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Coincident onset of multiple sclerosis and Herpes simplex virus 1 encephalitis: a case report

Coincident onset of multiple sclerosis and Herpes simplex virus 1 encephalitis: a case report Background: Along with vitamin D, smoking, body mass index and others, Epstein Barr virus, other herpesviruses and human endogenous retroviruses represent plausible environmental risk factors for multiple sclerosis. However, it is difficult to obtain direct proof of their involvement in the etiology of this condition. Case presentation: In order to contribute further evidence of the importance of these viruses, and speculate about disease-relevant interactions between these agents and a predisposed genetic background of the host, we describe the temporal association between multiple sclerosis onset and Herpes simplex 1-encephalitis in a female patient. Conclusions: This case illustrates a possible relationship between HSV-1 encephalitis and multiple sclerosis. Bearing in mind that association does not imply causation, some speculations about the etiology and pathophysiology of the two diseases can be made. The hypothesis of a genetic background predisposing to HSV-1 encephalitis and to immune-mediated demyelination is supported by the coincidence of the two conditions in this patient, along with data from animal models and genetic studies. Keywords: Multiple sclerosis, Environmental factors, HSV-1 encephalitis Background the MS central nervous system. On the other hand, her- Heritable and nonheritable factors, and their interac- pesviruses are sound candidates as well, because of tions, may be responsible for the autoimmune response neurotropism and, in the case of Epsein Barr virus, that leads to multiple sclerosis (MS) [1]. extraordinary ability to modulate the human immune Genome-wide association studies are improving our response. understanding of the heritable basis of the disease, most In order to contribute further evidence of the import- probably involving subtle defects of the regulation of ance of these viruses, and speculate about disease- transcription [2]. Though these studies are indeed ad- relevant interactions between these agents and a predis- vancing our knowledge, the nonheritable or “environ- posed genetic background of the host, we describe the mental” component of the risk shows a slower progress. temporal association between MS onset and Herpes sim- Among the environmental risk factors, viruses are inten- plex 1 (HSV)-encephalitis in a female patient. sively investigated as possible culprits [3]. Human en- dogenous retroviruses such as MSRV have attracted Case Presentation interest because of their capacity to hide by integrating A 32 year-old woman presented acute dysesthesia in the in the human DNA and then trigger immunological right face. Except for this symptom, her neurological mechanisms: a scenario that is compatible with the long examination was unremarkable and neither the patient standing difficulties in detecting any infectious agent in nor her relatives could recall any previous neurological episode. Her neurologist requested an MRI of the brain * Correspondence: mariachiara.buscarinu@uniroma1.it and spinal cord that showed the simultaneous presence Centre for Experimental Neurological Therapies, Department of of enhancing and nonenhancing white matter abnormal- Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and ities in MS-typical regions of the brain, compatible with Psychology, Sapienza University of Rome, Rome, Italy Full list of author information is available at the end of the article the diagnosis of a first episode of the disease (Fig. 1). © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 2 of 4 Fig. 1 a Axial FLAIR MRI that highlights hyperintense left periventricular areas; b left periventricular and frontal subcortical; c right cerebellar peduncle She was then treated with methylprednisolone 1 g evolution of the right temporal lesion, with a reduction intravenously for five days with a clear improvement of of the brainstem lesions and of the corpus callosum, the symptom. Ten days after the completion of the cor- and with evidence of a C5 spinal cord area, compat- ticosteroid course, she presented fever, severe headache ible with an inflammatory lesion. The enhancement of and confusion. A brain CT scan was obtained, highlight- lesions in MS-typical regions was not evident at this ing a hypodense area that involved right temporal pole, point (Fig. 4). insula and hippocampus. She was then hospitalized and She was transferred to a rehabilitation facility (GCS: 7) her cerebrospinal fluid (CSF) tested positive for HSV-1 and, after ten months, discharged home with a remark- DNA. All other CSF tests were negative including: Cyto- able improvement: left hemiparesis and left sensory syn- megalovirus, Varicella Zoster, Epstein Barr virus, John drome but able to walk with assistance, short term Cunningham virus, enteroviruses, Toxoplasma, Crypto- memory loss, fluctuating hyperactive state with mild agi- coccus, Mycobacterium tuberculosis and Treponema, tation. After additional six months of follow-up, she has oligoclonal bands. With the exception of a positive test now slightly improved the strength of her left limbs. The for recent HSV-1 infection, all other serologies were number and volume of areas in MS-typical regions is re- negative for recent infections including: Coxiella, duced though still increased with respect to the first Coxsackie, Chlamydia pneumoniae, Borrelia burgdoferi, MRI and no new areas have appeared at brain and spinal Mycoplasma pneumoniae, echovirus and adenovirus. cord MRI follow-up (Fig. 5). Peripheral blood screening tests for autoimmune dis- eases were negative. Intravenous acyclovir was started but she rapidly worsened (GCS: 4; E1, V1, M2) requiring orotracheal intubation, tracheostomy, mechanical ventilation and antiepileptic and antiedema therapy. Brain MRI ob- tained 3 and 6 days after the CT scan showed the involvement of the right hemisphere with diffuse swelling and contralateral shift of the septum pelluci- dum (Fig. 2). After 22 days, HSV1 DNA in the CSF was negative while a third MRI, contemporary to the CSF sampling, showed a remarkable increase in the number and vol- ume of lesions in MS-typical areas (some of them en- hancing) and necrotic-malacic evolution of the herpetic lesion (Fig. 3) In view of the apparent flare of the “autoimmune” con- dition, the patient was started on intravenous immuno- globulins (IVIG) at 0.4gr/kg/daily for 5 days and Methilprendisolone 40mg/daily for 15 days. She also continued therapy with Valacyclovir 3g/ daily. Fig. 2 Axial T2 image showing hyperintensity of the right temporal The MRI carried out as a control at the end of intra- lobe and right brainstem with less obvious contralateral alterations venous steroid therapy confirmed the necrotic-malacic Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 3 of 4 of a coincident onset of MS and HSV-1 encephalitis. Other reports have provided laboratory evidence of the intrathecal presence of HSV-1 at disease onset. This sup- ports the possibility that, in an individual with a peculiar genetic predisposition, this presence may turn into overt HSV-1 encephalitis [5, 6]. However, other viruses such as the John Cunningham (JC) virus have been described as replicating in the cerebrospinal fluid during the first symptoms of MS [7] though a coincident onset of MS and progressive multifocal encaphalomyelitis have never been described to our knowledge. Most interestingly, the HSV-1 encephalitis develops in individuals with inborn errors of immune response genes that impair central nervous system-intrinsic inter- feron alpha/beta production [8]. The therapeutic re- sponse of persons with MS to interferon beta suggests that a portion of the pathophysiology of the two diseases may be shared. This possibility may be supported also by the sharing of a predisposing gene, TRAF3, between the Fig. 3 Axial FLAIR showing the temporal encephalitis outcome two conditions (though this speculation has to be taken with caution because the effects of the observed variants may not be the same) [8, 9]. Discussion and conclusions The role of a genetic predisposition emerges also from This case illustrates a possible relationship between studies in inbred mouse strains with variable degrees of HSV-1 encephalitis and MS. resistance to EAE/HSV [10]. In these models, the lip in- Bearing in mind that association does not imply caus- oculation of the virus causes either no disease, or isolated ation, some speculations about the etiology and patho- lesions, or a diffuse picture of demyelination, depending physiology of the two diseases can be made. on the genetic background of the mice. Interestingly, the To our knowledge, while the onset of MS after hemi- multifocal lesions in the susceptible mice were first ob- thorax zoster, with intrathecal reactivation of HSV-1 and served when the virus could no longer be isolated from HHV-6 has been reported [4] this is the first description the CNS of the animals. This is in line with the diffuse worsening of the bona-fide demyelinating lesions observed in the patient, when the viral DNA became undetectable in the CSF. Both observations are in harmony with an immune-mediated process, triggered by the virus, in hosts with a susceptible genetic background. Other sequences of events cannot be excluded: the autoimmune damage might have been present before the HSV-1 infection with the latter being exacerbated by the corticosteroids course. Nonetheless, the effects of corticosteroids in these patients are debated, as clinical trials are ongoing to assess their therapeutic effects in overt HSV-1 encephalitis. Also the role played by the diffuse alteration of the blood brain bar- rier (somehow resembling an acute disseminated enceph- alomyelitis process, secondary to the HSV-1 infection) remains unclear in the context of the whole process. A longitudinal follow-up with, for example, IEF-overlay technique with radiolabeled HSV glycoprotein B (gB), for studying qualitative aspects of the HSV humoral immune response [11, 12], would have been of use but was not per- formed. More in general, as common pathophysiologies emerge between MS and host immune response to vi- Fig. 4 Cervical spinal cord sagittal image showing demyelinating ruses, tests for the detection of antiviral antibodies may hyperintense areas at C4 acquire more importance in the near future. Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 4 of 4 Fig. 5 Comparison of MRIs obtained at 4 months (a) and at 18 months after onset (b) showing a reduction of the areas in MS-typical regions though the lesion load remains higher compared with the first MRI (Fig. 1) All in all, the hypothesis of a genetic background pre- Received: 2 February 2017 Accepted: 30 March 2017 disposing to HSV-1 encephalitis and to immune- mediated demyelination is supported by the coincidence References of the two conditions in this patient, along with data 1. Bordi I, Ricigliano VA, Umeton R, Ristori G, Grassi F, Crisanti A, Sutera A, Salvetti M. Noise in multiple sclerosis: unwanted and necessary. Ann Clin from animal models and genetic studies. Transl Neurol. 2014;1(7):502–11. doi:10.1002/acn3.72. Epub 2014 Jun 19. 2. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Acknowledgements Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, The authors would like to thank the patient for consent for publication. Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal Funding autoimmune disease variants. Nature. 2015;518(7539):337–43. doi:10.1038/ No funding was received. nature13835. Epub 2014 Oct 29. 3. Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Availability of data and material Curr Opin Neurol. 2009;22(3):201–6. doi:10.1097/WCO.0b013e32832b4c8d. Not applicable. 4. Ferrò MT,FranciottaD,PrelleA,BestettiA, CinqueP.Activeintrathecal herpes simplex virus type 1 (HSV-1) and human herpesvirus-6 (HHV-6) Authors’ contributions infection at onset of multiple sclerosis. J Neurovirol. 2012;18:437–40. MCB, MS and GR: contributed equally for writing and critical reading of the doi:10.1007/s13365-012-0110-5. manuscript; GT provided interpretation of MRI imaging; AF, SR, MF, RR: 5. Franciotta D, Bestetti A, Sala S, Perucca P, Jarius S, Price RW, Di Stefano AL, provided critical reading of the manuscript. All authors read and approved Cinque P. Broad screening for human herpesviridae DNA in multiple the final manuscript. sclerosis cerebrospinal fluid and serum. Acta Neurol Belg. 2009;109:277–82. 6. Bergström T, Andersen O, Vahlne A. Isolation of herpes simplex virus Competing interests type 1 during first attack of multiple sclerosis. Ann Neurol. 1989;26:283–5. The authors declare that they have no competing interests. doi:10.1002/ana.410260218. 7. Ribeiro T, Fleury MJ, Granieri E, et al. Investigation of the prevalence of Consent for publication antibodies against neurotropic polyomaviruses BK, JC and SV40 in sera from Informed consent was obtained from the patient for publication of this case patients affected by multiple sclerosis. Neurol Sci. 2010;31(4):517–21. report and any accompanying images. doi:10.1007/s10072-010-0353-y. 8. Alcaïs A, Abel L, Casanova JL. Human genetics of infectious diseases: Ethics approval and consent to participate between proof of principle and paradigm. J Clin Invest. 2009;119:9. Not applicable. 9. Zhang SY, Casanova JL. Inborn errors underlying herpes simplex encephalitis: From TLR3 to IRF3. INSIGHTS |. J Exp Med. 2015;24. 10. Kastrukoff LF, Lau AS, Kim SU. Multifocal CNS demyelination following Publisher’sNote peripheral inoculation with herpes simplex virus type 1. Ann Neurol. Springer Nature remains neutral with regard to jurisdictional claims in 1987;22(1):52–9. published maps and institutional affiliations. 11. Grimaldi LME, Roos RP, Manservigi R, Spear PG, Lakeman FD, Whitley RJ. An Isoelectric Focusing Study in Herpes Simplex Virus Encephalitis. Ann Neurol. Author details 1 1988;24:2. Centre for Experimental Neurological Therapies, Department of 12. Martino GV, Grimaldi LME, Franciotta DM, Piccolo G, Brustia R, Minali L, Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and 2 GV M d'E. Isoelectric focusing herpes simplex virus-gB overlay study in Psychology, Sapienza University of Rome, Rome, Italy. IRCCS Istituto 3 brainstem encephalitis. Acta Neurol Scand. 1990;82(6):364–7. Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy. Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. Neuroradiology Unit, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Multiple Sclerosis and Demyelinating Disorders Springer Journals

Coincident onset of multiple sclerosis and Herpes simplex virus 1 encephalitis: a case report

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Springer Journals
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Copyright © 2017 by The Author(s).
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Medicine & Public Health; Neurology; Rehabilitation Medicine
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Abstract

Background: Along with vitamin D, smoking, body mass index and others, Epstein Barr virus, other herpesviruses and human endogenous retroviruses represent plausible environmental risk factors for multiple sclerosis. However, it is difficult to obtain direct proof of their involvement in the etiology of this condition. Case presentation: In order to contribute further evidence of the importance of these viruses, and speculate about disease-relevant interactions between these agents and a predisposed genetic background of the host, we describe the temporal association between multiple sclerosis onset and Herpes simplex 1-encephalitis in a female patient. Conclusions: This case illustrates a possible relationship between HSV-1 encephalitis and multiple sclerosis. Bearing in mind that association does not imply causation, some speculations about the etiology and pathophysiology of the two diseases can be made. The hypothesis of a genetic background predisposing to HSV-1 encephalitis and to immune-mediated demyelination is supported by the coincidence of the two conditions in this patient, along with data from animal models and genetic studies. Keywords: Multiple sclerosis, Environmental factors, HSV-1 encephalitis Background the MS central nervous system. On the other hand, her- Heritable and nonheritable factors, and their interac- pesviruses are sound candidates as well, because of tions, may be responsible for the autoimmune response neurotropism and, in the case of Epsein Barr virus, that leads to multiple sclerosis (MS) [1]. extraordinary ability to modulate the human immune Genome-wide association studies are improving our response. understanding of the heritable basis of the disease, most In order to contribute further evidence of the import- probably involving subtle defects of the regulation of ance of these viruses, and speculate about disease- transcription [2]. Though these studies are indeed ad- relevant interactions between these agents and a predis- vancing our knowledge, the nonheritable or “environ- posed genetic background of the host, we describe the mental” component of the risk shows a slower progress. temporal association between MS onset and Herpes sim- Among the environmental risk factors, viruses are inten- plex 1 (HSV)-encephalitis in a female patient. sively investigated as possible culprits [3]. Human en- dogenous retroviruses such as MSRV have attracted Case Presentation interest because of their capacity to hide by integrating A 32 year-old woman presented acute dysesthesia in the in the human DNA and then trigger immunological right face. Except for this symptom, her neurological mechanisms: a scenario that is compatible with the long examination was unremarkable and neither the patient standing difficulties in detecting any infectious agent in nor her relatives could recall any previous neurological episode. Her neurologist requested an MRI of the brain * Correspondence: mariachiara.buscarinu@uniroma1.it and spinal cord that showed the simultaneous presence Centre for Experimental Neurological Therapies, Department of of enhancing and nonenhancing white matter abnormal- Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and ities in MS-typical regions of the brain, compatible with Psychology, Sapienza University of Rome, Rome, Italy Full list of author information is available at the end of the article the diagnosis of a first episode of the disease (Fig. 1). © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 2 of 4 Fig. 1 a Axial FLAIR MRI that highlights hyperintense left periventricular areas; b left periventricular and frontal subcortical; c right cerebellar peduncle She was then treated with methylprednisolone 1 g evolution of the right temporal lesion, with a reduction intravenously for five days with a clear improvement of of the brainstem lesions and of the corpus callosum, the symptom. Ten days after the completion of the cor- and with evidence of a C5 spinal cord area, compat- ticosteroid course, she presented fever, severe headache ible with an inflammatory lesion. The enhancement of and confusion. A brain CT scan was obtained, highlight- lesions in MS-typical regions was not evident at this ing a hypodense area that involved right temporal pole, point (Fig. 4). insula and hippocampus. She was then hospitalized and She was transferred to a rehabilitation facility (GCS: 7) her cerebrospinal fluid (CSF) tested positive for HSV-1 and, after ten months, discharged home with a remark- DNA. All other CSF tests were negative including: Cyto- able improvement: left hemiparesis and left sensory syn- megalovirus, Varicella Zoster, Epstein Barr virus, John drome but able to walk with assistance, short term Cunningham virus, enteroviruses, Toxoplasma, Crypto- memory loss, fluctuating hyperactive state with mild agi- coccus, Mycobacterium tuberculosis and Treponema, tation. After additional six months of follow-up, she has oligoclonal bands. With the exception of a positive test now slightly improved the strength of her left limbs. The for recent HSV-1 infection, all other serologies were number and volume of areas in MS-typical regions is re- negative for recent infections including: Coxiella, duced though still increased with respect to the first Coxsackie, Chlamydia pneumoniae, Borrelia burgdoferi, MRI and no new areas have appeared at brain and spinal Mycoplasma pneumoniae, echovirus and adenovirus. cord MRI follow-up (Fig. 5). Peripheral blood screening tests for autoimmune dis- eases were negative. Intravenous acyclovir was started but she rapidly worsened (GCS: 4; E1, V1, M2) requiring orotracheal intubation, tracheostomy, mechanical ventilation and antiepileptic and antiedema therapy. Brain MRI ob- tained 3 and 6 days after the CT scan showed the involvement of the right hemisphere with diffuse swelling and contralateral shift of the septum pelluci- dum (Fig. 2). After 22 days, HSV1 DNA in the CSF was negative while a third MRI, contemporary to the CSF sampling, showed a remarkable increase in the number and vol- ume of lesions in MS-typical areas (some of them en- hancing) and necrotic-malacic evolution of the herpetic lesion (Fig. 3) In view of the apparent flare of the “autoimmune” con- dition, the patient was started on intravenous immuno- globulins (IVIG) at 0.4gr/kg/daily for 5 days and Methilprendisolone 40mg/daily for 15 days. She also continued therapy with Valacyclovir 3g/ daily. Fig. 2 Axial T2 image showing hyperintensity of the right temporal The MRI carried out as a control at the end of intra- lobe and right brainstem with less obvious contralateral alterations venous steroid therapy confirmed the necrotic-malacic Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 3 of 4 of a coincident onset of MS and HSV-1 encephalitis. Other reports have provided laboratory evidence of the intrathecal presence of HSV-1 at disease onset. This sup- ports the possibility that, in an individual with a peculiar genetic predisposition, this presence may turn into overt HSV-1 encephalitis [5, 6]. However, other viruses such as the John Cunningham (JC) virus have been described as replicating in the cerebrospinal fluid during the first symptoms of MS [7] though a coincident onset of MS and progressive multifocal encaphalomyelitis have never been described to our knowledge. Most interestingly, the HSV-1 encephalitis develops in individuals with inborn errors of immune response genes that impair central nervous system-intrinsic inter- feron alpha/beta production [8]. The therapeutic re- sponse of persons with MS to interferon beta suggests that a portion of the pathophysiology of the two diseases may be shared. This possibility may be supported also by the sharing of a predisposing gene, TRAF3, between the Fig. 3 Axial FLAIR showing the temporal encephalitis outcome two conditions (though this speculation has to be taken with caution because the effects of the observed variants may not be the same) [8, 9]. Discussion and conclusions The role of a genetic predisposition emerges also from This case illustrates a possible relationship between studies in inbred mouse strains with variable degrees of HSV-1 encephalitis and MS. resistance to EAE/HSV [10]. In these models, the lip in- Bearing in mind that association does not imply caus- oculation of the virus causes either no disease, or isolated ation, some speculations about the etiology and patho- lesions, or a diffuse picture of demyelination, depending physiology of the two diseases can be made. on the genetic background of the mice. Interestingly, the To our knowledge, while the onset of MS after hemi- multifocal lesions in the susceptible mice were first ob- thorax zoster, with intrathecal reactivation of HSV-1 and served when the virus could no longer be isolated from HHV-6 has been reported [4] this is the first description the CNS of the animals. This is in line with the diffuse worsening of the bona-fide demyelinating lesions observed in the patient, when the viral DNA became undetectable in the CSF. Both observations are in harmony with an immune-mediated process, triggered by the virus, in hosts with a susceptible genetic background. Other sequences of events cannot be excluded: the autoimmune damage might have been present before the HSV-1 infection with the latter being exacerbated by the corticosteroids course. Nonetheless, the effects of corticosteroids in these patients are debated, as clinical trials are ongoing to assess their therapeutic effects in overt HSV-1 encephalitis. Also the role played by the diffuse alteration of the blood brain bar- rier (somehow resembling an acute disseminated enceph- alomyelitis process, secondary to the HSV-1 infection) remains unclear in the context of the whole process. A longitudinal follow-up with, for example, IEF-overlay technique with radiolabeled HSV glycoprotein B (gB), for studying qualitative aspects of the HSV humoral immune response [11, 12], would have been of use but was not per- formed. More in general, as common pathophysiologies emerge between MS and host immune response to vi- Fig. 4 Cervical spinal cord sagittal image showing demyelinating ruses, tests for the detection of antiviral antibodies may hyperintense areas at C4 acquire more importance in the near future. Buscarinu et al. Multiple Sclerosis and Demyelinating Disorders (2017) 2:6 Page 4 of 4 Fig. 5 Comparison of MRIs obtained at 4 months (a) and at 18 months after onset (b) showing a reduction of the areas in MS-typical regions though the lesion load remains higher compared with the first MRI (Fig. 1) All in all, the hypothesis of a genetic background pre- Received: 2 February 2017 Accepted: 30 March 2017 disposing to HSV-1 encephalitis and to immune- mediated demyelination is supported by the coincidence References of the two conditions in this patient, along with data 1. Bordi I, Ricigliano VA, Umeton R, Ristori G, Grassi F, Crisanti A, Sutera A, Salvetti M. Noise in multiple sclerosis: unwanted and necessary. Ann Clin from animal models and genetic studies. Transl Neurol. 2014;1(7):502–11. doi:10.1002/acn3.72. Epub 2014 Jun 19. 2. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Acknowledgements Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, The authors would like to thank the patient for consent for publication. Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal Funding autoimmune disease variants. Nature. 2015;518(7539):337–43. doi:10.1038/ No funding was received. nature13835. Epub 2014 Oct 29. 3. Salvetti M, Giovannoni G, Aloisi F. Epstein-Barr virus and multiple sclerosis. Availability of data and material Curr Opin Neurol. 2009;22(3):201–6. doi:10.1097/WCO.0b013e32832b4c8d. Not applicable. 4. Ferrò MT,FranciottaD,PrelleA,BestettiA, CinqueP.Activeintrathecal herpes simplex virus type 1 (HSV-1) and human herpesvirus-6 (HHV-6) Authors’ contributions infection at onset of multiple sclerosis. J Neurovirol. 2012;18:437–40. MCB, MS and GR: contributed equally for writing and critical reading of the doi:10.1007/s13365-012-0110-5. manuscript; GT provided interpretation of MRI imaging; AF, SR, MF, RR: 5. Franciotta D, Bestetti A, Sala S, Perucca P, Jarius S, Price RW, Di Stefano AL, provided critical reading of the manuscript. All authors read and approved Cinque P. Broad screening for human herpesviridae DNA in multiple the final manuscript. sclerosis cerebrospinal fluid and serum. Acta Neurol Belg. 2009;109:277–82. 6. Bergström T, Andersen O, Vahlne A. Isolation of herpes simplex virus Competing interests type 1 during first attack of multiple sclerosis. Ann Neurol. 1989;26:283–5. The authors declare that they have no competing interests. doi:10.1002/ana.410260218. 7. Ribeiro T, Fleury MJ, Granieri E, et al. Investigation of the prevalence of Consent for publication antibodies against neurotropic polyomaviruses BK, JC and SV40 in sera from Informed consent was obtained from the patient for publication of this case patients affected by multiple sclerosis. Neurol Sci. 2010;31(4):517–21. report and any accompanying images. doi:10.1007/s10072-010-0353-y. 8. Alcaïs A, Abel L, Casanova JL. Human genetics of infectious diseases: Ethics approval and consent to participate between proof of principle and paradigm. J Clin Invest. 2009;119:9. Not applicable. 9. Zhang SY, Casanova JL. Inborn errors underlying herpes simplex encephalitis: From TLR3 to IRF3. INSIGHTS |. J Exp Med. 2015;24. 10. Kastrukoff LF, Lau AS, Kim SU. Multifocal CNS demyelination following Publisher’sNote peripheral inoculation with herpes simplex virus type 1. Ann Neurol. Springer Nature remains neutral with regard to jurisdictional claims in 1987;22(1):52–9. published maps and institutional affiliations. 11. Grimaldi LME, Roos RP, Manservigi R, Spear PG, Lakeman FD, Whitley RJ. An Isoelectric Focusing Study in Herpes Simplex Virus Encephalitis. Ann Neurol. Author details 1 1988;24:2. Centre for Experimental Neurological Therapies, Department of 12. Martino GV, Grimaldi LME, Franciotta DM, Piccolo G, Brustia R, Minali L, Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and 2 GV M d'E. Isoelectric focusing herpes simplex virus-gB overlay study in Psychology, Sapienza University of Rome, Rome, Italy. IRCCS Istituto 3 brainstem encephalitis. Acta Neurol Scand. 1990;82(6):364–7. Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy. Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. Neuroradiology Unit, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Journal

Multiple Sclerosis and Demyelinating Disorders – Springer Journals

Published: Apr 28, 2017

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