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Pre-eruptive neurologic manifestations associated with multiple cerebral infarcts in varicella
ELSEVIER
Pre-eruptive Neurologic Manifestations Associated With Multiple Cerebral Infarcts in Varicella
vasculopathy has been described in numerous reports. Adults with herpes zoster ophthalmicus (HZO) occasionally develop delayed contralateral hemiplegia as a result of local cerebral vasculitis [1-4]. Recently, there have been a few reports of primary VZV infection associated with cerebral vasculitis and ischemic infarcts that usually develop weeks to months after varicella [5-9]. We describe a child who presented with acute hemiparesis, ataxia, dysarthria, and radiologic findings compatible with multiple ischemic infarcts 24 hours prior to the eruption of typical varicella exanthem. To our knowledge, this is the first patient reported in whom cerebrovascular infarcts developed before varicella became clinically apparent.
Maria Tsolia, MD, Angeliki Skardoutsou, MD, George Tsolas, MD, Christina Karayanni, MD, Panayotis Spyridis, MD, and Constantine Sinaniotis, MD
Case Report
A boy, 4 years, 9 months of age, presented with acute hemiplegia, lethargy, ataxia, and dysarthria 24 hours prior to the eruption of typical varicella exanthem. Magnetic resonance imaging findings were typical of multiple cerebral ischemic infarcts. It is suggested that during the period of secondary viremia varicella zoster virus invaded the cerebral blood vessels causing vasculopathy and cerebrovascular infarcts. Tsolia M, Skardoutsou A, Tsolas G, Karayanni C, Spyridis P, Sinaniotis C. Pre-eruptive neurologic manifestations associated with multiple cerebral infarcts in varicelia. Pediatr Neurol 1995; 12:165-168.
Introduction Varicella-associated central nervous system (CNS) complications are common in pediatric practice and include cerebellar ataxia, encephalitis, aseptic meningitis, transverse myelitis, and Reye syndrome [1,2]. The association of varicella zoster virus (VZV) infection with CNS
From the Second Department of Pediatrics; University of Athens School of Medicine; P. and A. Kyfiakou Children's Hospital; Athens, Greece.
© 1995 by Elsevier Science Inc. • 0887-8994/95/$9.50 SSDI 0887-8994(94)00126-M
This boy, 4 years, 9 months of age, was in good health until 48 hours prior to admission when he developed diarrhea and vomiting. He was admitted to a local hospital with the diagnosis of mild gastroenteritis without dehydration. Initial symptoms resolved upon admission but the following day he suddenly developed headache, lethargy, right hemiparesis, ataxia, and dysarthria. Cranial computed tomography (CT) was obtained at the local hospital and revealed hypodense areas in the left thalamus, right cerebellar hemisphere, and cerebellar vermis. Dexamethasone and antibiotics were initiated and he was transferred to P. and A. Kyriakou Children's Hospital in Athens for further evaluation and treatment. His medical history was remarkable only for occasional headaches and recurrent episodes of acute otitis media. He had been exposed to chickenpox 2 weeks prior to his illness. Vital signs on admission to our hospital were pulse rate 28/rain, temperature 37°C, and blood pressure 95/65 mm Hg. Physical examination revealed a mildly lethargic, easily arousable boy who was oriented to person and place and could answer questions appropriately. His speech was slurred. Cranial nerves were intact except for facial asymmetry due to right VIIth nerve palsy, lie had weakness of the right arm and leg. Deep tendon reflexes were normal and there was no clonus. Gait was ataxic and Romberg sign was positive on the right. He had adiadochokinesis and dysmetria of the right hand. No nystagmus was present. There were no abnormal findings from the rest of the systemic examination. Leukocyte cell count on admission was 6,000/ram 3 (64% polymorphonuclears, 3% metamyelocytes, 21% lymphocytes, 11% mononuclears, 1% basophils). Hemoglobin was 13 gm/dl and hematocrit 37%. Erythrocyte sedimentation rate was 15 ram/hr. Cerebrospinal fluid (CSF) was clear with 140 leukocytes/mm3 (74% polymorphonuclears, 26% lymphocytes); glucose and protein were normal. Bacterial CSF and blood cultures were negative. The following laboratory tests were normal: serum electrolytes, glucose, calcium, creatinine, liver enzymes, lipid profile, immunoglobulins and complement, prothrombin time, partial thromboplastin time, coagulation factors, proteins C and S, antithrombin III, CSF and serum lactate and pyruvate, and serum and urine amino acids. Sickle cell test was negative. Antinuclear antibodies, anti-DNA antibodies, and lupus anticoagulant were not detected. Chest radiogra-
Communications should be addressed to: Dr. Skardoutsou; Second Department of Pediatrics; University of Athens School of Medicine; P. and A. Kyriakou Children's Hospital; 117 27 Athens, Greece. Received August 1, 1994; accepted November 3, 1994.
Tsolia et al: Multiple Cerebral Infarcts and Varicella
165
phy, electrocardiography, echocardiography, and electroencephalography did not reveal any abnormality. Cranial magnetic resonance imaging (MRI) was obtained on the fourth day of illness and revealed areas of low intensity in the T~-weighted and high intensity in the T2-weighted and proton density images in the region of the left thalamus, left temporal lobe, fight temporooccipital lobe, right cerebellar hemisphere, and vermis (Fig 1). There was mild compression of the IVth ventricle. The medulla was slightly depressed anteriorly, probably because of pressure exerted by the enlarged vermis. These findings were suggestive of multiple ischemic infarcts. Twenty-four hours after admission he developed a vesicular rash that was typical of chickenpox. New lesions continued to erupt for 4 days. He remained afebrile throughout the entire illness. Acyclovir was initiated when the rash first developed and was continued for 10 days. Dexamethasone was given for 15 days and was subsequently withdrawn gradually over 22 days. Neurologic signs gradually improved. He was discharged 17 days after
A
admission and at that time had no facial asymmetry but there was some residual weakness of the right ann and leg. Gait was ataxic, speech was mildly dysarthric, and he had some dysmetria on the fight. Serum serology during the acute and convalescent stage of the illness failed to reveal any elevation of antibody titers to cytomegalovirus, Epstein-Barr virus, herpes simplex virus, adenovirus, enteroviruses, and mycoplasma. Seroconversion to VZV occurred with a complement fixation IgG antibody titer of 1/160 and detection of IgM antibodies by immunofluorescence. CSF was reexamined during convalescence for antibodies to VZV by complement fixation and was negative. Angiography was suggested but the patient's parents refused. He was reexamined 1 year later and his neurologic signs had completely resolved with the exception of some mild dystonia on the right arm. Cranial CT was obtained at that time and revealed an extensive hypodense area on the right posterior cranial fossa and a linear area of decreased density in the basal ganglia on the left (Fig 2). These roentgenographic findings were typical of old ischemic infarcts.
B
C
D
Figure 1. T2-weighted cranial MRI revealing infarcts in the areas of (A) left thalamus, (B) left temporal lobe, (B,C) right occipitotemporal lobe, and (D) right cerebellar hemisphere and vermis.
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A
B
Figure 2. Cranial CT obtained 1 year later revealing old ischemic infarcts in (A) the right cerebellar hemisphere and (B) the basal ganglia on the left.
Discussion The association of VZV infection with cerebral infarcts has long been established. Adults with HZO occasionally develop contralateral hemiparesis as a result of local cerebral vasculitis ipsilateral to infection, weeks to months after the zoster [3,4]. Angiographic findings in these patients resemble those of CNS granulomatous angiitis. It has been proposed that the virus spreads directly from the Gasserian ganglion to the adjacent carotid artery or through sensory branches of the ophthalmic nerve to the internal carotid artery and its branches. Alternatively, the virus may gain access to the CNS through the hematogenous or CSF route. An immune-mediated mechanism has also been suggested. Virus-like particles have been identified in smooth muscle cells from the affected vessels by electron microscopy and VZV antigen has been detected. Prognosis is usually good in these patients and symptoms gradually resolve without sequelae. In the last few years there have been a few reports of CNS infarcts in children following primary infection with VZV [5-8]. The reported patients developed acute hemiplegia 1-3 months following the onset of varicella. Cranial CT or MRI in these patients revealed infarcts of the internal capsule, basal ganglia, and temporal and parietal lobes. Angiographic findings included segmental narrowing of the anterior, middle, and posterior cerebral arteries. These findings were identical to those in adults with HZO and contralateral hemiparesis. Histopathology was reported in a 41/2-year-old girl with AIDS who had persistent and recurrent VZV infection and developed multiple ce-
rebral infarcts [9]. CNS vasculitis was demonstrated but VZV antigen was not identified by immunohistochemical staining in brain tissue or cerebral vessels. Our patient is noteworthy because the CNS symptoms and cerebrovascular infarcts preceded the eruption of the typical varicella exanthem by 24 hours. Neurologic complications of varicella antedating the eruption of the typical rash have been described but are rare and include cerebellar ataxia or encephalitis [ 10,11]. To our knowledge, this is the first patient in whom cerebral infarcts developed before primary VZV infection became clinically apparent. It may be hypothesized that, during the secondary viremia [2,12], the virus invaded the cerebral blood vessels causing vasculopathy and thrombosis. Alternatively, an immune-mediated mechanism may have been responsible. However, the early development of CNS manifestations and radiologic findings in this patient, preceding the cutaneous manifestations of varicella by 24 hours, support direct viral invasion rather than an autoimmune process. Moderate CSF pleocytosis may suggest that the patient had meningoencephalitis. Mild CSF pleocytosis was noted in only 1 reported patient with varicella-associated CNS vasculopathy [6] but this finding is not uncommon in adults with HZO and delayed contralateral hemiparesis [4]. Furthermore, typical varicella-associated encephalitis usually presents with serious mental status changes, abnormal EEG findings, and a severe clinical course [I]. Finally, CT and MRI findings in our patient were typical of ischemic infarcts. The association of varicella with cerebral infarcts in this
Tsolia et al: MultipleCerebral Infarctsand Varicella 167
patient was only temporal and a causal role for the VZV virus was not established. The demonstration of CNS invasion by this virus with detection of antibodies [13] or, more importantly, isolation of the virus in tissue culture or detection of VZV DNA in the CSF by polymerase chain reaction [14,15], would have further supported the hypothesis for a causal relationship. Definite proof of the etiologic role of this virus can only be obtained by histopathologic examination and demonstration of its presence in affected blood vessels. VZV antibodies were not detected in our patient's CSF during convalescence. However, the complement fixation technique is less sensitive than others [13]. One may also hypothesize that the early use of acyclovir may have had a negative effect on antibody production in the CNS. However, early treatment of children and adolescents with varicella with a short course of oral acyclovir has not resulted in lower antibody titers to VZV by the fluorescent antibody to membrane antigen (FAMA) or enzyme-linked immunosorbent assay (ELISA) techniques 1 month after the onset of varicella [16,17]. Many questions arise regarding the role of antivirals and steroids in treatment that cannot be answered as long as the pathogenesis remains unclear, especially because the number of similar reported patients is too small and the natural course of this entity is not known. By analogy, the treatment of HZO also remains a matter of speculation and the role of antivirals or steroids has not been studied formally. However, it is reasonable to assume that if there were direct viral invasion, therapy with acyclovir may be warranted. Although evidence is lacking, we believe that, in this patient, the similarity of clinical manifestations and radiologic findings with those of previously reported patients, the benign clinical course, and failure to identify another cause, all point to a relationship between VZV infection and CNS symptoms that does not rest merely on coincidence. Pediatricians and neurologists treating children with strokes should be aware of a possible association with chickenpox and should inquire about recent exposure to or infection with VZV.
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References [1] Barnes DW, Whitley RJ. CNS diseases associated with varicella zoster virus and herpes simplex infection. Infect Dis Centr Nerv Syst 1986;4:265-81. [2] Grose C, Giller RH. Varicella zoster virus infection and immunization in the healthy and immunocompromised host. Crit Rev Oncol Hematol 1988;8:217-62. [3] Eidelberg D, Sorrel A, Horroupian S, Neuman PE, PumarolaSune I, Pice RW. Thrombotic cerebral vasculopatby associated with herpes zoster. Ann Neurol 1986;19:7-14. [4] Sigal LH. The neurologic presentation of vasculitic and rheumatologic syndromes. Medicine 1987;66:157-80. [5] Eda I, Takashima S, Takashima K. Acute hemiplegia with lacunar infarct after varicella infection in childhood. Brain Dev 1983,5: 494-9. [6] Kamholz J, Tremblay G. Chickenpox with delayed contralateral hemiparesis caused by cerebral angiitis. Ann Neurol 1985;18:358-60. [7] Liu GT, Holmes GL. Varicella with delayed contralateral hemiparesis detected by MRI. Pediatr Neurol 1990;6:131-4. [8] Shuper A, Vining EP, Freeman JM. Central nervous system vasculitis after chickenpox--Cause or coincidence? Arch Dis Child 1990;65:1245-8. [9] Yitzchak F, Wilma L, Kahn E, Farmer P, Corey M, Pahwa S. MultipLe ischemic infarcts in a child with AIDS, varicella zoster virus infection and cerebral vasculitis. Pediatr Neurol 1989;5:64-7. [10] Liu GT, Urion DK. Pre-eruptive varicella encephalitis and cerebellar ataxia. Pediatr Neurol 1992;8:69-70. 111] Takeuchi Y, Yoshihara T, Ishimura K, Amano T, Kadomoto Y, Sawada T. Recurrent and pre-eruptive cerebellar ataxia: A rare case of varicella. Pediatr Neurol 1987;3:240-1. [12] Asano Y, Itakura N, Hiroishi Y, et al. Viremia is present in incubation period in non-immunocompromised children with varicella. J Pediatr 1985;106:69-71. [13] Gershon A, Steinberg S, Greenberg S, Taber L. Varicellazoster associated encephalitis detection of specific antibody in cerebrospinal fluid. J Clin Microbiol 1980;12:764-7. [14] Puchhamer-Stockle E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C. Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chickenpox or herpes zoster. J Clin Microbiol 1991;29:1513-6. [151 Dangond F, Engle E, Yessayan L, Sawyer M. Pre-eruptive varicella cerebellitis confirmed by PCR. Pediatr Neurol 1993;9:491-3. [16] Dunkle LM, Arvin AM, Whitley RJ, et al. A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med 1991 ;325: 1539-44. [17] Balfour HH Jr, Rotbart HA, Feldman S, et al. Acyclovir treatment of varicella in otherwise healthy adolescents. J Pediatr 1992;120: 627-33.
Pre-eruptive Neurologic Manifestations Associated With Multiple Cerebral Infarcts in Varicella
vasculopathy has been described in numerous reports. Adults with herpes zoster ophthalmicus (HZO) occasionally develop delayed contralateral hemiplegia as a result of local cerebral vasculitis [1-4]. Recently, there have been a few reports of primary VZV infection associated with cerebral vasculitis and ischemic infarcts that usually develop weeks to months after varicella [5-9]. We describe a child who presented with acute hemiparesis, ataxia, dysarthria, and radiologic findings compatible with multiple ischemic infarcts 24 hours prior to the eruption of typical varicella exanthem. To our knowledge, this is the first patient reported in whom cerebrovascular infarcts developed before varicella became clinically apparent.
Maria Tsolia, MD, Angeliki Skardoutsou, MD, George Tsolas, MD, Christina Karayanni, MD, Panayotis Spyridis, MD, and Constantine Sinaniotis, MD
Case Report
A boy, 4 years, 9 months of age, presented with acute hemiplegia, lethargy, ataxia, and dysarthria 24 hours prior to the eruption of typical varicella exanthem. Magnetic resonance imaging findings were typical of multiple cerebral ischemic infarcts. It is suggested that during the period of secondary viremia varicella zoster virus invaded the cerebral blood vessels causing vasculopathy and cerebrovascular infarcts. Tsolia M, Skardoutsou A, Tsolas G, Karayanni C, Spyridis P, Sinaniotis C. Pre-eruptive neurologic manifestations associated with multiple cerebral infarcts in varicelia. Pediatr Neurol 1995; 12:165-168.
Introduction Varicella-associated central nervous system (CNS) complications are common in pediatric practice and include cerebellar ataxia, encephalitis, aseptic meningitis, transverse myelitis, and Reye syndrome [1,2]. The association of varicella zoster virus (VZV) infection with CNS
From the Second Department of Pediatrics; University of Athens School of Medicine; P. and A. Kyfiakou Children's Hospital; Athens, Greece.
© 1995 by Elsevier Science Inc. • 0887-8994/95/$9.50 SSDI 0887-8994(94)00126-M
This boy, 4 years, 9 months of age, was in good health until 48 hours prior to admission when he developed diarrhea and vomiting. He was admitted to a local hospital with the diagnosis of mild gastroenteritis without dehydration. Initial symptoms resolved upon admission but the following day he suddenly developed headache, lethargy, right hemiparesis, ataxia, and dysarthria. Cranial computed tomography (CT) was obtained at the local hospital and revealed hypodense areas in the left thalamus, right cerebellar hemisphere, and cerebellar vermis. Dexamethasone and antibiotics were initiated and he was transferred to P. and A. Kyriakou Children's Hospital in Athens for further evaluation and treatment. His medical history was remarkable only for occasional headaches and recurrent episodes of acute otitis media. He had been exposed to chickenpox 2 weeks prior to his illness. Vital signs on admission to our hospital were pulse rate 28/rain, temperature 37°C, and blood pressure 95/65 mm Hg. Physical examination revealed a mildly lethargic, easily arousable boy who was oriented to person and place and could answer questions appropriately. His speech was slurred. Cranial nerves were intact except for facial asymmetry due to right VIIth nerve palsy, lie had weakness of the right arm and leg. Deep tendon reflexes were normal and there was no clonus. Gait was ataxic and Romberg sign was positive on the right. He had adiadochokinesis and dysmetria of the right hand. No nystagmus was present. There were no abnormal findings from the rest of the systemic examination. Leukocyte cell count on admission was 6,000/ram 3 (64% polymorphonuclears, 3% metamyelocytes, 21% lymphocytes, 11% mononuclears, 1% basophils). Hemoglobin was 13 gm/dl and hematocrit 37%. Erythrocyte sedimentation rate was 15 ram/hr. Cerebrospinal fluid (CSF) was clear with 140 leukocytes/mm3 (74% polymorphonuclears, 26% lymphocytes); glucose and protein were normal. Bacterial CSF and blood cultures were negative. The following laboratory tests were normal: serum electrolytes, glucose, calcium, creatinine, liver enzymes, lipid profile, immunoglobulins and complement, prothrombin time, partial thromboplastin time, coagulation factors, proteins C and S, antithrombin III, CSF and serum lactate and pyruvate, and serum and urine amino acids. Sickle cell test was negative. Antinuclear antibodies, anti-DNA antibodies, and lupus anticoagulant were not detected. Chest radiogra-
Communications should be addressed to: Dr. Skardoutsou; Second Department of Pediatrics; University of Athens School of Medicine; P. and A. Kyriakou Children's Hospital; 117 27 Athens, Greece. Received August 1, 1994; accepted November 3, 1994.
Tsolia et al: Multiple Cerebral Infarcts and Varicella
165
phy, electrocardiography, echocardiography, and electroencephalography did not reveal any abnormality. Cranial magnetic resonance imaging (MRI) was obtained on the fourth day of illness and revealed areas of low intensity in the T~-weighted and high intensity in the T2-weighted and proton density images in the region of the left thalamus, left temporal lobe, fight temporooccipital lobe, right cerebellar hemisphere, and vermis (Fig 1). There was mild compression of the IVth ventricle. The medulla was slightly depressed anteriorly, probably because of pressure exerted by the enlarged vermis. These findings were suggestive of multiple ischemic infarcts. Twenty-four hours after admission he developed a vesicular rash that was typical of chickenpox. New lesions continued to erupt for 4 days. He remained afebrile throughout the entire illness. Acyclovir was initiated when the rash first developed and was continued for 10 days. Dexamethasone was given for 15 days and was subsequently withdrawn gradually over 22 days. Neurologic signs gradually improved. He was discharged 17 days after
A
admission and at that time had no facial asymmetry but there was some residual weakness of the right ann and leg. Gait was ataxic, speech was mildly dysarthric, and he had some dysmetria on the fight. Serum serology during the acute and convalescent stage of the illness failed to reveal any elevation of antibody titers to cytomegalovirus, Epstein-Barr virus, herpes simplex virus, adenovirus, enteroviruses, and mycoplasma. Seroconversion to VZV occurred with a complement fixation IgG antibody titer of 1/160 and detection of IgM antibodies by immunofluorescence. CSF was reexamined during convalescence for antibodies to VZV by complement fixation and was negative. Angiography was suggested but the patient's parents refused. He was reexamined 1 year later and his neurologic signs had completely resolved with the exception of some mild dystonia on the right arm. Cranial CT was obtained at that time and revealed an extensive hypodense area on the right posterior cranial fossa and a linear area of decreased density in the basal ganglia on the left (Fig 2). These roentgenographic findings were typical of old ischemic infarcts.
B
C
D
Figure 1. T2-weighted cranial MRI revealing infarcts in the areas of (A) left thalamus, (B) left temporal lobe, (B,C) right occipitotemporal lobe, and (D) right cerebellar hemisphere and vermis.
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A
B
Figure 2. Cranial CT obtained 1 year later revealing old ischemic infarcts in (A) the right cerebellar hemisphere and (B) the basal ganglia on the left.
Discussion The association of VZV infection with cerebral infarcts has long been established. Adults with HZO occasionally develop contralateral hemiparesis as a result of local cerebral vasculitis ipsilateral to infection, weeks to months after the zoster [3,4]. Angiographic findings in these patients resemble those of CNS granulomatous angiitis. It has been proposed that the virus spreads directly from the Gasserian ganglion to the adjacent carotid artery or through sensory branches of the ophthalmic nerve to the internal carotid artery and its branches. Alternatively, the virus may gain access to the CNS through the hematogenous or CSF route. An immune-mediated mechanism has also been suggested. Virus-like particles have been identified in smooth muscle cells from the affected vessels by electron microscopy and VZV antigen has been detected. Prognosis is usually good in these patients and symptoms gradually resolve without sequelae. In the last few years there have been a few reports of CNS infarcts in children following primary infection with VZV [5-8]. The reported patients developed acute hemiplegia 1-3 months following the onset of varicella. Cranial CT or MRI in these patients revealed infarcts of the internal capsule, basal ganglia, and temporal and parietal lobes. Angiographic findings included segmental narrowing of the anterior, middle, and posterior cerebral arteries. These findings were identical to those in adults with HZO and contralateral hemiparesis. Histopathology was reported in a 41/2-year-old girl with AIDS who had persistent and recurrent VZV infection and developed multiple ce-
rebral infarcts [9]. CNS vasculitis was demonstrated but VZV antigen was not identified by immunohistochemical staining in brain tissue or cerebral vessels. Our patient is noteworthy because the CNS symptoms and cerebrovascular infarcts preceded the eruption of the typical varicella exanthem by 24 hours. Neurologic complications of varicella antedating the eruption of the typical rash have been described but are rare and include cerebellar ataxia or encephalitis [ 10,11]. To our knowledge, this is the first patient in whom cerebral infarcts developed before primary VZV infection became clinically apparent. It may be hypothesized that, during the secondary viremia [2,12], the virus invaded the cerebral blood vessels causing vasculopathy and thrombosis. Alternatively, an immune-mediated mechanism may have been responsible. However, the early development of CNS manifestations and radiologic findings in this patient, preceding the cutaneous manifestations of varicella by 24 hours, support direct viral invasion rather than an autoimmune process. Moderate CSF pleocytosis may suggest that the patient had meningoencephalitis. Mild CSF pleocytosis was noted in only 1 reported patient with varicella-associated CNS vasculopathy [6] but this finding is not uncommon in adults with HZO and delayed contralateral hemiparesis [4]. Furthermore, typical varicella-associated encephalitis usually presents with serious mental status changes, abnormal EEG findings, and a severe clinical course [I]. Finally, CT and MRI findings in our patient were typical of ischemic infarcts. The association of varicella with cerebral infarcts in this
Tsolia et al: MultipleCerebral Infarctsand Varicella 167
patient was only temporal and a causal role for the VZV virus was not established. The demonstration of CNS invasion by this virus with detection of antibodies [13] or, more importantly, isolation of the virus in tissue culture or detection of VZV DNA in the CSF by polymerase chain reaction [14,15], would have further supported the hypothesis for a causal relationship. Definite proof of the etiologic role of this virus can only be obtained by histopathologic examination and demonstration of its presence in affected blood vessels. VZV antibodies were not detected in our patient's CSF during convalescence. However, the complement fixation technique is less sensitive than others [13]. One may also hypothesize that the early use of acyclovir may have had a negative effect on antibody production in the CNS. However, early treatment of children and adolescents with varicella with a short course of oral acyclovir has not resulted in lower antibody titers to VZV by the fluorescent antibody to membrane antigen (FAMA) or enzyme-linked immunosorbent assay (ELISA) techniques 1 month after the onset of varicella [16,17]. Many questions arise regarding the role of antivirals and steroids in treatment that cannot be answered as long as the pathogenesis remains unclear, especially because the number of similar reported patients is too small and the natural course of this entity is not known. By analogy, the treatment of HZO also remains a matter of speculation and the role of antivirals or steroids has not been studied formally. However, it is reasonable to assume that if there were direct viral invasion, therapy with acyclovir may be warranted. Although evidence is lacking, we believe that, in this patient, the similarity of clinical manifestations and radiologic findings with those of previously reported patients, the benign clinical course, and failure to identify another cause, all point to a relationship between VZV infection and CNS symptoms that does not rest merely on coincidence. Pediatricians and neurologists treating children with strokes should be aware of a possible association with chickenpox and should inquire about recent exposure to or infection with VZV.
168 PEDIATRIC NEUROLOGY
Vol. 12 No. 2
References [1] Barnes DW, Whitley RJ. CNS diseases associated with varicella zoster virus and herpes simplex infection. Infect Dis Centr Nerv Syst 1986;4:265-81. [2] Grose C, Giller RH. Varicella zoster virus infection and immunization in the healthy and immunocompromised host. Crit Rev Oncol Hematol 1988;8:217-62. [3] Eidelberg D, Sorrel A, Horroupian S, Neuman PE, PumarolaSune I, Pice RW. Thrombotic cerebral vasculopatby associated with herpes zoster. Ann Neurol 1986;19:7-14. [4] Sigal LH. The neurologic presentation of vasculitic and rheumatologic syndromes. Medicine 1987;66:157-80. [5] Eda I, Takashima S, Takashima K. Acute hemiplegia with lacunar infarct after varicella infection in childhood. Brain Dev 1983,5: 494-9. [6] Kamholz J, Tremblay G. Chickenpox with delayed contralateral hemiparesis caused by cerebral angiitis. Ann Neurol 1985;18:358-60. [7] Liu GT, Holmes GL. Varicella with delayed contralateral hemiparesis detected by MRI. Pediatr Neurol 1990;6:131-4. [8] Shuper A, Vining EP, Freeman JM. Central nervous system vasculitis after chickenpox--Cause or coincidence? Arch Dis Child 1990;65:1245-8. [9] Yitzchak F, Wilma L, Kahn E, Farmer P, Corey M, Pahwa S. MultipLe ischemic infarcts in a child with AIDS, varicella zoster virus infection and cerebral vasculitis. Pediatr Neurol 1989;5:64-7. [10] Liu GT, Urion DK. Pre-eruptive varicella encephalitis and cerebellar ataxia. Pediatr Neurol 1992;8:69-70. 111] Takeuchi Y, Yoshihara T, Ishimura K, Amano T, Kadomoto Y, Sawada T. Recurrent and pre-eruptive cerebellar ataxia: A rare case of varicella. Pediatr Neurol 1987;3:240-1. [12] Asano Y, Itakura N, Hiroishi Y, et al. Viremia is present in incubation period in non-immunocompromised children with varicella. J Pediatr 1985;106:69-71. [13] Gershon A, Steinberg S, Greenberg S, Taber L. Varicellazoster associated encephalitis detection of specific antibody in cerebrospinal fluid. J Clin Microbiol 1980;12:764-7. [14] Puchhamer-Stockle E, Popow-Kraupp T, Heinz FX, Mandl CW, Kunz C. Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chickenpox or herpes zoster. J Clin Microbiol 1991;29:1513-6. [151 Dangond F, Engle E, Yessayan L, Sawyer M. Pre-eruptive varicella cerebellitis confirmed by PCR. Pediatr Neurol 1993;9:491-3. [16] Dunkle LM, Arvin AM, Whitley RJ, et al. A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med 1991 ;325: 1539-44. [17] Balfour HH Jr, Rotbart HA, Feldman S, et al. Acyclovir treatment of varicella in otherwise healthy adolescents. J Pediatr 1992;120: 627-33.