Cook detachable coil embolization of a symptomatic, isolated orbital arteriovenous fistula via a superior ophthalmic vein approach.

Isolated arteriovenous fistulas of the posterior orbit occur with exceptional rarity, and their evaluation and management are not well characterized. We describe the clinical presentation and treatment of a spontaneous arteriovenous fistula of the right posterior orbit via a superior ophthalmic vein approach for embolization using platinum detachable coils.

Long term visual and neurological prognosis in patients with treated and untreated cavernous sinus aneurysms.

OBJECTIVE: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Oculomotor function in the rhesus monkey after deafferentation of the extraocular muscles.

The function of extraocular muscle proprioception in the control of eye movements remains uncertain. In this study, we examined the effect of bilateral proprioceptive deafferentation of the extraocular muscles on eye movements in two rhesus monkeys. Before and after deafferentation, we analyzed baseline ocular alignment, saccades, pursuit, and vestibular eye movements. We also examined visually mediated adaptation of ocular alignment, saccades, and pursuit. Deafferentation of the eye muscles did not affect baseline ocular motor control, either acutely or over a 5-week period of study. Furthermore, visually mediated adaptation of the eye movement subtypes was also unaffected by deafferentation. These results suggest that ocular proprioception in primates is not used in the immediate, on-line control of eye movements and does not interact with visual cues in the adaptive modification of ocular motor function. We conclude that the efferent command (efference copy) provides sufficient information about eye kinematics to the brain for accurate eye movement control in normal monkeys, and that this information is modified by visual feedback independently of proprioception. We hypothesize that proprioception may be used to calibrate the efference copy during development and in response to perturbations by signaling potential mismatches between eye movement information derived from the efferent command and the actual motion of the eye transduced by the proprioceptive organs.

Lack of evidence for an association between neurofibromatosis type I and intracranial aneurysms: autopsy study and review of the literature.

BACKGROUND AND PURPOSE: Neurofibromatosis type I (NF1) is an autosomal dominant, hereditary, neurocutaneous syndrome purported to be associated with intracranial aneurysms. To study the relationship between NF1 and intracranial aneurysms, we have analyzed all intracranial autopsies of NF1 patients performed at our institution from 1889 to 1999 and analyzed all intracranial aneurysm cases at our institution from 1990 to 1999 in an attempt to identify patients with NF1. In addition, we have reviewed published clinical series of NF1 patients. METHODS: The autopsy database at our institution, which contains 50 000 cases from 1889 to 1999, was searched to identify NF1 patients, and the results of these autopsies were reviewed. The prevalence of intracranial aneurysms in these NF1 patients was compared with the prevalence of intracranial aneurysms in our hospital's autopsy population and with the published prevalence of intracranial aneurysms in the general population. To identify patients with intracranial aneurysms and NF1, our institution's intracranial aneurysm database was searched for patients with clinical manifestations of NF1. Published clinical series of NF1 patients were identified through searches of the literature. RESULTS: None of the 25 autopsy patients with NF1 had an intracranial aneurysm. None of the 925 patients treated for intracranial aneurysms were affected by NF1. A review of the literature identified 8 comprehensive clinical studies, all of which failed to document any relationship between NF1 and intracranial aneurysms. CONCLUSIONS: The autopsy prevalence of no NF1 patients with intracranial aneurysms out of 25 is not different from the prevalence of intracranial aneurysms in the general autopsy population. In addition, no patients treated for intracranial aneurysms at this institution had NF1. These findings are supported by the observation that an association between NF1 and intracranial aneurysms has never been identified in 8 large clinical studies of NF1 patients. We conclude that there is a lack of evidence for any association between NF1 and intracranial aneurysms.

Intra-arterial papaverine-induced seizures: case report and review of the literature.

BACKGROUND: Microcatheter-guided intra-arterial (IA) papaverine infusion in conjunction with balloon angioplasty is an available therapy for patients with symptomatic vasospasm after subarachnoid hemorrhage (SAH) that is refractory to hypertensive, hypervolemic therapy. However, side effects and complications have been reported in association with its use. CASE DESCRIPTION: We report on a patient who developed symptomatic vasospasm after subarachnoid hemorrhage due to rupture of a left terminal internal carotid artery (ICA) saccular aneurysm. Seven days after the hemorrhage and 4 days after surgical clipping, the patient developed aphasia and right hemiparesis due to vasospasm, which was refractory to maximal medical treatment with volume and blood pressure elevation. Cerebral angiography identified severe narrowing of distal ICA and proximal middle cerebral artery segments bilaterally. These findings partially resolved after balloon angioplasty. However, after 300 mg of IA papaverine, the patient developed generalized convulsions. This occurred despite therapeutic serum levels of phenytoin. Twenty-four hours later, after brief neurologic improvement, recurrent neurologic deficits prompted repeat papaverine administration. Seizures again occurred after the administration of 240 mg of IA papaverine and prevented administration of the full dose. The patient did not develop further seizures and her neurologic deficits continue to resolve. CONCLUSIONS: IA papaverine-induced seizures are infrequently reported. This potential complication should be considered when papaverine administration is entertained in the treatment of anterior circulation refractory symptomatic vasospasm after SAH.

Cocaine use is an independent risk factor for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Although acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH), the prevalence of vasospasm and the clinical outcome of patients experiencing aSAH associated with cocaine exposure are unclear. We have analyzed this patient population in our institution to address these issues. METHODS: Between 1992 and 1999, 440 patients presented to our institution with aSAH. This sample was retrospectively analyzed to determine which patients had used cocaine within 72 hours of aSAH as documented by urine toxicology studies or patient history. These patients were then compared with control aSAH patients without recent cocaine exposure through univariable and multivariable analyses. RESULTS: Twenty-seven aSAH patients (6.1% of total) had either urine toxicology positive for cocaine metabolites (20 patients, 74%) or a history of cocaine use within 72 hours of aSAH (7 patients, 26%). Cocaine users were more likely to experience cerebral vasospasm defined as a delayed clinical deficit (from 3 to 16 days after aSAH) unexplained by concurrent CT scan and either responsive to hypervolemic and/or hypertensive therapy or accompanied by angiographic confirmation of vessel narrowing than control subjects (63% versus 30%; odds ratio [OR], 3.90; 95% confidence interval [CI], 1.77 to 8.62; P=0.001). Patients using cocaine were younger than control subjects (mean age, 36 versus 52 years; P<0.0001). Aneurysms of the anterior circulation were observed more frequently in cocaine users than in control subjects (97% versus 84%; OR, 6.89; 95% CI, 1.18 to 47.47; P=0.029). A significant difference was not observed, however, in the discharge Glasgow Outcome Scale (GOS) scores between the 2 groups (P=0.73). Differences were not observed between the 2 groups when the distributions of sex, hypertension, admission Glasgow Coma Scale subarachnoid hemorrhage grade, and multiple aneurysms were analyzed. Logistic regression models identified variables independently associated with vasospasm and discharge GOS score. Only a thick blood clot on the admission CT (OR, 7.46; 95% CI, 3.95 to 14.08; P<0.0001) and recent cocaine use (OR, 6.41; 95% CI, 2.14 to 19.23; P=0.0009) were independently associated with vasospasm. Cocaine use was not independently associated with the discharge GOS score. CONCLUSIONS: We conclude that there is an increased prevalence of vasospasm in aSAH patients with recent cocaine exposure but no difference in clinical outcome. In addition, these patients are younger and more likely to have anterior circulation aneurysms.

Prevention and reversal of experimental posthemorrhagic vasospasm by the periadventitial administration of nitric oxide from a controlled-release polymer.

OBJECTIVE: Despite improvements in the care of patients with aneurysmal subarachnoid hemorrhage, delayed cerebral vasospasm remains a major cause of morbidity and death. There is now evidence that a decrease in the local availability of nitric oxide (NO) plays a role in delayed cerebral vasospasm. We evaluated a controlled-release polymer containing the NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) for the treatment of chronic posthemorrhagic vasospasm in the rat femoral artery model. METHODS: The release kinetics of ethylene/vinyl acetate copolymers loaded with 20% (w/w) DETA/NO were determined in vitro. Chronic vasospasm was induced in the left femoral artery of adult male Fischer 344 rats (n = 35) by exposure to autologous blood. At 1, 3, or 7 days after blood exposure, either a 5-mg polymer loaded with 20% (w/w) DETA/NO or an empty 5-mg polymer was placed in the periadventitial space next to the left femoral artery. At the same time, an empty 5-mg polymer was placed next to the right femoral artery. On the 8th day after blood exposure (at the peak of vasospasm in this model), rats were transcardially perfused with 4% paraformaldehyde, and the left and right femoral arteries were removed for histological processing and morphometric analyses. Vasospasm was expressed as the percent lumen patency of the treated left artery, compared with the control right artery. RESULTS: The in vitro release kinetics demonstrated that the 20% DETA/NO-loaded polymers released up to 15% of their total drug load during a 9-day period. DETA/NO treatments initiated at 1, 3, or 7 days after blood deposition all significantly inhibited vasospasm, compared with control values (94.6 +/- 7.2% versus 67.6 +/- 5.8%, 104.6 +/- 5.5% versus 64.9 +/- 1.7%, and 102.4 +/- 5.1% versus 73.6 +/- 1.4%, respectively; mean +/- standard error of the mean percent lumen patency; P < 0.001). No adverse effects of treatment were observed. CONCLUSION: The diazeniumdiolate NO donor DETA/NO can be effectively released from ethylene/vinyl acetate polymers. Administration of DETA/NO into the periadventitial space can prevent the development of chronic posthemorrhagic vasospasm in the rat femoral artery and can reverse established vasospasm. No adverse effects of DETA/NO were observed in this model.

Risk factors for subarachnoid hemorrhage.

OBJECTIVE: Cigarette smoking has been demonstrated to increase the risk of subarachnoid hemorrhage (SAH). Whether cessation of smoking decreases this risk remains unclear. We performed a case-control study to examine the effect of smoking and other known risk factors for cerebrovascular disease on the risk of SAH. METHODS: We reviewed the medical records of all patients with a diagnosis of SAH (n = 323) admitted to Johns Hopkins Hospital between January 1990 and June 1997. Controls matched for age, sex, and ethnicity (n = 969) were selected from a nationally representative sample of the Third National Health and Nutrition Examination Survey. We determined the independent association between smoking (current and previous) and various cerebrovascular risk factors and SAH by use of multivariate logistic regression analysis. A separate analysis was performed to determine associated risk factors for aneurysmal SAH. RESULTS: Of 323 patients admitted with SAH (mean age, 52.7+/-14 yr; 93 were men), 173 (54%) were hypertensive, 149 (46%) were currently smoking, and 125 (39%) were previous smokers. In the multivariate analysis, both previous smoking (odds ratio [OR], 4.5; 95% confidence interval [CI], 3.1-6.5) and current smoking (OR, 5.2; 95% CI, 3.6-7.5) were significantly associated with SAH. Hypertension was also significantly associated with SAH (OR, 2.4; 95% CI, 1.8-3.1). The risk factors for 290 patients with aneurysmal SAH were similar and included hypertension (OR, 2.4; 95% CI, 1.8-3.2), previous smoking (OR, 4.1; 95% CI, 2.7-6.0), and current smoking (OR, 5.4; 95% CI, 3.7-7.8). CONCLUSION: Hypertension and cigarette smoking increase the risk for development of SAH, as found in previous studies. However, the increased risk persists even after cessation of cigarette smoking, which suggests the importance of early abstinence from smoking.

Cerebellar lesions impair context-dependent adaptation of reaching movements in primates.

To produce accurate movements when conditions change suddenly, the brain must be capable of learning multiple versions of a given motor task and must be able to access the appropriate program using sensory information linked to the context of the movement. The neural basis for context-dependent motor learning is uncertain, but the cerebellum is thought to play a fundamental role. In this study, we examined the effect of lesions of the dorsal vermal and paravermal cerebellar cortex on the adaptation of reaching movements produced by modified visual feedback and accessed with a visual cue. Two rhesus monkeys were trained to point to targets displayed on a video monitor while viewing monocularly with either eye. During the experimental sessions, visual information received by one eye (the "modified" eye) was displaced horizontally, while the information received by the other ("normal") eye remained unaltered. In the first set of experiments (noncontextual paradigm), the animals pointed to targets while viewing with the modified eye. This paradigm resulted in a gradual improvement in pointing accuracy when viewing with that eye, but also produced a shift in pointing responses of equivalent size when viewing with the normal eye. In the second set of experiments (contextual paradigm), the animals alternated six blocks of reaches while viewing monocularly with the modified eye with six blocks viewing with the normal eye. This paradigm improved the pointing accuracy when viewing with the modified eye, but produced only a small shift in pointing responses when viewing with the normal eye. After the dorsal vermal and paravermal cerebellar cortex were resected, no change occurred in the pattern of adaptation produced by the noncontextual paradigm. The contextual paradigm, however, no longer selectively adapted pointing responses for each eye, but rather produced a pointing shift of equivalent size when viewing with either eye. The results indicate that pointing responses can be differentially adapted for each viewing eye, which is a form of context-dependent motor learning. This capability was lost after focal lesions of the dorsal vermal and paravermal cerebellar cortex, suggesting that these regions of cerebellar cortex are required to learn or store multiple representations of a movement, or to retrieve the appropriate motor program in a given sensory context.

Recurrent artery of Heubner: Otto Heubner's description of the artery and his influence on pediatrics in Germany.

Although the recurrent artery of Heubner is one of the best known cerebral arteries, little has been written in the neurosurgical or anatomical literature about its discovery. The artery is of primary importance to cerebrovascular surgeons, who identify it during clipping of anterior communicating artery aneurysms. Johann Otto Leonhardt Heubner (1843-1926), who described this artery in 1872, is better known as the father of German pediatrics. He was appointed to the first professorship in Germany exclusively devoted to pediatrics at the Charité Children's Clinic of Berlin University. Although he initially studied internal medicine in Leipzig under Carl Reinhold August Wunderlich and Ernst Leberecht Wagner, his early research involved anatomical studies of the circulation of the brain, from which he described syphilitic endarteritis (Heubner's disease). Finding morphological studies inconclusive, he turned to more physiological experiments. Together with the physiologist Max Rubner, Heubner performed important studies on energy metabolism in infancy, creating the notion of the nutrition quotient. In this article the authors review Heubner's life and scientific discoveries.

Effects of lesions of the oculomotor cerebellar vermis on eye movements in primate: smooth pursuit.

We studied the effects on smooth pursuit eye movements of ablation of the dorsal cerebellar vermis (lesions centered on lobules VI and VII) in three monkeys in which the cerebellar nuclei were spared. Following the lesion the latencies to pursuit initiation were unchanged. Monkeys showed a small decrease (up to 15%) in gain during triangular-wave tracking. More striking were changes in the dynamic properties of pursuit as determined in the open-loop period (the 1st 100 ms) of smooth tracking. Changes included a decrease in peak eye acceleration (e.g., in one monkey from approximately 650 degrees /s(2), prelesion to approximately 220-380 degrees /s(2), postlesion) and a decrease in the velocity at the end of the open-loop period [e.g., in another monkey from a gain (eye velocity/target velocity at 100 ms of tracking) of 0.93, prelesion to 0.53, postlesion]. In individual monkeys, the pattern of deficits in the open-loop period of pursuit was usually comparable to that of saccades, especially when comparing the changes in the acceleration of pursuit to the changes in the velocity of saccades. These findings support the hypothesis that saccades and the open-loop period of pursuit are controlled by the cerebellar vermis in an analogous way. Saccades could be generated by eye velocity commands to bring the eyes to a certain position and pursuit by eye acceleration commands to bring the eyes toward a certain velocity. On the other hand, changes in gain during triangular-wave tracking did not correlate with either the saccade or the open-loop pursuit deficits, implying different contributions of the oculomotor vermis to the open loop and to the sustained portions of pursuit tracking. Finally, in a pursuit adaptation paradigm (x0.5 or x2, calling for a halving or doubling of eye velocity, respectively) intact animals could adaptively adjust eye acceleration in the open-loop period. The main pattern of change was a decrease in peak acceleration for x0.5 training and an increase in the duration of peak acceleration for x2 training. Following the lesion in the oculomotor vermis, this adaptive capability was impaired. In conclusion, as for saccades, the oculomotor vermis plays a critical role both in the immediate on-line and in the short-term adaptive control of pursuit.

Ischemic events associated with unruptured intracranial aneurysms: multicenter clinical study and review of the literature.

OBJECTIVE: To determine the prevalence, clinical characteristics, and long-term outcomes in cases involving transient ischemic attacks (TIAs) or ischemic strokes secondary to embolization from unruptured intracranial aneurysms. METHODS: We identified all available patients with intracranial aneurysms and ischemic strokes in three university-affiliated hospitals, using either International Classification of Diseases-9th Revision codes or local registries. Patients with clinically or radiologically detected cerebral infarctions distal to intracranial aneurysms, in the absence of other causes for the infarctions, were included. An aneurysmal embolic source was considered highly probable by the primary neurosurgeon/neurologist in all cases. Follow-up data for the patients were acquired through reviews of clinical visits or telephone interviews. A review of the literature was performed to identify characteristics of previously reported patients. RESULTS: Ischemic strokes or TIAs attributable to embolization from the aneurysmal sac were observed for 9 of 269 patients (3.3%) with unruptured aneurysms. Of these nine patients, five were women and four were men (mean age, 62 yr; age range, 45-72 yr). Symptomatic aneurysms were located in the middle cerebral artery (n = 4), internal carotid artery (n = 3), posterior cerebral artery (n = 1), or vertebral artery (n = 1). The mean maximal diameter was 12.5 mm (range, 5-45 mm). Six patients underwent surgical treatment, of whom two experienced postoperative cerebral infarctions referable to the distribution of the artery harboring the aneurysm. Two patients were treated with aspirin, and one patient received no treatment. The mean follow-up period was 38 months (range, 1-60 mo). None of the patients experienced additional ischemic events during the follow-up period. Among the 41 previously reported patients, conservative treatment was used for 20 patients (mean follow-up period, 50.7 +/- 44.5 mo). Four of the 20 patients experienced recurrent TIAs, 1 patient experienced worsening of symptoms, and 1 patient died during the follow-up period. A total of 21 patients underwent surgical treatment (mean follow-up period, 33.6 +/- 32.3 mo). Of these patients, only one experienced recurrent TIAs. Two patients experienced postoperative seizures, and one patient died during the follow-up period. All recurrent symptoms with either surgical or conservative treatment were transient, and no patient experienced a major or disabling stroke during the follow-up period. CONCLUSION: Ischemic events can occur distal to both small and large unruptured intracranial aneurysms (predominantly in the anterior circulation). The long-term risk of recurrent ischemic events, particularly major or disabling strokes, seems to be low with either surgical or conservative treatment.

Early predictors of outcome in patients receiving hypervolemic and hypertensive therapy for symptomatic vasospasm after subarachnoid hemorrhage.

OBJECTIVE: Symptomatic vasospasm after subarachnoid hemorrhage (SAH) is associated with a high incidence of permanent disability and death. For early identification of patients who are at risk for poor outcome, we determined the predictors of outcome in patients with symptomatic vasospasm after SAH. DESIGN: We retrospectively determined the prognostic value of clinical characteristics and computed tomographic scan both at admission and at the time of initiation of hypervolemic and hypertensive therapy. SETTINGS: Neurosciences critical care unit at a University hospital. PATIENTS: A total of 70 consecutive patients who developed symptomatic vasospasm after SAH. INTERVENTION: Treatment with oral nimodipine, hypervolemic therapy, and hypertensive therapy. Angioplasty and intra-arterial papaverine were used in patients with vasospasm resistant to standard treatment. MEASUREMENTS AND MAIN RESULTS: Poor outcome, defined as Glasgow Outcome Scale Score of 3-5 at 2 months or discharge, was observed in 32 (46%) patients. In the logistic regression analysis, a Glasgow Coma Scale (GCS) score of < or =11 (odds ratio, 11.0; 95% confidence interval, 3.6-39.3) and hydrocephalus (odds ratio, 4.3; 95% confidence interval, 1.2-18.2) at the time of initiation of hypervolemic and hypertensive therapy were significantly associated with poor outcome. Poor outcome was observed in 91% of the patients who had both a GCS score of < or =11 and hydrocephalus compared with 15% of patients with a GCS score of >11 and no hydrocephalus at the time of initiation of hypervolemic and hypertensive therapy. A GCS score of < or =11 was also independently associated with length of intensive care unit stay (F ratio = 18.0; p = .0011) and hospital stay (F ratio = 9.2; p = .0034) after initiation of hypervolemic and hypertensive therapy. CONCLUSIONS: The results of this study suggest that outcome in patients with symptomatic vasospasm can be effectively predicted by routinely available information, including GCS score at the time of initiation of hypervolemic and hypertensive therapy. This information can be used for selection and stratification of patients in future treatment studies of patients with symptomatic vasospasm.

Lytic Paget disease as a cause of orbital cholesterol granuloma.

A case of histologically confirmed Paget disease of the orbit produced a lesion that appeared both clinically and histologically similar to a cholesterol granuloma. This case is unique because of the unusual location of the lesion, its presentation in a patient with no other manifestations of Paget disease, and the histological picture produced by the disease.

Marfan syndrome is not associated with intracranial aneurysms.

BACKGROUND AND PURPOSE: It has been proposed that patients with Marfan syndrome have an increased prevalence of intracranial aneurysms. This proposition is based on 10 clinical reports, 1 pathology case, and an autopsy series of 7 patients. By contrast, 5 clinical series of Marfan patients have failed to document any such relationship. We present our institution's autopsy and clinical experience with Marfan syndrome and analyze in our patient population the purported association between this condition and intracranial aneurysms. METHODS: The results of an autopsy series at the Johns Hopkins Hospital of 25 confirmed Marfan syndrome patients from 1939 to the present were reviewed retrospectively. The prevalence of intracranial aneurysms in this Marfan syndrome autopsy series was compared with that in the autopsy population at this institution and with that in the general autopsy population as reported in the literature. In addition, the prevalence of Marfan syndrome in a recent neurosurgical series of 710 consecutive aneurysm cases (1990-1998) was determined. RESULTS: Of the 25 autopsy cases, only 1 had evidence on autopsy of an unruptured, 2-mm aneurysmal dilatation at the anterior communicating artery complex. Three autopsy patients suffered intracranial hemorrhages but had negative angiography and postmortem examinations for intracranial aneurysms. The remaining 21 patients had negative autopsies for intracranial hemorrhages or intracranial aneurysms. The neurosurgical series of 710 patients treated for intracranial aneurysms did not include any patient with Marfan syndrome. CONCLUSIONS: The prevalence of 1 patient of 25 with an intracranial aneurysm is not statistically different from the 1.3% prevalence of intracranial aneurysms in the autopsy population at this institution (P=0.24) or from the 2.0% prevalence of intracranial aneurysms in the general autopsy population (P=0.31). We therefore conclude that there exists no evidence that Marfan syndrome is associated with an increased prevalence of intracranial aneurysms.

Administration of hypertonic (3%) sodium chloride/acetate in hyponatremic patients with symptomatic vasospasm following subarachnoid hemorrhage.

A retrospective study was carried out to evaluate the effect of hypertonic (3%) saline chloride/acetate on various hemodynamic parameters in mildly hyponatremic patients with symptomatic vasospasm following aneurysmal subarachnoid hemorrhage (SAH). We identified 29 hyponatremic (serum sodium < 135 mEq/L) patients who received hypertonic (3%) sodium chloride/acetate as a continuous infusion. Administration of hypertonic (3%) sodium chloride/acetate resulted in higher central venous pressures and positive fluid balance, with a concomitant increase in serum sodium and chloride concentrations without metabolic acidosis. There were no changes in mean cerebral blood flow velocities after infusion of hypertonic (3%) sodium chloride/acetate. We found no reports of congestive heart failure, pulmonary edema, metabolic acidosis, coagulopathy, intracranial hemorrhages, or central pontine myelinolysis in any of these patients. We conclude that hypertonic (3%) sodium chloride/acetate can be administered to patients with mild hyponatremia in the setting of symptomatic vasospasm following SAH without untoward effects. Sample size and limitations of a retrospective analysis preclude conclusions about safety and efficacy of hypertonic (3%) sodium chloride/acetate administration in this patient population. However, our results support justification for a prospective, randomized, double-blind trial of hypertonic (3%) sodium chloride/acetate versus normal saline in patients with symptomatic vasospasm following SAH.

Inhibition of experimental vasospasm in rats with the periadventitial administration of ibuprofen using controlled-release polymers.

BACKGROUND AND PURPOSE: The chronic phase of vasospasm after an aneurysmal subarachnoid hemorrhage may be mediated in part by early leukocyte-endothelial cell interactions. Ibuprofen is an anti-inflammatory agent that inhibits expression of certain cell adhesion molecules and therefore disrupts leukocyte-endothelial cell interactions. Its systemic administration, however, has dose-limiting side effects. We evaluated the effect of the periadventitial delivery of ibuprofen using controlled-release polymers in the rat femoral artery model of chronic posthemorrhagic vasospasm. METHODS: Before the animal studies, the release pharmacokinetics of the ibuprofen-loaded ethylene-vinyl acetate polymers were determined in vitro. Subsequently, the femoral arteries (n=266) of Fischer 344 rats (n=133) were enclosed in latex pouches bilaterally. In the toxicity study (n=15 rats), the animals were randomized into 5 dose groups in which 0%-, 10%-, 20%-, 30%-, or 50%-loaded ibuprofen polymers were evaluated. In the efficacy study, the animals were randomized into 5 time groups in which 50%-loaded ibuprofen polymers were inserted at 0 (n=58 rats), 6 (n=16), 12 (n=13), 24 (n=11), or 48 hours (n=12) after blood injection into the pouch. The rats were killed 12 days after blood exposure, at the time of maximal vasospasm in this model. Vasospasm was expressed as percent lumen patency. To evaluate the effect of ibuprofen on leukocyte migration, 8 rats were randomized into 2 groups. Macrophages and granulocytes were stained by immunohistochemistry with the use of a mouse OX-41 monoclonal antibody and counted in the periadventitial space 24 hours after blood exposure. RESULTS: In vitro pharmacokinetics showed that the 50%-loaded ibuprofen polymer released its total drug load over a 12-day period. In the toxicity study, a nonsignificant arterial vasodilatation with ibuprofen treatment was seen at higher doses, and no deleterious effects were noted on the vessel wall histologically. In the efficacy study, ibuprofen treatment resulted in significant vasospasm inhibition when treatment was initiated at 0 hour (73.7+/-4.9% versus 94.5+/-3.3% [mean+/-SEM percent lumen patency]; P<0.001) and 6 hours (69.2+/-5.7% versus 98.0+/-3.9%; P=0. 002) after blood exposure, but not at 12, 24, or 48 hours. Leukocyte immunohistochemistry showed that ibuprofen treatment resulted in significantly lower periadventitial macrophage and granulocyte counts of 25.0+/-3.9 cells per high-powered field compared with counts of 140.5+/-18.2 cells per high-powered field in the untreated vessels (P<0.001). CONCLUSIONS: The periadventitial, controlled release of ibuprofen from surgically implanted polymers significantly inhibits chronic posthemorrhagic vasospasm in this model when treatment is initiated within 6 hours of blood exposure. Vasospasm inhibition with ibuprofen correlates with a significant decrease in the number of macrophages and granulocytes in the periadventitial space. This study supports the hypothesis that inflammation mediates in part the chronic phase of posthemorrhagic vasospasm and suggests a potential alternative treatment for this condition.

Effects of lesions of the oculomotor vermis on eye movements in primate: saccades.

We studied the effects on saccades of ablation of the dorsal cerebellar vermis (lesions centered on lobules VI and VII) in three monkeys in which the deep cerebellar nuclei were spared. One animal, with a symmetrical lesion, showed bilateral hypometric horizontal saccades. Two animals, with asymmetrical lesions, showed hypometric ipsilateral saccades, and saccades to vertically positioned targets were misdirected, usually deviating away from the side to which horizontal saccades were hypometric. Postlesion, all animals showed an increase (2- to 5-fold) in trial-to-trial variability of saccade amplitude. They also showed a change in the ratio of the amplitudes of centripetal to centrifugal saccades (orbital-position effect); usually centrifugal saccades became smaller. In the two animals with asymmetrical lesions, for saccades in the hypometric direction, latencies were markedly increased (up to approximately 500 ms). There was also an absence of express and anticipatory saccades in the hypometric direction. When overall saccade latency was increased, centrifugal saccades became relatively more delayed than centripetal saccades. The dynamic characteristics of saccades were affected to some extent in all monkeys with changes in peak velocity, eye acceleration, and especially eye deceleration. There was relatively little effect of orbital position on saccade dynamics, however, with the exception of one animal that showed an orbital position effect for eye acceleration. In a double-step adaptation paradigm, animals showed an impaired ability to adaptively adjust saccade amplitude, though increased amplitude variability postlesion may have played a role in this deficit. During a single training session, however, the latency to corrective saccades-which had been increased postlesion-gradually decreased and so enabled the animal to reach the final position of the target more quickly. Overall, both in the early postlesion period and during recovery, changes in saccade amplitude and latency tended to vary together but not with changes in saccade dynamics or adaptive capability, both of which behaved relatively independently. These findings suggest that the cerebellum can adjust saccade amplitude and saccade dynamics independently. Our results implicate the cerebellar vermis directly in every aspect of the on-line control of saccades: initiation (latency), accuracy (amplitude and direction), and dynamics (velocity and acceleration) and also in the acquisition of adaptive ocular motor behavior.