Pre-eruptive Varicella Encephalitis and Cerebellar Ataxia Grant T. Liu, MD and David K. Urion, MD
Varicella-related neurologic symptoms usually appear during or following the exanthem. Pre-eruptive neurologic manifestations are extremely rare. We report a 6-year-old boy who developed encephalitis, characterized by drowsiness and left-sided hyperactive deep tendon reflexes and cerebellar ataxia, both of which antedated the exanthem by 16 days. The diagnostic and public health implications are discussed. Liu GT, Urion DK. Pre-emptive varicella encephalitis and cerebellar ataxia. Pediatr Neurol 1992;8:69-70.
Introduction The neurologic complications of primary varicella infection, which include encephalitis, cerebellar ataxia, transverse myelitis, Reye syndrome, Guillain-Barr6 syndrome, and basal ganglia infarction [1,2], typically occur during or after the exanthem. We report a child with varicella who developed encephalitis and cerebellar ataxia 16 days before the onset of the rash.
Case Report A previously healthy 2-year-old boy was admitted to our hospital for lethargy and difficulty walking. His older 5-year-old brother had developed varicella 4 days previously. On the morning of admission his parents found the patient sleepier and more tired than usual and he walked with a staggering, wobbly gait. No aspirin had been given. The patient had no vesicles and was afebrile and drowsy. He knew his name and recognized his parents easily, but quickly fell asleep if not stimulated. There was coarse end-gaze nystagmus, bilateral appendicular dysmetria, and gait ataxia. Motor function was difficult to assess because of drowsiness, but there were no gross asymmetries. He was able to stand unassisted and his limbs had normal tone. The left knee and ankle reflexes were hyperactive and the left plantar reflex was extensor. Liver function tests, serum ammonia, and cranial computed tomography were normal. Cerebrospinal fluid (CSF) was acellular with normal protein. Serum varicella-zoster IgG was absent. Electroencephalography (EEG) revealed bilateral theta slowing, mostly in the temporal regions and more prominent in the right hemisphere.
From the Department of Neurology; Children's Hospital; Harvard Longwood Neurology Program; Harvard Medical School; Boston, Massachusetts.
Within 2 days his mental status had returned to normal, but he remained ataxic with asymmetric reflexes and was discharged from the hospital. Sixteen days after initial presentation the patient developed a typical varicella rash. Subsequent examination 3 weeks after discharge was normal. Repeat EEG at 5 weeks was also normal and the varicellazoster IgG was 69.6 ELISA units/ml, indicative of previous infection.
Discussion Varicella encephalitis is a likely, though not absolutely certain, diagnosis in our patient given the previous exposure to varicella, the rise in antibody titers, the altered sensorium, asymmetric deep tendon and plantar reflexes, and abnormal EEG [1]. Concomitant cerebellar ataxia, manifested by nystagmus, dysmetria, and gait unsteadiness, was present. The sudden onset of symptoms and eventual recovery could be consistent with either an infectious etiology or stroke; however, the neuroimaging study excluded any structural abnormality or cerebrovascular event. As in this case, in some instances of varicella encephalitis or cerebellar ataxia the CSF can be normal [1,3, 4]. Reye syndrome was unlikely without an elevation in liver enzyme activities. Our patient is noteworthy because of the 16-day delay between the neurologic symptoms and the exanthem. Varicella encephalitis usually follows the onset of the rash after 3-8 days [3]. Cerebellar ataxia on average occurs 51/2 days after the rash [4]. Pre-emptive neurologic complications of varicella have been previously described but are rare. Goldston et al. reported a 5-year-old boy similar to ours with ataxia and encephalitis 11 days before the rash developed [5]. They reviewed the literature for reports of pre-eruptiv_e neurologic complications and were able to find only 15 such patients reported between 1873 and 1963. Seizures, coma, delirium, meningomyelitis, aseptic meningitis, headache, facial paralysis, ataxia, and meningoencephalitis were the reported pre-emptive manifestations. Underwood reported the patient with the longest delay [6]: an individual with cerebellar ataxia antedating the exanthem by 18 days. Early neurologic involvement in these patients may have occurred during the initial exposure and viremia [5]. The rash then followed after the usual 14-16-day incubation period [7]. The pathogenesis of varicella-related neurologic complications is not clearly defined but has been attributed to immune-mediated postinfectious demyelination or direct viral invasion [8]. We do not know which of these 2 mechanisms is more likely in our patient. Physicians evaluating patients with ataxia or encephalitis should inquire about recent exposure to varicella; they should be aware that these complications may precede the
Communications should be addressed to: Dr. Urion; Department of Neurology; Children's Hospital; 3010 Longwood Avenue; Boston, MA 02115. Received August 8, 1991; accepted September 24, 1991.
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e x a n t h e m by as l o n g as 21/2 weeks. E x p o s e d i n d i v i d u a l s s h o u l d be i s o l a t e d f r o m i m m u n o c o m p r o m i s e d patients, p r e g n a n t w o m e n , a n d p r e v i o u s l y u n a f f e c t e d adults [7]; they are i n f e c t i o u s f r o m 2 d a y s p r i o r to the e x a n t h e m until 5 d a y s a f t e r the v e s i c l e s h a v e c r u s t e d [91. References [1] McKendall RR, Klawans HL. Nervous-system complications of varicella-zoster virus. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology, vol 34. Amsterdam: North-Holland, 1978;161-83. [2] Liu GT, Holmes GL. Varicella with delayed contralateral hemiparesis detected by MRI. Pediatr Neurol 1990;6:131-4. [3] Appelbaum E, Rachelson MH, Dolgopol VB. Varicella encephalitis. Am J Med 1953; 15:223-30.
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[4] Johnson R, Milbourn PE. Central nervous %slem mantlL'stations of chickenpox. Can Med Assoc. J 1970; 102:831.4 [5] Goldston AS, Millichap JG, Miller RH. Cerebellar aiaxfil x~iih pre-eruptive varicella. Am J Dis Child 1963;106: lt~7-20fl. [6] Underwood EA. The neurological complications o[' varicella. A clinical and epidemiological study. Br .I Chikl Dis 1935;32:83-107,177 96,241-63. [7] Preblud SR, Orenstein WA, Bait KJ. Varicella: Clinical manifestations, epidemiology and health impact in children. Pediatr Infect Dis 1984;3:505-9. [8] Barnes DW, Whitley RJ. CNS diseases associated with varicella zoster virus and herpes simplex virus infection. Pathogenesis and current therapy. Neurol Clin 1986;4:265-83. [9] Whitley RJ. Varicella-zoster virus. In: Mandcll GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone, 1990;1!53-9.
Varicella-related neurologic symptoms usually appear during or following the exanthem. Pre-eruptive neurologic manifestations are extremely rare. We report a 6-year-old boy who developed encephalitis, characterized by drowsiness and left-sided hyperactive deep tendon reflexes and cerebellar ataxia, both of which antedated the exanthem by 16 days. The diagnostic and public health implications are discussed. Liu GT, Urion DK. Pre-emptive varicella encephalitis and cerebellar ataxia. Pediatr Neurol 1992;8:69-70.
Introduction The neurologic complications of primary varicella infection, which include encephalitis, cerebellar ataxia, transverse myelitis, Reye syndrome, Guillain-Barr6 syndrome, and basal ganglia infarction [1,2], typically occur during or after the exanthem. We report a child with varicella who developed encephalitis and cerebellar ataxia 16 days before the onset of the rash.
Case Report A previously healthy 2-year-old boy was admitted to our hospital for lethargy and difficulty walking. His older 5-year-old brother had developed varicella 4 days previously. On the morning of admission his parents found the patient sleepier and more tired than usual and he walked with a staggering, wobbly gait. No aspirin had been given. The patient had no vesicles and was afebrile and drowsy. He knew his name and recognized his parents easily, but quickly fell asleep if not stimulated. There was coarse end-gaze nystagmus, bilateral appendicular dysmetria, and gait ataxia. Motor function was difficult to assess because of drowsiness, but there were no gross asymmetries. He was able to stand unassisted and his limbs had normal tone. The left knee and ankle reflexes were hyperactive and the left plantar reflex was extensor. Liver function tests, serum ammonia, and cranial computed tomography were normal. Cerebrospinal fluid (CSF) was acellular with normal protein. Serum varicella-zoster IgG was absent. Electroencephalography (EEG) revealed bilateral theta slowing, mostly in the temporal regions and more prominent in the right hemisphere.
From the Department of Neurology; Children's Hospital; Harvard Longwood Neurology Program; Harvard Medical School; Boston, Massachusetts.
Within 2 days his mental status had returned to normal, but he remained ataxic with asymmetric reflexes and was discharged from the hospital. Sixteen days after initial presentation the patient developed a typical varicella rash. Subsequent examination 3 weeks after discharge was normal. Repeat EEG at 5 weeks was also normal and the varicellazoster IgG was 69.6 ELISA units/ml, indicative of previous infection.
Discussion Varicella encephalitis is a likely, though not absolutely certain, diagnosis in our patient given the previous exposure to varicella, the rise in antibody titers, the altered sensorium, asymmetric deep tendon and plantar reflexes, and abnormal EEG [1]. Concomitant cerebellar ataxia, manifested by nystagmus, dysmetria, and gait unsteadiness, was present. The sudden onset of symptoms and eventual recovery could be consistent with either an infectious etiology or stroke; however, the neuroimaging study excluded any structural abnormality or cerebrovascular event. As in this case, in some instances of varicella encephalitis or cerebellar ataxia the CSF can be normal [1,3, 4]. Reye syndrome was unlikely without an elevation in liver enzyme activities. Our patient is noteworthy because of the 16-day delay between the neurologic symptoms and the exanthem. Varicella encephalitis usually follows the onset of the rash after 3-8 days [3]. Cerebellar ataxia on average occurs 51/2 days after the rash [4]. Pre-emptive neurologic complications of varicella have been previously described but are rare. Goldston et al. reported a 5-year-old boy similar to ours with ataxia and encephalitis 11 days before the rash developed [5]. They reviewed the literature for reports of pre-eruptiv_e neurologic complications and were able to find only 15 such patients reported between 1873 and 1963. Seizures, coma, delirium, meningomyelitis, aseptic meningitis, headache, facial paralysis, ataxia, and meningoencephalitis were the reported pre-emptive manifestations. Underwood reported the patient with the longest delay [6]: an individual with cerebellar ataxia antedating the exanthem by 18 days. Early neurologic involvement in these patients may have occurred during the initial exposure and viremia [5]. The rash then followed after the usual 14-16-day incubation period [7]. The pathogenesis of varicella-related neurologic complications is not clearly defined but has been attributed to immune-mediated postinfectious demyelination or direct viral invasion [8]. We do not know which of these 2 mechanisms is more likely in our patient. Physicians evaluating patients with ataxia or encephalitis should inquire about recent exposure to varicella; they should be aware that these complications may precede the
Communications should be addressed to: Dr. Urion; Department of Neurology; Children's Hospital; 3010 Longwood Avenue; Boston, MA 02115. Received August 8, 1991; accepted September 24, 1991.
Liu and Urion: Varicella Encephalitis
69
e x a n t h e m by as l o n g as 21/2 weeks. E x p o s e d i n d i v i d u a l s s h o u l d be i s o l a t e d f r o m i m m u n o c o m p r o m i s e d patients, p r e g n a n t w o m e n , a n d p r e v i o u s l y u n a f f e c t e d adults [7]; they are i n f e c t i o u s f r o m 2 d a y s p r i o r to the e x a n t h e m until 5 d a y s a f t e r the v e s i c l e s h a v e c r u s t e d [91. References [1] McKendall RR, Klawans HL. Nervous-system complications of varicella-zoster virus. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology, vol 34. Amsterdam: North-Holland, 1978;161-83. [2] Liu GT, Holmes GL. Varicella with delayed contralateral hemiparesis detected by MRI. Pediatr Neurol 1990;6:131-4. [3] Appelbaum E, Rachelson MH, Dolgopol VB. Varicella encephalitis. Am J Med 1953; 15:223-30.
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Vol. 8 No. 1
[4] Johnson R, Milbourn PE. Central nervous %slem mantlL'stations of chickenpox. Can Med Assoc. J 1970; 102:831.4 [5] Goldston AS, Millichap JG, Miller RH. Cerebellar aiaxfil x~iih pre-eruptive varicella. Am J Dis Child 1963;106: lt~7-20fl. [6] Underwood EA. The neurological complications o[' varicella. A clinical and epidemiological study. Br .I Chikl Dis 1935;32:83-107,177 96,241-63. [7] Preblud SR, Orenstein WA, Bait KJ. Varicella: Clinical manifestations, epidemiology and health impact in children. Pediatr Infect Dis 1984;3:505-9. [8] Barnes DW, Whitley RJ. CNS diseases associated with varicella zoster virus and herpes simplex virus infection. Pathogenesis and current therapy. Neurol Clin 1986;4:265-83. [9] Whitley RJ. Varicella-zoster virus. In: Mandcll GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases, 3rd ed. New York: Churchill Livingstone, 1990;1!53-9.
