Journal of the Neurological Sciences 381 (2017) 269–271
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Aseptic meningitis due to reperfusion injury after carotid artery stenting
MARK
A R T I C L E I N F O Keywords: Carotid artery stenting Carotid revascularization Cerebral hyperperfusion syndrome Reperfusion injury Aseptic meningitis
1. Case A 78-year-old man with hypertension and diabetes mellitus had a 20-min episode of expressive aphasia. Computed tomography (CT) head and neck angiogram showed a near occlusion of the proximal left internal carotid artery (ICA) with distal collapse of the vessel. He was already on optimal medical management and agreed to undergo carotid artery stenting (CAS). Fifteen days after onset of symptoms balloon angioplasty and stenting of the left ICA was performed under distal embolic protection (Fig. 1A, B). He was initially well after the procedure but then developed aphasia and right-sided weakness, with a peak blood pressure of 191/95 mmHg. Repeat CT head and neck angiogram with perfusion imaging two hours post-procedure showed patency of the ICA stent without large vessel occlusion, infarction or hemorrhage. There was mildly increased blood flow and blood volume in the left frontal cerebral convexity, suggesting hyperperfusion (Fig. 1C, D). His blood pressure target was set to less than 160/90 mmHg. Repeat CT head performed 11 h post-procedure showed cortical edema of the left frontal lobe (Fig. 1E) that was resolving on magnetic resonance imaging (MRI) head performed 18 h post-procedure (Fig. 1F). His body temperature rose to 39.4 °C with no identifiable extracranial cause so lumbar puncture was performed 30 h post-procedure to rule out infection. Cerebrospinal fluid (CSF) revealed a corrected white blood cell count of 767 × 106/L (normal 0–5 × 106/L) that was 90% neutrophils, elevated protein of 1538 mg/L (normal 200–400 mg/L) and normal glucose, with negative bacterial culture and viral polymerase chain reaction testing. Stringent blood pressure control was continued and his body temperature normalized after six hours, with improvement of aphasia and right-sided weakness two days post-procedure. Electroencephalography showed left hemispheric slowing with periodic epileptiform discharges but given his clinical improvement no anti-seizure medication was administered. Six days post-procedure his neurologic symptoms had resolved and he was discharged home. 2. Discussion Symptomatic increased regional blood flow after CAS or carotid endarterectomy (CEA) is commonly referred to as cerebral reperfusion or hyperperfusion syndrome (CHS). It is characterized by hypertension, headache, focal neurologic deficits and seizures, with cerebral edema or hemorrhage in severe cases [1]. Impaired cerebrovascular autoregulation due to chronic ischemia causes symptoms after carotid revascularization in patients with CHS, and stringent blood pressure control is the mainstay of treatment [1]. Interestingly, CHS typically occurs within 12 h of CAS compared to six days after carotid endarterectomy (CEA), suggesting possible disease heterogeneity with distinct mechanisms between acute and more delayed presentations [2]. Recently, reperfusion injury causing blood–brain barrier disruption on gadolinium-enhanced MRI has been identified in patients acutely after carotid revascularization even in the absence of marked cerebral hyperperfusion, and may be more common after CAS than CEA [3,4]. It remains unclear how this imaging finding, termed a hyperintense acute reperfusion marker, relates to the clinical symptomatology seen in CHS [3,4]. Cho et al. posited that this blood–brain barrier disruption was distinct from meningeal inflammation due to lack of symptoms indicating meningitis in their patients [3]. However, we present the first reported human case of CHS presenting acutely after CAS with markedly inflammatory CSF in the absence of infection, compatible with aseptic meningitis. Although aseptic meningitis is classically associated with a lymphocytic CSF pleocytosis, a predominance of neutrophils may occur early on in the disease course [5]. Moreover, early neutrophil accumulation and blood–brain barrier disruption through the release of neutrophil-derived oxidants and proteolytic enzymes is seen in experimental models of cerebral reperfusion injury, consistent with the neutrophilic CSF pleocytosis found in our patient [6]. Reperfusion injury may therefore elicit a clinically significant inflammatory response that contributes to the cerebral dysfunction seen in rare patients acutely after carotid revascularization. In contrast, inflammation may not be prominent in more delayed presentations, as suggested by a case of CHS eight days after CEA with unremarkable CSF [7]. Further study into the role of inflammation among patients with CHS, especially those who present acutely after carotid revascularization, may help elucidate disease mechanisms and direct future therapeutic development.
http://dx.doi.org/10.1016/j.jns.2017.08.3255 Received 8 July 2017; Received in revised form 21 August 2017; Accepted 28 August 2017 Available online 31 August 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 381 (2017) 269–271
Letter to the Editor
Fig. 1. Digital subtraction angiogram confirms near-occlusion of the left ICA (A). There is no residual stenosis after balloon angioplasty and stent placement (B). Two hours postprocedure, CT head perfusion shows mildly increased cerebral blood flow (C) and blood volume (D) in the left frontal convexity gyri compared to the contralateral side, suggesting hyperperfusion. Repeat CT head 11 h post-procedure shows left frontal convexity cortical edema with sulcal effacement (E), while MRI head 18 h post-procedure shows subtle left frontal gyral T2-hyperintensity with resolving sulcal effacement on fluid-attenuated inversion recovery imaging (F).
Funding Dr. Sposato was supported by the Edward and Alma Saraydar Neurosciences Fund (London Health Sciences Foundation, London, Ontario, Canada), the Kathleen & Dr Henry Barnett Research Chair in Stroke Research (Western University, London, Ontario, Canada), and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario –AMOSO– (Ontario, Canada). Conflict of interest The authors have no relevant conflicts of interest to disclose. References [1] W.N. van Mook, R.J. Rennenberg, G.W. Schurink, et al., Cerebral hyperperfusion syndrome, Lancet Neurol. 4 (12) (2005) 877–888. [2] K. Ogasawara, N. Sakai, T. Kuroiwa, et al., Intracranial hemorrhage associated with cerebral hyperperfusion syndrome following carotid endarterectomy and carotid artery stenting: retrospective review of 4494 patients, J. Neurosurg. 107 (6) (2007) 1130–1136. [3] H.-J. Cho, Y.J. Kim, J.H. Lee, et al., Post-carotid stenting reperfusion injury with blood–brain barrier disruption on gadolinium-enhanced FLAIR MRI, BMC Neurol. 14 (1) (2014) 178. [4] A.-H. Cho, Y.-P. Cho, D.H. Lee, et al., Reperfusion injury on magnetic resonance imaging after carotid revascularization, Stroke 45 (2) (2014). [5] R. Straussberg, L. Harel, M. Nussinovitch, J. Amir, Absolute neutrophil count in aseptic and bacterial meningitis related to time of lumbar puncture, Pediatr. Neurol. 28 (5) (2003) 365–369. [6] J. Pan, A.-A. Konstas, B. Bateman, G.A. Ortolano, J. Pile-Spellman, Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies, Neuroradiology 49 (2) (2007) 93–102. [7] K. Sanders, P. Demaerel, R. Lemmens, Aphasia 1 week after carotid endarterectomy, Stroke 47 (4) (2016).
270
Journal of the Neurological Sciences 381 (2017) 269–271
Letter to the Editor
Adrian Budhram⁎, Seth A. Climans, Christine Le, Courtney S. Casserly Department of Clinical Neurological Sciences, Division of Neurology, Western University, London, Ontario, Canada E-mail address: [email protected] Michael Mayich Department of Medical Imaging, Division of Radiology, Western University, London, Ontario, Canada Stephen P. Lownie Department of Medical Imaging, Division of Radiology, Western University, London, Ontario, Canada Department of Clinical Neurological Sciences, Division of Neurosurgery, Western University, London, Ontario, Canada Department of Clinical Neurological Sciences, Division of Neurology, Department of Epidemiology and Biostatistics, Department of Anatomy and Cell Biology, Stroke, Dementia & Heart Disease Laboratory,
⁎
Corresponding author at: University Hospital, 339 Windermere Rd, London N6A 5A5, Ontario, Canada.
271
Western Western Western Western
University, University, University, University,
Luciano A. Sposato London, Ontario, Canada London, Ontario, Canada London, Ontario, Canada London, Ontario, Canada
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Aseptic meningitis due to reperfusion injury after carotid artery stenting
MARK
A R T I C L E I N F O Keywords: Carotid artery stenting Carotid revascularization Cerebral hyperperfusion syndrome Reperfusion injury Aseptic meningitis
1. Case A 78-year-old man with hypertension and diabetes mellitus had a 20-min episode of expressive aphasia. Computed tomography (CT) head and neck angiogram showed a near occlusion of the proximal left internal carotid artery (ICA) with distal collapse of the vessel. He was already on optimal medical management and agreed to undergo carotid artery stenting (CAS). Fifteen days after onset of symptoms balloon angioplasty and stenting of the left ICA was performed under distal embolic protection (Fig. 1A, B). He was initially well after the procedure but then developed aphasia and right-sided weakness, with a peak blood pressure of 191/95 mmHg. Repeat CT head and neck angiogram with perfusion imaging two hours post-procedure showed patency of the ICA stent without large vessel occlusion, infarction or hemorrhage. There was mildly increased blood flow and blood volume in the left frontal cerebral convexity, suggesting hyperperfusion (Fig. 1C, D). His blood pressure target was set to less than 160/90 mmHg. Repeat CT head performed 11 h post-procedure showed cortical edema of the left frontal lobe (Fig. 1E) that was resolving on magnetic resonance imaging (MRI) head performed 18 h post-procedure (Fig. 1F). His body temperature rose to 39.4 °C with no identifiable extracranial cause so lumbar puncture was performed 30 h post-procedure to rule out infection. Cerebrospinal fluid (CSF) revealed a corrected white blood cell count of 767 × 106/L (normal 0–5 × 106/L) that was 90% neutrophils, elevated protein of 1538 mg/L (normal 200–400 mg/L) and normal glucose, with negative bacterial culture and viral polymerase chain reaction testing. Stringent blood pressure control was continued and his body temperature normalized after six hours, with improvement of aphasia and right-sided weakness two days post-procedure. Electroencephalography showed left hemispheric slowing with periodic epileptiform discharges but given his clinical improvement no anti-seizure medication was administered. Six days post-procedure his neurologic symptoms had resolved and he was discharged home. 2. Discussion Symptomatic increased regional blood flow after CAS or carotid endarterectomy (CEA) is commonly referred to as cerebral reperfusion or hyperperfusion syndrome (CHS). It is characterized by hypertension, headache, focal neurologic deficits and seizures, with cerebral edema or hemorrhage in severe cases [1]. Impaired cerebrovascular autoregulation due to chronic ischemia causes symptoms after carotid revascularization in patients with CHS, and stringent blood pressure control is the mainstay of treatment [1]. Interestingly, CHS typically occurs within 12 h of CAS compared to six days after carotid endarterectomy (CEA), suggesting possible disease heterogeneity with distinct mechanisms between acute and more delayed presentations [2]. Recently, reperfusion injury causing blood–brain barrier disruption on gadolinium-enhanced MRI has been identified in patients acutely after carotid revascularization even in the absence of marked cerebral hyperperfusion, and may be more common after CAS than CEA [3,4]. It remains unclear how this imaging finding, termed a hyperintense acute reperfusion marker, relates to the clinical symptomatology seen in CHS [3,4]. Cho et al. posited that this blood–brain barrier disruption was distinct from meningeal inflammation due to lack of symptoms indicating meningitis in their patients [3]. However, we present the first reported human case of CHS presenting acutely after CAS with markedly inflammatory CSF in the absence of infection, compatible with aseptic meningitis. Although aseptic meningitis is classically associated with a lymphocytic CSF pleocytosis, a predominance of neutrophils may occur early on in the disease course [5]. Moreover, early neutrophil accumulation and blood–brain barrier disruption through the release of neutrophil-derived oxidants and proteolytic enzymes is seen in experimental models of cerebral reperfusion injury, consistent with the neutrophilic CSF pleocytosis found in our patient [6]. Reperfusion injury may therefore elicit a clinically significant inflammatory response that contributes to the cerebral dysfunction seen in rare patients acutely after carotid revascularization. In contrast, inflammation may not be prominent in more delayed presentations, as suggested by a case of CHS eight days after CEA with unremarkable CSF [7]. Further study into the role of inflammation among patients with CHS, especially those who present acutely after carotid revascularization, may help elucidate disease mechanisms and direct future therapeutic development.
http://dx.doi.org/10.1016/j.jns.2017.08.3255 Received 8 July 2017; Received in revised form 21 August 2017; Accepted 28 August 2017 Available online 31 August 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 381 (2017) 269–271
Letter to the Editor
Fig. 1. Digital subtraction angiogram confirms near-occlusion of the left ICA (A). There is no residual stenosis after balloon angioplasty and stent placement (B). Two hours postprocedure, CT head perfusion shows mildly increased cerebral blood flow (C) and blood volume (D) in the left frontal convexity gyri compared to the contralateral side, suggesting hyperperfusion. Repeat CT head 11 h post-procedure shows left frontal convexity cortical edema with sulcal effacement (E), while MRI head 18 h post-procedure shows subtle left frontal gyral T2-hyperintensity with resolving sulcal effacement on fluid-attenuated inversion recovery imaging (F).
Funding Dr. Sposato was supported by the Edward and Alma Saraydar Neurosciences Fund (London Health Sciences Foundation, London, Ontario, Canada), the Kathleen & Dr Henry Barnett Research Chair in Stroke Research (Western University, London, Ontario, Canada), and the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario –AMOSO– (Ontario, Canada). Conflict of interest The authors have no relevant conflicts of interest to disclose. References [1] W.N. van Mook, R.J. Rennenberg, G.W. Schurink, et al., Cerebral hyperperfusion syndrome, Lancet Neurol. 4 (12) (2005) 877–888. [2] K. Ogasawara, N. Sakai, T. Kuroiwa, et al., Intracranial hemorrhage associated with cerebral hyperperfusion syndrome following carotid endarterectomy and carotid artery stenting: retrospective review of 4494 patients, J. Neurosurg. 107 (6) (2007) 1130–1136. [3] H.-J. Cho, Y.J. Kim, J.H. Lee, et al., Post-carotid stenting reperfusion injury with blood–brain barrier disruption on gadolinium-enhanced FLAIR MRI, BMC Neurol. 14 (1) (2014) 178. [4] A.-H. Cho, Y.-P. Cho, D.H. Lee, et al., Reperfusion injury on magnetic resonance imaging after carotid revascularization, Stroke 45 (2) (2014). [5] R. Straussberg, L. Harel, M. Nussinovitch, J. Amir, Absolute neutrophil count in aseptic and bacterial meningitis related to time of lumbar puncture, Pediatr. Neurol. 28 (5) (2003) 365–369. [6] J. Pan, A.-A. Konstas, B. Bateman, G.A. Ortolano, J. Pile-Spellman, Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies, Neuroradiology 49 (2) (2007) 93–102. [7] K. Sanders, P. Demaerel, R. Lemmens, Aphasia 1 week after carotid endarterectomy, Stroke 47 (4) (2016).
270
Journal of the Neurological Sciences 381 (2017) 269–271
Letter to the Editor
Adrian Budhram⁎, Seth A. Climans, Christine Le, Courtney S. Casserly Department of Clinical Neurological Sciences, Division of Neurology, Western University, London, Ontario, Canada E-mail address: [email protected] Michael Mayich Department of Medical Imaging, Division of Radiology, Western University, London, Ontario, Canada Stephen P. Lownie Department of Medical Imaging, Division of Radiology, Western University, London, Ontario, Canada Department of Clinical Neurological Sciences, Division of Neurosurgery, Western University, London, Ontario, Canada Department of Clinical Neurological Sciences, Division of Neurology, Department of Epidemiology and Biostatistics, Department of Anatomy and Cell Biology, Stroke, Dementia & Heart Disease Laboratory,
⁎
Corresponding author at: University Hospital, 339 Windermere Rd, London N6A 5A5, Ontario, Canada.
271
Western Western Western Western
University, University, University, University,
Luciano A. Sposato London, Ontario, Canada London, Ontario, Canada London, Ontario, Canada London, Ontario, Canada
