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Molecular mechanisms of traumatic brain injury in children
A review
Pavan Jagannathan and Jay Jagannathan
Review of spinal radiosurgery: a minimally invasive approach for the treatment of spinal and paraspinal metastases
Jason P. Sheehan and Jay Jagannathan
Intracranial radiosurgery has been proved effective for the treatment of brain metastasis. The treatment of paraspinal and spinal metastasis with spinal radiosurgery represents a natural extension of the principles of intracranial radiosurgery. However, spinal radiosurgery is a far more complicated process than intracranial radiosurgery. Larger treatment volumes, numerous organs at risk, and the inability to utilize rigid, frame-based immobilization all contribute to the substantially more complex process of spinal radiosurgery.
Beyond the convenience of a shorter duration of treatment for the patient, spinal radiosurgery affords a greater biological equivalent dose to a metastatic lesion than conventional radiotherapy fractionation schemes. This appears to translate into a high rate of tumor control and fast pain relief for patients. The minimally invasive nature of this approach is consistent with trends in open spinal surgery and helps to maintain or improve a patient's quality of life. Spinal radiosurgery has expanded the neurosurgical treatment armamentarium for patients with spinal and paraspinal metastasis.
Editorial
Pituitary surgery
Martin H. Weiss
Evaluation and management of Cushing syndrome in cases of negative sellar magnetic resonance imaging
Jay Jagannathan, Jason P. Sheehan, and John A. Jane Jr.
✓ The treatment of patients with Cushing disease and without magnetic resonance (MR) imaging evidence of Cushing disease (that is, negative MR imaging) is discussed in this paper. Magnetic resonance imaging is the diagnostic modality of choice in Cushing disease, but in up to 40% of these patients negative imaging can be caused by tumor-related factors and limitations in imaging techniques. In cases in which the MR imaging is negative, it is critical to make sure that the diagnosis of Cushing disease is correct. This can be accomplished by performing a complete laboratory and imaging workup, including dexamethasone suppression tests, imaging of the adrenal glands, and inferior petrosal sinus sampling when appropriate. If these evaluations suggest a pituitary source of the hypercortisolemia, then transsphenoidal surgery remains the treatment of choice. The authors favor the endoscopic approach because it gives a wider and more magnified view of the sella and allows inspection of the medial cavernous sinus walls. Radiosurgery is an effective treatment option in patients with persistent Cushing disease. When a target cannot be found on MR imaging, one can target the entire sellar region with radiosurgery.
Pediatric sellar tumors: diagnostic procedures and management
Jay Jagannathan, Aaron S. Dumont, John A. Jane Jr., and Edward R. Laws Jr.
The diagnosis and management of pediatric sellar lesions is discussed in this paper. Craniopharyngiomas account for the majority of pediatric sellar masses, and pituitary adenomas are extremely uncommon during childhood. The diagnosis of sellar lesions involves a multidisciplinary effort, and detailed endocrinological, ophthalmological, and neurological testing is critical in the evaluation of a new sellar mass. The management of pituitary adenomas varies depending on the entity. For most tumors other than prolactinomas, transsphenoidal resection remains the mainstay of treatment. Less invasive methods, such as endoscopic transsphenoidal surgery and stereotactic radiosurgery, have shown promise as primary and adjuvant treatment modalities, respectively.
The posterior cervical foraminotomy in the treatment of cervical disc/osteophyte disease: a single-surgeon experience with a minimum of 5 years' clinical and radiographic follow-up
Clinical article
Jay Jagannathan, Jonathan H. Sherman, Tom Szabo, Christopher I. Shaffrey, and John A. Jane Sr.
Object
This study details long-term clinical and radiographic outcomes following single-level posterior cervical foraminotomy for degenerative disc or osteophyte disease.
Methods
The authors conducted a retrospective review of 162 cases involving patients treated by a single surgeon using a posterior cervical foraminotomy. Inclusion criteria were a minimum of 5 years' clinical and radiographic follow-up and unilateral single-level posterior cervical foraminotomy for degenerative disease between C-3 and C-7. Patients who had undergone previous operations, those who underwent bilateral procedures, and those who underwent foraminotomy as part of a larger laminectomy were excluded. The Neck Disability Index (NDI) was used for clinical follow-up, and radiographic follow-up was performed using static and dynamic lateral radiographs to compare focal and segmental alignment and changes in disc-space height.
Results
The mean presenting NDI score was 18 (range 2–39). The most common presenting symptoms were radiculopathy (110 patients [68%]), neck pain (85 patients [52%]), and subjective weakness (91 patients [56%]). The mean preoperative focal angulation at the surgically treated level was 4.2° (median 4.1°, range 7.3–15.3°), and the mean preoperative segmental curvature between C-2 and C-7 was 18.0° (median 19.3°, range −22.1 to 39.3°). The mean postoperative NDI score was 8 (range 0–39). Improvement in NDI scores was seen in 150 patients (93%). Resolution of radiculopathy was experienced by 104 patients (95% of patients with radiculopathy). The mean radiographic follow-up was 77.3 months (range 60–177 months). No statistically significant changes in focal or segmental kyphosis or disc-space height were seen among the overall cohort with time (Cox proportional hazards analysis and Student t-test, p > 0.05). The mean postoperative focal angulation was 4.1° (median 3.9°, range −9.9° to 15.1°) and mean postoperative segmental angulation was 17.6° (median 15.4°, range −40.2 to 35.3°). Postoperative instability on dynamic imaging was present in 8 patients (4.9%); 7 of these patients were clinically asymptomatic and were treated conservatively, and 1 required cervical fusion. Postoperative loss of lordosis (defined as segmental Cobb angle < 10°) was seen in 30 patients (20%), 9 of whom had clinical symptoms and 4 of whom required further surgical correction. Factors associated with worsening sagittal alignment (Cox proportional hazards analysis, p < 0.05) included age > 60 at initial surgery, the presence of preoperative cervical lordosis of < 10°, and the need for posterior surgery after the initial foraminotomy
Conclusions
The posterior cervical foraminotomy is highly effective in treating patients with cervical radiculopathy and results in long-lasting pain relief and improved quality-of-life outcomes in most patients. Long-term radiographic follow-up shows no significant trend toward kyphosis, although select patient subsets (patients older than 60 years, patients who had previous posterior surgery, and patients with < 10° of lordosis preoperatively) appear to be at higher risk and require closer follow-up.
History of endoscopic skull base surgery: its evolution and current reality
Daniel M. Prevedello, Francesco Doglietto, John A. Jane Jr., Jay Jagannathan, Joseph Han, and Edward R. Laws Jr.
✓The history of the endoscope exemplifies the manner in which technological advances influence medicine and surgery. Endoscopic systems have evolved and improved, and they currently provide detailed visualization of a variety of deep organ structures. Otorhinolaryngological surgeons have used the endoscope for more than 30 years. In the 1990s, a number of influential neurosurgeons and otorhinolaryngological surgeons began performing purely endoscopic pituitary surgery. Endoscopic transsphenoidal operations are now extending beyond the sella. The collaboration between otorhinolaryngologists and neurosurgeons has produced a new subspecialty of “endoscopic skull base surgery.” There is a great deal of progress still to be made in developing skills, instruments, and improving skull base repair. The extended skull base approaches allow surgical exposures from the olfactory groove to C-2 and to the infratemporal region and jugular fossa laterally. This article discusses the history of the endoscope, the pivotal technological advances, and the key figures in the burgeoning field of endoneurosurgery.
Surgical management of cerebellar hemangioblastomas in patients with von Hippel–Lindau disease
Jay Jagannathan, Russell R. Lonser, Rene Smith, Hetty L. DeVroom, and Edward H. Oldfield
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.
Effect of ependymal and pial surfaces on convectionenhanced delivery
Laboratory investigation
Jay Jagannathan, Stuart Walbridge, John A. Butman, Edward H. Oldfield, and Russell R. Lonser
Object
Convection-enhanced delivery (CED) is increasingly used to investigate new treatments for central nervous system disorders. Although the properties of CED are well established in normal gray and white matter central nervous system structures, the effects on drug distribution imposed by ependymal and pial surfaces are not precisely defined. To determine the effect of these anatomical boundaries on CED, the authors infused low MW and high MW tracers for MR imaging near ependymal (periventricular) and pial (pericisternal) surfaces.
Methods
Five primates underwent CED of Gd-diethylenetriamine pentaacetic acid (Gd-DTPA; MW 590 D) or Gd-bound albumin (Gd-albumin; MW 72,000 D) during serial real-time MR imaging (FLAIR and T1-weighted sequences). Periventricular (caudate) infusions were performed unilaterally in 1 animal (volume of infusion [Vi] 57 μl) and bilaterally in 1 animal with Gd-DTPA (Vi = 40 μl on each side), and bilaterally in 1 animal with Gd-albumin (Vi = 80 μl on each side). Pericisternal infusions were performed in 2 animals with Gd-DTPA (Vi = 190 μl) or with Gd-albumin (Vi = 185 μl) (1 animal each). Clinical effects, MR imaging, and histology were analyzed.
Results
Large regions of the brain and brainstem were perfused with both tracers. Intraparenchymal distribution was successfully tracked in real time by using T1-weighted MR imaging. During infusion, the volume of distribution (Vd) increased linearly (R2 = 0.98) with periventricular (mean Vd/Vi ratio ± standard deviation; 4.5 ± 0.5) and pericisternal (5.2 ± 0.3) Vi, but did so only until the leading edge of distribution reached the ependymal or pial surfaces, respectively. After the infusate reached either surface, the Vd/Vi decreased significantly (ependyma 2.9 ± 0.8, pia mater 3.6 ± 1.0; p < 0.05) and infusate entry into the ventricular or cisternal cerebrospinal fluid (CSF) was identified on FLAIR but not on T1-weighted MR images.
Conclusions
Ependymal and pial boundaries are permeable to small and large molecules delivered interstitially by convection. Once infusate reaches these surfaces, a portion enters the adjacent ventricular or cisternal CSF and the tissue Vd/Vi ratio decreases. Although T1-weighted MR imaging is best for tracking intraparenchymal infusate distribution, FLAIR MR imaging is the most sensitive and accurate for detecting entry of Gd-labeled imaging compounds into CSF during CED.
Effect of trans sodium crocetinate on brain tumor oxgenation
Laboratory investigation
Jason Sheehan, Jonathan Sherman, Christopher Cifarelli, Jay Jagannathan, Kasandra Dassoulas, Claire Olson, Jessica Rainey, and Shaojie Han
Object
Glioblastoma multiforme tumors typically exhibit regions of hypoxia. Hypoxic regions within the tumor make cells less sensitive to radiosurgery and radiation therapy. Trans sodium crocetinate (TSC) has been shown to be a radiosensitizer. The goal of this research was to elucidate the underlying mechanism of TSC's radiosensitizing effect.
Methods
A rat C6 glioma model was used. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Two weeks later, MR imaging was used to confirm the presence of a glioma. Following demonstration on MR imaging of a brain tumor, animals were randomized into 1 of 2 groups: 1) TSC alone (100 μg/kg), or 2) saline control. Licox probes were inserted into the brain tumor and contralateral cerebral hemisphere. Tissue oxygenation measurements were recorded before and after intravenous infusion of either TSC or saline.
Results
Not surprisingly, tissue oxygenation measurements revealed that the brain tumor was hypoxic relative to the contralateral cerebral hemisphere brain tissue. Two to 8 minutes after TSC was infused, tissue oxygenation measurements in the brain tumor increased above baseline by as much as 60%. After this temporary elevation following TSC infusion, tumor oxygenation measurements returned to baseline. No significant elevations in tissue oxygenation were seen on the contralateral side. Similarly, the saline vehicle was not observed to increase tissue oxygenation in either the brain tumor or the contralateral brain tissue.
Conclusions
Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.
