RESUMEN
BACKGROUND: The origin of syrinx fluid is controversial. OBJECTIVE: To elucidate the mechanisms of syringomyelia associated with cerebrospinal fluid pathway obstruction and with intramedullary tumors, contrast transport from the spinal subarachnoid space (SAS) to syrinx was evaluated in syringomyelia patients. METHODS: We prospectively studied patients with syringomyelia: 22 with Chiari I malformation and 16 with SAS obstruction-related syringomyelia before and 1 wk after surgery, and 9 with tumor-related syringomyelia before surgery only. Computed tomography-myelography quantified dye transport into the syrinx before and 0.5, 2, 4, 6, 8, 10, and 22 h after contrast injection by measuring contrast density in Hounsfield units (HU). RESULTS: Before surgery, more contrast passed into the syrinx in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia than in tumor-related syringomyelia, as measured by (1) maximum syrinx HU, (2) area under the syrinx concentration-time curve (HU AUC), (3) ratio of syrinx HU to subarachnoid cerebrospinal fluid (CSF; SAS) HU, and (4) AUC syrinx/AUC SAS. More contrast (AUC) accumulated in the syrinx and subarachnoid space before than after surgery. CONCLUSION: Transparenchymal bulk flow of CSF from the subarachnoid space to syrinx occurs in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia. Before surgery, more subarachnoid contrast entered syringes associated with CSF pathway obstruction than with tumor, consistent with syrinx fluid originating from the subarachnoid space in Chiari I malformation and spinal obstruction-related syringomyelia and not from the subarachnoid space in tumor-related syringomyelia. Decompressive surgery opened subarachnoid CSF pathways and reduced contrast entry into syringes associated with CSF pathway obstruction.
Asunto(s)
Líquido Cefalorraquídeo/diagnóstico por imagen , Siringomielia/líquido cefalorraquídeo , Siringomielia/diagnóstico por imagen , Siringomielia/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Espacio Subaracnoideo/diagnóstico por imagen , Espacio Subaracnoideo/patologíaRESUMEN
OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. RESULTS: In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. CONCLUSIONS: These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245.
Asunto(s)
Espacio Subaracnoideo/fisiopatología , Siringomielia/fisiopatología , Siringomielia/cirugía , Adulto , Malformación de Arnold-Chiari/líquido cefalorraquídeo , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/fisiopatología , Malformación de Arnold-Chiari/cirugía , Presión del Líquido Cefalorraquídeo , Diagnóstico por Imagen , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Siringomielia/líquido cefalorraquídeo , Siringomielia/etiologíaRESUMEN
BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov; NCT00103025.
Asunto(s)
Nitrito de Sodio/farmacocinética , Nitrito de Sodio/toxicidad , Adulto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Estudios de Factibilidad , Femenino , Semivida , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Nitrito de Sodio/administración & dosificación , Factores de TiempoRESUMEN
OBJECT: Craniocervical decompression for Chiari malformation Type I (CM-I) and syringomyelia has been reported to fail in 10%-40% of patients. The present prospective clinical study was designed to test the hypothesis that in cases in which syringomyelia persists after surgery, craniocervical decompression relieves neither the physiological block at the foramen magnum nor the mechanism of syringomyelia progression. METHODS: The authors prospectively evaluated and treated 16 patients with CM-I who had persistent syringomyelia despite previous craniocervical decompression. Testing before surgery included the following: 1) clinical examination; 2) evaluation of the anatomy using T1-weighted MR imaging; 3) assessment of the syrinx and CSF velocity and flow using cine phase-contrast MR imaging; and 4) appraisal of the lumbar and cervical subarachnoid pressures at rest, during a Valsalva maneuver, during jugular compression, and following the removal of CSF (CSF compliance measurement). During surgery, ultrasonography was performed to observe the motion of the cerebellar tonsils and syrinx walls; pressure measurements were obtained from the intracranial and lumbar intrathecal spaces. The surgical procedure involved enlarging the previous craniectomy and performing an expansile duraplasty with autologous pericranium. Three to 6 months after surgery, clinical examination, MR imaging, and CSF pressure recordings were repeated. Clinical examination and MR imaging studies were then repeated annually. RESULTS: Before reexploration, patients had a decreased size of the CSF pathways and a partial blockage in CSF transmission at the foramen magnum. Cervical subarachnoid pressure and pulse pressure were abnormally elevated. During surgery, ultrasonographic imaging demonstrated active pulsation of the cerebellar tonsils, with the tonsils descending during cardiac systole and concomitant narrowing of the upper pole of the syrinx. Three months after reoperation, patency of the CSF pathways was restored and pressure transmission was improved. The flow of syrinx fluid and the diameter of the syrinx decreased after surgery in 15 of 16 patients. CONCLUSIONS: Persistent blockage of the CSF pathways at the foramen magnum resulted in increased pulsation of the cerebellar tonsils, which acted on a partially enclosed cervical subarachnoid space to create elevated cervical CSF pressure waves, which in turn affected the external surface of the spinal cord to force CSF into the spinal cord through the Virchow-Robin spaces and to propel the syrinx fluid caudally, leading to syrinx progression. A surgical procedure that reestablished the CSF pathways at the foramen magnum reversed this pathophysiological mechanism and resolved syringomyelia. Elucidating the pathophysiology of persistent syringomyelia has implications for its primary and secondary treatment.
Asunto(s)
Malformación de Arnold-Chiari/cirugía , Craniectomía Descompresiva , Foramen Magno/cirugía , Laminectomía , Siringomielia/etiología , Siringomielia/cirugía , Adolescente , Adulto , Malformación de Arnold-Chiari/diagnóstico por imagen , Presión del Líquido Cefalorraquídeo , Niño , Progresión de la Enfermedad , Femenino , Foramen Magno/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Espacio Subaracnoideo/diagnóstico por imagen , Espacio Subaracnoideo/cirugía , Siringomielia/diagnóstico por imagen , Insuficiencia del TratamientoRESUMEN
OBJECT: Many patients with Cushing disease still have active or recurrent disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing disease. METHODS: The authors reviewed a prospective database of data obtained in patients with Cushing disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery-challenging cases for surgical success-were excluded from analysis. RESULTS: In 261 patients an encapsulated adenoma was identified at surgery. Tumor was visible on MR imaging in 135 patients (52%); in 126 patients (48%) MR imaging detected no tumor. The range of tumor size overlapped considerably in the groups with positive and negative MR imaging results, indicating that in addition to size other features of the adenoma influence the results of MR imaging. In 252 patients hypercortisolism resolved after the first operation, whereas in 9 patients (3 with positive MR imaging and 6 with negative MR imaging) early reoperation was required. Hypercortisolism resolved in all 261 patients (256 with hypocortisolism and 5 with eucortisolism) before hospital discharge. Forty-six patients (18%) had postoperative electrolyte abnormalities (30 with hyponatremia and 16 with diabetes insipidus), but only 2 patients required treatment at discharge. The mean clinical follow-up duration was 84 months (range 12-215 months). Six patients (2%) had recurrence of hypercortisolism, all of whom were treated successfully with reoperation. CONCLUSIONS: Because of their small size, adenomas can be challenging to identify in patients with Cushing disease. Use of the histological pseudocapsule of an adenoma allows accurate identification of the tumor and helps guide its complete excision. With this approach the overall remission rate is high and the rate of complications is low.
Asunto(s)
Adenoma/cirugía , Síndrome de Cushing/cirugía , Hipofisectomía/métodos , Neoplasias Hipofisarias/cirugía , Adenoma/patología , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/patología , Recurrencia , ReoperaciónRESUMEN
OBJECT: Despite the frequency of cerebellar hemangioblastomas in von Hippel-Lindau (VHL) disease, their optimum contemporary management has not been defined, and is made complex because of the multiple, progressive, and protean nature of the tumors found in patients with this disorder. To examine modern management and outcomes of cerebellar hemangioblastomas in VHL disease, the authors reviewed findings in patients with this disease who underwent resection of cerebellar hemangioblastomas. METHODS: Consecutive patients with VHL disease who underwent surgery for cerebellar hemangioblastoma(s) at the National Institutes of Health were included. Eighty consecutive patients (44 female and 36 male patients) underwent 126 operations for removal of 164 cerebellar hemangioblastomas (age at surgery 37.8+/-10.3 years, follow-up duration 96.0+/-60.3 months). Serial clinical examinations, imaging studies, and operative records were analyzed. RESULTS: Symptoms and signs included headache (94 operations; 75%), ataxia (55%), dysmetria (29%), and hydrocephalus (28%). Although the primary objective of surgery was resection of the hemangioblastoma considered responsible for symptoms (136 of the hemangioblastomas [83%]), 28 additional hemangioblastomas (17%) were removed during the same surgeries. Tumors associated with symptoms were larger (diameter 1.8+/-1.9 cm; volume 2.8+/-3.4 cm3; p<0.05) and more likely to be associated with peritumoral edema or peritumoral cysts (100% associated with edema and/or cyst; p<0.05) than asymptomatic tumors (diameter 1.1+/-0.9 cm; volume 0.7+/-0.4 cm3; 18%). More tumors were located in the posterior (74%) compared with the anterior (26%) half of the cerebellum (p<0.05). Three months after resection, symptom improvement/stabilization had occurred following 124 of the operations (98%). Preoperative hydrocephalus resolved after tumor removal in 33 cases (94%) and did not require cerebrospinal fluid diversion. Long-term imaging follow-up (61.5+/-15.0 months) revealed no recurrences. CONCLUSIONS: Symptoms and signs caused by cerebellar hemangioblastomas in VHL disease are associated with edema and peritumoral cyst formation/propagation and are treated safely and effectively with resection. Cerebrospinal fluid diversion is rarely necessary after complete tumor removal in patients with preoperative hydrocephalus. Cerebellar hemangioblastomas are preferentially distributed in the posterior half of the cerebellum, as they are in the brainstem and spinal cord. Tumor recurrence is avoided by meticulous extracapsular resection.
Asunto(s)
Neoplasias Cerebelosas/cirugía , Hemangioblastoma/cirugía , Enfermedad de von Hippel-Lindau/complicaciones , Adulto , Ataxia/fisiopatología , Edema Encefálico/fisiopatología , Ataxia Cerebelosa/fisiopatología , Neoplasias Cerebelosas/fisiopatología , Irradiación Craneana , Quistes/fisiopatología , Disección/métodos , Electrocoagulación/métodos , Femenino , Estudios de Seguimiento , Cefalea/fisiopatología , Hemangioblastoma/fisiopatología , Humanos , Hidrocefalia/fisiopatología , Masculino , Microdisección/métodos , Complicaciones Posoperatorias , Radiocirugia , Radioterapia Adyuvante , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedad de von Hippel-Lindau/fisiopatologíaRESUMEN
BACKGROUND AND PURPOSE: The American Stroke Association (ASA) assembled a multidisciplinary group of experts to develop recommendations regarding the potential effectiveness of establishing an identification program for stroke centers and systems. "Identification" refers to the full spectrum of models for assessing and recognizing standards of quality care (self-assessment, verification, certification, and accreditation). A primary consideration is whether stroke center identification might improve patient outcomes. METHODS: In February 2001, ASA, with the support of the Stroke Council's Executive Committee, decided to embark on an evaluation of the potential impact of stroke center identification. HealthPolicy R&D was selected to prepare a comprehensive report. The investigators reported on models outside the area of stroke, ongoing initiatives within the stroke community (such as Operation Stroke), and state and federal activities designed to improve care for stroke patients. The investigators also conducted interviews with thought leaders in the stroke community, representing a diverse sampling of specialties and affiliations. In October 2001, the Advisory Working Group on Stroke Center Identification developed its consensus recommendations. This group included recognized experts in neurology, emergency medicine, emergency medical services, neurological surgery, neurointensive care, vascular disease, and stroke program planning. RESULTS: There are a variety of existing identification programs, generally falling within 1 of 4 categories (self-assessment, verification, certification, and accreditation) along a continuum with respect to intensity and scope of review and consumption of resources. Ten programs were evaluated, including Peer Review Organizations, trauma centers, and new efforts by the National Committee on Quality Assurance and the Joint Commission on the Accreditation of Healthcare Organizations to identify providers and disease management programs. The largest body of literature on clinical outcomes associated with identification programs involves trauma centers. Most studies support that trauma centers and systems lead to improved mortality rates and patient outcomes. The Advisory Working Group felt that comparison to the trauma model was most relevant given the need for urgent evaluation and treatment of stroke. The literature in other areas generally supports the positive impact of identification programs, although patient outcomes data have less often been published. In the leadership interviews, participants generally expressed strong support for pursuing some form of voluntary identification program, although concerns were raised that this effort could meet with some resistance. CONCLUSIONS: Identification of stroke centers and stroke systems competencies is in the best interest of stroke patients in the United States, and ASA should support the development and implementation of such processes. The purpose of a stroke center/systems identification program is to increase the capacity for all hospitals to treat stroke patients according to standards of care, recognizing that levels of involvement will vary according to the resources of hospitals and systems.