- Email: [email protected]
Opsoclonus–myoclonus syndrome associated with human herpes virus-6 rhomboencephalitis
Journal of the Neurological Sciences 341 (2014) 165–166
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Opsoclonus–myoclonus syndrome associated with human herpes virus-6 rhomboencephalitis Vincenzo Belcastro a,⁎, Mirko Piola a, Sandro Binda b, Domenico Santoro c, Monica Rezzonico a, Marco Arnaboldi a a b c
Neurology Unit, Department of Medicine, S. Anna Hospital, Como, Italy Department of Biomedical Sciences for Health, University of Milan, Milan, Italy Department of Medicine, S. Anna Hospital, Como, Italy
a r t i c l e
i n f o
Article history: Received 9 March 2014 Received in revised form 7 April 2014 Accepted 9 April 2014 Available online 18 April 2014 Keywords: Opsoclonus–myoclonus syndrome Human herpes virus-6 infection Rhomboencephalitis
a b s t r a c t Opsoclonus–myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitis in immunocompetent children and adults. Here we report on a case of OMS associated with HHV-6 rhomboencephalitis. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases. © 2014 Elsevier B.V. All rights reserved.
1. Introduction 1.1. Case report A 63-year-old man presented with balance difficulties, nausea and vision abnormalities. At admission, the patient showed bursts of high-frequency, conjugate ocular oscillations with horizontal, vertical, and torsional components, all of which indicated opsoclonus. “Tremor-like” head movements were also observed, suggestive of opsoclonus–myoclonus syndrome (OMS) (Video 1). Moreover, cerebellar ataxia and arrhythmic-action myoclonus that predominantly involves the trunk and the arms were also present. Screen for autoimmune disease, malignancy and paraneoplastic antibodies (anti-amphiphysin, anti-Ri, anti-Yo, anti-Hu) as well as MRI of the brain were unremarkable. Cerebrospinal fluid (CSF) analysis revealed pleocytosis (93 WBCs/mm3) and elevated protein (158 mg/dL). A viral rhomboencephalitis was suspected on the basis of the patient's clinical presentation and CSF findings, and antiviral therapy with intravenous acyclovir (12.5 mg/kg every 8 h) was started. The patient first received 14-day intravenous acyclovir with poor recovery. Myoclonus was managed with clonazepam and sodium valproate. Despite treatment there was no notable improvement over a 3-week period while investigation was ongoing. ⁎ Corresponding author at: Neurology Unit, Department of Medicine, S. Anna Hospital, via Ravona, 22100 Como, Italy. Tel.: +39 0 31 5859682; fax: +39 0 31 5859684. E-mail address: [email protected] (V. Belcastro).
http://dx.doi.org/10.1016/j.jns.2014.04.013 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Noteworthy, human herpes virus-6 (HHV-6) was detected in both CSF and blood specimens by using a nested polymerase chain reaction (PCR) assay amplifying a fragment (258 nt.) of the gene encoding for the major capsid protein [1]. HHV-6 DNA was then quantified by a commercial real time-PCR assay (CMV HHV6,7,8 R-gene™ quantification kit, Argene), which amplifies a region of the U57 gene. HHV-6 DNA concentration was 2959.5 copies/mL in CSF and 9.83 × 106 in blood. HHV-6positive samples were also subtyped by sequence analysis of viral gene encoding for the immediate early protein and the virus demonstrated homology to the B (HST) variant. Notable, herpes viruses (HSV 1-2, CMV, EBV, VZV), HIV, JCV, West Nile virus, fleboviruses, and enteroviruses were excluded. Thus, we gave the patient ganciclovir (5 mg/kg every 12 h) for two weeks with remarkable recovery. At the last neurological assessment, the patient was able to walk and the eye movements were normal (Video 2).
2. Discussion OMS is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. The syndrome is associated with multiple aetiologies, most commonly infection and underlying neoplasm [2]. In adult onset OMS, paraneoplastic etiology is relatively rare with most patient having presumable parainfectious cause [2]. HHV-6 is one of the more recently identified herpes viruses and it can rarely cause encephalitis in immunocompetent children and adults
166
V. Belcastro et al. / Journal of the Neurological Sciences 341 (2014) 165–166
[3]. Noteworthy, HHV-6 infections are benign and self-limited illnesses, although the virus appears to be the major cause of the syndrome of post-transplant acute limbic encephalitis [3]. Most adults have been infected with HHV-6 in the childhood and virus then persists for life in a latent form in blood and vascular endothelial cells. HHV-6 can reactivate typically in immunocompromised individuals and reactivation can occur after stem cell or bone marrow transplant, pregnancy, hypersensitivity syndromes, critical illness, and acute infection with other viruses (measles, influenza, dengue) [4]. Notably, our patient was not immunocompromised and other neurotropic viruses were excluded. The diagnosis of HHV-6 infection is a complex issue and most widely used diagnostic tests for HHV-6 are unable to distinguish between latent and active forms of infection. However, the detection by PCR of HHV-6 DNA in both CSF and blood, indicative of active viral replication [1,3], the clinical improvement after ganciclovir treatment [5] and a negative paraneoplastic screen strongly suggest that the patient's OMS was caused by HHV-6 infection. Of note, ganciclovir is superior to acyclovir for HHV-6 but it treats only lytic phase infection [5]. The lifetime consequences of infection with HHV-6 are not well known and the follow-up of our patient is still ongoing. OMS associated with HHV-6 infection has not previously been reported in immunocompetent adults. In our patient, the precise mechanism of how HHV-6 infection resulted in rhomboencephalitis still remains to be defined.
Interactions between host immunity and CNS glial cells after exposure to herpesviruses could contribute to neuropathology of OMS [3]. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases [3]. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2014.04.013. Conflict of interest All authors report no disclosures. References [1] Secchiero P, Carrigan DR, Asano Y, Benedetti L, Crowley RW, Komaroff AL, et al. Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis 1995;171:273–80. [2] Klaas JP, Ahlskog JE, Pittock SJ, Matsumoto JY, Aksamit AJ, Bartleson JD, et al. Adultonset opsoclonus–myoclonus syndrome. Arch Neurol 2012;69:1598–607. [3] Yao K, Honarmand S, Espinosa A, Akhyani N, Glaser C, Jacobson S. Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol 2009;65:257–67. [4] Razonable RR, Fanning C, Brown RA, Espy MJ, Rivero A, Wilson J, et al. Selective reactivation of human herpesvirus 6 variant a occurs in critically ill immunocompetent hosts. J Infect Dis 2002;185:110–3. [5] Yamanishi K, Mori Y, Pellett PE. Human herpesviruses 6 and 7. In: Knipe DM, Howley PM, editors. Fields virology. 5th ed. Philadelphia: Lippincott William & Wilkins; 2007.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Opsoclonus–myoclonus syndrome associated with human herpes virus-6 rhomboencephalitis Vincenzo Belcastro a,⁎, Mirko Piola a, Sandro Binda b, Domenico Santoro c, Monica Rezzonico a, Marco Arnaboldi a a b c
Neurology Unit, Department of Medicine, S. Anna Hospital, Como, Italy Department of Biomedical Sciences for Health, University of Milan, Milan, Italy Department of Medicine, S. Anna Hospital, Como, Italy
a r t i c l e
i n f o
Article history: Received 9 March 2014 Received in revised form 7 April 2014 Accepted 9 April 2014 Available online 18 April 2014 Keywords: Opsoclonus–myoclonus syndrome Human herpes virus-6 infection Rhomboencephalitis
a b s t r a c t Opsoclonus–myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitis in immunocompetent children and adults. Here we report on a case of OMS associated with HHV-6 rhomboencephalitis. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases. © 2014 Elsevier B.V. All rights reserved.
1. Introduction 1.1. Case report A 63-year-old man presented with balance difficulties, nausea and vision abnormalities. At admission, the patient showed bursts of high-frequency, conjugate ocular oscillations with horizontal, vertical, and torsional components, all of which indicated opsoclonus. “Tremor-like” head movements were also observed, suggestive of opsoclonus–myoclonus syndrome (OMS) (Video 1). Moreover, cerebellar ataxia and arrhythmic-action myoclonus that predominantly involves the trunk and the arms were also present. Screen for autoimmune disease, malignancy and paraneoplastic antibodies (anti-amphiphysin, anti-Ri, anti-Yo, anti-Hu) as well as MRI of the brain were unremarkable. Cerebrospinal fluid (CSF) analysis revealed pleocytosis (93 WBCs/mm3) and elevated protein (158 mg/dL). A viral rhomboencephalitis was suspected on the basis of the patient's clinical presentation and CSF findings, and antiviral therapy with intravenous acyclovir (12.5 mg/kg every 8 h) was started. The patient first received 14-day intravenous acyclovir with poor recovery. Myoclonus was managed with clonazepam and sodium valproate. Despite treatment there was no notable improvement over a 3-week period while investigation was ongoing. ⁎ Corresponding author at: Neurology Unit, Department of Medicine, S. Anna Hospital, via Ravona, 22100 Como, Italy. Tel.: +39 0 31 5859682; fax: +39 0 31 5859684. E-mail address: [email protected] (V. Belcastro).
http://dx.doi.org/10.1016/j.jns.2014.04.013 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Noteworthy, human herpes virus-6 (HHV-6) was detected in both CSF and blood specimens by using a nested polymerase chain reaction (PCR) assay amplifying a fragment (258 nt.) of the gene encoding for the major capsid protein [1]. HHV-6 DNA was then quantified by a commercial real time-PCR assay (CMV HHV6,7,8 R-gene™ quantification kit, Argene), which amplifies a region of the U57 gene. HHV-6 DNA concentration was 2959.5 copies/mL in CSF and 9.83 × 106 in blood. HHV-6positive samples were also subtyped by sequence analysis of viral gene encoding for the immediate early protein and the virus demonstrated homology to the B (HST) variant. Notable, herpes viruses (HSV 1-2, CMV, EBV, VZV), HIV, JCV, West Nile virus, fleboviruses, and enteroviruses were excluded. Thus, we gave the patient ganciclovir (5 mg/kg every 12 h) for two weeks with remarkable recovery. At the last neurological assessment, the patient was able to walk and the eye movements were normal (Video 2).
2. Discussion OMS is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. The syndrome is associated with multiple aetiologies, most commonly infection and underlying neoplasm [2]. In adult onset OMS, paraneoplastic etiology is relatively rare with most patient having presumable parainfectious cause [2]. HHV-6 is one of the more recently identified herpes viruses and it can rarely cause encephalitis in immunocompetent children and adults
166
V. Belcastro et al. / Journal of the Neurological Sciences 341 (2014) 165–166
[3]. Noteworthy, HHV-6 infections are benign and self-limited illnesses, although the virus appears to be the major cause of the syndrome of post-transplant acute limbic encephalitis [3]. Most adults have been infected with HHV-6 in the childhood and virus then persists for life in a latent form in blood and vascular endothelial cells. HHV-6 can reactivate typically in immunocompromised individuals and reactivation can occur after stem cell or bone marrow transplant, pregnancy, hypersensitivity syndromes, critical illness, and acute infection with other viruses (measles, influenza, dengue) [4]. Notably, our patient was not immunocompromised and other neurotropic viruses were excluded. The diagnosis of HHV-6 infection is a complex issue and most widely used diagnostic tests for HHV-6 are unable to distinguish between latent and active forms of infection. However, the detection by PCR of HHV-6 DNA in both CSF and blood, indicative of active viral replication [1,3], the clinical improvement after ganciclovir treatment [5] and a negative paraneoplastic screen strongly suggest that the patient's OMS was caused by HHV-6 infection. Of note, ganciclovir is superior to acyclovir for HHV-6 but it treats only lytic phase infection [5]. The lifetime consequences of infection with HHV-6 are not well known and the follow-up of our patient is still ongoing. OMS associated with HHV-6 infection has not previously been reported in immunocompetent adults. In our patient, the precise mechanism of how HHV-6 infection resulted in rhomboencephalitis still remains to be defined.
Interactions between host immunity and CNS glial cells after exposure to herpesviruses could contribute to neuropathology of OMS [3]. HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases [3]. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2014.04.013. Conflict of interest All authors report no disclosures. References [1] Secchiero P, Carrigan DR, Asano Y, Benedetti L, Crowley RW, Komaroff AL, et al. Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis 1995;171:273–80. [2] Klaas JP, Ahlskog JE, Pittock SJ, Matsumoto JY, Aksamit AJ, Bartleson JD, et al. Adultonset opsoclonus–myoclonus syndrome. Arch Neurol 2012;69:1598–607. [3] Yao K, Honarmand S, Espinosa A, Akhyani N, Glaser C, Jacobson S. Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol 2009;65:257–67. [4] Razonable RR, Fanning C, Brown RA, Espy MJ, Rivero A, Wilson J, et al. Selective reactivation of human herpesvirus 6 variant a occurs in critically ill immunocompetent hosts. J Infect Dis 2002;185:110–3. [5] Yamanishi K, Mori Y, Pellett PE. Human herpesviruses 6 and 7. In: Knipe DM, Howley PM, editors. Fields virology. 5th ed. Philadelphia: Lippincott William & Wilkins; 2007.