Grant Sinson

Nerve Growth Factor Administration Attenuates Cognitive but Not Neurobehavioral Motor Dysfunction or Hippocampal Cell Loss Following Fluid-Percussion Brain Injury in Rats

Abstract: Lateral fluid‐percussion brain injury in rats results in cognitive deficits, motor dysfunction, and selective hippocampal cell loss. Neurotrophic factors have been shown to have potential therapeutic applications in neurodegenerative diseases, and nerve growth factor (NGF) has been shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague‐Dawley rats received lateral fluid‐percussion brain injury of moderate severity (2.1–2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34) or vehicle (n = 16) directly into the region of maximal cortical injury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive dysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Although an improvement in memory scores was not observed at 72 h after injury, animals receiving NGF infusions showed significantly improved memory scores when tested at 1 or 2 weeks after injury compared with injured animals receiving vehicle infusions (p < 0.05). Motor scores and CA3 hippocampal cell loss were not significantly different in any group of NGF‐treated animals when compared with controls. These data suggest that NGF administration, in the acute, posttraumatic period following fluid‐percussion brain injury, may have potential in improving post‐traumatic cognitive deficits.

Magnetization transfer imaging of traumatic brain injury

Magnetization transfer imaging (MTI) has been shown to be sensitive for the detection of white matter abnormalities in entities such as multiple sclerosis, progressive multifocal leukencephalopathy, and wallerian degeneration. Our hypothesis was that MTI would detect traumatic white matter abnormalities (TWMA) and provide information additional to that obtainable with routine spin‐ and gradient‐echo imaging. We hypothesized that the presence of TWMA defined by MTI would correlate with outcome following TBI. Twenty‐eight victims of head trauma and 15 normal controls underwent magnetic resonance imaging including MTI. Magnetization transfer ratios (MTR) were calculated for areas of shearing injury and for normal‐appearing white matter (NAWM) in locations frequently subject to diffuse axonal injury. Abnormal MTRs were detected in NAWM in eight patients. All eight had persistent neurologic deficits, including cognitive deficits, aphasia, and extremity weakness. Seven of the 28 patients had no abnormal findings on neurologic exam at discharge, transfer, or follow‐up. None of these patients had an abnormal MTR in NAWM. In the remaining 13 patients, who had persistent neurologic deficits, no regions of abnormal MTR were detected in NAWM. MTI is a sensitive method for the detection of TWMA. Detection of abnormal MTR in NAWM that is prone to axonal injury may predict a poor patient outcome. The presence of normal MTR in NAWM in these areas does not necessarily confer a good outcome, however. J. Magn. Reson. Imaging 2000;11:1–8.

Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: Pilot study of treatment with intraventricular tissue plasminogen activator

OBJECTIVE:Intraventricular (IVen) hemorrhage is considered a predictor of poor outcome after subarachnoid hemorrhage (SAH). This prospective study examines the feasibility and outcome of administration of IVen tissue plasminogen activator (tPA) after aneurysmal SAH. METHODS:Ten patients with SAH who received IVen tPA after the aneurysm had been secured were compared with 10 age-, sex-, and Glasgow Coma Scale score-matched control patients. The primary end point was third and fourth ventricle clot resolution. IVen blood was quantified by use of the Graeb and Le Roux scales on admission and at an additional time (equal or longer for the control group) after the injection was terminated. RESULTS:Six men and four women with a mean age of 52 years in each group were evaluated. On average, 3.5 mg tPA was injected 68 ± 51 hours after admission without ensuing complications. Although the treated group had significantly more IVen blood on admission than control subjects (mean Le Roux scale ± standard deviation, 11 ± 3 versus 7.6 ± 4.2, P = 0.055, and mean Graeb scale ± standard deviation, 8.5 ± 2.3 in tPA versus 5.3 ± 3, P < 0.02), it also had a significant decrease in the amount of IVen blood (mean Le Roux and Graeb scale decrease ± standard deviation, 6.7 ± 3.3 and 4.8 ± 2 in tPA patients versus 0.9 ± 3.2 and 0.5 ± 2.6 in control subjects, P = 0.002). The tPA group had a non-statistically significantly shorter length of stay, decreased mortality, and better Glasgow Outcome Scale and modified Rankin Scale scores at discharge. Treated survivors showed a decreased need for shunt placement (2 [22%] of 9 patients versus 5 [83%] of 6 control subjects, P = 0.04). CONCLUSION:This pilot study shows that IVen tPA administration is feasible without complications after SAH and may be associated with better outcomes. These results warrant a randomized clinical trial.

Clipping or coiling of ruptured cerebral aneurysms and shunt-dependent hydrocephalus

BackgroundHydrocephalus may develop either early in the course of aneurysmal subarachnoid hemorrhage (SAH) or after the first 2 weeks. Because the amount of SAH is a predictor of hydrocephalus, the two available aneurysmal treatments, clipping or coiling, may lead to differences in the need for cerebrospinal fluid (CSF) diversion, as only surgery permits clot removal.MethodsHospital and University Hospitals Consortium (UHC) databases were used to retrieve data on all patients admitted to our hospital with aneurysmal SAH during the last 4 years. The incidence of permanent ventricular shunt (VS) according to treatment modality used was evaluated.ResultsOne hundred eighty-eight patients were admitted with aneurysmal SAH. Coiling was performed on 48 (26%) and clipping on 135 (73.8%) patients. Fifty-six (31%) patients required CSF diversion. External ventricular drain was placed in 30 (22.2%) clipped and 13 (27.1%) coiled patients (p=0.5), and VS in 6 patients of the two treatment groups (4.4 versus 12.5%, respectively; p=0.08). Patients requiring VS had longer UHC-expected hospital length of stay (LOS), as well as observed ICU and hospital LOS, compared to patients with temporary or no CSF diversion (24±14 versus 15±8, 20.5±9 versus 11±7, and 30±13 versus 16±11 days, respectively; p≤0.01). In a logistic regression model, VS was independently associated with rebleeding, external ventricular drain placement, coiling, and UHC-expected LOS (odds ratios, 95% confidence interval 12.1, 2.3–62.6, 6.9, 1.6–30, 6.25, 1.3–29, and 1.1, 1.02–1.14, respectively).ConclusionsOne-third of patients admitted with aneurysmal SAH require temporary or permanent CSF diversion. Permanent shunting was found to be associated with coiling in our patient population.

Subependymal Giant Cell Astrocytomas in Children

Between 1977 and 1991, at the Childrens Hospital of Philadelphia, 10 patients, 5-16 years of age, were diagnosed as having subependymal giant cell astrocytomas. These patients accounted for 1.4% of all pediatric brain tumors seen during that time interval. One patient received a course of radiation therapy, which was ineffective in preventing tumor growth. All underwent surgical resections with the goal being maximal tumor debulking, if not complete resection. In 6 patients this was accomplished by the frontal transventricular route and, in the more recent patients, surgery was performed using a transcallosal approach. There were 2 perioperative deaths, and 2 other patients died later of causes unrelated to tumor progression. The remaining 6 patients remain alive and stable at a mean of 6.7 years of follow-up (range 1.8-12.4). None of these patients has received additional radiation therapy. Two patients have no other evidence of tuberous sclerosis. The use of modern radiographic and surgical techniques has made the treatment of this disease safer than in the past.

Alternative management considerations for ethmoidal dural arteriovenous fistulas

BACKGROUND Ethmoidal dural arteriovenous fistulas (EDAFs) are an unusual type of intracranial vascular lesion that commonly present with acute hemorrhage. They are often best treated surgically; however, recent endovascular advances raise questions concerning the best therapeutic approach. METHODS We present 7 cases of EDAFs managed at this institution over a 6-year period, which demonstrate the broad spectrum of clinical behavior associated with the lesions. Four patients presented with intracranial hemorrhage, 1 patient with rapidly progressive dementia, 1 patient with a proptotic, red eye, and 1 with a retro-orbital headache. RESULTS One patient underwent no treatment, 1 underwent embolization alone, 2 underwent embolization and resection, and 3 patients underwent resection alone. There was complete obliteration of the EDAF in all of the patients who underwent surgical resection. Embolization was performed through the external carotid circulation and not the ophthalmic artery. There were no treatment-related neurologic deficits. CONCLUSIONS Treatment is best managed with a multidisciplinary approach, which emphasizes complete resection of the lesions with assistance from interventional neuroradiology techniques. However, each patient must be evaluated independently as treatment may vary depending on the angioarchitecture of the lesion.

Perioperative assessment of coagulability in neurosurgical patients using thromboelastography

BACKGROUND Thrombelastography is a useful technique for evaluating coagulability. We hypothesized that it could be used to determine postoperative hematologic complications during and after neurologic surgery. METHODS Forty-six neurosurgical patients were stratified by diagnosis: subarachnoid hemorrhage from ruptured intracranially aneurysms, intracranial-axial lesions, intracranial-extra-axial lesions, and degenerative spine disease. Thromboelastograms were performed before, during, and after surgery. Hematologic data were collected preoperatively and postoperatively; computed tomography scans and lower extremity Doppler sonography were performed postoperatively. A thrombosis index (TI) was used to assess coagulability. RESULTS Coagulability increased over the course of surgery for all patients (p < 0.0001). In craniotomy patients, coagulability increased over the course of surgery (p < 0.05) with the most dramatic increase from intubation to skin incision (p < 0.05), and then after tumor removal or aneurysm clipping (p < 0.10). Univariate analysis among craniotomy patients showed that female gender (p < 0.0004) and smoking (p < 0.06) were associated with hypercoagulability. Among craniotomy patients, younger age was associated with hypercoagulability in the preoperative period (p < 0.01). There was no significant association between coagulability and aspirin or NSAID use, or intraoperative fluid volume. No patient developed a postoperative hematoma and one patient (2.2%) developed a lower extremity deep vein thrombosis. CONCLUSIONS Increased coagulability begins between induction of anesthesia and skin incision, and continues to increase throughout surgery. These changes are more pronounced in patients undergoing craniotomy compared to patients undergoing spine procedures.

Cavernous Malformations of the Third Ventricle

CAVERNOUS MALFORMATIONS ARE uncommon lesions that are usually present in the cerebral hemispheres. Less frequently, these malformations are seen in the brain stem, basal ganglia, or paraventricular regions. We report four cases of cavernous malformations of the third ventricle. Patients presented with symptoms of hydrocephalus, memory loss, and signs of hypothalamic dysfunction. Magnetic resonance imaging and computed tomography provided characteristic images of the three lesions preoperatively. All patients underwent direct surgical excision of the malformations. Two patients had a transcallosal, transventricular approach, the third underwent a transcortical, transventricular approach, and the fourth had an infratentorial supracerebellar approach. Postoperatively, the patient with hypothalamic dysfunction has not improved and underwent ventriculoperitoneal shunting. The second patient did well initially; however, 8 days postoperatively, she became comatose and later died. The presumed cause of her deterioration was a hypothalamic venous infarction. The third and fourth patients have returned to their normal neurological baseline. The presenting signs and symptoms, magnetic resonance imaging and computed tomography findings, and treatment options for this rare lesion are discussed and illustrated.

Subdural Hematomas in Chronic Dialysis Patients: Significant and Increasing

BACKGROUND AND OBJECTIVES Subdural hematoma is a known complication of long-term hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS The US Renal Data System was used to determine the occurrence rate of nontraumatic subdural hematoma in long-term dialysis patients and to evaluate time trends. RESULTS The occurrence rate of subdural hematoma in long-term dialysis patients is 10 times higher than that of the general population. From 1991 to 2002, the occurrence rate of subdural hematoma in hemodialysis patients doubled, whereas it did not change in peritoneal dialysis patients. CONCLUSIONS This high occurrence rate of subdural hematoma and its recent increase may be related to increased use of anticoagulants in long-term hemodialysis patients.

Suprasellar osteolipoma : Case report

BACKGROUND Osteolipomas are distinguished from other intracranial lipomas by their arrangement of central adipose and peripheral osseous tissues and by characteristically arising in the suprasellar/interpeduncular region. METHODS We report computed tomography (CT), magnetic resonance imaging (MRI), and pathology findings from this 34-year-old man who underwent surgical removal of this benign lesion. RESULTS This case displays the distinctive histopathology that has been reported in 13 of 31 (42%) lipomas in this region. In contrast, ossification of lipomas at other intracranial sites is relatively rare. CONCLUSIONS Ossification should be expected in many suprasellar/interpeduncular lipomas, and osteolipoma should be included in the radiologic differential diagnosis of fat-intensity masses with calcification in this region.