Case Report
Varicella-Zoster Vasculitis Presenting with Cerebellar Hemorrhage Kazuya Matsuo, MD,* Yoichi Uozumi, MD, PhD,* Hirohito Miyamoto, MD, PhD,* Shotaro Tatsumi, MD, PhD,* and Eiji Kohmura, MD, PhD†
Background: Varicella zoster virus (VZV) is known as one of the rare, but important, causes of both ischemic and hemorrhagic stroke. Most previously reported VZV-related hemorrhagic stroke and cerebral vasculitis are associated with anterior circulation because VZV spreads from trigeminal ganglia to the anterior circulation of Willis. The present study presents a patient with cerebellar hemorrhage, who was diagnosed with VZV encephalitis and vasculitis of the posterior inferior cerebellar artery. Case Report: A 75-year-old man with stupor was admitted to our hospital. Computed tomography revealed right intracerebellar hemorrhage, and magnetic resonance imaging revealed multiple high-intense signals throughout the brainstem and temporal lobe on fluid attenuation inversion recovery, suggestive of encephalitis. Cerebral angiography revealed stenosis of left posterior inferior cerebellar artery. Based on cerebrospinal fluid analysis, including anti-VZV IgG antibody and VZV DNA polymerase chain reaction, the patient was diagnosed with VZV encephalitis, vasculitis, and cerebellar hemorrhage. Conclusions: Both cerebral vasculitis and hemorrhagic stroke due to VZV can occur in the vertebrobasilar system. VZV may enter the central nervous system not only from trigeminal ganglia but also from other pathways. We should be aware that a VZV infection could cause cerebral vasculitis and hemorrhagic stroke in the vertebrobasilar system and in anterior circulation. Key Words: Varicella zoster—vasculitis—hemorrhagic stroke— encephalitis. Ó 2015 by National Stroke Association
Varicella zoster virus (VZV) is a known cause of cerebral vasculitis and has been described as one of the rare, but important, causes of ischemic and hemorrhagic stroke.1 Most previously reported cases regarding VZV-induced intracerebral hemorrhage were supratentorial.2 Several studies show that VZV spreads from the trigeminal ganglia to the carotid artery and primarily
the anterior circulation of Willis.3,4 However, it remains unclear whether other pathways are involved in the spread of VZV into the cranial vessel, especially the vertebrobasilar system. We present here a patient with cerebellar hemorrhage, who was diagnosed with VZV encephalitis and posterior inferior cerebellar artery stenosis due to VZV vasculitis.
From the *Department of Neurosurgery, Hirohata Steel Memorial Hospital, Himeji; and †Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan. Received February 11, 2015; accepted March 3, 2015. The authors do not have any relevant conflicts of interest to report. There was no grant support for this study. Address correspondence to Kazuya Matsuo, MD, Department of Neurosurgery, Hirohata Steel Memorial Hospital, 3-1 Yumesaki-cho,
Hirohata-ku, Himeji, Hyogo 671-1122, Japan. E-mail: kazukins. [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.003
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2015: pp e1-e3
e1
K. MATSUO ET AL.
e2
Case Report A 75-year-old man presented to our department with stupor. The patient had been treated for varicella zoster with valacyclovir 2 days before presentation. On examination, his Glasgow Coma Scale score was 6 (E1V1M4), his pupils were 5 mm, and light reflex was diminished bilaterally. Motor strength was 1/5 in left lower extremity and 3/5 in other extremities. The patient required intubation because of coma. Computed tomography scan revealed right intracerebellar hemorrhage (Fig 1, A). Magnetic resonance imaging of the brain revealed multiple symmetrical high-intense signals throughout the brainstem and temporal white matter on fluid attenuation inversion recovery imaging, suggestive of encephalitis (Fig 1, B,C). Diffusion-weighted imaging did not reveal any ischemic lesions (Fig 1, D). Cerebral angiography performed on day 3 revealed some short narrowing segments in the left posterior inferior cerebellar artery, suggestive of vasculitis (Fig 1, E). No abnormalities were seen in other vessels. The patient was treated with intravenous acyclovir (10 mg/kg [650 mg] every 8 hours) for 14 days, and methylprednisolone 500 mg daily for 3 days for suspected VZV encephalitis and vasculitis. External ventricular drainage was conducted on day 10 because hydrocephalus worsened. Cerebrospinal fluid analysis showed high anti-VZV IgG antibodies (7.68
index value), and VZV DNA was positive according to polymerase chain reaction. Other viral or bacterial infections were not detected. The patient was diagnosed with VZV encephalitis, vasculitis, and right cerebellar hemorrhage. He was not infected with human immunodeficiency virus, and also, did not have a history of any systemic illness, malignant neoplasm, or immunosuppressive treatment. Tracheostomy was performed on day 27, and a ventriculoperitoneal shunt was inserted for hydrocephalus on day 34. His course was complicated by pneumonia and disseminated intravascular coagulation, which were successfully treated with intravenous antibiotics and unfractionated heparin, respectively. During hospitalization, his consciousness gradually improved. Two months later, he was awake, but not well oriented. He could speak simple words, although quadriparesis was persistent. Sixty-three days later, a follow-up brain magnetic resonance imaging showed that the previous abnormal signals were substantially decreased at the brainstem, although bilateral temporal lesions remained. He was transferred to a rehabilitation hospital on day 89, and died 251 days after admission.
Discussion Observations from this case study revealed 2 important clinical issues. Both cerebral vasculitis and hemorrhagic
Figure 1. Characteristic imaging abnormalities in varicella zoster virus vasculitis and encephalitis. (A) Computed tomography scan shows right cerebellar hemorrhage. (B, C) Brain magnetic resonance imaging (MRI) scan shows multiple high-intense signals throughout the brainstem and temporal white matter on fluid attenuation inversion recovery. (D) Diffusion-weighted MRI shows no acute ischemic lesion. (E) (white arrowheads) Cerebral angiography shows some stenotic lesions in left posterior inferior cerebellar artery.
VZ VASCULITIS PRESENTS WITH CEREBELLAR HEMORRHAGE
stroke due to VZV can occur in the vertebrobasilar system. VZV may enter the central nervous system (CNS) not only from trigeminal ganglia but also from other pathways. The first clinical issue is that both cerebral vasculitis and hemorrhagic stroke due to VZV can occur in the vertebrobasilar system. There have been a few reports of cerebral hemorrhage caused by VZV. Of the 62 patients of VZV vasculitis, at least 1 had hemorrhagic stroke.2 Almost all previously reported cerebral hemorrhages due to VZV were supratentorial. There is a report of brainstem hemorrhage located in the posterior fossa.5 Typically, angiography of large-vessel cerebrovascular disease caused by VZV shows segmental narrowing, mainly in the middle cerebral artery, anterior cerebral artery, and internal carotid artery.3 There have been few reports of VZV vasculitis involved in vertebrobasilar system.6,7 VZV vasculitis presenting with cerebellar hemorrhage has not been previously described in the literature. Any level of neuraxis can be involved in VZV, with thoracic zoster being the most common, followed by face lesions, most often in the ophthalmic division of the trigeminal nerve. VZV can spread transaxonally along trigeminal ganglionic afferent fibers to vessels of the anterior cerebral circulation.3 For this reason, anterior circulation may be more frequently associated with VZV. The cause of right cerebellar hemorrhage in the present case is unknown. However, we speculate that associated vessels might have been infected with VZV when the cerebellar hemorrhage occurred. The second clinical issue is that VZV may enter the CNS not only from trigeminal ganglia but also from other pathways. It is well known that VZV enters the CNS from the trigeminal ganglia. In fact, the risk of stroke after herpes zoster ophthalmicus, the reactivation of VZV in the ophthalmic division of the trigeminal nerve, is high.8 In animal experiments, it has been suggested that fibers from trigeminal ganglia spread to the internal carotid artery, anterior cerebral artery, middle cerebral artery, posterior cerebral artery, and upper two thirds of the basilar artery.4 Therefore, in the present study, we hypothesized that VZV invaded the wall of posterior inferior cerebellar artery from other pathways. Although the existence of fibers from upper cervical dorsal root ganglia and satella ganglia to vertebrobasilar artery is known, these have only been reported in animal experiments.9,10 Generally, immunocompromised patients are more likely to be aggravated by CNS complication of VZV,
e3
but that is not necessarily the case in the present study. Recently, epidemiologic studies about the incidence of stroke after herpes zoster have been reported, although there are no data regarding the location of stroke.8 There may be more involvement of VZV infection in vertebrobasilar system than we expect. In conclusion, vasculitis and hemorrhage due to VZV can occur in the vertebrobasilar system, and VZV may enter the CNS not only from trigeminal ganglia but also from other pathways. We should be aware that VZV infection could cause cerebral vasculitis and hemorrhagic stroke in the vertebrobasilar system and in anterior circulation. Further pathophysiological studies are needed to determine, which CNS pathway allows for VZV entry.
References 1. Nagel MA, Cohrs RJ, Mahalingam R, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008;70:853-860. 2. Gonzalez-Suarez I, Fuentes-Gimeno B, Ruiz-Ares G, et al. Varicella-zoster virus vasculopathy. A review description of a new case with multifocal brain hemorrhage. J Neurol Sci 2014;338:34-38. 3. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, et al. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000;342:635-645. 4. Zhang QJ, Hara H, Kobayashi S. Distribution patterns of sensory innervation from the trigeminal ganglion to cerebral arteries in rabbits studied by wheat germ agglutininconjugated horseradish peroxidase anterograde tracing. Neurosurgery 1993;32:993-999. 5. Baek W, Lee SG, Kim YS, et al. Fatal varicella-zoster virus vasculopathy associated with adalimumab therapy. Arch Neurol 2012;69:1193-1196. 6. Fukumoto S, Kinjo M, Hokamura K, et al. Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster-virus in the basilar artery lesions. Stroke 1986;17:1024-1028. 7. Bhayani N, Ranade P, Clark NM, et al. Varicella-zoster virus and cerebral aneurysm: case report and review of the literature. Clin Infect Dis 2008;47:e1-3. 8. Kang JH, Ho JD, Chen YH, et al. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke 2009;40:3443-3448. 9. Saito K, Moskowitz MA. Contributions from the upper cervical dorsal roots and trigeminal ganglia to the feline circle of Willis. Stroke 1989;20:524-526. 10. Arbab MA, Wiklund L, Delgado T, et al. Stellate ganglion innervation of the vertebro-basilar arterial system demonstrated in the rat with anterograde and retrograde WGA-HRP tracing. Brain Res 1988;445:175-180.
Varicella-Zoster Vasculitis Presenting with Cerebellar Hemorrhage Kazuya Matsuo, MD,* Yoichi Uozumi, MD, PhD,* Hirohito Miyamoto, MD, PhD,* Shotaro Tatsumi, MD, PhD,* and Eiji Kohmura, MD, PhD†
Background: Varicella zoster virus (VZV) is known as one of the rare, but important, causes of both ischemic and hemorrhagic stroke. Most previously reported VZV-related hemorrhagic stroke and cerebral vasculitis are associated with anterior circulation because VZV spreads from trigeminal ganglia to the anterior circulation of Willis. The present study presents a patient with cerebellar hemorrhage, who was diagnosed with VZV encephalitis and vasculitis of the posterior inferior cerebellar artery. Case Report: A 75-year-old man with stupor was admitted to our hospital. Computed tomography revealed right intracerebellar hemorrhage, and magnetic resonance imaging revealed multiple high-intense signals throughout the brainstem and temporal lobe on fluid attenuation inversion recovery, suggestive of encephalitis. Cerebral angiography revealed stenosis of left posterior inferior cerebellar artery. Based on cerebrospinal fluid analysis, including anti-VZV IgG antibody and VZV DNA polymerase chain reaction, the patient was diagnosed with VZV encephalitis, vasculitis, and cerebellar hemorrhage. Conclusions: Both cerebral vasculitis and hemorrhagic stroke due to VZV can occur in the vertebrobasilar system. VZV may enter the central nervous system not only from trigeminal ganglia but also from other pathways. We should be aware that a VZV infection could cause cerebral vasculitis and hemorrhagic stroke in the vertebrobasilar system and in anterior circulation. Key Words: Varicella zoster—vasculitis—hemorrhagic stroke— encephalitis. Ó 2015 by National Stroke Association
Varicella zoster virus (VZV) is a known cause of cerebral vasculitis and has been described as one of the rare, but important, causes of ischemic and hemorrhagic stroke.1 Most previously reported cases regarding VZV-induced intracerebral hemorrhage were supratentorial.2 Several studies show that VZV spreads from the trigeminal ganglia to the carotid artery and primarily
the anterior circulation of Willis.3,4 However, it remains unclear whether other pathways are involved in the spread of VZV into the cranial vessel, especially the vertebrobasilar system. We present here a patient with cerebellar hemorrhage, who was diagnosed with VZV encephalitis and posterior inferior cerebellar artery stenosis due to VZV vasculitis.
From the *Department of Neurosurgery, Hirohata Steel Memorial Hospital, Himeji; and †Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan. Received February 11, 2015; accepted March 3, 2015. The authors do not have any relevant conflicts of interest to report. There was no grant support for this study. Address correspondence to Kazuya Matsuo, MD, Department of Neurosurgery, Hirohata Steel Memorial Hospital, 3-1 Yumesaki-cho,
Hirohata-ku, Himeji, Hyogo 671-1122, Japan. E-mail: kazukins. [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.003
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2015: pp e1-e3
e1
K. MATSUO ET AL.
e2
Case Report A 75-year-old man presented to our department with stupor. The patient had been treated for varicella zoster with valacyclovir 2 days before presentation. On examination, his Glasgow Coma Scale score was 6 (E1V1M4), his pupils were 5 mm, and light reflex was diminished bilaterally. Motor strength was 1/5 in left lower extremity and 3/5 in other extremities. The patient required intubation because of coma. Computed tomography scan revealed right intracerebellar hemorrhage (Fig 1, A). Magnetic resonance imaging of the brain revealed multiple symmetrical high-intense signals throughout the brainstem and temporal white matter on fluid attenuation inversion recovery imaging, suggestive of encephalitis (Fig 1, B,C). Diffusion-weighted imaging did not reveal any ischemic lesions (Fig 1, D). Cerebral angiography performed on day 3 revealed some short narrowing segments in the left posterior inferior cerebellar artery, suggestive of vasculitis (Fig 1, E). No abnormalities were seen in other vessels. The patient was treated with intravenous acyclovir (10 mg/kg [650 mg] every 8 hours) for 14 days, and methylprednisolone 500 mg daily for 3 days for suspected VZV encephalitis and vasculitis. External ventricular drainage was conducted on day 10 because hydrocephalus worsened. Cerebrospinal fluid analysis showed high anti-VZV IgG antibodies (7.68
index value), and VZV DNA was positive according to polymerase chain reaction. Other viral or bacterial infections were not detected. The patient was diagnosed with VZV encephalitis, vasculitis, and right cerebellar hemorrhage. He was not infected with human immunodeficiency virus, and also, did not have a history of any systemic illness, malignant neoplasm, or immunosuppressive treatment. Tracheostomy was performed on day 27, and a ventriculoperitoneal shunt was inserted for hydrocephalus on day 34. His course was complicated by pneumonia and disseminated intravascular coagulation, which were successfully treated with intravenous antibiotics and unfractionated heparin, respectively. During hospitalization, his consciousness gradually improved. Two months later, he was awake, but not well oriented. He could speak simple words, although quadriparesis was persistent. Sixty-three days later, a follow-up brain magnetic resonance imaging showed that the previous abnormal signals were substantially decreased at the brainstem, although bilateral temporal lesions remained. He was transferred to a rehabilitation hospital on day 89, and died 251 days after admission.
Discussion Observations from this case study revealed 2 important clinical issues. Both cerebral vasculitis and hemorrhagic
Figure 1. Characteristic imaging abnormalities in varicella zoster virus vasculitis and encephalitis. (A) Computed tomography scan shows right cerebellar hemorrhage. (B, C) Brain magnetic resonance imaging (MRI) scan shows multiple high-intense signals throughout the brainstem and temporal white matter on fluid attenuation inversion recovery. (D) Diffusion-weighted MRI shows no acute ischemic lesion. (E) (white arrowheads) Cerebral angiography shows some stenotic lesions in left posterior inferior cerebellar artery.
VZ VASCULITIS PRESENTS WITH CEREBELLAR HEMORRHAGE
stroke due to VZV can occur in the vertebrobasilar system. VZV may enter the central nervous system (CNS) not only from trigeminal ganglia but also from other pathways. The first clinical issue is that both cerebral vasculitis and hemorrhagic stroke due to VZV can occur in the vertebrobasilar system. There have been a few reports of cerebral hemorrhage caused by VZV. Of the 62 patients of VZV vasculitis, at least 1 had hemorrhagic stroke.2 Almost all previously reported cerebral hemorrhages due to VZV were supratentorial. There is a report of brainstem hemorrhage located in the posterior fossa.5 Typically, angiography of large-vessel cerebrovascular disease caused by VZV shows segmental narrowing, mainly in the middle cerebral artery, anterior cerebral artery, and internal carotid artery.3 There have been few reports of VZV vasculitis involved in vertebrobasilar system.6,7 VZV vasculitis presenting with cerebellar hemorrhage has not been previously described in the literature. Any level of neuraxis can be involved in VZV, with thoracic zoster being the most common, followed by face lesions, most often in the ophthalmic division of the trigeminal nerve. VZV can spread transaxonally along trigeminal ganglionic afferent fibers to vessels of the anterior cerebral circulation.3 For this reason, anterior circulation may be more frequently associated with VZV. The cause of right cerebellar hemorrhage in the present case is unknown. However, we speculate that associated vessels might have been infected with VZV when the cerebellar hemorrhage occurred. The second clinical issue is that VZV may enter the CNS not only from trigeminal ganglia but also from other pathways. It is well known that VZV enters the CNS from the trigeminal ganglia. In fact, the risk of stroke after herpes zoster ophthalmicus, the reactivation of VZV in the ophthalmic division of the trigeminal nerve, is high.8 In animal experiments, it has been suggested that fibers from trigeminal ganglia spread to the internal carotid artery, anterior cerebral artery, middle cerebral artery, posterior cerebral artery, and upper two thirds of the basilar artery.4 Therefore, in the present study, we hypothesized that VZV invaded the wall of posterior inferior cerebellar artery from other pathways. Although the existence of fibers from upper cervical dorsal root ganglia and satella ganglia to vertebrobasilar artery is known, these have only been reported in animal experiments.9,10 Generally, immunocompromised patients are more likely to be aggravated by CNS complication of VZV,
e3
but that is not necessarily the case in the present study. Recently, epidemiologic studies about the incidence of stroke after herpes zoster have been reported, although there are no data regarding the location of stroke.8 There may be more involvement of VZV infection in vertebrobasilar system than we expect. In conclusion, vasculitis and hemorrhage due to VZV can occur in the vertebrobasilar system, and VZV may enter the CNS not only from trigeminal ganglia but also from other pathways. We should be aware that VZV infection could cause cerebral vasculitis and hemorrhagic stroke in the vertebrobasilar system and in anterior circulation. Further pathophysiological studies are needed to determine, which CNS pathway allows for VZV entry.
References 1. Nagel MA, Cohrs RJ, Mahalingam R, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008;70:853-860. 2. Gonzalez-Suarez I, Fuentes-Gimeno B, Ruiz-Ares G, et al. Varicella-zoster virus vasculopathy. A review description of a new case with multifocal brain hemorrhage. J Neurol Sci 2014;338:34-38. 3. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, et al. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000;342:635-645. 4. Zhang QJ, Hara H, Kobayashi S. Distribution patterns of sensory innervation from the trigeminal ganglion to cerebral arteries in rabbits studied by wheat germ agglutininconjugated horseradish peroxidase anterograde tracing. Neurosurgery 1993;32:993-999. 5. Baek W, Lee SG, Kim YS, et al. Fatal varicella-zoster virus vasculopathy associated with adalimumab therapy. Arch Neurol 2012;69:1193-1196. 6. Fukumoto S, Kinjo M, Hokamura K, et al. Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster-virus in the basilar artery lesions. Stroke 1986;17:1024-1028. 7. Bhayani N, Ranade P, Clark NM, et al. Varicella-zoster virus and cerebral aneurysm: case report and review of the literature. Clin Infect Dis 2008;47:e1-3. 8. Kang JH, Ho JD, Chen YH, et al. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke 2009;40:3443-3448. 9. Saito K, Moskowitz MA. Contributions from the upper cervical dorsal roots and trigeminal ganglia to the feline circle of Willis. Stroke 1989;20:524-526. 10. Arbab MA, Wiklund L, Delgado T, et al. Stellate ganglion innervation of the vertebro-basilar arterial system demonstrated in the rat with anterograde and retrograde WGA-HRP tracing. Brain Res 1988;445:175-180.
