Stroke caused by varicella zoster virus
- Maria A Nagel, MD
Maria A Nagel, MD
- Assistant Professor
- University of Colorado Denver School of Medicine
Varicella zoster virus (VZV) infection of cerebral arteries produces a vasculopathy, manifesting most often as ischemic stroke and less often as hemorrhagic stroke. Vasculopathy can occur after either primary infection with VZV (ie, varicella; chickenpox) or after viral reactivation (ie, herpes zoster; shingles) .
This topic will review the pathogenesis, epidemiology, risk factors for, clinical features, diagnosis, and treatment of VZV vasculopathy. The major clinical manifestations and complications of chickenpox and herpes zoster are discussed separately. (See "Epidemiology of varicella-zoster virus infection: Chickenpox" and "Treatment of varicella (chickenpox) infection" and "Vaccination for the prevention of chickenpox (primary varicella infection)" and "Clinical manifestations of varicella-zoster virus infection: Herpes zoster" and "Vaccination for the prevention of shingles (herpes zoster)".)
VZV vasculopathy has previously been called granulomatous angiitis, VZV vasculitis, or post-varicella arteriopathy; a subset of patients has specific ocular and motor findings known as herpes zoster ophthalmicus with delayed contralateral hemiparesis.
Early reports described ischemic large vessel strokes, although it is now appreciated that both large and small arteries are commonly involved. An expanded spectrum of stroke caused by VZV infection has been increasingly recognized including aneurysm, subarachnoid and intracerebral hemorrhage, arterial ectasia, and possibly dissection [2-4].
VZV is a ubiquitous human DNA virus of the herpesvirus family. Primary infection occurs via respiratory aerosols or contact with vesicles from an infected individual and results in the characteristic, disseminated rash of varicella (ie, chickenpox).To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 2009; 8:731.
- Fukumoto S, Kinjo M, Hokamura K, Tanaka K. Subarachnoid hemorrhage and granulomatous angiitis of the basilar artery: demonstration of the varicella-zoster-virus in the basilar artery lesions. Stroke 1986; 17:1024.
- Constantinescu CS. Association of varicella-zoster virus with cervical artery dissection in 2 cases. Arch Neurol 2000; 57:427.
- Bhayani N, Ranade P, Clark NM, McGuinn M. Varicella-zoster virus and cerebral aneurysm: case report and review of the literature. Clin Infect Dis 2008; 47:e1.
- Cohrs RJ, Gilden DH. Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia. J Virol 2007; 81:2950.
- Holland GN. The progressive outer retinal necrosis syndrome. Int Ophthalmol 1994; 18:163.
- Gilden DH, Beinlich BR, Rubinstien EM, et al. Varicella-zoster virus myelitis: an expanding spectrum. Neurology 1994; 44:1818.
- Nagel MA, Cohrs RJ, Mahalingam R, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008; 70:853.
- Kleinschmidt-DeMasters BK, Gilden DH. Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates. Arch Pathol Lab Med 2001; 125:770.
- Mayberg M, Langer RS, Zervas NT, Moskowitz MA. Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. Science 1981; 213:228.
- Mayberg MR, Zervas NT, Moskowitz MA. Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J Comp Neurol 1984; 223:46.
- Saito K, Moskowitz MA. Contributions from the upper cervical dorsal roots and trigeminal ganglia to the feline circle of Willis. Stroke 1989; 20:524.
- Linnemann CC Jr, Alvira MM. Pathogenesis of varicella-zoster angiitis in the CNS. Arch Neurol 1980; 37:239.
- Doyle PW, Gibson G, Dolman CL. Herpes zoster ophthalmicus with contralateral hemiplegia: identification of cause. Ann Neurol 1983; 14:84.
- Eidelberg D, Sotrel A, Horoupian DS, et al. Thrombotic cerebral vasculopathy associated with herpes zoster. Ann Neurol 1986; 19:7.
- Morgello S, Block GA, Price RW, Petito CK. Varicella-zoster virus leukoencephalitis and cerebral vasculopathy. Arch Pathol Lab Med 1988; 112:173.
- Gray F, Bélec L, Lescs MC, et al. Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome. Brain 1994; 117 ( Pt 5):987.
- Amlie-Lefond C, Kleinschmidt-DeMasters BK, Mahalingam R, et al. The vasculopathy of varicella-zoster virus encephalitis. Ann Neurol 1995; 37:784.
- Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, et al. Varicella zoster virus, a cause of waxing and waning vasculitis: the New England Journal of Medicine case 5-1995 revisited. Neurology 1996; 47:1441.
- Melanson M, Chalk C, Georgevich L, et al. Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries. Neurology 1996; 47:569.
- Kleinschmidt-DeMasters BK, Mahalingam R, Shimek C, et al. Profound cerebrospinal fluid pleocytosis and Froin's Syndrome secondary to widespread necrotizing vasculitis in an HIV-positive patient with varicella zoster virus encephalomyelitis. J Neurol Sci 1998; 159:213.
- Manco-Johnson MJ, Nuss R, Key N, et al. Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 1996; 128:319.
- Josephson C, Nuss R, Jacobson L, et al. The varicella-autoantibody syndrome. Pediatr Res 2001; 50:345.
- Massano J, Ferreira D, Toledo T, et al. Stroke and multiple peripheral thrombotic events in an adult with varicella. Eur J Neurol 2008; 15:e90.
- Kurugöl Z, Vardar F, Ozkinay F, et al. Lupus anticoagulant and protein S deficiency in a child who developed disseminated intravascular coagulation in association with varicella. Turk J Pediatr 2001; 43:139.
- Regnault V, Boehlen F, Ozsahin H, et al. Anti-protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation. J Thromb Haemost 2005; 3:1243.
- Askalan R, Laughlin S, Mayank S, et al. Chickenpox and stroke in childhood: a study of frequency and causation. Stroke 2001; 32:1257.
- Amlie-Lefond C, Bernard TJ, Sébire G, et al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation 2009; 119:1417.
- Braun KP, Bulder MM, Chabrier S, et al. The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain 2009; 132:544.
- Kang JH, Ho JD, Chen YH, Lin HC. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke 2009; 40:3443.
- Sreenivasan N, Basit S, Wohlfahrt J, et al. The short- and long-term risk of stroke after herpes zoster - a nationwide population-based cohort study. PLoS One 2013; 8:e69156.
- Breuer J, Pacou M, Gauthier A, Brown MM. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology 2014; 82:206.
- Langan SM, Minassian C, Smeeth L, Thomas SL. Risk of stroke following herpes zoster: a self-controlled case-series study. Clin Infect Dis 2014; 58:1497.
- Lin HC, Chien CW, Ho JD. Herpes zoster ophthalmicus and the risk of stroke: a population-based follow-up study. Neurology 2010; 74:792.
- Picard O, Brunereau L, Pelosse B, et al. Cerebral infarction associated with vasculitis due to varicella zoster virus in patients infected with the human immunodeficiency virus. Biomed Pharmacother 1997; 51:449.
- Berkefeld J, Enzensberger W, Lanfermann H. MRI in human immunodeficiency virus-associated cerebral vasculitis. Neuroradiology 2000; 42:526.
- Hovens MM, Vaessen N, Sijpkens YW, de Fijter JW. Unusual presentation of central nervous system manifestations of Varicella zoster virus vasculopathy in renal transplant recipients. Transpl Infect Dis 2007; 9:237.
- Gray F, Mohr M, Rozenberg F, et al. Varicella-zoster virus encephalitis in acquired immunodeficiency syndrome: report of four cases. Neuropathol Appl Neurobiol 1992; 18:502.
- Petito CK, Cho ES, Lemann W, et al. Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol 1986; 45:635.
- Ryder JW, Croen K, Kleinschmidt-DeMasters BK, et al. Progressive encephalitis three months after resolution of cutaneous zoster in a patient with AIDS. Ann Neurol 1986; 19:182.
- Hall S, Carlin L, Roach ES, McLean WT Jr. Herpes zoster and central retinal artery occlusion. Ann Neurol 1983; 13:217.
- Gilden DH, Lipton HL, Wolf JS, et al. Two patients with unusual forms of varicella-zoster virus vasculopathy. N Engl J Med 2002; 347:1500.
- Mathias M, Nagel MA, Khmeleva N, et al. VZV multifocal vasculopathy with ischemic optic neuropathy, acute retinal necrosis and temporal artery infection in the absence of zoster rash. J Neurol Sci 2013; 325:180.
- Teodoro T, Nagel MA, Geraldes R, et al. Biopsy-negative, varicella zoster virus (VZV)-positive giant cell arteritis, zoster, VZV encephalitis and ischemic optic neuropathy, all in one. J Neurol Sci 2014; 343:195.
- Salazar R, Russman AN, Nagel MA, et al. Varicella zoster virus ischemic optic neuropathy and subclinical temporal artery involvement. Arch Neurol 2011; 68:517.
- Nagel MA, Bennett JL, Khmeleva N, et al. Multifocal VZV vasculopathy with temporal artery infection mimics giant cell arteritis. Neurology 2013; 80:2017.
- Nagel MA, Khmeleva N, Boyer PJ, et al. Varicella zoster virus in the temporal artery of a patient with giant cell arteritis. J Neurol Sci 2013; 335:228.
- Nagel MA, Russman AN, Feit H, et al. VZV ischemic optic neuropathy and subclinical temporal artery infection without rash. Neurology 2013; 80:220.
- Persson A, Bergström T, Lindh M, et al. Varicella-zoster virus CNS disease--viral load, clinical manifestations and sequels. J Clin Virol 2009; 46:249.
- Katchanov J, Siebert E, Klingebiel R, Endres M. Infectious vasculopathy of intracranial large- and medium-sized vessels in neurological intensive care unit: a clinico-radiological study. Neurocrit Care 2010; 12:369.
- Gregoire SM, van Pesch V, Goffette S, et al. Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system. J Neurol Neurosurg Psychiatry 2006; 77:938.
- Haug A, Mahalingam R, Cohrs RJ, et al. Recurrent polymorphonuclear pleocytosis with increased red blood cells caused by varicella zoster virus infection of the central nervous system: Case report and review of the literature. J Neurol Sci 2010; 292:85.
- Schubert J, Weissbrich B. Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system. BMC Neurol 2007; 7:12.
- Nagel MA, Forghani B, Mahalingam R, et al. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007; 68:1069.
- Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005; 352:2271.
- Tseng HF, Smith N, Harpaz R, et al. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease. JAMA 2011; 305:160.
- GENERAL BACKGROUND
- Direct infection of blood vessels by VZV
- Role of autoantibodies
- CLINICAL MANIFESTATIONS
- Neurologic manifestations
- VZV vasculopathy with temporal artery infection
- Other complications
- Brain imaging
- Angiographic features
- CEREBROSPINAL FLUID TESTING
- Laboratory testing
- DIFFERENTIAL DIAGNOSIS
- PATIENT MONITORING DURING THERAPY
- DURATION OF TREATMENT
- SUMMARY AND RECOMMENDATIONS