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Table of Contents    
LETTERS TO EDITOR
Year : 2019  |  Volume : 67  |  Issue : 4  |  Page : 1147-1149

Varicella-related Multifocal Vasculopathy: Under-recognized Cause of Young Stroke


1 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neuroradiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication10-Sep-2019

Correspondence Address:
Dr. Dheeraj Khurana
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.266233

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How to cite this article:
Kumar AS, Naheed D, Khurana D, Ahuja C. Varicella-related Multifocal Vasculopathy: Under-recognized Cause of Young Stroke. Neurol India 2019;67:1147-9

How to cite this URL:
Kumar AS, Naheed D, Khurana D, Ahuja C. Varicella-related Multifocal Vasculopathy: Under-recognized Cause of Young Stroke. Neurol India [serial online] 2019 [cited 2019 Sep 23];67:1147-9. Available from: http://www.neurologyindia.com/text.asp?2019/67/4/1147/266233




Sir,

Varicella zoster virus (VZV) vasculopathy is an infection of intracranial arteries often manifesting as stroke, mostly ischemic and less often hemorrhagic. It may occur either after primary infection with VZV or after viral reactivation. It has been presented with various nomenclatures, namely, granulomatous angitis, VZV vasculitis, or post-varicella arteriopathy.[1] Being an under-reported entity, the exact incidence of VZV-associated stroke in adults is difficult to estimate, but in children it accounts for ~31% of all arterial ischemic strokes.[2] Common clinical features seen associated with VZV vasculopathy include headache, changes in mental status, aphasia, ataxia, hemianaesthesia/paresis, and visual loss.

A 32-year-old self-employed gentleman, with no prior comorbidities, presented with vesiculo-papular eruptions all over the body [Figure 1]c with sudden onset weakness of the right side of the body and difficulty in speaking before presentation. Five members of his family including his wife, children, and brothers had similar eruptions. Detailed evaluation showed right hemiparesis with global aphasia. There were no other neurologic abnormalities including nuchal rigidity. Magnetic resonance imaging (MRI) brain showed multiple patchy T2/FLAIR hyperintensities in the grey and white matter in left frontal, parietal, and temporal lobes [Figure 1]a. MR angiography showed normal M1 and M2 segments with attenuated M3 and M4 segment of the left middle cerebral artery (MCA) [Figure 2]a and [Figure 2]b.
Figure 1: (a and b) Axial T2W and FLAIR MRI brain showing subacute infarct in left MCA territory. (c) Vesiculo-papular skin eruptions

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Figure 2: (a and b) Baseline 2D TOF images showing normal bilateral extracranial vessels with attenuated left M2-MCA. (c and d) Two months follow-up CT angiogram showing normal bilateral extracranial vessels with attenuated cortical branches of left MCA

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Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis (10 cells) with high proteins (78 mg/dL) and normal sugars (114 g/dL, against random blood sugar of 166 g/dL). India ink preparation for Cryptococcus spp. and adenosine deaminase (ADA), ZN staining, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis were all negative. CSF IgM/IgG antibodies against VZV were negative. Serum PCR for varicella zoster was positive. CSF and serum herpes simplex virus (HSV) PCR and IgM/IgG antibodies were negative. The results of laboratory blood tests, including glycemia, coagulation panel, and thrombophilia screening, were normal. Immune diseases' markers were negative. Human immunodeficiency virus, hepatitis B virus surface antigen, and anti-hepatitis C virus antibody tests were negative. Echocardiography and electrocardiography were normal ruling out the possibility of cardioembolic origin of stroke.

Clinical history with MRI findings and positive VZV PCR in serum added up to the diagnosis of VZV vasculopathy-related acute ischemic stroke. He was managed conservatively with intravenous acyclovir (30 mg/kg/day in three divided doses) for 14 days along with intravenous methyl prednisolone for 5 days. Over the next 2 weeks, his aphasia improved with improved comprehension and word output with occasional literal paraphasias. At 3 months follow-up, his weakness has improved completely, but continues to have naming difficulty.

VZV is the only virus in human beings that has been demonstrated to replicate in arteries and produce vasculopathy.[1] Contrary to the common presentation, it per se is not primarily encephalitis, but a vasculopathy due to secondary to VZV infection within cerebral arteries. The clinical diagnosis is based on a continuum of recent zoster infection followed by focal neurological signs with radiologic abnormalities proving cerebral ischemia/hemorrhage. Narrowing or beading in cerebral arteries, as demonstrated in cerebral angiography, with CSF pleocytosis aids clinical possibility.

VZV vasculopathy may be unifocal or multifocal. The most common location unifocal vasculopathy affects is the ophthalmic distribution zoster in elderly adults or childhood varicella infection. Multifocal vasculopathy usually affects branches of large cerebral arteries or small cerebral arteries, mostly in immunocompromised individuals.[3] Most often, both large and small arteries are involved, followed by small arteries alone, and, least often, by large arteries alone.[4] Various animal studies have put forth the hypothesis of direct spread of VZV to cerebral arterial walls, with replication and damage of the cerebral vessels. Both intracranial and extracranial blood vessels receive the afferent fibers from trigeminal and other ganglia, thus providing an anatomical pathway for the transaxonal spread of virus.[5]

Common radiological abnormalities in VZV vasculopathy include cortical and deep grey and white matter involvement, especially at the grey–white matter junction.[6] Segmental constriction, often with poststenotic dilatation, is a common angiographic finding.[7] A detailed description of 30 subjects with virologically verified VZV vasculopathy, brain imaging, and vascular studies indicated involvement of both large and small arteries in 50%, pure small-artery involvement in 37%, and pure large-artery disease in four (13%) patients.[4] VZV vasculopathy resulting in intracranial hemorrhages has been reported in literature.[8],[9]

CSF analysis usually shows pleocytosis (usually <100 cells, predominantly mononuclear), in two-thirds of patients.[4] CSF VZV PCR and anti-VZV IgG antibody tests are the cornerstone in confirming the diagnosis of VZV vasculopathy. The detection of VZV antibody is more sensitive than VZV DNA for diagnosis and the former generally lasts for weeks to months.

VZV vasculopathy is often underdiagnosed because (1) symptoms and signs may occur months after zoster;[4] (2) around 30% of patients do not have a preceding zoster rash; (3) up to one-third of patients do not have CSF pleocytosis; and (4) sensitivity of PCR analysis of CSF for VZV DNA is only 30% and that of IgM VZV antibodies 96%.[10]

In our patient, prima facie clinical features of eruptions all over the body with similar features in his family members and MRI features of prominent grey and white matter involvement along with angiography showing attenuation of distal left MCA narrowed in on the diagnosis of VZV vasculopathy-related stroke. Positive VZV PCR in serum was contributory to the diagnosis. This article aims to sensitize the readers toward VZV vasculopathy and its features, which would help in early identification and management, decreasing the morbidity and mortality caused by the disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: Diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 2009;8:731-40.  Back to cited text no. 1
    
2.
Askalan R, Laughlin S, Mayank S, Chan A, MacGregor D, Andrew M, et al. Chickenpox and stroke in childhood: A study of frequency and causation. Stroke 2001;32:1257-62.  Back to cited text no. 2
    
3.
Nagel MA. Varicella zoster virus vasculopathy: Clinical features and pathogenesis. J Neurovirol 2014;20:157-63.  Back to cited text no. 3
    
4.
Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, et al. The varicella zoster virus vasculopathies: Clinical, CSF, imaging, and virologic features. Neurology 2008;70:853-60.  Back to cited text no. 4
    
5.
Mayberg M, Langer RS, Zervas NT, Moskowitz MA. Perivascular meningeal projections from cat trigeminal ganglia: Possible pathway for vascular headaches in man. Science 1981;213:228-30.  Back to cited text no. 5
    
6.
Gilden DH, Mahalingam R, Cohrs RJ, Kleinschmidt-DeMasters BK, Forghani B. The protean manifestations of varicella-zoster virus vasculopathy. J Neurovirol 2002;8(Suppl 2):75-9.  Back to cited text no. 6
    
7.
Russman AN, Lederman RJ, Calabrese LH, Embi PJ, Forghani B, Gilden DH. Multifocal varicella-zoster virus vasculopathy without rash. Arch Neurol 2003;60:1607-9.  Back to cited text no. 7
    
8.
Artemiadis AK, Karantoni E, Nikolaou G, Terentiou A. Varicella-zoster virus vasculopathy in a 75-year-old immunocompetent man. Neurol India 2016;64(Suppl):S118-20.  Back to cited text no. 8
    
9.
Harsha KJ, Parameswaran K. Adult post-varicella small vessel vaculopathy mimicking hypertensive basal ganglia hemorrhage with coexisting infarcts. Neurol India 2016;64:1323-6.  Back to cited text no. 9
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10.
Nagel MA, Forghani B, Mahalingam R, Wellish MC, Cohrs RJ, Russman AN, et al. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007;68:1069-73.  Back to cited text no. 10
    


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