Two Patients with Unusual Forms of Varicella–Zoster Virus Vasculopathy

Abstract

NFECTION of cerebral arteries by varicellazoster virus (VZV) can produce unifocal or multifocal vasculopathy. Unifocal large-vessel vasculopathy (granulomatous arteritis) usually affects elderly immunocompetent persons, whereas multifocal vasculopathy occurs primarily in persons who are immunocompromised. 1 Unifocal large-vessel infarcts may follow zoster in a trigeminal distribution and are presumed to result from transaxonal transport of virus from trigeminal afferent fibers that innervate vessels of the anterior circulation. 2 Similarly, smaller infarcts in deep white and gray matter may reflect transport of VZV from trigeminal or cervical afferent fibers to smaller branches of vessels of the posterior circulation. 2,3 We encountered two patients with unusual forms of VZV vasculopathy. Detection of VZV antibody in cerebrospinal fluid and reduced ratios of the concentration of anti-VZV IgG in serum to that in cerebrospinal fluid, in conjunction with normally high ratios for total IgG and albumin, verified the viral cause of their vascular disease. CASE REPORTS Patient 1In April 2001, zoster in a left sacral (S2) distribution developed in Patient 1, a 71-year-old man with chronic lymphocytic leukemia that was in remission. Despite treatment with oral valacyclovir (1000 mg three times daily for seven days), zoster spread to the right S2 dermatome. Lesions resolved in three to four weeks. In May 2001, bitemporal headaches developed, along with mild confusion, foot numbness, and unsteady gait. Vibratory sensation was reduced in the toes, ankle jerks were absent, and gait was mildly I wide-based. The white-cell count was 12,100 per cubic millimeter, with a normal differential count. Magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography were normal (Fig. 1B). Two cerebrospinal fluid examinations revealed extensive mononuclear pleocytosis, an elevated protein level, and a normal glucose level (Table 1). Polymerase-chain-reaction (PCR) analysis of the cerebrospinal fluid revealed no amplifiable VZV DNA.Headaches, confusion, and imbalance resolved within two months. On October 15, 2001, the patient noted that he had difficulty finding words, numbness of the left hand, weakness of the left leg, and urinary urgency. Neurologic examination revealed halting speech, a flattened left nasolabial fold, mild weakness of the left side, an extensor plantar response on the left, and bilateral grasp reflexes. A complete blood count, electrolyte values, a blood-chemistry panel, and urinalysis were normal. MRI of the brain revealed an infarction in the right pericallosal distribution (Fig. 1A). Magnetic resonance angiography revealed occlusion of the anterior cerebral artery on the right side and stenosis on the left side (Fig. 1C). A third sample of cerebrospinal fluid (Table 1) was acellular, but the protein level, the total IgG level, and the rate of IgG synthesis were elevated, with three to four oligoclonal bands. PCR analysis revealed no amplifiable herpes simplex virus (HSV) or VZV DNA or antibody to...

Increased Risk of Stroke After a Herpes Zoster Attack

“…7,26,27 Similarly, we found that the overall risk for having a stroke increased in patients with herpes zoster. The pathomechanisms explaining this phenomenon are still unknown; however, there is some speculation that it involves the dissemination or cooccurrence of viral reactivation in cerebral ganglia spreading to the supplying vessels.…”

“…6 It is hypothesized to spread along the nerve fibers to the blood vessels where it induces further inflammatory and thrombotic responses. 2,7,8 Two major spectrums of VZV vasculopathy have been identified: large-and small-vessel VZV vasculopathy. 9 In large-vessel VZV vasculopathy, the involved vessels are damaged by virus-induced inflammation, 2 presented as granulomatous angiitis in pathology, and can result in stroke.…”

Herpes zoster as a risk factor for stroke and TIA

“…2,3 This possibility is supported by findings from a Taiwanese population study showing a 30% increase in the …”

“…2 Similar pathology has also been found in strokes and TIA, which follow HZ occurring at nonophthalmic sites and even in the absence of rash, raising the possibility that VZV is more widely implicated in the pathogenesis of cerebrovascular disease. 2,3 This possibility is supported by findings from a Taiwanese population study showing a 30% increase in the incidence of stroke for up to a year after acute HZ, and a 4.5-fold increase after HZ ophthalmicus (HZO). 4,5 Herein, we analyze the risk of stroke and TIA after HZ in a large retrospective UK population-based matched cohort study followed for up to 24 years (median 6.3 years).…”

Recurrent hemiplegia associated with cerebral vasculopathy following third trimester maternal herpes zoster infection

“…3 Single episode or recurrent ischaemic strokes have been recorded in infants and the elderly and may respond to treatment with acyclovir. 5 We report here on a female aged 2 years 6 months with a right cerebral hemisphere multifocal VZV-small-vessel vasculopathy. The child suffered from recurrent strokes triggered by intercurrent viral upper respiratory tract infections (URTI), until treatment was started with acyclovir.…”