the developed model.

Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy.

Although conventional proton magnetic resonance imaging has increased our ability to detect brain tumors, it has not enhanced to nearly the same degree our ability to diagnose tumor type. Proton magnetic resonance spectroscopy is a safe, noninvasive means of performing biochemical analysis in vivo. Using this technique, we characterized and classified tissue from normal brains, as well as tissue from the five most common types of adult supratentorial brain tumors. These six tissue types differed in their pattern across the six metabolites measured. 'Leaving-one-out' linear discriminant analyses based on these resonance profiles correctly classified 104 of 105 spectra, and, whereas conventional preoperative clinical diagnosis misclassified 20 of 91 tumors, the linear discriminant analysis approach missed only 1. Thus, we have found that a pattern-recognition analysis of the biochemical information obtained from proton magnetic resonance spectroscopy can enable accurate, noninvasive diagnosis of the most prevalent types of supratentorial brain tumors.

Role of computer technology in neurosurgery.

In the clinical office, during surgical planning, or in the operating room, neurosurgeons have been surrounded by the digital world either recreating old tools or introducing new ones. Technological refinements, chiefly based on the use of computer systems, have altered the modus operandi for neurosurgery. In the emergency room or in the office, patient data are entered, digitally dictated, or gathered from electronic medical records. Images from every modality can be examined on a Picture Archiving and Communication System (PACS) or can be seen remotely on cell phones. Surgical planning is based on high-resolution reconstructions, and microsurgical or radiosurgical approaches can be assessed precisely using stereotaxy. Tumor resection, abscess or hematoma evacuation, or the management of vascular lesions can be assisted intraoperatively by new imaging resources integrated into the surgical microscope. Mathematical models can dictate how a lesion may recur as well as how often a particular patient should be followed. Finally, virtual reality is being developed as a training tool for residents and surgeons by preoperatively simulating complex surgical scenarios. Altogether, computerization at each level of patient care has been affected by digital technology to help enhance the safety of procedures and thereby improve outcomes of patients undergoing neurosurgical procedures.

Trigeminal depressor response during percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia.

Percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia was performed 23 times on 21 patients. Significant abrupt drops in heart rate and blood pressure (P less than 0.0002) occurred when the needle entered the foramen ovale or upon balloon advancement or inflation. In 16 of 23 (70%) procedures, the heart rate fell abruptly to 60 or less, by a mean of 38%. Mean arterial blood pressure decreased transiently by 31% during 12 of 23 (55%) procedures. Our findings of transient bradycardia and hypotension upon mechanical stimulation or compression of the mandibular nerve or trigeminal ganglion show for the first time the presence of a trigeminal depressor response in humans. We recommend that heart rate and arterial blood pressure be monitored continuously during percutaneous microcompression of the trigeminal ganglion. Intravenous atropine should be available for immediate use, and an external pacemaker should be fitted preoperatively.

Intracranial aneurysms and sickle cell anemia: multiplicity and propensity for the vertebrobasilar territory.

OBJECTIVE: We describe a case of sickle cell anemia and multiple intracranial aneurysms and review the English-language-reported cases of sickle cell disease associated with intracranial aneurysms proven angiographically or by autopsy, to assess whether there are associations with aneurysm multiplicity and sites of aneurysm occurrence. CLINICAL PRESENTATION: A 28-year-old woman with sickle cell disease and a subarachnoid hemorrhage underwent successful clipping of three intracranial aneurysms. RESULTS: Among 44 reviewed cases, 57% of patients demonstrated multiple aneurysms, and aneurysms from patients with multiple aneurysms comprised nearly 80% of the total number of aneurysms. There were, on average, three aneurysms per patient for patients with multiple aneurysms. There was a predominance of female patients (female/male ratio, 1.6:1), although there existed no significant differences in age or gender for patients with single or multiple aneurysms. None of the patients with multiple aneurysms was older than 40 years of age at the time of presentation. Patients with multiple aneurysms and sickle cell disease showed a significant difference in the distribution of the aneurysm sites, with a significantly large number occurring in the vertebrobasilar axis. Multiple aneurysms associated with sickle cell disease showed a higher rate of simultaneous occurrence in the posterior and anterior circulation, compared with multiple aneurysms in the general population. CONCLUSION: There are strong statistical associations for aneurysm multiplicity and sites of aneurysm occurrence among reported patients with sickle cell disease. Patients with sickle cell anemia and neurological symptoms should undergo magnetic resonance angiography or four-vessel angiography to detect potentially harmful, but neurosurgically treatable, pathological conditions.

Using proton magnetic resonance spectroscopic imaging to predict in vivo the response of recurrent malignant gliomas to tamoxifen chemotherapy.

OBJECTIVE: Most patients with a malignant glioma spend considerable time on a treatment protocol before their response (or nonresponse) to the therapy can be determined. Because survival time in the absence of effective therapy is short, the ability to predict the potential chemosensitivity of individual brain tumors noninvasively would represent a significant advance in chemotherapy planning. METHODS: Using proton magnetic resonance spectroscopic imaging (1H MRSI), we studied 16 patients with a recurrent malignant glioma before and during treatment with high-dose orally administered tamoxifen. We evaluated whether 1H MRSI data could predict eventual therapeutic response to tamoxifen at the pretreatment and early treatment stages. RESULTS: Seven patients responded to tamoxifen therapy (three with glioblastomas multiforme; four with anaplastic astrocytomas), and nine did not (six with glioblastomas multiforme; three with anaplastic astrocytomas). Responders and nonresponders exhibited no differences in their age, sex, tumor type, mean tumor volume, mean Karnofsky scale score, mean number of weeks postradiotherapy, or mean amount of prior radiation exposure. Resonance profiles across the five metabolites measured on 1H MRSI spectra (choline-containing compounds, creatine and phosphocreatine, N-acetyl groups, lactate, and lipids) differed significantly between these two groups before and during treatment. Furthermore, linear discriminant analyses based on patients' in vivo biochemical information accurately predicted individual response to tamoxifen both before and at very early treatment stages (2 and 4 wk). Similar analyses based on patient sex, age, Karnofsky scale score, tumor type, and tumor volume could not reliably predict the response to tamoxifen treatment at the same time periods. CONCLUSION: It is possible to accurately predict the response of a tumor to tamoxifen on the basis of noninvasively acquired in vivo biochemical information. 1H MRSI has potential as a prognostic tool in the pharmacological treatment of recurrent malignant gliomas.

"The art is long and the life short": the letters of Wilder Penfield and Harvey Cushing.

Wilder Penfield and Harvey Cushing created legacies to neurosurgery, both in terms of those they trained and in their philosophical approach to the field. Their biographies provide only brief comments on their relationship without any thorough examination of their personal correspondence. In this article the Penfield-Cushing relationship is examined through an analysis of their unpublished personal letters. The Penfield-Cushing correspondence is a treasure for neurosurgery: it provides remarkable insight into the embryonic period of the discipline and into the relationship of two of the most influential figures in modern neurosurgery.

Percutaneous trigeminal ganglion compression for trigeminal neuralgia. Experience in 22 patients and review of the literature.

Between 1983 and 1988, a percutaneous trigeminal ganglion compression (PTGC) procedure for trigeminal neuralgia was performed on 22 patients. All patients were initially relieved of their pain. There were three recurrences (14%); two of these patients underwent a second PTGC procedure and one a partial trigeminal nerve root section. Follow-up examination 3 to 53 months after the procedure showed that all patients were free of pain. Morbidity included persistent minor hypesthesia in five patients, persistent minor dysesthesias in three, persistent minor weakness in three, aseptic meningitis in one, transient sixth nerve palsy in one, and transient otalgia in three. None of the patients had either anesthesia dolorosa or an absent corneal reflex.

Origins of Wilder Penfield's surgical technique. The role of the "Cushing ritual" and influences from the European experience.

Wilder Penfield left two great legacies: the development of successful surgical treatment of epilepsy and the establishment with his colleagues of the Montreal Neurological Institute as a world-renowned medical center, "dedicated to relief of pain and suffering and to the study of neurology." That Harvey Cushing's surgical ritual (which stemmed from the painstaking operative methods of Halsted) played a paramount role in the origins of Penfield's surgical technique is revealed by a set of notes and drawings by Penfield during repeated visits in the 1920's to Cushing's clinic at the Peter Bent Brigham Hospital. Penfield's intellectual approach to the nervous system was derived from his studies with Sherrington. Holmes, Cajal, and Hortega. His eclectic surgical style emerged from his familiarity with the operating techniques of Halsted, Dandy, Horsely, Sargent, Cushing, Frazier, Whipple, Leriche, and Foerster. Penfield's debt to these teachers is documented in his memoirs and in an unpublished report on European neurosurgery which he sent ot the Rockefeller Foundation in 1928.

Mercury water and cauterizing stones: Nicolas André and tic douloureux.

In his 1756 text, Observations pratiques sur les maladies de l'urèthre et sur plusiers faits convulsifs, Nicolas André coined the term "tic douloureux." He believed that this pain originated from compression of facial sensory peripheral nerves. Using scientific observation and experimentation to confirm this hypothesis, he reproduced the tic pain and treated it by using careful efforts to remove adhesions from the nerve with a caustic solution of mercury water. Believing that recurrence of the pain was a result of early closure of the wound, with recompression of the nerve being the direct cause, André prevented recompression by ensuring open wound drainage. André's surgical technique of using cauterizing stones ensured that there was minimal blood loss and little danger of rebleeding and recompression of the nerve by an accumulated blood clot. His case reports include lengthy follow-up periods that documented the benefits of his procedures, which were confirmed by testimonials from uninvolved colleagues. Although remembered for the two words, "tic douloureux," Nicolas André has long been ignored for his prescient treatment and scientific analysis of a disease for which the modern standard of care has only been defined during the last generation.

Neurosurgeon as innovator: William V. Cone (1897-1959).

Neurosurgeons are well known for being productive researchers and innovators. Few, however, have possessed the prolific ingenuity of William Cone. In 1934, he and William Penfield were cofounders of the Montreal Neurological Institute where, until 1959, he filled the twin roles of neurosurgeon-in-chief and neuropathologist. Because he did not find writing easy, many of his technical inventions and refinements remained unpublished. His numerous innovations included the extensive use of twist-drill technique for biopsy, drainage for subdural hematoma and cerebral abscess, and ventriculography. In the mid-1940's, he developed power tools driven by nitrogen that led to the modern, universally used air-driven tool systems. He had a special interest in the treatment of spinal dysfunction, for which he invented the Cone-Barton skull-traction tongs along with the Cone spinal operating table. He also devised operative procedures for vertebral fracture-dislocation and craniospinal anomalies. For the maintenance of muscle tone in the paralyzed bladder, he constructed a tidal drainage system. He introduced and popularized ventriculoperitoneal shunting techniques and carried out some of the earliest experimental trails to treat brain infections with sulphonamide and antibiotic drugs. He designed his own set of surgical suction devices, bone rongeurs, and a personal suction "air-conditioning" system for each surgeon. He had a keen early interest in intracranial tumors, and also demonstrated on monkeys how subdural mass lesions caused pupillary dilation and mesial temporal lobe damage due to cerebral compression. His work for the military during World War II on effects of altitude on brain pressure remained classified for many years. The first clipping and excision of an intracranial aneurysm is attributed to Cone. Although Penfield was known as "the Chief," Cone was referred to as "the Boss." His fervent dedication to provide total care to his patients was expressed in round-the-clock vigils; he did not separate "nursing" from "surgical" care. Ultimately, Cone's driving passion for perfection led in part to his tragic death. His accomplishments, inventions, and his example as teacher and physician have become part of neurosurgery's collective legacy.

Spinal angiolipomas. Report of three cases.

Spinal angiolipomas are distinct, benign lesions composed of mature lipocytes admixed with abnormal blood vessels. Three new cases of spinal angiolipoma are presented and 34 previously reported cases are analyzed. The 37 total cases (23 females and 14 males) ranged in age from 17 to 73 years (mean 43 years; median 45 years). The mean age of the female patients was older than that for the males (45.0 vs. 41.6 years; p < 0.001, Student's t-test) and most were peri- or postmenopausal. Prior to diagnosis, 97% of the patients had weakness of the lower extremities, 94% had sensory dysfunction, 84% had hyperreflexia and spasticity, 51% had sphincter dysfunction, and 41% had back pain lasting from 1 to 180 months (mean 28 months). Five (22%) of the 23 female patients were pregnant and two had exhibited significant weight gain coincident with the onset of symptoms. The angiolipomas were extradural in 35 patients and intramedullary in two; seven of the extradural lesions infiltrated the surrounding bone. The tumors extended from C-6 to L-4 and had a predilection for the midthoracic region (53% of cases). Plain radiographs were abnormal in 11 (39%) of 28 patients and in all patients with bone infiltration. Myelograms were abnormal in 97% of 32 patients and showed a complete block in 63% of patients. Computerized tomography (CT) and magnetic resonance (MR) imaging revealed the fat-density lesions in all cases studied. There was vascular enhancement in three of five cases with contrast-infused CT and in the one case with gadolinium-infused MR imaging. All patients improved following resection of the epidural lesions and internal decompression of the intramedullary lesions. It is concluded that spinal angiolipomas predominantly affect women. They involve the thoracic (especially the midthoracic) region, and produce symptoms and signs of spinal compression and, in some cases, bone erosion and pathological fractures. Their symptomatology can be exacerbated by pregnancy and weight gain, suggesting that vascular engorgement and the presence of obesity influence their evolution. Their preponderance in older, peri-, or postmenopausal women, and their clinical exacerbation in pregnant women support a role for hormonal influence. Magnetic resonance imaging is the investigation of choice for the diagnosis of these lesions. Surgery is universally successful in relieving symptoms.

Autonomic and histopathological effects of percutaneous trigeminal ganglion compression in the rabbit.

The histopathological and autonomic effects of percutaneous trigeminal ganglion compression for trigeminal neuralgia were studied in New Zealand White rabbits. Drops in mean arterial blood pressure of 38% and in heart rate of 30% were observed during compression (p less than 0.0001). Corneal reflex, pinprick sensation, and mastication strength were intact in 13 of 14 rabbits after compression. These findings resembled the effects of percutaneous compression in humans and suggested that the New Zealand White rabbit is a useful model for the study of percutaneous compression. Trigeminal sensory roots and ganglia from 14 rabbits killed at intervals from 1 to 84 days after percutaneous compression were sectioned and stained using immunoperoxidase for neurofilaments, hematoxylin and eosin, luxol fast blue, and cresyl echt violet. Focal axonal damage and demyelination were present 7 days after compression. No difference could be detected in the perikaryonal distribution of neurofilaments between compressed and control trigeminal ganglia. Focal demyelination and Schwann cell proliferation preceding remyelination were present in the trigeminal sensory root at 84 days. Differential injury of axons compared to trigeminal ganglion cell bodies suggests that axonal regeneration is possible and may contribute to the recovery of motor and sensory function in patients after percutaneous compression.

Arthur Roland Elvidge (1899-1985): contributions to the diagnosis of brain tumors and cerebrovascular disease.

The contributions of Arthur Elvidge (1899-1985), Wilder Penfield's first neurosurgical recruit, to the development of neurosurgery have been relatively neglected, although his work in brain tumors extended the previous work of Percival Bailey and Harvey Cushing. He published rigorous correlations of clinical and histological information and formulated a revised, modern nosology for neuroepithelial tumors, including a modern histological definition of glioblastoma multiforme. Well ahead of his time, he believed that glioblastoma was not strictly localized and was the first to comment that the tumor frequently showed "satellitosis." He was the first neurosurgeon in North America to use angiography as a radiographic aid in the diagnosis of cerebrovascular disease. Having studied with Egas Moniz, he was the first to detail the use of angiographic examinations specifically for demonstrating cerebrovascular disorders, believing that it would make possible routine surgery of the intracranial blood vessels. Seeking to visualize all phases of angiography, he was the impetus behind the design of one of the first semi-automatic film changers. Elvidge and Egas Moniz made the first observations on thrombosis of the carotid vessels independently of each other. Elvidge elucidated the significance of embolic stroke and commented on the ischemic sequelae of subarachnoid hemorrhage. Besides his contributions to neurosurgery, he codiscovered the mode of transmission of poliomyelitis. Elvidge's soft-spoken manner, his dry wit and candor, mastery of the understatement, love of exotic travel, and consummate dedication to neurosurgery made him a favorite of patients, neurosurgery residents, nurses, and other hospital staff. His accomplishments and example as teacher and physician have become part of neurosurgery's growing legacy.

Function and organization in dysgenic cortex. Case report.

Cerebral dysgenesis is a subject of interest because of its relationship to cerebral development and dysfunction and to epilepsy. The authors present a detailed study of a 16-year-old boy who underwent surgery for a severe seizure disorder. This patient had dysgenesis of the right hemisphere, which was composed of a giant central frontoparietal nodular gray matter heterotopia with overlying large islands of cortical dysplasia around a displaced central fissure. Exceptional insight into the function, biochemistry, electrophysiology, and histological structure of this lesion was obtained from neurological studies that revealed complementary information: magnetic resonance (MR) imaging, [18]fluoro-2-deoxy-D-glucose positron emission tomography (PET), functional PET scanning, proton MR spectroscopic (1H-MRS) imaging, intraoperative cortical mapping and electrocorticography, in vitro electrophysiology, and immunocytochemistry. These studies demonstrated compensatory cortical reorganization and showed that large areas of heterotopia and cortical dysplasia in the central area may retain normal motor and sensory function despite strikingly altered cytoarchitectonic organization and neuronal metabolism. Such lesions necessitate appropriate functional imaging studies prior to surgery and cortical mapping to avoid creating neurological deficits. Integrated studies, such as PET, 1H-MRS imaging, cortical mapping, immunocytochemistry, and electrophysiology may provide information on the function of developmental disorders of cerebral organization.

Unusual evolution and computerized tomographic appearance of a gliosarcoma.

A patient with a remote infarct, seizures, mild hemiparesis, and dysphasia became obtunded over four months and died. Computerized tomography (CT) over 5 years showed a consistent, large, wedge-shaped left hemisphere hypodensity with a central calcification, but without signs of mass effect. This was interpreted as an infarct of the left middle cerebral artery territory. Post-mortem examination of the brain revealed the entire area appearing as infarct on CT was a gliosarcoma. We suspect that the unusual CT appearance of the lesion was likely caused by multiple pathologies: a low grade glioma transforming into a gliosarcoma that was able to spread throughout the area of infarct encephalomalacia without revealing a typical CT appearance of mass effect. The patient's brief period of deterioration probably coincided with transformation of the tumor into a gliosarcoma. The variable CT characteristics of gliosarcomas are reviewed.

MRI diagnosis of brainstem cavernous angiomas presenting as tumours.

We report experience with 11 patients misdiagnosed for years, on the basis of computed tomography (CT) and angiography, as harbouring brainstem tumours in whom magnetic resonance imaging (MRI) demonstrated cavernous angiomas. Seven had undergone external irradiation, 2 had a ventriculo-peritoneal shunt, 2 developed aseptic femur necrosis following corticosteroid treatment, 1 had undergone a biopsy with a pathological diagnosis of glioma. CT had depicted ill-defined, hyperdense, faintly enhancing lesions. Angiography was normal, or showed an avascular mass or subtle venous pooling. MRI delineated discrete lesions, typical of cavernous angiomas, with a mixed hyperintense, reticulated, central core surrounded by a hypointense rim. Six patients subsequently underwent stereotactic radiosurgery without changes in clinical status or lesion. Although hemorrhagic neoplasms may mimic the clinical course and MRI appearance of cavernous angiomas, MRI is useful in the diagnosis of brainstem cavernous angiomas and should be performed in patients with suspected brainstem tumours.

Magnetic resonance spectroscopy guided brain tumor resection: differentiation between recurrent glioma and radiation change in two diagnostically difficult cases.

BACKGROUND: It is often difficult to differentiate a recurrent glioma from the effects of post-operative radiotherapy by means of conventional neurodiagnostic imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows in vivo measurements of the concentration of brain metabolites such as choline-containing phospholipids (Cho), may provide in vivo biochemical information helpful in distinguishing areas of tumor recurrence from areas of radiation effect. PATIENTS AND METHODS: Two patients who had undergone resection and post-operative radiotherapy for a cerebral glioma became newly symptomatic. Computed tomographic (CT) and magnetic resonance imaging (MRI) performed after the intravenous infusion of contrast material, and in one case, [18F]fluorodeoxyglucose positron emission tomography (PET), could not differentiate between the possibilities of recurrent glioma and radiation effect. The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were compared to histological findings originating from the same locations. RESULTS: A high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven dense tumor recurrence, while low Cho signal was present where radiation changes predominated. CONCLUSIONS: The differentiation between the recurrence of a cerebral glioma and the effects of post-operative irradiation was achieved using 1H-MRSI in these two patients whose conventional neurodiagnostic imaging was equivocal for such a distinction. Where these two conditions are present, metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered with other imaging modalities such as MRI and may also be integrated with functional MRI or functional PET within a multimodal imaging-guided surgical navigation system to assure maximal resection of recurrent tumor while minimizing the risk of added neurological damage.

Historical considerations of the diagnosis and treatment of facial pain.

Most forms of facial pain remain neurologic disorders that, although not life threatening, can be debilitating. Modern descriptions of the various forms of facial pain according to their clinical and anatomic patterns did not develop until after the contributions of the early modern neuroanatomists and physiologists in the first quarter of the nineteenth century. These contributions allowed the recognition of relatively distinct painful afflictions of the face, and permitted surgeons in the late nineteenth century to embark confidently on a variety of approaches to cranial and peripheral nerves using decompressive or destructive procedures to alleviate facial pain.