varicella zoster virus ( vzv ) is a neurotropic dna alpha herpesvirus that infects more than 95% of the world population . usually , varicella results from primary infection .
the virus then becomes latent in ganglion neurons along the entire neuroaxis , and after reactivation , vzv moves transaxonally to the skin resulting in zoster .
less often , vzv reactivation leads to neurologic complications more common in immunocompromised patients , such as vzv vasculopathy .
vasculitis has , however , been reported in patients with dermatomal herpes zoster infection without trigeminal nerve involvement .
the average time from rash to neurologic symptoms and signs is 4.1 months , but sporadically the patient can present with rash and stroke simultaneously .
nonetheless , approximately one third of patients have no history of rash . in recent years
, the number of recognized vzv vasculopathies has grown , but the diagnosis is not easy because , frequently , clinical presentation and imaging features are not specific of this entity .
antiviral and antithrombotic treatment should probably be considered in stroke associated with vzv vasculopathy , but data on which to base therapeutic decisions are lacking .
a 31-year - old right - handed female was admitted to the emergency department because of headache associated with visual disturbance .
she had no previous history of headache and no known vascular risk factors but she used an oral contraceptive pill . on admission , she reported a 9-hour progressive pulsatile headache , with nausea and photophobia , followed by a sudden left visual field defect . neurological examination
a head computed tomography ( ct ) scan was judged to be normal ( fig .
the next day , the patient was observed at an outpatient consultation and subsequently admitted in the neurology ward because the headache had worsened and she felt weakness and numbness of the left limbs .
she also recalled a history of thoracic rash 1 month before and she reported having had varicella at the age of 7 years .
neurological examination at that time revealed slight drowsiness , mild left hemiparesis , left hemihypesthesia and homolateral homonymous hemianopia .
a new ct scan showed an ischemic infarct on the territory of the right posterior cerebral artery ( fig .
two days after admission , the neurological picture worsened with acute onset of left central facial palsy , visual and tactile inattention and worsening of the left motor deficit .
a new ct scan showed enlargement of the ischemic lesion with involvement of the right thalamus ( fig .
1c ) and new areas of infarction involving different arterial territories , further depicted on mri ( fig .
mr angiography showed an occlusion of the right posterior cerebral artery 5 mm after its origin ( fig . 2c ) .
transthoracic and transesophageal echocardiography and holter ecg were within the norms , as were the of laboratory blood tests ( including hiv antibodies ) .
clinical deterioration continued with further motor compromise , and although no cardiac or large vessel embolic source had been documented , facing neurological worsening , acetylsalicylic acid was substituted by low molecular weight heparin ( 60 mg subcutaneously twice a day ) 6 days after admission .
the patient remained stable for a week , but then a new episode occurred , with headache and slight drowsiness associated with hemorrhagic transformation involving the thalamus but sparing the cortical territory of the posterior cerebral artery ( fig .
because of the medical history of recent vzv reactivation , it was then hypothesized that the stroke could be secondary to vzv vasculopathy .
however , at that time , evidence of increased intracranial pressure contraindicated the lumbar puncture .
acyclovir and prednisolone were started empirically ( acyclovir 750 mg three times daily , and prednisolone 60 mg once a day for 21 days ) , with slow but steady improvement .
digital subtraction angiography ( dsa ) showed narrowing at the origin of the right posterior cerebral artery and demonstrated an irregular lumen of the posterior segment of the pericallosal artery with beading - like pattern appearance ( fig .
she underwent a lumbar puncture 11 days after initiation of therapy ( 27 days after admission ) .
cerebrospinal fluid ( csf ) protein content was slightly increased ( 48 mg / dl ) , glucose 59 mg / dl , and a discrete mononuclear pleocytosis was detected ( 6 cells ) .
vzv - dna was not detected by polymerase chain reaction , but there was an increased csf / serum ratio of vzv igg ( 3.3 ) , confirming intrathecal production of anti - vzv antibodies .
motor function improved , but the patient was discharged with persistent left homonymous hemianopia and spatial inattention , unable to walk without assistance [ modified rankin scale ( mrs ) score 4 ] .
after antiviral therapy , she restarted acetylsalicylic acid 150 mg once a day . on the 6-month follow - up , only a mild to moderate paresis of the left limbs was present .
the patient was able to walk unassisted and look after her own affairs ( mrs score 2 ) .
recognition of vzv vasculopathy was not straightforward because this is an uncommon entity and strokes of other etiologies may present with a similar neurologic picture and imaging abnormalities . on the other hand ,
finally , vzv - induced central nervous system ( cns ) disease seems to be rare in immunocompetent patients . despite no previous history of headache and sudden presentation of the visual deficit
, migrainous infarction could be considered in our patient on account of presentation with pulsatile progressive headache in a young female and the known predilection of this complication for the posterior circulation .
cryptogenic stroke , which may be responsible for as much as 50% of strokes in young adults [ 6 , 7 ] , was also considered in the absence of findings that supported cardiac embolism , atherosclerosis , arterial dissection , inflammatory or drug - induced etiologies .
although there was no evidence to support the decision , anticoagulation was considered because of the stepwise deterioration of the neurological status under aspirin , with new ischemic areas in different territories , and a mr angiography not indicative of vasculitis . looking backwards , anticoagulation may not have been the most suitable therapeutic choice and should probably be avoided with in - patients with stroke and recent vzv infection , as hemorrhagic transformation occurred probably in the context of vessel wall damage but may also have been triggered by anticoagulation .
the biological mechanisms are probably multifactorial : inflammation associated with systemic infection may lead to endothelial dysfunction ; in addition , the vzv virus spreads along nerve fibers and directly involves the vessels .
vasculitis has been described in patients with dermatomal herpes zoster infection without trigeminal nerve involvement , as in our case .
the vasculopathy typically involves the anterior circulation , but vzv vasculitis involvement of the vertebrobasilar system has also been reported .
these studies suggest that vzv may enter the cns not only from trigeminal ganglia but also from other pathways .
as suggested in previous reports , this case highlights the usefulness of dsa and csf / serum ratio of vzv igg for the diagnosis of vzv vasculopathy .
vzv dna was not present in csf , but several studies with serial analysis revealed its presence only during the first 2 weeks of disease , while anti - vzv igg antibodies become detectable during the second week after infection .
the diagnostic value of detecting anti - vzv igg antibody in csf is greater than that of detecting vzv dna .
the multifocal nature of vzv vasculopathy makes biopsy a test with low sensitivity and high morbidity .
when the diagnosis of vzv vasculopathy was considered , a lumbar puncture was contraindicated due to increased intracranial pressure ; nevertheless , we began treatment with intravenous acyclovir and steroids . although there are no controlled trials to access the optimal treatment schemes , we continued treatment during 21 days .
duration of antiviral treatment as well as acyclovir dosage and benefit of steroids are issues that deserve further research . in conclusion , our case underlines that vasculopathy and stroke related to vzv infection should be borne in mind when dealing with stroke in young adults .
in fact , available data suggest that this complication of a frequent infection may be more common than usually reported , not only after herpes zoster or varicella but also in cases of a stroke of unknown origin [ 1 , 2 ] .
dsa seems to be important to the diagnosis of vzv vasculopathy , which is confirmed by intrathecal synthesis of anti - vzv igg antibody .
the authors declare that there are no conflicts of interest and that no funding was received for this report .
 ischemic and hemorrhagic stroke are recognized complications of varicella zoster virus ( vzv ) infections , although uncommon and poorly documented . 
 the authors report the case of a 31-year - old woman admitted with acute ischemic stroke of the right posterior cerebral artery and a history of a thoracic rash 1 month before . 
 aspirin and simvastatin were prescribed , but the patient suffered a stepwise deterioration the following days , with new areas of infarction on brain imaging . despite no evidence of cardiac or large vessel embolic sources , anticoagulation was started empirically 6 days after stroke onset . 
 one week later , symptomatic hemorrhagic transformation occurred . 
 the diagnosis of vzv vasculopathy was then considered , and treatment with acyclovir and prednisolone was started with no further vascular events . 
 cerebrospinal fluid analysis and digital subtraction angiography findings corroborated the diagnosis . 
 the patient was discharged to the rehabilitation center with a modified rankin scale ( mrs ) score of 4 . on the 6-month follow - up 
 , she presented only a slight disability ( mrs score 2 ) . in conclusion 
 , vzv vasculopathy needs to be considered in young adults with stroke . 
 a high index of suspicion and early treatment seem to be important to minimize morbidity and mortality . 
 anticoagulation should probably be avoided in stroke associated with vzv vasculopathy . 
Introduction
Case Report
Discussion
Statement of Ethics
Disclosure Statement