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Cervical cord exostosis compressing the axis in a boy with hereditary multiple exostoses

Case illustration

Marcus C. Korinth, Vincent T. Ramaekers, and Veit Rohde

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Editorial: Vasospasm

Nicholas C. Bambakidis and Warren R. Selman

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Early surgery of multiple versus single aneurysms after subarachnoid hemorrhage: an increased risk for cerebral vasospasm?

Clinical article

Dorothee Wachter, Ilonka Kreitschmann-Andermahr, Joachim Michael Gilsbach, and Veit Rohde

Object

As many as 33% of patients suffering from subarachnoid hemorrhage (SAH) present with multiple intracranial aneurysms (MIAs). It is believed that aneurysm surgery has the potential to increase the risk of cerebral vasospasm due to surgical manipulations of the parent vessels and brain tissue. Consequently, 1-stage surgery of MIAs, which usually takes longer and requires more manipulation, could even further increase the risk of vasospasm. The aim of this study is to define the correlation between vasospasm and the operative treatment of single intracranial aneurysms versus MIAs in a 1-stage operation.

Methods

The authors analyzed a database including 1016 patients with SAH, identified retrospectively between 1989 and 1996 and prospectively collected between 1997 and 2004. Exclusion criteria were endovascular treatment, surgery after SAH Day 3, and, in patients with MIAs, undergoing more than 1 operation. Cerebral vasospasm was diagnosed by transcranial Doppler (TCD) ultrasonography and was defined as a maximum mean blood flow velocity > 120 cm/second. The diagnosis of symptomatic vasospasm was made if a new neurological deficit occurred that could not be explained by concomitant complications.

Results

A total of 643 patients who experienced 810 aneurysms were included. Four hundred twenty-four patients were female (65.9%) and 219 were male (34.1%) with an average age of 53.1 years. One hundred twenty-one patients (18.8%) were diagnosed with MIAs. Maximum mean flow velocities measured by TCD were 131 cm/second in patients with MIAs and 129.5 cm/second in patients with single intracranial aneurysms. The incidence of TCD vasospasm (p = 0.561) as well as of symptomatic vasospasm (p = 0.241) was not significantly different in the 2 groups.

Conclusions

Clipping of more than 1 aneurysm in a 1-stage operation within 72 hours after SAH can be performed without increasing the risk of cerebral (TCD) vasospasm and symptomatic vasospasm.

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Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation

Veit Rohde, Ina Rohde, Ruth Thiex, Azize Ince, Axel Jung, Gregor Dückers, Klaus Gröschel, Carina Röttger, Wilhelm Küker, Harald D. Müller, and Joachim M. Gilsbach

Object. Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume.

Methods. A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43 ± 0.42 ml on Day 0 to 0.85 ± 0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 ± 0.28 ml on Day 0 to 0.52 ± 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 ± 0.61 ml to 1.73 ± 0.73 ml on Day 4, before dropping to 1.17 ± 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 ± 0.21 ml on Day 0 to 1.93 ± 0.79 ml on Day 4, and further to 3.34 ± 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04).

Conclusions. Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.

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Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages

Ruth Thiex, Joachim Weis, Timo Krings, Sonia Barreiro, Funda Yakisikli-Alemi, Joachim M. Gilsbach, and Veit Rohde

Object

Fibrinolytic therapy with recombinant tissue plasminogen activator (rtPA) is considered a treatment option in patients with deep-seated intracerebral hemorrhage (ICH). Nevertheless, the results of animal experiments have shown that tPA exerts pleiotropic actions in the brain, including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases, which increase excitotoxicity, damage the blood–brain barrier, and worsen edema. The authors investigated whether the noncompetitive NMDA receptor antagonist MK801 can be used as an adjuvant therapy in combination with rtPA to attenuate the unfavorable delayed edema formation and inflammation observed following rtPA therapy in an experimental porcine model of ICH.

Methods

Twenty pigs were used in this study; MK801 (0.3 mg/kg) was administered to each pig intravenously immediately after hematoma induction and on the 1st and 3rd day after hematoma induction. Ten of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA (MK801–tPA group), whereas in the remaining 10 control animals (MK801 group) the hematomas were allowed to follow their natural courses of resorption. The extent of edema formation was evaluated using magnetic resonance (MR) imaging volumetry on Days 0, 4, and 10 after hematoma induction and was compared with histopathological changes found at necropsy. The mean edema volumes in these two groups were also compared with that in the group of nine pigs examined in a preceding experimental series, in which the animals’ hematomas were only treated with rtPA (tPA group).

In the 10 animals in the MK801–tPA group, the mean perihematoma edema volume on MR images had not significantly increased by Day 4 (p < 0.08) or Day 10 (p < 0.35) after hematoma induction. In the 10 animals in the MK801 group, the increase in mean perifocal edema size was significant after 4 days (p < 0.001) and nonsignificant after 10 days (p < 0.09). In the nine animals in the tPA group, the mean edema volume significantly increased by Days 4 (p < 0.002) and 10 (p < 0.03).

Conclusions

As suggested by the reduction in delayed edema volume and the inflammatory response, MK801 modifies the neurotoxic properties of rtPA but not those of blood degradation products. Possibly, fibrinolytic therapy of ICH is more beneficial if combined with agents such as MK801.

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Intracerebral Hematoma Lysis

Veit Rohde and Uzma Samadani

Object

Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model.

Methods

Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed.

The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (±standard error of the mean [SEM]) thrombus volume of 1.43 ±0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (±SEM) thrombus volume of 19.99 ±3.74 mm3 (p <0.001).

Conclusions

Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.

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Spontaneous adrenal hemorrhage: a little-known complication of intracranial tumor surgery

Case report

Angelika Gutenberg, Bettina Lange, Bastian Gunawan, Joerg Larsen, Wolfgang Brück, Veit Rohde, and Raphaela Verheggen

✓ Nontraumatic adrenal hemorrhage in adults is uncommon and unexpected in the context of intracranial surgery. The authors report on a patient in whom hemodynamically relevant retroperitoneal bleeding developed within hours after an otherwise uneventful operation for a falcine meningioma. In this brief report they seek to draw attention to this rare but life-threatening complication, because rapid diagnosis can be life-saving.

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The impact of temporary clipping during aneurysm surgery on the incidence of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Vesna Malinova, Bawarjan Schatlo, Martin Voit, Patricia Suntheim, Veit Rohde, and Dorothee Mielke

OBJECTIVE

Clipping of a ruptured intracranial aneurysm requires some degree of vessel manipulation, which in turn is believed to contribute to vasoconstriction. One of the techniques used during surgery is temporary clipping of the parent vessel. Temporary clipping may either be mandatory in cases of premature rupture (rescue) or represent a precautionary or facilitating surgical step (elective). The aim of this study was to study the association between temporary clipping during aneurysm surgery and the incidence of vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) in a large clinical series.

METHODS

Seven hundred seventy-eight patients who underwent surgical aneurysm treatment after aSAH were retrospectively included in the study. In addition to surgical parameters, the authors recorded transcranial Doppler (TCD) sonography–documented vasospasm (TCD-vasospasm, blood flow acceleration > 120 cm/sec), delayed ischemic neurological deficits (DINDs), and delayed cerebral infarction (DCI). Multivariate binary logistic regression analysis was applied to assess the association between temporary clipping, vasospasm, DIND, and DCI.

RESULTS

Temporary clipping was performed in 338 (43.4%) of 778 patients during aneurysm surgery. TCD sonographic flow acceleration developed in 370 (47.6%), DINDs in 123 (15.8%), and DCI in 97 (12.5%). Patients with temporary clipping showed no significant increase in the incidence of TCD-vasospasm compared with patients without temporary clipping (49% vs 48%, respectively; p = 0.60). DINDs developed in 12% of patients with temporary clipping and 18% of those without temporary clipping (p = 0.01). DCI occurred in 9% of patients with temporary clipping and 15% of those without temporary clipping (p = 0.02). The need for rescue temporary clipping was a predictor for DCI; 19.5% of patients in the rescue temporary clipping group but only 11.3% in the elective temporary clipping group had infarcts (p = 0.02). Elective temporary clipping was not associated with TCD-vasospasm (p = 0.31), DIND (p = 0.18), or DCI (p = 0.06).

CONCLUSIONS

Temporary clipping did not contribute to a higher rate of TCD-vasospasm, DIND, or DCI in comparison with rates in patients without temporary clipping. In contrast, there was an association between temporary clipping and a lower incidence of DINDs and DCI. There is no reason to be hesitant in using elective temporary clipping if deemed appropriate.

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Endoscope-assisted visualization of 5-aminolevulinic acid fluorescence in surgery for brain metastases

Christoph Bettag, Abdelhalim Hussein, Bawarjan Schatlo, Alonso Barrantes-Freer, Tammam Abboud, Veit Rohde, and Dorothee Mielke

OBJECTIVE

Fluorescence-guided resection of cerebral metastases has been proposed as an approach to visualize residual tumor tissue and maximize the extent of resection. Critics have argued that tumor cells at the resection margins might be overlooked under microscopic visualization because of technical limitations. Therefore, an endoscope, which is capable of inducing fluorescence, has been applied with the aim of improving exposure of fluorescent tumor tissue. In this retrospective analysis, authors assessed the utility of endoscope assistance in 5-aminolevulinic acid (5-ALA) fluorescence–guided resection of brain metastases.

METHODS

Between June 2013 and December 2016, a standard 20-mg/kg dose of 5-ALA was administered 4 hours prior to surgery in 26 patients with suspected single brain metastases. After standard neuronavigated microsurgical tumor resection, a microscope capable of inducing fluorescence was used to examine tumor margins. The authors classified the remaining fluorescence into 3 grades (0 = none, 1 = weak, and 2 = strong). Endoscopic assistance was employed if no or only weak fluorescence was visualized at the resection margins under the microscope. Endoscopically identified fluorescent tissue at the margins was resected and evaluated separately via histological examination to prove or disprove tumor infiltration.

RESULTS

Under the microscope, weakly fluorescent tissue was seen at the margins of the resection cavity in 15/26 (57.7%) patients. In contrast, endoscopic inspection revealed strongly fluorescent tissue in 22/26 (84.6%) metastases. In 11/26 (42.3%) metastases no fluorescence at the tumor margins was detected by the microscope; however, strong fluorescence was visualized under the endoscope in 7 (63.6%) of these 11 metastases. In the 15 metastases with microscopically weak fluorescence, strong fluorescence was seen when using the endoscope. Neither microscopic nor endoscopic fluorescence was found in 4/26 (15.4%) cases. In the 26 patients, 96 histological specimens were obtained from the margins of the resection cavity. Findings from these specimens were in conjunction with the histopathological findings, allowing identification of metastatic infiltration with a sensitivity of 95.5% and a specificity of 75% using endoscope assistance.

CONCLUSIONS

Fluorescence-guided endoscope assistance may overcome the technical limitations of the conventional microscopic exposure of 5-ALA–fluorescent metastases and thereby increase visualization of fluorescent tumor tissue at the margins of the resection cavity with high sensitivity and acceptable specificity.

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Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage

Vesna Malinova, Karoline Dolatowski, Peter Schramm, Onnen Moerer, Veit Rohde, and Dorothee Mielke

OBJECT

This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI).

METHODS

Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)–measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated.

RESULTS

Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD–measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI.

CONCLUSIONS

Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD–measured BFV increase or persisting coma, do not contribute to information gain.