✓ The purpose of this investigation was to study the effects of a selective thromboxane A2 (TXA2) synthetase inhibitor (TSI) upon the evolution of cerebral infarction in the cat. Adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion for 4 hours followed by a 2-hour period of reperfusion before sacrifice. Ten cats received 3 mg/kg TSI intravenously immediately before, and 10 cats received 3 mg/kg TSI intravenously immediately after MCA occlusion. Ten cats were used as controls receiving no treatment. The bleeding time was determined at baseline and at the end of each experiment. Electroencephalographic (EEG) recordings were obtained before and after MCA clipping and MCA release, and at hourly intervals thereafter. Regional cerebral blood flow (rCBF) was measured using the xenon-133 (133Xe) clearance technique before and after MCA occlusion, after MCA reopening, and before terminating each experiment. Thirty minutes before each cat was sacrificed, Evans blue dye and sodium fluorescein were given intravenously. The animals were then perfused with colloidal carbon and the brains removed and evaluated for midline shift, Evans blue dye and sodium fluorescein extravasation, carbon staining, and infarct size. The bleeding time, arterial blood pressure, rCBF changes, brain swelling, and vital dye extravasation were not statistically different between the three treatment groups. The EEG changes, carbon staining, and infarct size differences between the three groups also failed to reach statistical significance, but there was a suggestion that these parameters were adversely affected in the cats pretreated with TSI. Ten additional cats undergoing MCA occlusion and reperfusion were used for pharmacological studies. Five of them received 3 mg/kg TSI intravenously immediately after MCA occlusion, and serial drug and thromboxane B2 (TXB2) levels (a stable metabolite of TXA2) were determined. Another five cats were not treated and serial TXB2 levels were obtained. Production of TXA2 was inhibited by 95% in cats receiving TSI. In conclusion, thromboxane synthetase inhibition failed to modify favorably the evolution of cerebral infarction. When TSI was given before MCA occlusion, cerebral infarction tended to be more extensive.
Nazih A. Moufarrij, John R. Little, Victor Skrinska, Fred V. Lucas, John P. Latchaw, Robert M. Slugg and Ronald P. Lesser
Alois A. Obwegeser, Ryan J. Uitti, John A. Lucas, Robert J. Witte, Margaret F. Turk and Robert E. Wharen Jr.
Object. The authors studied neuropsychological performance following microelectrode-guided posteroventral pallidotomy in patients with Parkinson's disease (PD) and evaluated correlations with presurgical and surgical factors.
Methods. Neuropsychological changes 3 months (43 patients) and 12 months (27 patients) after microelectrode-guided pallidotomy for PD are reported in a series of 44 consecutive patients with the disease, who improved neurologically, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the “off” (p < 0.001) and best “on” (p < 0.001) states.
Findings of the vocabulary subtest of the Wechsler Adult Intelligence Scale—Revised (p < 0.01), Letter Fluency (p < 0.001), Verbal Fluency for semantic categories (p < 0.001), and the Wisconsin Card Sorting Test (p < 0.01) showed a significant decline in neuropsychological performance in patients 3 months after undergoing left-sided pallidotomy. Impairment in the language domain (semantic fluency) persisted at the 12-month follow-up examination (p < 0.01). Visual memory improved after right-sided pallidotomies (p < 0.01 after 3 months), with a nonsignificant trend toward persistent improvement 1 year postsurgery (p < 0.02 after 12 months). Preoperative semantic fluency was influenced by patient age (p < 0.001) and by the width of the third ventricle (p < 0.05), as measured by magnetic resonance imaging.
A regression model revealed that semantic fluency 3 months postoperatively was significantly affected by the baseline score (p < 0.001), side of surgery (p < 0.001), handedness (p < 0.01), and patient age (p < 0.05). However, postoperative lesion volume, lesion location, number of tracks, number of lesions, distance from anatomical landmarks, or UPDRS score did not significantly contribute to neuropsychological outcome.
Conclusions. Neuropsychological changes in a cohort of patients with PD who underwent pallidotomy and experienced excellent clinical benefits and minimum postoperative complications, emphasize the importance of neuropsychological examinations and further investigation of predictive factors.
Jerzy L. Slowinski, John D. Putzke, Ryan J. Uitti, John A. Lucas, Margaret F. Turk, Bruce A. Kall and Robert E. Wharen
The object of this study was to assess the results of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for management of advanced Parkinson disease (PD).
A clinical series of 24 patients (mean age 71 years, range 56–80 years) with medically intractable PD, who were undergoing unilateral magnetic resonance imaging–targeted, electrophysiologically guided STN DBS, completed a battery of qualitative and quantitative outcome measures preoperatively (baseline) and postoperatively, using a modified Core Assessment Program for Intracerebral Transplantations protocol.
The mean follow-up period was 9 months. Statistically significant improvement was observed in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and scores for axial motor features (19%), contralateral tremor (88%), rigidity (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's Disease Quality of Life questionnaire score (15%) in the on-stimulation state compared with baseline. Ipsilateral symptoms improved by approximately 15% or less. Performance on the Purdue pegboard test improved in the contralateral hand in the on-stimulation state compared with the off-stimulation state (38%, p < 0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018). Neuropsychological tests revealed an improvement in mental flexibility and a trend toward reduced letter fluency. There were no permanent surgical complications. Of the 16 participants with symmetrical disease, five required implantation of the DBS unit on the second side.
Unilateral STN DBS is an effective and safe treatment for selected patients with advanced PD. Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as well as quality of life, reduces requirements for medication, and possibly enhances mental flexibility. This method of surgical treatment may be associated with a reduced risk and may provide an alternative to bilateral STN DBS for PD, especially in older patients or patients with asymmetry of parkinsonism.
Ben A. Strickland, Joshua Lucas, Brianna Harris, Edwin Kulubya, Joshua Bakhsheshian, Charles Liu, Bozena Wrobel, John D. Carmichael, Martin Weiss and Gabriel Zada
Cerebrospinal fluid (CSF) rhinorrhea is among the most common complications following transsphenoidal surgery for sellar region lesions. The aim of this study was to review the authors’ institutional experience in identifying, repairing, and treating CSF leaks associated with direct endonasal transsphenoidal operations.
The authors performed a retrospective review of cases involving surgical treatment of pituitary adenomas and other sellar lesions at the University of Southern California between December 1995 and March 2016. Inclusion criteria included all pathology of the sellar region approached via a direct microscopic or endoscopic endonasal transsphenoidal approach. Demographics, pathology, intraoperative and postoperative CSF leak rates, and other complications were recorded and analyzed. A literature review of the incidence of CSF leaks associated with the direct endonasal transsphenoidal approach to pituitary lesions was conducted.
A total of 1002 patients met the inclusion criteria and their cases were subsequently analyzed. Preoperative diagnoses included pituitary adenomas in 855 cases (85.4%), Rathke’s cleft cyst in 94 (9.4%), and other sellar lesions in 53 (5.2%). Lesions with a diameter ≥ 1 cm made up 49% of the series. Intraoperative repair of an identified CSF leak was performed in 375 cases (37.4%) using autologous fat, fascia, or both. An additional 92 patients (9.2%) underwent empirical sellar reconstruction without evidence of an intraoperative CSF leak. Postoperative CSF leaks developed in 26 patients (2.6%), including 13 (1.3% of the overall group) in whom no intraoperative leak was identified. Among the 26 patients who developed a postoperative CSF leak, 13 were noted to have intraoperative leak and underwent sellar repair while the remaining 13 did not have an intraoperative leak or sellar repair. No patients who underwent empirical sellar repair without an intraoperative leak developed a postoperative leak. Eight patients underwent additional surgery (0.8% reoperation rate) for CSF leak repair, and 18 were successfully treated with lumbar drainage or lumbar puncture alone. The incidence of postoperative CSF rhinorrhea in this series was compared with that in 11 other reported series that met inclusion criteria, with incidence rates ranging between 0.6% and 12.1%.
In this large series, half of the patients who developed postoperative CSF rhinorrhea had no evidence of intraoperative CSF leakage. Unidentified intraoperative CSF leaks and/or delayed development of CSF fistulas are equally important sources of postoperative CSF rhinorrhea as the lack of employing effective CSF leak repair methods. Empirical sellar reconstruction in the absence of an intraoperative CSF leak may be of benefit following resection of large tumors, especially if the arachnoid is thinned out and herniates into the sella.
Corbin A. Helis, Emory McTyre, Michael T. Munley, J. Daniel Bourland, John T. Lucas Jr., Christina K. Cramer, Stephen B. Tatter, Adrian W. Laxton and Michael D. Chan
A small subset of patients with trigeminal neuralgia (TN) will experience bilateral symptoms. Treatment in these patients is controversial because the population is heterogeneous and patients may have nonvascular etiologies of their pain. This study reports treatment outcomes in the largest cohort of patients with bilateral TN who have undergone Gamma Knife radiosurgery (GKRS) to date.
A retrospective chart review identified 51 individual nerves in 34 patients with bilateral TN who were treated with GKRS at the authors’ institution between 2001 and 2015, with 12 nerves in 11 patients undergoing repeat GKRS for recurrent or persistent symptoms. Long-term follow-up was obtained by telephone interview. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain scale, with BNI IIIb or better considered a successful treatment.
There was sufficient follow-up to determine treatment outcomes for 48 individual nerves in 33 patients. Of these nerves, 42 (88%) achieved at least BNI IIIb pain relief. The median duration of pain relief was 1.9 years, and 1-, 3-, and 5-year pain relief rates were 64%, 44%, and 44%, respectively. No patients experienced bothersome facial numbness, and 1 case of anesthesia dolorosa and 2 cases of corneal dryness were reported. Patients with a history of definite or possible multiple sclerosis were significantly more likely to experience BNI IV–V relapse. There was no statistically significant difference in treatment outcomes between patients in this series versus a large cohort of patients with unilateral TN treated at the authors’ institution. There was sufficient follow-up to determine treatment outcomes for 11 individual nerves in 10 patients treated with repeat GKRS. Ten nerves (91%) improved to at least BNI IIIb after treatment. The median duration of pain relief was 2.8 years, with 1-, 3-, and 5-year rates of pain relief of 79%, 53%, and 53%, respectively. There was no statistically significant difference in outcomes between initial and repeat GKRS. One case of bothersome facial numbness and 1 case of corneal dryness were reported, with no patients developing anesthesia dolorosa with retreatment.
GKRS is a safe, well-tolerated treatment for patients with medically refractory bilateral TN. Efficacy of treatment appears similar to that in patients with unilateral TN. GKRS can be safely repeated in this population if necessary.
Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan McShane, John Lee, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Mohana Rao Patibandla, Christopher P. Cifarelli, Gabriella Paisan, John A. Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan
In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome.
Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose.
A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5–18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration.
GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.
Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan J. McShane, John Lee, Mohana Rao Patibandla, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Christopher P. Cifarelli, Gabriella Paisan, John Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Nanthiya Sujijantarat, Charles Matouk, Veronica Chiang, Judith Hess, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan
The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).
Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.
A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2–3 dAVFs and Borden type 2–3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).
Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.