The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2015 Copyright Ó 2015 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2015.01.012
Selected Topics: Neurological Emergencies
REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME Kenneth R. L. Bernard, MD, MBA* and Morris Rivera, MD† *Harvard Affiliated Emergency Medicine Program, Department of Emergency Medicine, Brigham and Womens/Massachusetts General Hospital, Boston, Massachusetts and †Partners Healthcare, Martha’s Vineyard Hospital, Oak Bluffs, Massachusetts Reprint Address: Kenneth R. L. Bernard, MD, MBA, Harvard Affiliated Emergency Medicine Progam, Department of Emergency Medicine, Brigham and Womens/Massachusetts General Hospital, 75 Francis Street, Neville House, Boston, MA 02115
, Abstract—Background: Reversible cerebral vasoconstriction syndrome (RCVS) is an underappreciated and poorly understood cause of thunderclap headache (TCH). Although self-limited in the majority of patients, incidence is increasing, with presentations overlapping considerably with life-threatening conditions, such as aneurysmal subarachnoid hemorrhage and stroke. In addition, radiographic findings seen in RCVS are also present in primary angiitis of the central nervous system (PACNS). Misdiagnosis of RCVS might subject patients to unnecessary invasive testing and immunosuppressive therapy. Furthermore, the recommended treatment of glucocorticoids used in PACNS can be harmful in RCVS. RCVS is not a benign condition, as patients can have ischemic or hemorrhagic complications leading to persistent neurologic deficits and even death. Current treatments, guided only by expert consensus, have no proven effect on these complications, which argues the need for accurate identification of patients with RCVS and prospective studies to validate treatment and inform prognoses. Case Report: We describe a previously healthy male who presented to the emergency department after 2 episodes of TCH and angiography consistent with RCVS. Why Should An Emergency Physician Be Aware of This?: RCVS is a common but underappreciated cause of TCH. The likelihood of misdiagnosing RCVS following the accepted diagnostic algorithm of acute headache in the emergency department is high due to a lack of clinical awareness and common features shared with other headache syndromes. Emergency department physicians must broaden the differential in patients presenting to the emergency department with TCH to include RCVS and be familiar with the
accepted treatments and appropriate follow-up. Elsevier Inc.
Ó 2015
, Keywords—headache; thunderclap; subarachnoid hemorrhage; reversible cerebrovasconstriction syndrome
INTRODUCTION Headache is a common presenting symptom to the emergency department (ED), prompting >2 million ED visits per year and contributing to 2.2% of yearly ED visits (1). A subset of these headaches is described as thunderclap headaches (TCH), a testament to both the abrupt onset as well as the severity of the discomfort that patients experience. The differential of TCH is broad and includes intracranial aneurysm, subarachnoid hemorrhage (SAH), cerebral venous thrombosis, caudocervical artery dissection, ischemic stroke, and hypertensive crisis (2). An underappreciated cause of TCH is the recently clinically defined reversible cerebral vasospasm syndrome (RCVS), which now unifies a spectrum of conditions previously referred to as Call-Fleming syndrome, migraine angiitis, postpartum angiopathy, or drug-induced vasospasm (3). The exact prevalence is unknown and mortality is 90% of patients with SAH can be identified with NCHCT (sensitivity 91%; 95% confidence
Figure 3. Secondary causes of reversible cerebral vasoconstriction syndrome. EtOH = alcohol; IVIG = intravenous immunoglobulin; RBC = red blood cells. Adapted from Tan and Flower (11), with permission.
Calcium channel blocker, magnesium, analgesia, avoid triggers Treatment
Embolization, coiling, surgery
Reversible, diffuse segmental stenosis and adjacent dilatation of intradural vessels Angiographic characteristics
CSF
CT/MRI findings
AVM = arteriovenous malformation; CSF = cerebrospinal fluid; CT/MRI = computed tomography/magnetic resonance imaging; ICH = intracerebral hemorrhage; PACNS = primary angiitis of the central nervous system; PRES, posterior reversible encephalopathy syndrome; RBCs = red blood cells; RCVS = reversible cerebral vasoconstriction syndrome; SAH = subarachnoid hemorrhage; TCH, thunderclap headache.
Anticoagulation, antiplatelet therapy, angioplasty with stenting, surgery
Segmental stenosis of intra- and extradural vessels, intimal flaps/ hematoma, pseudoaneurysm
Normal
Majority abnormal—diffuse infarcts, ICH Majority abnormal—pleocytosis, elevated total protein Irreversible ‘‘string and bead’’ appearance, majority small vessel changes (confirmed by biopsy) Glucocorticoids, immunosuppression
40–60 Males > females Insidious, progressive, dull
50–60 Females/males = 2/1 TCH Family history, polycystic kidney disease, connective tissue disorder Majority abnormal—SAH, edema, hydrocephalus Majority abnormal—elevated RBCs, xanthochromia Aneurysm, AVMs, local vasospasm 40–60 Females >> males TCH, recurrent Vasoactive drugs, puerperium, eclampsia, brain injury, immunosuppression Majority normal, cortical SAH, ICH, PRES, infarct Normal Median age of presentation, y Sex Character of headache Risk factors
PACNS SAH RCVS
Majority normal—infarct, edema
Table 1. Differentiating Reversible Cerebral Vasoconstriction Syndrome and Overlapping Conditions (3,8,9)
interval [CI] 82% to 97%) (12). The sensitivity of NCHCT within the first 6 h is even higher, at 100% (95% CI 97% to 100%) (13). The remaining patients with SAH can be identified by abnormal CSF findings, including xanthochromia or elevated red blood cell count (14). The vasospasm seen in SAH is typically localized to the vascular territory involving the aneurysm, as opposed to the diffuse pattern seen in RCVS. The headache of PACNS is insidious and progressive course, and the CSF often exhibits pleocytosis, elevated protein, and occasionally oligoclonal bands. Finally, dissection usually presents with head or neck pain due to involvement of extradural vessels, which are not affected in RCVS (3,11). The key feature that distinguishes RCVS from other causes of TCH is reversible vasoconstriction, which warrants serial imaging to confirm the diagnosis and usually resolves over 2 to 3 months (3,11). The authors note that the sequence of tests performed in this case deviated from the standard diagnostic approach to acute headache in the ED, which includes NCHCT followed by lumbar puncture (LP) if imaging is nondiagnostic (15). The initial intent had been to follow a minimally invasive pathway for exclusion of SAH or symptomatic cerebral aneurysm with CT angiography following a nondiagnostic NCHCT, a suggested diagnostic course in select patients (16). After the CTA results were obtained, there was lingering concern for a falsenegative CT result in the setting of SAH, as well as, Lyme meningitis or vasculitis, so an LP was performed in addition to inflammatory markers. The authors note that if the current American College of Emergency Physicians guidelines for diagnostic approach to acute headache in the adult were followed in this patient, the diagnosis would have been missed (15). At this point, we cannot recommend that angiography be performed in all patients presenting to the ED with TCH, but at some institutions this is standard practice (9). However, given the incidence of RCVS and known risk factors, such as recurrent TCHs, female sex, use of vasoactive substances, peripartum state, or headaches triggered by bathing or exertion, it may be prudent to obtain cerebral angiography in patients with normal NCHCT and CSF studies (Figure 4). Prognosis is favorable compared to aneurysmal SAH or PACNS, with the majority of patients experiencing no or minor disability (10). Even in the absence of treatment, a majority of patients will have significant resolution of angiographic abnormalities on the order of weeks or months (2). Despite potential complications,
http://dx.doi.org/10.1016/j.jemermed.2015.01.012
Selected Topics: Neurological Emergencies
REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME Kenneth R. L. Bernard, MD, MBA* and Morris Rivera, MD† *Harvard Affiliated Emergency Medicine Program, Department of Emergency Medicine, Brigham and Womens/Massachusetts General Hospital, Boston, Massachusetts and †Partners Healthcare, Martha’s Vineyard Hospital, Oak Bluffs, Massachusetts Reprint Address: Kenneth R. L. Bernard, MD, MBA, Harvard Affiliated Emergency Medicine Progam, Department of Emergency Medicine, Brigham and Womens/Massachusetts General Hospital, 75 Francis Street, Neville House, Boston, MA 02115
, Abstract—Background: Reversible cerebral vasoconstriction syndrome (RCVS) is an underappreciated and poorly understood cause of thunderclap headache (TCH). Although self-limited in the majority of patients, incidence is increasing, with presentations overlapping considerably with life-threatening conditions, such as aneurysmal subarachnoid hemorrhage and stroke. In addition, radiographic findings seen in RCVS are also present in primary angiitis of the central nervous system (PACNS). Misdiagnosis of RCVS might subject patients to unnecessary invasive testing and immunosuppressive therapy. Furthermore, the recommended treatment of glucocorticoids used in PACNS can be harmful in RCVS. RCVS is not a benign condition, as patients can have ischemic or hemorrhagic complications leading to persistent neurologic deficits and even death. Current treatments, guided only by expert consensus, have no proven effect on these complications, which argues the need for accurate identification of patients with RCVS and prospective studies to validate treatment and inform prognoses. Case Report: We describe a previously healthy male who presented to the emergency department after 2 episodes of TCH and angiography consistent with RCVS. Why Should An Emergency Physician Be Aware of This?: RCVS is a common but underappreciated cause of TCH. The likelihood of misdiagnosing RCVS following the accepted diagnostic algorithm of acute headache in the emergency department is high due to a lack of clinical awareness and common features shared with other headache syndromes. Emergency department physicians must broaden the differential in patients presenting to the emergency department with TCH to include RCVS and be familiar with the
accepted treatments and appropriate follow-up. Elsevier Inc.
Ó 2015
, Keywords—headache; thunderclap; subarachnoid hemorrhage; reversible cerebrovasconstriction syndrome
INTRODUCTION Headache is a common presenting symptom to the emergency department (ED), prompting >2 million ED visits per year and contributing to 2.2% of yearly ED visits (1). A subset of these headaches is described as thunderclap headaches (TCH), a testament to both the abrupt onset as well as the severity of the discomfort that patients experience. The differential of TCH is broad and includes intracranial aneurysm, subarachnoid hemorrhage (SAH), cerebral venous thrombosis, caudocervical artery dissection, ischemic stroke, and hypertensive crisis (2). An underappreciated cause of TCH is the recently clinically defined reversible cerebral vasospasm syndrome (RCVS), which now unifies a spectrum of conditions previously referred to as Call-Fleming syndrome, migraine angiitis, postpartum angiopathy, or drug-induced vasospasm (3). The exact prevalence is unknown and mortality is 90% of patients with SAH can be identified with NCHCT (sensitivity 91%; 95% confidence
Figure 3. Secondary causes of reversible cerebral vasoconstriction syndrome. EtOH = alcohol; IVIG = intravenous immunoglobulin; RBC = red blood cells. Adapted from Tan and Flower (11), with permission.
Calcium channel blocker, magnesium, analgesia, avoid triggers Treatment
Embolization, coiling, surgery
Reversible, diffuse segmental stenosis and adjacent dilatation of intradural vessels Angiographic characteristics
CSF
CT/MRI findings
AVM = arteriovenous malformation; CSF = cerebrospinal fluid; CT/MRI = computed tomography/magnetic resonance imaging; ICH = intracerebral hemorrhage; PACNS = primary angiitis of the central nervous system; PRES, posterior reversible encephalopathy syndrome; RBCs = red blood cells; RCVS = reversible cerebral vasoconstriction syndrome; SAH = subarachnoid hemorrhage; TCH, thunderclap headache.
Anticoagulation, antiplatelet therapy, angioplasty with stenting, surgery
Segmental stenosis of intra- and extradural vessels, intimal flaps/ hematoma, pseudoaneurysm
Normal
Majority abnormal—diffuse infarcts, ICH Majority abnormal—pleocytosis, elevated total protein Irreversible ‘‘string and bead’’ appearance, majority small vessel changes (confirmed by biopsy) Glucocorticoids, immunosuppression
40–60 Males > females Insidious, progressive, dull
50–60 Females/males = 2/1 TCH Family history, polycystic kidney disease, connective tissue disorder Majority abnormal—SAH, edema, hydrocephalus Majority abnormal—elevated RBCs, xanthochromia Aneurysm, AVMs, local vasospasm 40–60 Females >> males TCH, recurrent Vasoactive drugs, puerperium, eclampsia, brain injury, immunosuppression Majority normal, cortical SAH, ICH, PRES, infarct Normal Median age of presentation, y Sex Character of headache Risk factors
PACNS SAH RCVS
Majority normal—infarct, edema
Table 1. Differentiating Reversible Cerebral Vasoconstriction Syndrome and Overlapping Conditions (3,8,9)
interval [CI] 82% to 97%) (12). The sensitivity of NCHCT within the first 6 h is even higher, at 100% (95% CI 97% to 100%) (13). The remaining patients with SAH can be identified by abnormal CSF findings, including xanthochromia or elevated red blood cell count (14). The vasospasm seen in SAH is typically localized to the vascular territory involving the aneurysm, as opposed to the diffuse pattern seen in RCVS. The headache of PACNS is insidious and progressive course, and the CSF often exhibits pleocytosis, elevated protein, and occasionally oligoclonal bands. Finally, dissection usually presents with head or neck pain due to involvement of extradural vessels, which are not affected in RCVS (3,11). The key feature that distinguishes RCVS from other causes of TCH is reversible vasoconstriction, which warrants serial imaging to confirm the diagnosis and usually resolves over 2 to 3 months (3,11). The authors note that the sequence of tests performed in this case deviated from the standard diagnostic approach to acute headache in the ED, which includes NCHCT followed by lumbar puncture (LP) if imaging is nondiagnostic (15). The initial intent had been to follow a minimally invasive pathway for exclusion of SAH or symptomatic cerebral aneurysm with CT angiography following a nondiagnostic NCHCT, a suggested diagnostic course in select patients (16). After the CTA results were obtained, there was lingering concern for a falsenegative CT result in the setting of SAH, as well as, Lyme meningitis or vasculitis, so an LP was performed in addition to inflammatory markers. The authors note that if the current American College of Emergency Physicians guidelines for diagnostic approach to acute headache in the adult were followed in this patient, the diagnosis would have been missed (15). At this point, we cannot recommend that angiography be performed in all patients presenting to the ED with TCH, but at some institutions this is standard practice (9). However, given the incidence of RCVS and known risk factors, such as recurrent TCHs, female sex, use of vasoactive substances, peripartum state, or headaches triggered by bathing or exertion, it may be prudent to obtain cerebral angiography in patients with normal NCHCT and CSF studies (Figure 4). Prognosis is favorable compared to aneurysmal SAH or PACNS, with the majority of patients experiencing no or minor disability (10). Even in the absence of treatment, a majority of patients will have significant resolution of angiographic abnormalities on the order of weeks or months (2). Despite potential complications,
