CORRESPONDENCE
for dabigatran (aDabi-Fab) have been published and studies are ongoing (5). Best literature recommendations regarding dabigatran include the discontinuation of therapy 12 days ahead of invasive procedures in patients with normal kidney function and 35 days in patients with impaired renal function. In patients in whom urgent surgery is mandated, no valid reversal treatment exists to date. A number of strategies have been proposed, and preclinical data suggest that prothrombin complex concentrates are a reasonable approach in an attempt to overcome the effect of dabigatran as a factor IIa inhibitor by raising the levels of vitamin Kdependent factors to supranormal levels. Hemodialysis may be considered for emergency reversal of dabigatran-induced anticoagulation, although it can be difficult to perform in a hemodynamically unstable patient, as it was the case in our 70-year-old patient who also suffered from autonomic instability (1-8). A consensus regarding the reversal of dabigatran-induced anticoagulation has not been reached yet. In the acute setting, we would recommend the discontinuation of dabigatran, meticulous local hemostatic control, and the use of prothrombin complex concentrate. Caregivers in general and neurologists and neurosurgeons in particular need to be aware of the possible complications of these newer oral anticoagulants. Sven Bamps1, Tomas Decramer1, Nicolas Vandenbussche2, Peter Verhamme3, Vincent Thijs2, Johan Van Loon1, Tom Theys1 From the 1KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurosurgery and Neuroanatomy, University Hospitals Leuven; 2KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, University Hospitals Leuven, Department of Neurology, VIB - Vesalius Research Center; and 3KU Leuven - University of Leuven, Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, University Hospitals Leuven, Department of Internal Medicine, Leuven, Belgium To whom correspondence should be addressed: Sven Bamps, M.D. [E-mail: [email protected]] Published online 16 October 2014; http://dx.doi.org/10.1016/j.wneu.2014.11.007.
REFERENCES 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139-1151, 2009. 2. Diaz M, Borobia A, Nuñez M, Virto A, Fabra S, Casado M, García-Erce J, Samama C: Use of prothrombin complex concentrates for urgent reversal of dabigatran in the emergency department. Haematologica 98:e143-e144, 2013. 3. Dickneite G, Hoffman M: Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost 111:189-198, 2014. 4. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P: EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 34: 2094-2106, 2013. 5. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T: A specific antidote for dabigatran: functional and structural characterization. Blood 121:3554-3562, 2013. 6. Stangier J, Clemens A: Pharmacology, pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 15(Suppl 1):9S-16S, 2009. 7. Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes D: Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (Dabigatran). Spine 37:E863-E865, 2012.
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8. van Ryn J, Stangier J, Haertter S, Liesenfeld K-H, Wienen W, Feuring M, Clemens A: Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103:1116-1127, 2010.
Vasospasm in Aneurysmal Subarachnoid Hemorrhage: An Evolving Knowledge read with great interest the paper by Billingsley et al. (1) on I have vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). It has been reported widely that cerebral vasospasm and the resulting cerebral ischemia occurring after subarachnoid hemorrhage (SAH) are responsible for the considerable morbidity and mortality in patients affected by cerebral aneurysms. In their article Billingsley et al. (1) have raised an important question from their accumulating data about cerebral vasospasm. Emerging data on vasospasm after SAH hold promise in changing what we still believe about such SAH-related complications. During the last century, a great consensus existed that cerebral vasospasm was the most important determinant of poor prognosis in patients with aSAH. Accordingly, many pharmacologic interventions have been assessed in experimental studies and unsuccessful clinical trials addressed to counteract the spastic activity of the cerebral arterial vessel. During the last decade, accumulating experimental and clinical evidence has demonstrated that the presence of delayed vasospasm of the major cerebral vessels may just be a contributing factor but not necessarily the principal determinant of delayed cerebral ischemia and delayed ischemic neurologic deficit. Cerebral infarction can occur when vasospasm is not angiographically detected in the territorial artery (2), and poor outcome in aSAH seems to be directly dependent on infarction but independent of vasospasm (5). There is increasing evidence that other contributing factors may be involved in the development of delayed cerebral ischemia, and their characterization and treatment could improve the consistently poor clinical outcome in patients with aSAH. It has been pointed out that may be an early, short-lived phase occurring immediately after SAH and a subsequent phase that is prolonged or chronic (3). Both phases of vasospasm are considered to result from an abnormal constriction of the muscular layers of both microcirculatory vessels and proximal vessel and have been considered the main cause of cerebral ischemia after SAH. However, whether the 2 phases are independent or interactive with respect to the clinical course has not been settled. Taken collectively, the role of vasospasm has probably been misinterpreted; therefore, treating vasospasm alone probably targets the wrong cause and may not lead to improvement in functional
Key words Aneurysmal subarachnoid hemorrhage - Cerebral vasospasm -
Abbreviations and Acronyms aSAH: Aneurysmal subarachnoid hemorrhage SAH: Subarachnoid hemorrhage
83 [2]: 257-260, FEBRUARY 2015 WORLD NEUROSURGERY
CORRESPONDENCE
outcome. In this scenario, new promising strategies should include pleiotropic molecules with neuroprotective properties (4). The mechanisms of neuroprotection appear to be multifaceted and may essentially range from vasodilation of the cerebral arteries to anti-inflammatory, antioxidative, and antiapoptotic effects. Giovanni Grasso Section of Neurosurgery, Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo, Palermo, Italy To whom correspondence should be addressed: Giovanni Grasso, M.D., Ph.D. [E-mail: [email protected]] Published online 20 November 2014; http://dx.doi.org/10.1016/j.wneu.2014.11.007.
REFERENCES 1. Billingsley JT, Hoh BL: Vasospasm in aneurysmal subarachnoid hemorrhage. World Neurosurg 83:250-251, 2014. 2. Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJ, Rinkel GJ: Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 51:813-819, 2009. 3. Grasso G: An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage brain research. Brain Res Brain Res Rev 44:49-63, 2004. 4. Grasso G, Tomasello F: Erythropoietin for subarachnoid hemorrhage: is there a reason for hope? World Neurosurg 77:46-48, 2012. 5. Vergouwen MD, Ilodigwe D, Macdonald RL: Cerebral infarction after subarachnoid hemorrhage contributes to poor outcome by vasospasm-dependent and -independent effects. Stroke 42:924-929, 2011.
Mavridis’ Area and Electrode Target Localization in Nucleus Accumbens Deep Brain Stimulation LETTER: brain stimulation (DBS) of the human nucleus accumbens D eep (NA) for the treatment of psychiatric disorders became a clinical reality during the first decade of the 21st century (6). I read the recent article by Voges et al. (7) entitled “Deep Brain Stimulation Surgery for Alcohol Addiction” with great interest, and I would like to make a few comments on this important article. These authors reported their first experiences with bilateral NA DBS for the treatment of severe alcohol addiction (7). It is one of the very first reports on the use of NA DBS for the treatment of human alcohol dependence. Motivated by an accidental observation, Voges et al. (7) used the NA, which has a central position in the dopaminergic reward system, as a target for DBS in alcohol addiction with promising results. Electrical NA stimulation probably counterbalances the effect of drugrelated stimuli triggering involuntarily drug-seeking behavior (7).
Regarding their surgical procedure, they defined the target, referred to the most distal contact of the electrode, to a point 2 mm rostral to the anterior commissure at the level of the midsagittal plane, 3e4 mm ventral and 6e8 mm lateral of the midline (7). This is translated into target area coordinates (X, X0 , Y, Y0 , Z, Z0 ) ¼ (6, 8, 2, 2, 3, 4), with the anterior commissure anterior border defining the stereotactic reference point with coordinates (X, Y, Z) ¼ (0, 0, 0).
WORLD NEUROSURGERY 83 [2]: 257-260, FEBRUARY 2015
Figure 1. Mavridis’ area (M) in comparison with the electrode target area used by Voges et al. (7) (human brain, left hemisphere, coronal section at stereotactic level Y ¼ 2, zoom on basal ganglia). The pinhead represents the target point with stereotactic coordinates (X, Y, Z) ¼ (7, 2, 4). 1) nucleus accumbens; 2) head of the caudate nucleus; 3) anterior limb of the internal capsule; 4) putamen; 5) external capsule; 6) claustrum; 7) extreme capsule; 8) corpus callosum; 9) frontal horn of the lateral ventricle. e, electrode trajectory coronal projection; T, target area reported by Voges et al. (7); Y, Z, stereotactic coordinates [modified from (6)].
Voges et al. (7) defined their target area in projection onto the caudomedial, subventricular part of the NA (respective of the shell area) (7). To confirm the desired electrode localization, they intraoperatively used stereotactic computed tomography (CT), integrating the preoperative treatment planning magnetic resonance imaging via image fusion, stereotactic x-ray imaging, and postoperatively CT examination. CT as well as radiographs were fused with the planning magnetic resonance imaging in each case, confirming that the distal contacts of the DBS electrode were placed in the caudomedial NA as intended and the third contact within the transition area to the medial border of the abutting internal capsule and the highest (fourth) contact at a point in the most medial part of the capsule or in the transition area to the caudate (7). Interestingly, their target area is close to the recently described Mavridis’ area (MA) (2-6), the most reliable stereotactically standard part of the human NA, regardless of side or sex (5). MA is defined by coordinates (X, X0 , Y, Y0 , Z, Z0 ) ¼ (6, 9, 2, 2, 0.8, 2) in stereotactic space, based on the same stereotactic reference point (2-6) as those used by Voges et al.
www.WORLDNEUROSURGERY.org
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for dabigatran (aDabi-Fab) have been published and studies are ongoing (5). Best literature recommendations regarding dabigatran include the discontinuation of therapy 12 days ahead of invasive procedures in patients with normal kidney function and 35 days in patients with impaired renal function. In patients in whom urgent surgery is mandated, no valid reversal treatment exists to date. A number of strategies have been proposed, and preclinical data suggest that prothrombin complex concentrates are a reasonable approach in an attempt to overcome the effect of dabigatran as a factor IIa inhibitor by raising the levels of vitamin Kdependent factors to supranormal levels. Hemodialysis may be considered for emergency reversal of dabigatran-induced anticoagulation, although it can be difficult to perform in a hemodynamically unstable patient, as it was the case in our 70-year-old patient who also suffered from autonomic instability (1-8). A consensus regarding the reversal of dabigatran-induced anticoagulation has not been reached yet. In the acute setting, we would recommend the discontinuation of dabigatran, meticulous local hemostatic control, and the use of prothrombin complex concentrate. Caregivers in general and neurologists and neurosurgeons in particular need to be aware of the possible complications of these newer oral anticoagulants. Sven Bamps1, Tomas Decramer1, Nicolas Vandenbussche2, Peter Verhamme3, Vincent Thijs2, Johan Van Loon1, Tom Theys1 From the 1KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurosurgery and Neuroanatomy, University Hospitals Leuven; 2KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, University Hospitals Leuven, Department of Neurology, VIB - Vesalius Research Center; and 3KU Leuven - University of Leuven, Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, University Hospitals Leuven, Department of Internal Medicine, Leuven, Belgium To whom correspondence should be addressed: Sven Bamps, M.D. [E-mail: [email protected]] Published online 16 October 2014; http://dx.doi.org/10.1016/j.wneu.2014.11.007.
REFERENCES 1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139-1151, 2009. 2. Diaz M, Borobia A, Nuñez M, Virto A, Fabra S, Casado M, García-Erce J, Samama C: Use of prothrombin complex concentrates for urgent reversal of dabigatran in the emergency department. Haematologica 98:e143-e144, 2013. 3. Dickneite G, Hoffman M: Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence? Thromb Haemost 111:189-198, 2014. 4. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P: EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 34: 2094-2106, 2013. 5. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T: A specific antidote for dabigatran: functional and structural characterization. Blood 121:3554-3562, 2013. 6. Stangier J, Clemens A: Pharmacology, pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 15(Suppl 1):9S-16S, 2009. 7. Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes D: Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (Dabigatran). Spine 37:E863-E865, 2012.
258
www.SCIENCEDIRECT.com
8. van Ryn J, Stangier J, Haertter S, Liesenfeld K-H, Wienen W, Feuring M, Clemens A: Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103:1116-1127, 2010.
Vasospasm in Aneurysmal Subarachnoid Hemorrhage: An Evolving Knowledge read with great interest the paper by Billingsley et al. (1) on I have vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). It has been reported widely that cerebral vasospasm and the resulting cerebral ischemia occurring after subarachnoid hemorrhage (SAH) are responsible for the considerable morbidity and mortality in patients affected by cerebral aneurysms. In their article Billingsley et al. (1) have raised an important question from their accumulating data about cerebral vasospasm. Emerging data on vasospasm after SAH hold promise in changing what we still believe about such SAH-related complications. During the last century, a great consensus existed that cerebral vasospasm was the most important determinant of poor prognosis in patients with aSAH. Accordingly, many pharmacologic interventions have been assessed in experimental studies and unsuccessful clinical trials addressed to counteract the spastic activity of the cerebral arterial vessel. During the last decade, accumulating experimental and clinical evidence has demonstrated that the presence of delayed vasospasm of the major cerebral vessels may just be a contributing factor but not necessarily the principal determinant of delayed cerebral ischemia and delayed ischemic neurologic deficit. Cerebral infarction can occur when vasospasm is not angiographically detected in the territorial artery (2), and poor outcome in aSAH seems to be directly dependent on infarction but independent of vasospasm (5). There is increasing evidence that other contributing factors may be involved in the development of delayed cerebral ischemia, and their characterization and treatment could improve the consistently poor clinical outcome in patients with aSAH. It has been pointed out that may be an early, short-lived phase occurring immediately after SAH and a subsequent phase that is prolonged or chronic (3). Both phases of vasospasm are considered to result from an abnormal constriction of the muscular layers of both microcirculatory vessels and proximal vessel and have been considered the main cause of cerebral ischemia after SAH. However, whether the 2 phases are independent or interactive with respect to the clinical course has not been settled. Taken collectively, the role of vasospasm has probably been misinterpreted; therefore, treating vasospasm alone probably targets the wrong cause and may not lead to improvement in functional
Key words Aneurysmal subarachnoid hemorrhage - Cerebral vasospasm -
Abbreviations and Acronyms aSAH: Aneurysmal subarachnoid hemorrhage SAH: Subarachnoid hemorrhage
83 [2]: 257-260, FEBRUARY 2015 WORLD NEUROSURGERY
CORRESPONDENCE
outcome. In this scenario, new promising strategies should include pleiotropic molecules with neuroprotective properties (4). The mechanisms of neuroprotection appear to be multifaceted and may essentially range from vasodilation of the cerebral arteries to anti-inflammatory, antioxidative, and antiapoptotic effects. Giovanni Grasso Section of Neurosurgery, Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo, Palermo, Italy To whom correspondence should be addressed: Giovanni Grasso, M.D., Ph.D. [E-mail: [email protected]] Published online 20 November 2014; http://dx.doi.org/10.1016/j.wneu.2014.11.007.
REFERENCES 1. Billingsley JT, Hoh BL: Vasospasm in aneurysmal subarachnoid hemorrhage. World Neurosurg 83:250-251, 2014. 2. Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJ, Rinkel GJ: Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 51:813-819, 2009. 3. Grasso G: An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage brain research. Brain Res Brain Res Rev 44:49-63, 2004. 4. Grasso G, Tomasello F: Erythropoietin for subarachnoid hemorrhage: is there a reason for hope? World Neurosurg 77:46-48, 2012. 5. Vergouwen MD, Ilodigwe D, Macdonald RL: Cerebral infarction after subarachnoid hemorrhage contributes to poor outcome by vasospasm-dependent and -independent effects. Stroke 42:924-929, 2011.
Mavridis’ Area and Electrode Target Localization in Nucleus Accumbens Deep Brain Stimulation LETTER: brain stimulation (DBS) of the human nucleus accumbens D eep (NA) for the treatment of psychiatric disorders became a clinical reality during the first decade of the 21st century (6). I read the recent article by Voges et al. (7) entitled “Deep Brain Stimulation Surgery for Alcohol Addiction” with great interest, and I would like to make a few comments on this important article. These authors reported their first experiences with bilateral NA DBS for the treatment of severe alcohol addiction (7). It is one of the very first reports on the use of NA DBS for the treatment of human alcohol dependence. Motivated by an accidental observation, Voges et al. (7) used the NA, which has a central position in the dopaminergic reward system, as a target for DBS in alcohol addiction with promising results. Electrical NA stimulation probably counterbalances the effect of drugrelated stimuli triggering involuntarily drug-seeking behavior (7).
Regarding their surgical procedure, they defined the target, referred to the most distal contact of the electrode, to a point 2 mm rostral to the anterior commissure at the level of the midsagittal plane, 3e4 mm ventral and 6e8 mm lateral of the midline (7). This is translated into target area coordinates (X, X0 , Y, Y0 , Z, Z0 ) ¼ (6, 8, 2, 2, 3, 4), with the anterior commissure anterior border defining the stereotactic reference point with coordinates (X, Y, Z) ¼ (0, 0, 0).
WORLD NEUROSURGERY 83 [2]: 257-260, FEBRUARY 2015
Figure 1. Mavridis’ area (M) in comparison with the electrode target area used by Voges et al. (7) (human brain, left hemisphere, coronal section at stereotactic level Y ¼ 2, zoom on basal ganglia). The pinhead represents the target point with stereotactic coordinates (X, Y, Z) ¼ (7, 2, 4). 1) nucleus accumbens; 2) head of the caudate nucleus; 3) anterior limb of the internal capsule; 4) putamen; 5) external capsule; 6) claustrum; 7) extreme capsule; 8) corpus callosum; 9) frontal horn of the lateral ventricle. e, electrode trajectory coronal projection; T, target area reported by Voges et al. (7); Y, Z, stereotactic coordinates [modified from (6)].
Voges et al. (7) defined their target area in projection onto the caudomedial, subventricular part of the NA (respective of the shell area) (7). To confirm the desired electrode localization, they intraoperatively used stereotactic computed tomography (CT), integrating the preoperative treatment planning magnetic resonance imaging via image fusion, stereotactic x-ray imaging, and postoperatively CT examination. CT as well as radiographs were fused with the planning magnetic resonance imaging in each case, confirming that the distal contacts of the DBS electrode were placed in the caudomedial NA as intended and the third contact within the transition area to the medial border of the abutting internal capsule and the highest (fourth) contact at a point in the most medial part of the capsule or in the transition area to the caudate (7). Interestingly, their target area is close to the recently described Mavridis’ area (MA) (2-6), the most reliable stereotactically standard part of the human NA, regardless of side or sex (5). MA is defined by coordinates (X, X0 , Y, Y0 , Z, Z0 ) ¼ (6, 9, 2, 2, 0.8, 2) in stereotactic space, based on the same stereotactic reference point (2-6) as those used by Voges et al.
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