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Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood
Brain & Development 24 (2002) 112–114 www.elsevier.com/locate/braindev
Case report
Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood Konstantinos A. Voudris a,*, Eleni A. Vagiakou b, Angeliki Skardoutsou c a
Department of Neurology, “P & A Kyriakou” Children’s Hospital, Thivon & Levadeias st., 115 27 Athens, Greece b Department of Microbiology, “G. Genimatas” General Hospital, Athens, Greece c Second Department of Paediatrics–University of Athens, “P & A Kyriakou” Children’s Hospital, Athens, Greece Received 22 July 2001; received in revised form 12 December 2001; accepted 18 December 2001
Abstract Acute disseminated encephalomyelitis associated with the parainfluenza virus has rarely been reported in childhood. A 2.5-year-old girl with acute disseminated encephalomyelitis, who developed bilateral symmetrical lesions in the basal ganglion, thalamus, corpus callosum, cerebral subcortical white matter, and cerebellar medulla on brain magnetic resonance imaging is described. Serological confirmation of parainfluenza virus infection was made 2 weeks following the onset of neurological symptoms. Four months later, the patient had a full recovery. At present, 3 years later, no relapse has been reported and she is leading a normal life. Our case is of interest because of its rarity, the striking brain magnetic resonance imaging, and the good neurological outcome. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Parainfluenza virus; Acute disseminated encephalomyelitis; Postinfectious encephalomyelitis; Acute encephalitis; Magnetic resonance imaging
1. Introduction Neurological involvement is rarely associated with parainfluenza virus infection [1–3]. Neurological complications associated with parainfluenza virus are: acute encephalitis, aseptic meningitis, Reye’s syndrome, and Guillain–Barre´ syndrome. Acute disseminated encephalomyelitis (ADEM), an immunologically mediated inflammatory demyelinating disease of the central nervous system (CNS), is usually a monophasic and polysymptomatic disease following a previous infection, vaccination, or even with no recognized preceding illness [4–7]. A girl with ADEM associated with parainfluenza virus infection is described. The patient developed multifocal symmetrical lesions on brain magnetic resonance imaging (MRI). 2. Case report A 2.5-year-old girl was admitted to our hospital because of sudden alteration of consciousness, unsteady gait and difficulty in speech. The neurological manifestations appeared 4 days after resolution of a 7 day episode of fever (39 8C), cough, headache, and vomiting. She is the * Corresponding author. Tel.: 130-1-6211354/7793000; fax: 130-17774383. E-mail address: [email protected] (K.A. Voudris).
first child in the family and was born at term by vaginal delivery. The past medical and family history were not of any significance. On examination, the patient had drowsiness, hand tremor, ataxia, dysarthria, and bilateral brisk deep tendon reflexes associated with extensor plantar responses. Walking was possible only with help. There was no neck stiffness, the gag reflex was preserved and the fundi were normal. In the following days, the level of consciousness deteriorated and she developed marked ataxia of gait, bilateral horizontal nystagmus, and stiffness on the right side. She did not experience any convulsions or respiratory problems. Laboratory investigations, such as full blood count, erythrocyte sedimentation rate, and serum urea, electrolytes, glucose, glutamic-oxaloacetic and glutamic-pyruvic transaminases, creatine kinase, ammonia, lactate, caeruloplasmin, and amino acids levels were normal. Prothrombin time, partial thromboplastin time, urinalysis, urine organic acids, and chest roentgenogram were also normal. Blood cultures, anti-DNA antibodies and antinuclear antibodies were negative. Cerebrospinal fluid (CSF) analysis revealed 25 white blood cells per mm 3 with 80% lymphocytes and 20% polymorphonuclear cells, and normal protein and glucose levels. Oligoclonal IgG band and myelin basic protein were not evaluated. The serum complement fixation titre for parainfluenza virus was less than 20 on admission; however, 2 weeks later it increased to more than 160, indi-
0387-7604/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S03 87- 7604(02)0000 8-6
K.A. Voudris et al. / Brain & Development 24 (2002) 112–114
113
Fig. 1. Axial brain T2-weighted MRI, on day 4 of the illness, showing bilateral lesions with high signal in centrum ovale (a), globus pallidum (b), and cerebellar medulla (c).
cating recent parainfluenza virus infection. Serological tests failed to demonstrate any other viral antibody response and thus we were not able to find any other cause for encephalitis. Parainfluenza or other viral antibodies were not found in the CSF. Electroencephalography (EEG) revealed diffuse slow background activities. Brain computed tomography (CT) scan, performed on day 1 of her illness, was normal. Brain MRI, performed
on day 4, showed bilateral, symmetrical, multifocal lesions of high signal intensity on both the T2-weighted and proton density images and low signal on the T1-weighted images in the globus pallidum, thalamus, corpus callosum, subcortical white matter, and cerebellar medulla (Fig. 1). The lesions showed no enhancement after gadolinium injection. The patient received supportive care and was not treated with corticosteroids; however, she received intravenous
114
K.A. Voudris et al. / Brain & Development 24 (2002) 112–114
acyclovir for 4 days until polymerase chain reaction revealed that there was no herpes virus DNA in the CSF. The level of consciousness and the neurological signs gradually improved and when she was discharged, 15 days later, she had only mild ataxia. On re-examination, 4 months later, no abnormal neurological signs could be detected. At present, 3 years after the illness, no relapse has been reported and the girl is now leading a normal life. A recent EEG was within normal limits and the serum complement fixation titre for parainfluenza virus was less than 80.
3. Discussion Our patient was considered to have parainfluenza-associated ADEM on the basis of her prodromal illness, clinical manifestations, laboratory data, neuroimaging findings and the fourfold rise in serum parainfluenza virus antibodies titre, 2 weeks after the onset of the neurological manifestations. The isolation of the parainfluenza virus in the throat, CSF or other tissues or secretions was not confirmed in our case but the isolation of the parainfluenza virus was unlikely because of the time which had elapsed after the onset of the preceding infection; moreover, viral invasion of the CNS in ADEM is thought to precede demyelination and virus isolation is almost always unsuccessful [8]. It has also been reported that the isolation of the parainfluenza virus from the CSF of patients with CNS involvement is rarer than CNS manifestations alone [1]. Parainfluenza antibodies were not found in the CSF of our patient. However, in postinfectious encephalomyelitis intrathecal synthesis of antibodies does not usually occur [9]. In the differential diagnosis of our case metabolic and vascular disorders and multiple sclerosis were also considered. The young age, the appearance of neurological manifestations shortly after recovery of the preceding infection, the negative results of specific laboratory findings, the multifocal location of the lesions in the white matter and deep gray matter on MRI studies, and the absence of recurrence during the 3 year follow-up support the diagnosis of ADEM in our case. The parainfluenza viruses are members of the paramyxovirus family, which includes parainfluenza virus types 1, 2, 3, and 4 as well as respiratory syncytial virus, mumps virus, and measles virus. Despite the increased frequency of parainfluenza infection in children, the virus has rarely been documented as a cause of CNS involvement. The scattered reports in the literature describing patients with CNS manifestations showed that the parainfluenza virus most commonly causes benign, self-limited aseptic meningitis and symptoms are often mild and recovery rates fast [3]. McCarthy et al. [1] have described three children with CNS manifestations of parainfluenza virus type 3 infections. The spectrum of clinical manifestations included apnea, opsoclonus with myoclonus, seizures, and coma. All three patients recovered without neurological residua as was the case with our child. Cranial
CT scan was normal in all the McCarthy et al. patients but no brain MRI studies had been performed. The authors have concluded that parainfluenza neurological symptoms are similar to those caused by other neurotropic viruses. ADEM involves more often the cerebral white matter and cerebellar medulla, and less often other areas of the brain such as the basal ganglion, thalamus, midbrain, and brain stem [4–7]. MRI is more sensitive than CT scan in revealing abnormalities in children with ADEM and MRI is the imaging method of choice for the diagnosis of ADEM [5]. Recently, diffusion-weighted MRI has been reported to be superior to conventional MRI in the demonstration of lesions in patients with viral or bacterial encephalitis and encephalopathy [10]. The superiority of MRI in our case could be the result of the time elapsed after the CT scan. To our knowledge, our case is the first reported ADEM with multifocal symmetrical lesions on brain MRI associated with parainfluenza virus infection. Treatment of ADEM is mostly supportive. Corticosteroids have been widely used, but the indication is often obscure [4–7]. Only supportive care was given to our patient and she had a good neurological outcome. The rapid recovery of our patient favors the suggestion of a previous report that the brain lesions in patients with ADEM are caused by allergic angiopathy without demyelination [4]. In conclusion, the parainfluenza virus may be a cause of ADEM with multifocal, symmetrical lesions on brain MRI. Our case confirms the generally favorable prognosis of CNS involvement associated with parainfluenza virus infection. The early identification of ADEM subsequent to parainfluenza virus infection can therefore lead to correct diagnosis and appropriate management.
References [1] McCarthy VP, Zimmerman AW, Miller CA. Central nervous system manifestations of parainfluenza virus type 3 infections in childhood. Pediatr Neurol 1990;6:197–201. [2] Arguedas A, Stutman HR, Blanding JG. Parainfluenza type 3 meningitis: report of two cases and review of the literature. Clin Pediatr (Phila) 1990;29:175–178. [3] Arisoy EM, Demmler GJ, Thakar S, Doerr C. Meningitis due to parainfluenza virus type 3: report of two cases and review. Clin Infect Dis 1993;17:995–997. [4] Kimura S, Nezu A, Ohtsuki N, Kobayashi T, Osaka H, Uehara S. Serial magnetic resonance imaging in children with postinfectious encephalitis. Brain Dev 1996;18:461–465. [5] Hung KL, Liao HT, Tsai ML. Postinfectious encephalomyelitis: etiology and diagnostic trends. J Child Neurol 2000;15:666–670. [6] Nasr JT, Andriola MR, Coyle PK. ADEM: literature review and case report of acute psychosis presentation. Pediatr Neurol 2000;22:8–18. [7] Hung KL, Liao HT, Tsai ML. The spectrum of postinfectious encephalomyelitis. Brain Dev 2001;23:42–45. [8] Booss J, Esili MM. Viral encephalitis. Oxford: Blackwell Scientific, 1986. [9] Johnson R. The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis. J Infect Dis 1987;155:359–364. [10] Tsuchiya K, Katase S, Yoshino A, Hachiya J. Diffusion-weighted MR imaging of encephalitis. Am J Roentgenol 1999;173:1097–1099.
Case report
Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood Konstantinos A. Voudris a,*, Eleni A. Vagiakou b, Angeliki Skardoutsou c a
Department of Neurology, “P & A Kyriakou” Children’s Hospital, Thivon & Levadeias st., 115 27 Athens, Greece b Department of Microbiology, “G. Genimatas” General Hospital, Athens, Greece c Second Department of Paediatrics–University of Athens, “P & A Kyriakou” Children’s Hospital, Athens, Greece Received 22 July 2001; received in revised form 12 December 2001; accepted 18 December 2001
Abstract Acute disseminated encephalomyelitis associated with the parainfluenza virus has rarely been reported in childhood. A 2.5-year-old girl with acute disseminated encephalomyelitis, who developed bilateral symmetrical lesions in the basal ganglion, thalamus, corpus callosum, cerebral subcortical white matter, and cerebellar medulla on brain magnetic resonance imaging is described. Serological confirmation of parainfluenza virus infection was made 2 weeks following the onset of neurological symptoms. Four months later, the patient had a full recovery. At present, 3 years later, no relapse has been reported and she is leading a normal life. Our case is of interest because of its rarity, the striking brain magnetic resonance imaging, and the good neurological outcome. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Parainfluenza virus; Acute disseminated encephalomyelitis; Postinfectious encephalomyelitis; Acute encephalitis; Magnetic resonance imaging
1. Introduction Neurological involvement is rarely associated with parainfluenza virus infection [1–3]. Neurological complications associated with parainfluenza virus are: acute encephalitis, aseptic meningitis, Reye’s syndrome, and Guillain–Barre´ syndrome. Acute disseminated encephalomyelitis (ADEM), an immunologically mediated inflammatory demyelinating disease of the central nervous system (CNS), is usually a monophasic and polysymptomatic disease following a previous infection, vaccination, or even with no recognized preceding illness [4–7]. A girl with ADEM associated with parainfluenza virus infection is described. The patient developed multifocal symmetrical lesions on brain magnetic resonance imaging (MRI). 2. Case report A 2.5-year-old girl was admitted to our hospital because of sudden alteration of consciousness, unsteady gait and difficulty in speech. The neurological manifestations appeared 4 days after resolution of a 7 day episode of fever (39 8C), cough, headache, and vomiting. She is the * Corresponding author. Tel.: 130-1-6211354/7793000; fax: 130-17774383. E-mail address: [email protected] (K.A. Voudris).
first child in the family and was born at term by vaginal delivery. The past medical and family history were not of any significance. On examination, the patient had drowsiness, hand tremor, ataxia, dysarthria, and bilateral brisk deep tendon reflexes associated with extensor plantar responses. Walking was possible only with help. There was no neck stiffness, the gag reflex was preserved and the fundi were normal. In the following days, the level of consciousness deteriorated and she developed marked ataxia of gait, bilateral horizontal nystagmus, and stiffness on the right side. She did not experience any convulsions or respiratory problems. Laboratory investigations, such as full blood count, erythrocyte sedimentation rate, and serum urea, electrolytes, glucose, glutamic-oxaloacetic and glutamic-pyruvic transaminases, creatine kinase, ammonia, lactate, caeruloplasmin, and amino acids levels were normal. Prothrombin time, partial thromboplastin time, urinalysis, urine organic acids, and chest roentgenogram were also normal. Blood cultures, anti-DNA antibodies and antinuclear antibodies were negative. Cerebrospinal fluid (CSF) analysis revealed 25 white blood cells per mm 3 with 80% lymphocytes and 20% polymorphonuclear cells, and normal protein and glucose levels. Oligoclonal IgG band and myelin basic protein were not evaluated. The serum complement fixation titre for parainfluenza virus was less than 20 on admission; however, 2 weeks later it increased to more than 160, indi-
0387-7604/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S03 87- 7604(02)0000 8-6
K.A. Voudris et al. / Brain & Development 24 (2002) 112–114
113
Fig. 1. Axial brain T2-weighted MRI, on day 4 of the illness, showing bilateral lesions with high signal in centrum ovale (a), globus pallidum (b), and cerebellar medulla (c).
cating recent parainfluenza virus infection. Serological tests failed to demonstrate any other viral antibody response and thus we were not able to find any other cause for encephalitis. Parainfluenza or other viral antibodies were not found in the CSF. Electroencephalography (EEG) revealed diffuse slow background activities. Brain computed tomography (CT) scan, performed on day 1 of her illness, was normal. Brain MRI, performed
on day 4, showed bilateral, symmetrical, multifocal lesions of high signal intensity on both the T2-weighted and proton density images and low signal on the T1-weighted images in the globus pallidum, thalamus, corpus callosum, subcortical white matter, and cerebellar medulla (Fig. 1). The lesions showed no enhancement after gadolinium injection. The patient received supportive care and was not treated with corticosteroids; however, she received intravenous
114
K.A. Voudris et al. / Brain & Development 24 (2002) 112–114
acyclovir for 4 days until polymerase chain reaction revealed that there was no herpes virus DNA in the CSF. The level of consciousness and the neurological signs gradually improved and when she was discharged, 15 days later, she had only mild ataxia. On re-examination, 4 months later, no abnormal neurological signs could be detected. At present, 3 years after the illness, no relapse has been reported and the girl is now leading a normal life. A recent EEG was within normal limits and the serum complement fixation titre for parainfluenza virus was less than 80.
3. Discussion Our patient was considered to have parainfluenza-associated ADEM on the basis of her prodromal illness, clinical manifestations, laboratory data, neuroimaging findings and the fourfold rise in serum parainfluenza virus antibodies titre, 2 weeks after the onset of the neurological manifestations. The isolation of the parainfluenza virus in the throat, CSF or other tissues or secretions was not confirmed in our case but the isolation of the parainfluenza virus was unlikely because of the time which had elapsed after the onset of the preceding infection; moreover, viral invasion of the CNS in ADEM is thought to precede demyelination and virus isolation is almost always unsuccessful [8]. It has also been reported that the isolation of the parainfluenza virus from the CSF of patients with CNS involvement is rarer than CNS manifestations alone [1]. Parainfluenza antibodies were not found in the CSF of our patient. However, in postinfectious encephalomyelitis intrathecal synthesis of antibodies does not usually occur [9]. In the differential diagnosis of our case metabolic and vascular disorders and multiple sclerosis were also considered. The young age, the appearance of neurological manifestations shortly after recovery of the preceding infection, the negative results of specific laboratory findings, the multifocal location of the lesions in the white matter and deep gray matter on MRI studies, and the absence of recurrence during the 3 year follow-up support the diagnosis of ADEM in our case. The parainfluenza viruses are members of the paramyxovirus family, which includes parainfluenza virus types 1, 2, 3, and 4 as well as respiratory syncytial virus, mumps virus, and measles virus. Despite the increased frequency of parainfluenza infection in children, the virus has rarely been documented as a cause of CNS involvement. The scattered reports in the literature describing patients with CNS manifestations showed that the parainfluenza virus most commonly causes benign, self-limited aseptic meningitis and symptoms are often mild and recovery rates fast [3]. McCarthy et al. [1] have described three children with CNS manifestations of parainfluenza virus type 3 infections. The spectrum of clinical manifestations included apnea, opsoclonus with myoclonus, seizures, and coma. All three patients recovered without neurological residua as was the case with our child. Cranial
CT scan was normal in all the McCarthy et al. patients but no brain MRI studies had been performed. The authors have concluded that parainfluenza neurological symptoms are similar to those caused by other neurotropic viruses. ADEM involves more often the cerebral white matter and cerebellar medulla, and less often other areas of the brain such as the basal ganglion, thalamus, midbrain, and brain stem [4–7]. MRI is more sensitive than CT scan in revealing abnormalities in children with ADEM and MRI is the imaging method of choice for the diagnosis of ADEM [5]. Recently, diffusion-weighted MRI has been reported to be superior to conventional MRI in the demonstration of lesions in patients with viral or bacterial encephalitis and encephalopathy [10]. The superiority of MRI in our case could be the result of the time elapsed after the CT scan. To our knowledge, our case is the first reported ADEM with multifocal symmetrical lesions on brain MRI associated with parainfluenza virus infection. Treatment of ADEM is mostly supportive. Corticosteroids have been widely used, but the indication is often obscure [4–7]. Only supportive care was given to our patient and she had a good neurological outcome. The rapid recovery of our patient favors the suggestion of a previous report that the brain lesions in patients with ADEM are caused by allergic angiopathy without demyelination [4]. In conclusion, the parainfluenza virus may be a cause of ADEM with multifocal, symmetrical lesions on brain MRI. Our case confirms the generally favorable prognosis of CNS involvement associated with parainfluenza virus infection. The early identification of ADEM subsequent to parainfluenza virus infection can therefore lead to correct diagnosis and appropriate management.
References [1] McCarthy VP, Zimmerman AW, Miller CA. Central nervous system manifestations of parainfluenza virus type 3 infections in childhood. Pediatr Neurol 1990;6:197–201. [2] Arguedas A, Stutman HR, Blanding JG. Parainfluenza type 3 meningitis: report of two cases and review of the literature. Clin Pediatr (Phila) 1990;29:175–178. [3] Arisoy EM, Demmler GJ, Thakar S, Doerr C. Meningitis due to parainfluenza virus type 3: report of two cases and review. Clin Infect Dis 1993;17:995–997. [4] Kimura S, Nezu A, Ohtsuki N, Kobayashi T, Osaka H, Uehara S. Serial magnetic resonance imaging in children with postinfectious encephalitis. Brain Dev 1996;18:461–465. [5] Hung KL, Liao HT, Tsai ML. Postinfectious encephalomyelitis: etiology and diagnostic trends. J Child Neurol 2000;15:666–670. [6] Nasr JT, Andriola MR, Coyle PK. ADEM: literature review and case report of acute psychosis presentation. Pediatr Neurol 2000;22:8–18. [7] Hung KL, Liao HT, Tsai ML. The spectrum of postinfectious encephalomyelitis. Brain Dev 2001;23:42–45. [8] Booss J, Esili MM. Viral encephalitis. Oxford: Blackwell Scientific, 1986. [9] Johnson R. The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis. J Infect Dis 1987;155:359–364. [10] Tsuchiya K, Katase S, Yoshino A, Hachiya J. Diffusion-weighted MR imaging of encephalitis. Am J Roentgenol 1999;173:1097–1099.