The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Pre-oxygenation with facemask oxygen vs high-flow nasal oxygen vs high-flow nasal oxygen plus mouthpiece: a randomised controlled trial.

High-flow nasal oxygen used before and during apnoea prolongs time to desaturation at induction of anaesthesia. It is unclear how much oxygenation before apnoea prolongs this time. We randomly allocated 84 participants to 3 minutes of pre-oxygenation by one of three methods: 15 l.min-1 by facemask; 50 l.min-1 by high-flow nasal cannulae only; or 50 l.min-1 by high-flow nasal cannulae plus 15 l.min-1 by mouthpiece. We then anaesthetised and intubated the trachea of 79 participants and waited for oxygen saturation to fall to 92%. Median (IQR [range]) times to desaturate to 92% after pre-oxygenation with facemask oxygen, high-flow nasal oxygen only and high-flow nasal oxygen with mouthpiece, were: 309 (208-417 [107-544]) s; 344 (250-393 [194-585]) s; and 386 (328-498 [182-852]) s, respectively, p = 0.014. Time to desaturation after facemask pre-oxygenation was shorter than after combined nasal and mouthpiece pre-oxygenation, p = 0.006. We could not statistically distinguish high-flow nasal oxygen without mouthpiece from the other two groups for this outcome. Median (IQR [range]) arterial oxygen partial pressure after 3 minutes of pre-oxygenation by facemask, nasal cannulae and nasal cannulae plus mouthpiece, was: 49 (36-61 [24-66]) kPa; 57 (48-62 [30-69]) kPa; and 61 (55-64 [36-72]) kPa, respectively, p = 0.003. Oxygen partial pressure after 3 minutes of pre-oxygenation with nasal and mouthpiece combination was greater than after facemask pre-oxygenation, p = 0.002, and after high-flow nasal oxygen alone, p = 0.016. We did not reject the null hypothesis for the pairwise comparison of facemask pre-oxygenation and high-flow nasal pre-oxygenation, p = 0.14.

Cardiac risk assessment before the use of stimulant medications in children and youth: A joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and pediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac subspecialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Cardiac risk assessment before the use of stimulant medications in children and youth.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and paediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac sub-specialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations.

OBJECTIVES: To determine the effect of stereotactic radiosurgery on seizure outcomes for patients with intracerebral arteriovenous malformations (AVM). METHODS: Between May 1990 and December 1998, 65 patients with a history of single or recurrent seizures underwent AVM radiosurgery, had more than 1 year of follow-up, and sufficient data to record an Engel seizure frequency score. The authors reviewed their records and updated clinical information when necessary with direct patient contact. Follow-up ranged from 12 to 144 months (median, 48 months). Seizure frequency was compared before and after radiosurgery with the Engel Seizure Frequency Scoring System. RESULTS: Overall, 26 patients (51%) were seizure-free (aura-free) after radiosurgery at 3-year follow-up; 40 patients (78%) had an excellent outcome (non-disabling simple partial seizures only) at 3-year follow-up. Factors associated with seizure-free or excellent outcomes include a low seizure frequency score (<4) before radiosurgery and smaller size and diameter AVM. Twenty-three patients had intractable partial epilepsy prior to treatment. Twelve (52%) of 23 and 11 of 18 (61%) patients with medically intractable partial epilepsy had excellent outcomes at years 1 and 3. CONCLUSION: Overall, stereotactic radiosurgery improves seizure outcomes in the majority of patients and more than half of the patients with medically intractable partial epilepsy had an excellent seizure outcome after radiosurgery.

High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction.

OBJECTIVE: Stereotactic radiosurgery is being used with more frequency in the management of patients with trigeminal neuralgia. To improve facial pain outcomes, many centers have increased the prescribed radiation dose to the trigeminal nerve. METHODS: Between April 1997 and December 1999, 68 patients underwent radiosurgery for trigeminal neuralgia with use of the Leksell gamma knife (Elekta Instruments, Norcross, GA) and a single 4-mm isocenter of radiation. Twenty-seven patients (40%) received 70 Gy (low dose) of irradiation and 41 patients (60%) received 90 Gy (high dose). The groups were similar with regard to age, sex, duration of pain, number of prior surgeries, and preexisting trigeminal deficits. The primary facial pain outcomes for analysis were excellent (pain-free, no medications) and good (pain-free, reduced medications). The mean length of follow-up after radiosurgery was 14.4 months (range, 2-36 mo). RESULTS: At last follow-up examination, 11 (41%) of the 27 patients with low-dose radiosurgery remained pain-free compared with 25 (61%) of the 41 patients with high-dose radiosurgery (P = 0.17). Additional surgery was performed in 12 low-dose patients (44%) and 8 high-dose patients (20%) (P = 0.05). High-dose radiosurgery was associated with an increased rate of permanent trigeminal nerve dysfunction (54% versus 15%, P = 0.003). Bothersome dysesthesias occurred in 13 high-dose patients (32%), whereas only 1 low-dose patient had this complication (P = 0.01). Three high-dose patients (8%) developed corneal numbness after radiosurgery. Pain recurred with more frequency in patients not developing trigeminal nerve dysfunction after radiosurgery (9 of 22 patients, 41 %) compared with those who sustained facial numbness, paresthesias, or dysesthesias (4 of 27 patients, 15%); however, the difference was not statistically significant (P = 0.08). CONCLUSION: Higher doses of radiation may correlate with better facial pain outcomes after radiosurgery for trigeminal neuralgia. However, the incidence of significant trigeminal nerve dysfunction is markedly increased after radiosurgery for patients receiving high-dose radiosurgery. Because of the nonselective nature of this ablative technique, dose prescription should be limited to less than 90 Gy.

Results of combined stereotactic radiosurgery and transarterial embolization for dural arteriovenous fistulas of the transverse and sigmoid sinuses.

OBJECT: Most dural arteriovenous fistulas (DAVFs) of the transverse and sigmoid sinuses do not have angiographically demonstrated features associated with intracranial hemorrhage and, therefore, may be treated nonsurgically. The authors report their experience using a staged combination of radiosurgery and transarterial embolization for treating DAVFs involving the transverse and sigmoid sinuses. METHODS: Between 1991 and 1998, 25 patients with DAVFs of the transverse and/or sigmoid sinuses were treated using stereotactic radiosurgery; 22 of these patients also underwent transarterial embolization. Two patients were lost to follow-up review. Clinical data, angiographic findings, and follow-up records for the remaining 23 patients were collected prospectively. The mean duration of clinical follow up after radiosurgery was 50 months (range 20-99 months). The 18 women and five men included in this series had a mean age of 57 years (range 33-79 years). Twenty-two (96%) of 23 patients presented with pulsatile tinnitus as the primary symptom; two patients had experienced an earlier intracerebral hemorrhage (ICH). Cognard classifications of the DAVFs included the following: I in 12 patients (52%), IIa in seven patients (30%), and III in four patients (17%). After treatment, symptoms resolved (20 patients) or improved significantly (two patients) in 96% of patients. One patient was clinically unchanged. No patient sustained an ICH or irradiation-related complication during the follow-up period. Seventeen patients underwent follow-up angiographic studies at a mean of 21 months after radiosurgery (range 11-38 months). Total or near-total obliteration (> 90%) was seen in 11 patients (65%), and more than a 50% reduction in six patients (35%). Two patients experienced recurrent tinnitus and underwent repeated radiosurgery and embolization at 21 and 38 months, respectively, after the first procedure. CONCLUSIONS: A staged combination of radiosurgery and transarterial embolization provides excellent symptom relief and a good angiographically verified cure rate for patients harboring low-risk DAVFs of the transverse and sigmoid sinuses. This combined approach is a safe and effective treatment strategy for patients without angiographically determined risk factors for hemorrhage and for elderly patients with significant comorbidities.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVE: To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODS: One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTS: Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSION: Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

Stereotactic radiosurgery for tumor-related trigeminal pain.

OBJECTIVE: Between 1 and 6% of patients who are diagnosed with facial pain syndromes have tumors that involve the trigeminal nerve. We report the effects of stereotactic radiosurgery on tumor-related trigeminal pain. METHODS: We reviewed results, from a prospective database, for 24 consecutive patients with cranial base tumors and either trigeminal neuralgia (n = 9) or painful trigeminal neuropathy (n = 15) who underwent stereotactic radiosurgery during an 8-year period. The tumor was the radiosurgical target for these patients (not the trigeminal nerve or ganglion). The median clinical follow-up period after radiosurgery was 45 months (range, 12-90 mo); the median neuroimaging follow-up period was 36 months (range, 5-86 mo). RESULTS: There were 20 women and 3 men, with an average age of 57 years (range, 33-79 yr). One patient had bilateral facial pain and underwent staged radiosurgery. Pathological classification indicated 16 meningiomas and 8 malignant cranial base tumors (adenoid cystic carcinoma, n = 6; squamous cell carcinoma, n = 2). Twelve of 24 patients (50%) were initially free of pain, and another 11 patients (46%) reported that they experienced significant improvements in their trigeminal pain syndromes after radiosurgery. The tumor histological type, quality of facial pain, preexisting facial numbness, and marginal and maximal radiation doses were not related to postradiosurgical facial pain outcomes. Three patients with malignant cranial base carcinomas developed recurrent facial pain, 1 to 9 months after radiosurgery, which was related to tumor progression outside the irradiated volume. One patient (4%) developed new partial V2 numbness after radiosurgery. CONCLUSION: Radiosurgery proved to be effective in improving tumor-related trigeminal pain for the majority of patients with either benign or malignant cranial base tumors. Recurrence of trigeminal pain is frequent for patients with malignant cranial base carcinomas and is related to tumor progression.

Stereotactic radiosurgery for recurrent ependymoma.

BACKGROUND: Patients with recurrent intracranial ependymomas were evaluated to assess local control, overall survival, and complications from stereotactic radiosurgery (SRS). METHODS: Twelve patients (with a total of 17 tumors) with recurrent ependymoma underwent SRS. Local failure was defined as tumor progression within the prescription isodose volume, and marginal failure was defined as tumor progression adjacent to the SRS prescription isodose volume. Tumor progression away from the prescription volume was considered distant failure. Eleven of the 12 patients had undergone previous resection and external beam radiation therapy (46-56 Grays [Gy]; median, 54 Gy) before radiosurgery, and 1 patient had failure after complete resection alone. Age at SRS ranged from 5-56 years (median, 29 years). Three patients were female. The marginal tumor dose was 12-24 Gy (median, 18 Gy). One to 14 isocenters (median, 4 isocenters) were utilized to irradiate volumes of 0.3-15.5 cm(3) (median, 3.2 cm(3)). RESULTS: The duration of follow-up ranged from 2.5-60 months (median, 22.5 months). The median overall survival after SRS was 3.4 years (range, 1.4-5 years). In-field local control was achieved in 14 of the 17 tumor sites and estimated 3-year local control was 68%. There were two in-field failures and one marginal failure. Distant failure occurred in two patients. Two patients developed treatment-related complications after SRS. CONCLUSIONS: SRS provides good local tumor control for patients with recurrent intracranial ependymoma and may have a favorable impact on survival. SRS should be evaluated more extensively in the initial treatment of patients with ependymoma to minimize local failure after surgical management.

Results of repeated gamma knife radiosurgery for medically unresponsive trigeminal neuralgia.

OBJECT: Gamma knife radiosurgery (GKS) is being increasing performed in the management of patients with medically unresponsive trigeminal neuralgia. The authors report the results of repeated GKS in patients with recurrent facial pain after their initial procedure. METHODS: Between April 1997 and December 1999, 100 patients with idiopathic trigeminal neuralgia underwent GKS at the authors' center. To date, 26 patients have required additional surgery because GKS provided no significant pain relief (15 patients) or because they had recurrent facial pain (11 patients). Ten of these patients underwent repeated GKS at a median of 13 months (range 4-27 months). All patients undergoing repeated GKS had a significant reduction in their facial pain after the first procedure (eight were pain free); no patient developed facial numbness or paresthesias. Initially, nine of 10 patients became pain free 1 to 4 weeks following repeated GKS. At a median follow up of 15 months (range 3-32 months), eight patients remained pain free and required no medication. All eight patients with persistent pain relief developed minor neurological dysfunction after repeated GKS (six patients had facial numbness and two had paresthesias). CONCLUSIONS: Repeated GKS can be associated with a high rate of pain relief for patients with trigeminal neuralgia who experienced a significant reduction in their facial pain after the first operation. However, every patient with sustained pain relief after the second operation also developed some degree of trigeminal dysfunction. These findings of improved pain relief for patients who develop facial numbness after GKS for trigeminal neuralgia support the experimental data currently available.

Stereotactic radiosurgery and particulate embolization for cavernous sinus dural arteriovenous fistulae.

OBJECTIVE: To evaluate the safety and efficacy of stereotactic radiosurgery, either with or without transarterial embolization, in the treatment of patients with dural arteriovenous fistulae (DAVFs) of the cavernous sinus. METHODS: We reviewed the findings, from a prospectively established database, for 20 patients with cavernous sinus DAVFs who were treated with either radiosurgery alone (n = 7) or radiosurgery and transarterial embolization (n = 13) in a 7-year period. The median follow-up period after radiosurgery was 36 months (range, 4-59 mo). RESULTS: Nineteen of 20 patients (95%) experienced improvement of their clinical symptoms. Fourteen of 15 patients (93%) experienced either total (n = 13) or nearly total (n = 1) obliteration of their DAVFs, as documented by angiography performed a median of 12 months after radiosurgery. No patient experienced a recurrence of symptoms after angiography showed DAVF obliteration. Two patients developed new neurological deficits after embolization procedures. One patient exhibited temporary aphasia secondary to a venous infarction; another patient exhibited permanent VIth cranial nerve weakness related to acute cavernous sinus thrombosis. Two patients experienced recurrent symptoms and underwent repeat transarterial embolization at 7 and 12 months; both patients achieved clinical and angiographic cures (5 and 10 mo later, respectively). One patient experienced recurrent visual symptoms and underwent transvenous embolization 4 months after radiosurgery. CONCLUSION: Staged radiosurgery and transarterial embolization provided both rapid symptom relief and long-term cures for patients with cavernous sinus DAVFs. Radiosurgery alone was effective for patients with DAVFs whose arterial supply was not accessible via a transarterial approach, although the time course of symptom improvement was longer, compared with patients who also underwent embolization.

A multi-institutional analysis of complication outcomes after arteriovenous malformation radiosurgery.

PURPOSE: To better understand radiation complications of arteriovenous malformation (AVM) radiosurgery and factors affecting their resolution. METHODS AND MATERIALS: AVM patients (102/1255) who developed neurological sequelae after radiosurgery were studied. The median AVM marginal dose (Dmin) was 19 Gy (range: 10-35). The median volume was 5.7 cc (range: 0.26-143). Median follow-up was 34 months (range: 9-140). RESULTS: Complications consisted of 80/102 patients with evidence of radiation injury to the brain parenchyma (7 also with cranial nerve deficits, 12 also with seizures, 5 with cyst formation), 12/102 patients with isolated cranial neuropathies, and 10/102 patients with only new or worsened seizures. Severity was classified as minimal in 39 patients, mild in 40, disabling in 21, and fatal in 2 patients. Symptoms resolved completely in 42 patients for an actuarial resolution rate of 54% +/- 7% at 3 years post-onset. Multivariate analysis identified significantly greater symptom resolution in patients with no prior history of hemorrhage (p = 0.01, 66% vs. 41%), and in patients with symptoms of minimal severity: headache or seizure as the only sequelae of radiosurgery (p < 0.0001, 88% vs. 34%). CONCLUSION: Late sequelae of radiosurgery manifest in varied ways. Further long-term studies of these problems are needed that take into account symptom severity and prior hemorrhage history.

The Mayo Clinic gamma knife experience: indications and initial results.

OBJECTIVE: To review the results and expectations of contemporary stereotactic radiosurgery. MATERIAL AND METHODS: We conducted a retrospective analysis of 1,033 consecutive patients who underwent gamma knife radiosurgery at Mayo Clinic Rochester between January 1990 and January 1998. RESULTS: The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. Of 97 patients with arteriovenous malformations who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of the vascular malformation. Of 209 patients who underwent radiosurgery for benign tumors (schwannomas, meningiomas, or pituitary adenomas) and had radiologic studies after 2 years or more of follow-up, tumor growth control was noted in 200 (96%). Tumor growth was also controlled in 90% of brain metastatic lesions at a median of 7 months after radiosurgery. Of 20 patients with trigeminal neuralgia and follow-up for more than 2 months, 14 (70%) were free of pain after radiosurgery. CONCLUSION: Radiosurgery is a safe and effective management strategy for a wide variety of intracranial disorders. Use of radiosurgical treatment should continue to increase as more data become available on the long-term results of this procedure.

Decrease in cranial nerve complications after radiosurgery for acoustic neuromas: a prospective study of dose and volume.

PURPOSE: To determine whether tumor control can be maintained, and cranial nerve complications decreased by reducing the radiosurgical dose to acoustic neuromas. METHODS AND MATERIALS: Forty-two consecutive patients with acoustic neuromas were treated prospectively using an initial standard-dose protocol in which the tumor-margin dose (50% isodose) was 20, 18, and 16 Gy for tumor diameters < or =2 cm, 2.1-3 cm, and 3.1-4 cm, respectively. After analysis of tumor control and complications, the next 40 patients were treated using a reduced-dose protocol in which the tumor-margin dose was 16, 14, and 12 Gy for tumor volumes < or =4.2 cm3, 4.2-14.1 cm3, and > or =14.1 cm3, respectively. RESULTS: Median follow-up was 2.3 years (range 0.1-6) for 80 of 82 patients. The actuarial incidence (Kaplan-Meier) of facial neuropathy at 2 years was 38% (95% confidence interval [CI], 23-53%) for the standard-dose protocol and 8% (95% CI, 0-17%) for the reduced-dose protocol (p = 0.006). Univariate analysis revealed an association between risk of facial neuropathy and use of CT planning, higher radiosurgical dose, and neurofibromatosis, type 2. Multivariate analysis revealed that the only factor associated with increased risk of post-treatment facial neuropathy was a tumor margin dose > or =18 Gy. The incidence of trigeminal neuropathy at 2 years was 29% (95% CI, 15-43%) for the standard-dose protocol and 15% (95% CI, 3-27%) for the reduced-dose protocol (p = 0.17). Univariate analysis revealed an association between maximal tumor diameter and increased risk of trigeminal neuropathy; multivariate analysis revealed no additional statistically significant associations between tumor and dosimetric and patient characteristics and risk of trigeminal neuropathy. Two tumors in the standard-dose protocol required salvage surgery for progression. To date, no tumor in the reduced-dose protocol has shown progression. CONCLUSION: Our analysis suggests that a tumor margin dose of > or =18 Gy is the most significant risk factor for facial nerve complications after acoustic neuroma radiosurgery. Patients receiving a minimal tumor dose of < or =16 Gy are at significantly lower risk for permanent facial neuropathy after radiosurgery. Longer follow-up is required before definitive conclusions can be made about the ultimate rate of tumor control using reduced radiosurgical doses.

Nefiracetam prevents propofol-induced anterograde and retrograde amnesia in the rodent without compromising quality of anesthesia.

BACKGROUND: Propofol is a short-acting intravenous anesthetic agent. However, cognitive function remains depressed for several hours thereafter. We have evaluated the ability of nefiracetam, a novel cognition-enhancing agent, to alleviate propofol-induced amnesia in a rodent model of learning. METHODS: Rats were trained in a one-trial, step-through, light-dark passive avoidance paradigm. Propofol (10 and 75 mg/kg) was administered by the intraperitoneal route at 15 min before training and separately at increasing times in the immediate 0-6 h post-training period (100 and 150 mg/kg). Nefiracetam, 9 mg/kg, was administered by the intraperitoneal route 1 h before training. Animals were tested for recall at the 12 h post-training time, and after their killing, immunocytochemistry was used to determine the increase in hippocampal neuronal polysialylation, an event associated with memory consolidation. Induction and duration of anesthesia induced by propofol was determined using tail pinch and pedal withdrawal reflexes. RESULTS: Propofol-induced anterograde amnesia occurred in a dose-dependent manner. Induction of retrograde amnesia required a higher dose of propofol, which anesthetized the animals and was effective only in the immediate 3-h post-training period. In the absence of any evident effect on the onset or duration of anesthesia, nefiracetam prevented both forms of propofol-induced amnesia and preserved the learning-associated changes of neuronal polysialylation state. CONCLUSIONS: The ability of nefiracetam to prevent propofol-induced anterograde and retrograde amnesia is proposed to be indirect and to result from modulation of gene transcription in a manner that initiates a cascade of events involving protein synthesis leading to synaptic growth associated with the formation of the long-term memory trace.

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors.

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.

Stereotactic radiosurgery for glomus jugulare tumors: a preliminary report.

PURPOSE: This study was conducted to evaluate the toxicity and efficacy of stereotactic radiosurgery treatment of glomus jugulare tumors. METHODS AND MATERIALS: Between March 1990 and January 1995, nine patients underwent stereotactic radiosurgery with the Leksell Gamma Knife Unit for glomus jugulare tumors. Previous treatment had failed in four patients. The seven female and two male patients had a median age of 67 years. RESULTS: The median time from stereotactic radiosurgery to the most recent clinical follow-up was 20 months (range 7-65 months). Subjectively, 7 of 9 patients noted a decrease in the intensity of their symptoms. Objectively, 8 of 9 tumors remained stable in size by serial magnetic resonance imaging scans and one was smaller. There was no acute or chronic toxicity. CONCLUSION: This early experience suggests that stereotactic radiosurgery is a promising treatment for glomus jugulare tumors.

The role of radiosurgery and particulate embolization in the treatment of dural arteriovenous fistulas.

Over the past 5 years 29 patients with dural arteriovenous fistulas (AVFs) were treated by the authors using the Leksell radiosurgical gamma knife unit. Within 2 days after radiosurgery, 17 patients with AVFs that exhibited retrograde pial or cortical venous drainage (12 patients) and/or produced intractable bruit (eight patients) underwent particulate embolization of external carotid feeding vessels. The rationale for this treatment strategy was that radiosurgery was expected to cause obliteration of most fistulas after 12 to 36 months. In patients with bruit, ocular symptoms, or in those at risk for hemorrhage, treatment with embolization after radiosurgery kept the fistulas angiographically visible for radiosurgical targeting yet offered palliation of symptoms and temporary, partial protection from hemorrhage during the latency period. In 12 patients, preobliteration embolization immediately reduced (10 patients) or eliminated (two patients) retrograde pial venous drainage. To date, no lesion has hemorrhaged after treatment. Angiography 1 to 3 years posttreatment in 18 patients showed total obliteration of 13 fistulas (72%) and partial obliteration of five (28%). Radiosurgery, followed by embolization when retrograde pial venous drainage, intractable bruit, and/or major external carotid artery supply is present, appears to be a promising treatment for selected patients with symptomatic dural AVFs.