Thomas Westermaier

Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: A randomized, placebo-controlled, clinical study

Objective:To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage. Design:Prospective, randomized, placebo-controlled study. Setting:Neurosurgical intensive care unit of a University hospital. Interventions:One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0–2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days. Measurements and Main Results:Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5. The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction. Conclusion:These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.

Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after experimental subarachnoid hemorrhage in rats.

Present knowledge about hemodynamic and metabolic changes after subarachnoid hemorrhage (SAH) originates from neuromonitoring usually starting with aneurysm surgery and animal studies that have been focusing on the first 1 to 3 h after SAH. Most patients, however, are referred to treatment several hours after the insult. We examined the course of hemodynamic parameters, cerebral blood flow, and tissue oxygenation (ptiO2) in the first 6 h after experimental SAH. Sixteen Sprague–Dawley rats were subjected to SAH using the endovascular filament model or served as controls (n = 8). Bilateral local cortical blood flow, intracranial pressure, cerebral perfusion pressure, and ptiO2 were followed for 6 h after SAH. After induction of SAH, local cortical blood flow rapidly declined to 22% of baseline and returned to 80% after 6 h. The decline of local cortical blood flow markedly exceeded the decline of cerebral perfusion pressure. ptiO2 declined to 57%, recovered after 2 h, and reached ≥140% of baseline after 6 h. Acute vasoconstriction after SAH is indicated by the marked discrepancy of cerebral perfusion pressure and local cortical blood flow. The excess tissue oxygenation several hours after SAH suggests disturbed oxygen utilization and cerebral metabolic depression. Aside from the sudden increase of intracranial pressure at the time of hemorrhage and delayed cerebral vasospasm, the occurrence of acute vasoconstriction and disturbed oxygen utilization may be additional factors contributing to secondary brain damage after SAH.

A modified double injection model of cisterna magna for the study of delayed cerebral vasospasm following subarachnoid hemorrhage in rats

Delayed cerebral vasospasm following subarachnoid hemorrhage (SAH) is a serious medical complication, characterized by constriction of cerebral arteries leading to varying degrees of cerebral ischemia. Numerous clinical and experimental studies have been performed in the last decades; however, the pathophysiologic mechanism of cerebral vasospasm after SAH still remains unclear. Among a variety of experimental SAH models, the double hemorrhage rat model involving direct injection of autologous arterial blood into the cisterna magna has been used most frequently for the study of delayed cerebral vasospasm following SAH in last years. Despite the simplicity of the technique, the second blood injection into the cisterna magna may result in brainstem injury leading to high mortality. Therefore, a modified double hemorrhage model of cisterna magna has been developed in rat recently. We describe here step by step the surgical technique to induce double SAH and compare the degree of vasospasm with other cisterna magna rat models using histological assessment of the diameter and cross-sectional area of the basilar artery.

The Temporal Profile of Cerebral Blood Flow and Tissue Metabolites Indicates Sustained Metabolic Depression After Experimental Subarachnoid Hemorrhage in Rats

BACKGROUND:Derangement of cerebral metabolism occurs after various insults such as ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). OBJECTIVE:To investigate the course of cerebral blood flow and metabolic parameters in the first hours after experimental SAH. METHODS:Sixteen Sprague-Dawley rats were subjected to SAH using the endovascular filament model or served as controls (8 rats in each group). Local cerebral blood flow and intracranial pressure were measured continuously. Microdialysis samples were acquired in 30-minute intervals for 6 hours after SAH. Concentrations of glucose, lactate, pyruvate, and glutamate were determined. RESULTS:After induction of SAH, cerebral perfusion pressure and local cerebral blood flow sharply decreased. The decrease in local cerebral blood flow exceeded the decrease in cerebral perfusion pressure throughout the observation period. Glutamate concentrations in microdialysis samples increased sixfold and recovered to baseline levels. Lactate concentrations immediately increased after SAH, recovered incompletely, and remained above the levels of control animals until the end of the sampling period. Pyruvate concentrations showed a delayed increase starting 2 hours after SAH. CONCLUSION:The course of cerebral blood flow after SAH resembles global ischemia followed by a continuous low-flow state caused by a sudden decrease in cerebral perfusion pressure and acute vasoconstriction. The courses of lactate and pyruvate concentrations indicate a persistently deranged aerobic metabolism.

Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial

OBJECTIVE A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.

Brain edema formation correlates with perfusion deficit during the first six hours after experimental subarachnoid hemorrhage in rats

BackgroundSevere brain edema is observed in a number of patients suffering from subarachnoid hemorrhage (SAH). Little is known about its pathogenesis and time-course in the first hours after SAH. This study was performed to investigate the development of brain edema and its correlation with brain perfusion after experimental SAH.MethodsMale Sprague–Dawley rats, randomly assigned to one of six groups (n = 8), were subjected to SAH using the endovascular filament model or underwent a sham operation. Animals were sacrificed 15, 30, 60, 180 or 360 minutes after SAH. Intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and bilateral local cerebral blood flow (LCBF) were continuously measured. Brain water content (BWC) was determined by the wet/dry-weight method.ResultsAfter SAH, CPP and LCBF rapidly decreased. The decline of LCBF markedly exceeded the decline of CPP and persisted until the end of the observation period. BWC continuously increased. A significant correlation was observed between the BWC and the extent of the perfusion deficit in animals sacrificed after 180 and 360 minutes.ConclusionsThe significant correlation with the perfusion deficit after SAH suggests that the development of brain edema is related to the extent of ischemia and acute vasoconstriction in the first hours after SAH.

Clinical features, treatment, and prognosis of patients with acute subdural hematomas presenting in critical condition.

OBJECTIVESpontaneous acute subdural hematoma (aSDH) may be caused by aneurysm rupture. Patients can present in very poor clinical condition with anisocoria or even bilaterally dilated pupils, absent brainstem reflexes, and cardiac insufficiency. For the clinician, the question is how should these patients be treated? Large series on this subject do not exist because aSDH is a rare event. This report focuses on the prognosis and adverse prognostic factors of these patients. CLINICAL PRESENTATIONWe present eight cases of aSDH and subarachnoid hemorrhage attributable to aneurysm rupture. All patients were World Federation of Neurosurgical Societies Grade 5. Four presented with anisocoria, three presented with bilaterally fixed and dilated pupils, and one developed anisocoria in the course of treatment. TREATMENTAs a result of prolonged hypoxia before admission, one patient was not treated and died. In one patient, surgical decompression could not be performed in the acute phase as a result of significant comorbidity. All other patients received decompressive surgery, obliteration of the aneurysm, and medical therapy as well as extensive rehabilitation measures. After 6 months, four had no or only minor neurological deficits; one patient was independent despite hemiparesis. Two patients whose surgical decompression had to be delayed as a result of severe cardiac instability recovered poorly, showed severe neurological deficits, and required permanent care. However, none of the patients survived in a persistent vegetative state. CONCLUSIONWithin the spectrum of aneurysmatic hemorrhage, patients with aSDH represent a distinct subgroup. Despite a very poor clinical condition on admission, recovery with only minor deficits or even without neurological deficit is possible. Mass effect and herniation induce a poor clinical condition, which is not directly related to the underlying subarachnoid hemorrhage. Hence, clinical grading systems such as the Hunt and Hess scale or World Federation of Neurosurgical Societies grading are not applicable. We suggest that whenever the medical condition allows, rapid surgical decompression should be performed even in patients who present in very poor neurological condition.

Surgical Treatment of Dural Arteriovenous Fistulas of the Petrous Apex

OBJECTIVE To report a series of four patients with dural arteriovenous fistulas (DAVF) at the petrous apex with drainage into the deep cerebral venous system and the surgical treatment employed. METHODS Four patients with DAVFs at the petrous apex are presented. One patient was admitted with cerebral hemorrhage from a second occipital DAVF, and three patients had cranial nerve palsies. All fistulas were type III or IV according to Cognards classification with venous drainage into the deep cerebral veins. RESULTS Transarterial embolization was performed in two patients. Partial transarterial embolization was possible resulting in a marked flow reduction. In one further patient, surgical treatment via a subtemporal approach was attempted, but complete obliteration of the fistula was impossible. In all patients, complete occlusion of the DAVF was achieved by surgical interruption via a standard retrosigmoid approach to the cerebellopontine angle. CONCLUSIONS Treatment of these type III or IV DAVFs was indicated. The fistulas were supplied by multiple meningeal feeders originating from the external and internal carotid and vertebral arteries. Preoperative transarterial embolization resulted in significant flow reduction. Complete cure at low risk was achieved by interruption of the venous drainage via a retrosigmoid approach.

Arachnoid cysts of the fourth ventricle - short illustrated review

SummaryArachnoid cysts are frequent anomalies of the CNS. They are benign lesions within the arachnoid membrane and have been reported to occur in virtually all locations where arachnoid is present. An intraventricular location, however, is rare and occurrence within the fourth ventricle is particularly uncommon. The first report was published in 1979 on a paediatric patient. Since then, only a few further examples have been reported. Most of these patients presented with hydrocephalus. Shunting procedures were performed, but did not afford long-term improvement of symptoms. Definitive treatment consisted of open resection of the cyst-wall. We report a 34-year-old woman with a large arachnoid cyst within the fourth ventricle who suffered from progressive cerebellar dysfunction. MRI showed massive enlargement of the fourth ventricle by an intraventricular arachnoid cyst which contained multiple septations. Complete excision of the cyst was necessary to reinstitute free CSF-flow and was performed via a median suboccipital approach. This report gives an overview of examples published to date and discusses pathogenesis and clinical features of arachnoid cysts in this location as well as operative strategies including neuroendoscopic techniques.

An anatomical assessment of the supracerebellar midline and paramedian approaches to the inferior colliculus for auditory midbrain implants using a neuronavigation model on cadaveric specimens

The inferior colliculus (IC) is an alternative site for electrode placement in neural deafness due to its surgical accessibility and its well-known tonotopic stratification. In patients where tumor surgery has already occurred and the cerebellopontine angle contains scar tissue or tumor-remnants, midline and paramedian supracerebellar approaches are alternative routes. They are often avoided due to concerns regarding the venous drainage of the cerebellum, the electrode trajectory and the course of the electrode cable. We studied these surgical routes in five neuronavigated fixed cadaveric specimens. For paramedian and midline approaches, the transverse sinus was exposed 5.8mm on average. A mean of 1.6 cerebellar veins, with an average diameter of 2.0mm, draining to the tentorium were transected to reach the tentorial notch. Only 0.4 arterial branches were met. We conclude that the supracerebellar midline and paramedian approaches provide a good exposure of the IC and offer safe and viable alternative routes to the IC. Additionally, they provide a wider angle of action for optimal electrode placement.