Acta Neurol Belg DOI 10.1007/s13760-013-0271-x
ORIGINAL ARTICLE
Delayed intravenous thrombolysis based on MRI mismatch in posterior circulation stroke Nele Deprez • Veerle De Herdt • Jelle Vandersteene Marjan Acou • Luc Defreyne • Dimitri Hemelsoet
•
Received: 26 August 2013 / Accepted: 12 December 2013 Ó Belgian Neurological Society 2013
Abstract The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI–PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI–PWI mismatch zone in the posterior circulation territory.
N. Deprez (&) Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium e-mail: [email protected] V. De Herdt D. Hemelsoet Department of Neurology, Ghent University Hospital, Ghent, Belgium J. Vandersteene Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium M. Acou Department of Radiology, Ghent University Hospital, Ghent, Belgium L. Defreyne Department of Vascular and Interventional Radiology, Ghent University Hospital, Ghent, Belgium
Keywords
Stroke Delayed Intravenous thrombolysis
Introduction The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow (CBF) impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI–PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery (PICA) with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI– PWI mismatch zone in the posterior circulation territory.
Case report A 43-year-old man presented at the emergency department of another hospital with a sudden onset of right frontoparietal headache with an intensity of 10/10 on the visual analogue scale (VAS). The headache was accompanied by a numb feeling at the right side of his face and the limbs on the left side. The headache and the concomitant sensory symptoms disappeared after 1 h. The next day, there was a short-lasting recurrence of the same symptoms with complete recovery. A brain MRI on the same day did not show any acute DWI abnormalities. The initial working hypothesis was migraine
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Acta Neurol Belg
with aura and a treatment with salicylic acid and corticosteroids was administered. In the early morning of the next day (8:00 a.m.), a right hemicranial headache returned with maximal intensity (VAS 10/10), accompanied by persistent numbness of the right side of his face and his left arm and leg. For the first time there was also severe vertigo. Because these symptoms did not recover the patient was transferred to our hospital for a second opinion. Upon arrival he had a pale facial appearance, he was sweating and suffered from severe vertigo, nausea, and vomitus. Neurological examination revealed a paresis of the inferior branch of the right facial nerve, a right-sided Horner syndrome, a third grade left-beating nystagmus and a hypoesthesia of the right side of his face and his left leg with a slightly diminished grasp force of the left hand. He also suffered from swallowing problems and hoarseness. He could not stand upright without any help. The National Institutes of Health Stroke Scale (NIHSS) score was 2 and the modified Rankin score (mRS) was 4. A new brain CT scan (including CT angiography) at the emergency department showed an occlusion of the right vertebral artery (image not shown). An urgent brain MRI revealed a recent ischaemic zone in the right lateral medulla oblongata due to a vertebral artery dissection (Fig. 1a, c, e) and a marked
DWI–PWI mismatch in the right cerebellar hemisphere (see Fig. 1a, b, d). Based on this MRI DWI–PWI mismatch, IV thrombolysis was given at 19 h 20 min, 11 h and 20 min following symptom onset. Most of the symptoms improved during the following days. The severe right-sided hemicranial headache persisted for which analgesic therapy was continued. Additional classical cerebral angiography confirmed a dissection of the right vertebral artery with an occlusion of the right PICA (image not shown). A control brain MRI 1 month after the event confirmed brain stem ischemia with sparing of the cerebellar DWI–PWI mismatch zone (see Fig. 1f). Additional investigations looking for possible causes of ischemic stroke (e.g., cardiac embolic sources, coagulation deficits, genetic causes) did not reveal other abnormalities. A treatment with warfarin was given and replaced by aspirin after 5 months. Clinical follow-up only showed a mild residual sensory deficit at the right side of the face and at the left arm (NIHSS 1, mRS 1).
Fig. 1 a Diffusion restriction in the medulla oblongata (arrow), without any cerebellar diffusion abnormality. b, c PWI Tmax: perfusion defect in the right cerebellum (1b, arrow) and right medulla oblongata (1c, arrow). d, e PWI time-to-peak (TTP): perfusion defect in the right cerebellum (1d, arrow) and right medulla oblongata (1e,
arrow). f FLAIR 1 month after the event: residual ischemic lesion in the right medulla oblongata (arrow) without cerebellar infarction. Figure 1b, c, d, e are obtained after post-processing with OleaSphereTM 2.2 (Olea Medical, La Ciotat, France)
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Discussion Current guidelines recommend initiation of IV thrombolysis in acute stroke within 3 h (grade 1A) and 4.5 h (grade
Acta Neurol Belg
2C) of symptom onset [1]. This time-based approach neglects the individual variation of CBF impairment and restricts the eligible patient population. The individual variation of CBF impairment can mainly be explained by the variable degree of collateral circulation [2]. It is presumed that MRI DWI–PWI mismatch permits to identify that area with normal diffusion but tissue hypoperfusion which reflects tissue that is likely to benefit from reperfusion [3]. In several studies enrolled with patients who presented with an infarction in the anterior cerebral circulation, IV thrombolysis more than 3 h following symptom onset based on MRI mismatch criteria appeared to be beneficial [4–7]. Only one case-report describes IV thrombolysis following an extended time-window for a posterior circulation stroke based upon DWI–PWI mismatch criteria [8]. To the best of our knowledge, our case describes the longest time interval between symptom onset and IV thrombolysis in the posterior circulation based upon MRI DWI–PWI with beneficial clinical outcome. Further research is needed to evaluate whether IV thrombolysis based on MRI mismatch is a reasonable treatment option in this therapeutically neglected group of patients who present beyond the current established time window for acute treatment and whether our findings can be generalized to patients with stroke affecting the posterior circulation. Conflict of interest The authors N. Deprez, V. De Herdt, J. Vandersteene, M. Acou, L. Defreyne, D. Hemelsoet declare that they have not conflict of interest.
References 1. Lansberg MG, O’Donnell MJ, Khatri P, Lang ES, Nguyen-Huynh MN, Schwartz NE et al (2012) Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 1(2 Suppl):e601S–e636S 2. Yoo AJ, Pulli B, Gonzalez RG (2011) Imaging-based treatment selection for intravenous and intra-arterial stroke therapies: a comprehensive review. Expert Rev Cardiovasc Ther 9(7):857–876 3. Rother J, Schellinger PD, Gass A, Siebler M, Villringer A, Fiebach JB et al (2002) Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke \6 hours. Stroke 33(10):2438–2445 4. Warach S, Al-Rawi Y, Furlan AJ, Fiebach JB, Wintermark M, Lindsten A et al (2012) Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials. Stroke 43(9):2313–2318 5. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E et al (2006) Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 60(5):508–517 6. Jakubowska MM, Michels P, Muller-Jensen A, Leppien A, Eckert B (2008) Endovascular treatment in proximal and intracranial carotid occlusion 9 hours after symptom onset. Neuroradiology 50(7):599–604 7. Joux J, Nazarov B, Olindo S, Smadja D (2012) Very late IV thrombolysis in acute ischemic stroke: a successful case in proximal MCA occlusion. Clin Neurol Neurosur 114(6):820–822 8. Kohrmann M, Sauer R, Huttner HB, Engelhorn T, Doerfler A, Schellinger PD (2009) MRI mismatch-based intravenous thrombolysis for isolated cerebellar infarction. Stroke 40(5):1897–1899
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ORIGINAL ARTICLE
Delayed intravenous thrombolysis based on MRI mismatch in posterior circulation stroke Nele Deprez • Veerle De Herdt • Jelle Vandersteene Marjan Acou • Luc Defreyne • Dimitri Hemelsoet
•
Received: 26 August 2013 / Accepted: 12 December 2013 Ó Belgian Neurological Society 2013
Abstract The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI–PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI–PWI mismatch zone in the posterior circulation territory.
N. Deprez (&) Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium e-mail: [email protected] V. De Herdt D. Hemelsoet Department of Neurology, Ghent University Hospital, Ghent, Belgium J. Vandersteene Department of Neurosurgery, Ghent University Hospital, Ghent, Belgium M. Acou Department of Radiology, Ghent University Hospital, Ghent, Belgium L. Defreyne Department of Vascular and Interventional Radiology, Ghent University Hospital, Ghent, Belgium
Keywords
Stroke Delayed Intravenous thrombolysis
Introduction The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow (CBF) impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI–PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery (PICA) with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI– PWI mismatch zone in the posterior circulation territory.
Case report A 43-year-old man presented at the emergency department of another hospital with a sudden onset of right frontoparietal headache with an intensity of 10/10 on the visual analogue scale (VAS). The headache was accompanied by a numb feeling at the right side of his face and the limbs on the left side. The headache and the concomitant sensory symptoms disappeared after 1 h. The next day, there was a short-lasting recurrence of the same symptoms with complete recovery. A brain MRI on the same day did not show any acute DWI abnormalities. The initial working hypothesis was migraine
123
Acta Neurol Belg
with aura and a treatment with salicylic acid and corticosteroids was administered. In the early morning of the next day (8:00 a.m.), a right hemicranial headache returned with maximal intensity (VAS 10/10), accompanied by persistent numbness of the right side of his face and his left arm and leg. For the first time there was also severe vertigo. Because these symptoms did not recover the patient was transferred to our hospital for a second opinion. Upon arrival he had a pale facial appearance, he was sweating and suffered from severe vertigo, nausea, and vomitus. Neurological examination revealed a paresis of the inferior branch of the right facial nerve, a right-sided Horner syndrome, a third grade left-beating nystagmus and a hypoesthesia of the right side of his face and his left leg with a slightly diminished grasp force of the left hand. He also suffered from swallowing problems and hoarseness. He could not stand upright without any help. The National Institutes of Health Stroke Scale (NIHSS) score was 2 and the modified Rankin score (mRS) was 4. A new brain CT scan (including CT angiography) at the emergency department showed an occlusion of the right vertebral artery (image not shown). An urgent brain MRI revealed a recent ischaemic zone in the right lateral medulla oblongata due to a vertebral artery dissection (Fig. 1a, c, e) and a marked
DWI–PWI mismatch in the right cerebellar hemisphere (see Fig. 1a, b, d). Based on this MRI DWI–PWI mismatch, IV thrombolysis was given at 19 h 20 min, 11 h and 20 min following symptom onset. Most of the symptoms improved during the following days. The severe right-sided hemicranial headache persisted for which analgesic therapy was continued. Additional classical cerebral angiography confirmed a dissection of the right vertebral artery with an occlusion of the right PICA (image not shown). A control brain MRI 1 month after the event confirmed brain stem ischemia with sparing of the cerebellar DWI–PWI mismatch zone (see Fig. 1f). Additional investigations looking for possible causes of ischemic stroke (e.g., cardiac embolic sources, coagulation deficits, genetic causes) did not reveal other abnormalities. A treatment with warfarin was given and replaced by aspirin after 5 months. Clinical follow-up only showed a mild residual sensory deficit at the right side of the face and at the left arm (NIHSS 1, mRS 1).
Fig. 1 a Diffusion restriction in the medulla oblongata (arrow), without any cerebellar diffusion abnormality. b, c PWI Tmax: perfusion defect in the right cerebellum (1b, arrow) and right medulla oblongata (1c, arrow). d, e PWI time-to-peak (TTP): perfusion defect in the right cerebellum (1d, arrow) and right medulla oblongata (1e,
arrow). f FLAIR 1 month after the event: residual ischemic lesion in the right medulla oblongata (arrow) without cerebellar infarction. Figure 1b, c, d, e are obtained after post-processing with OleaSphereTM 2.2 (Olea Medical, La Ciotat, France)
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Discussion Current guidelines recommend initiation of IV thrombolysis in acute stroke within 3 h (grade 1A) and 4.5 h (grade
Acta Neurol Belg
2C) of symptom onset [1]. This time-based approach neglects the individual variation of CBF impairment and restricts the eligible patient population. The individual variation of CBF impairment can mainly be explained by the variable degree of collateral circulation [2]. It is presumed that MRI DWI–PWI mismatch permits to identify that area with normal diffusion but tissue hypoperfusion which reflects tissue that is likely to benefit from reperfusion [3]. In several studies enrolled with patients who presented with an infarction in the anterior cerebral circulation, IV thrombolysis more than 3 h following symptom onset based on MRI mismatch criteria appeared to be beneficial [4–7]. Only one case-report describes IV thrombolysis following an extended time-window for a posterior circulation stroke based upon DWI–PWI mismatch criteria [8]. To the best of our knowledge, our case describes the longest time interval between symptom onset and IV thrombolysis in the posterior circulation based upon MRI DWI–PWI with beneficial clinical outcome. Further research is needed to evaluate whether IV thrombolysis based on MRI mismatch is a reasonable treatment option in this therapeutically neglected group of patients who present beyond the current established time window for acute treatment and whether our findings can be generalized to patients with stroke affecting the posterior circulation. Conflict of interest The authors N. Deprez, V. De Herdt, J. Vandersteene, M. Acou, L. Defreyne, D. Hemelsoet declare that they have not conflict of interest.
References 1. Lansberg MG, O’Donnell MJ, Khatri P, Lang ES, Nguyen-Huynh MN, Schwartz NE et al (2012) Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 1(2 Suppl):e601S–e636S 2. Yoo AJ, Pulli B, Gonzalez RG (2011) Imaging-based treatment selection for intravenous and intra-arterial stroke therapies: a comprehensive review. Expert Rev Cardiovasc Ther 9(7):857–876 3. Rother J, Schellinger PD, Gass A, Siebler M, Villringer A, Fiebach JB et al (2002) Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke \6 hours. Stroke 33(10):2438–2445 4. Warach S, Al-Rawi Y, Furlan AJ, Fiebach JB, Wintermark M, Lindsten A et al (2012) Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials. Stroke 43(9):2313–2318 5. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E et al (2006) Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 60(5):508–517 6. Jakubowska MM, Michels P, Muller-Jensen A, Leppien A, Eckert B (2008) Endovascular treatment in proximal and intracranial carotid occlusion 9 hours after symptom onset. Neuroradiology 50(7):599–604 7. Joux J, Nazarov B, Olindo S, Smadja D (2012) Very late IV thrombolysis in acute ischemic stroke: a successful case in proximal MCA occlusion. Clin Neurol Neurosur 114(6):820–822 8. Kohrmann M, Sauer R, Huttner HB, Engelhorn T, Doerfler A, Schellinger PD (2009) MRI mismatch-based intravenous thrombolysis for isolated cerebellar infarction. Stroke 40(5):1897–1899
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