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Bodilsen J, Duerlund LS, Nielsen H. Corticosteroids for viral central nervous system infections. Curr Opin Infect Dis 2025; 38:271-279. [PMID: 40167047 DOI: 10.1097/qco.0000000000001106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
PURPOSE OF REVIEW Viruses are frequent causes of central nervous system (CNS) infection. Lacking specific antiviral treatment or inadequate clinical response may lead to treatment with corticosteroids. This review describes the rationale for and clinical experience with the use of adjunctive corticosteroids for viral CNS infections. RECENT FINDINGS Corticosteroids display anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects by genomic and nongenomic regulation of human cells. Recent population-based studies consistently show that empiric dexamethasone during diagnostic work-up for meningitis has neither been associated with improved outcome nor adverse effects in viral meningitis. Myelitis is most often due to noninfectious causes and standard empiric treatment includes high-dose methylprednisolone. There are no convincing data on viral myelitis to support a change of this approach. Corticosteroids have occasionally been employed in different types of viral encephalitis. Observational data and a few randomized clinical trials have not documented any substantial beneficial effects of adjunctive corticosteroids in viral encephalitis. Risks of harm with current treatment regimens remained low in published studies. SUMMARY Except for myelitis, there are no data to support routine use of corticosteroids for viral CNS infections. Large, multidisciplinary syndromic platform trials of all-cause encephalitis may be a viable way to inform treatment guidelines.
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Affiliation(s)
- Jacob Bodilsen
- Department of Infectious Diseases, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- ESCMID Study Group of Infections of the Brain (ESGIB)
| | - Lærke Storgaard Duerlund
- Department of Infectious Diseases, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- ESCMID Study Group of Infections of the Brain (ESGIB)
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- ESCMID Study Group of Infections of the Brain (ESGIB)
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Arakawa K, Nakagawa M, Abe Y, Morimatsu H. T2 high-signal-intensity zone of the spinal cord dorsal horn in patients treated with spinal cord stimulation for herpes zoster-associated pain: a retrospective case-control study. J Anesth 2025; 39:273-281. [PMID: 39976687 PMCID: PMC11937087 DOI: 10.1007/s00540-025-03458-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 01/20/2025] [Indexed: 03/27/2025]
Abstract
PURPOSE In patients with herpes zoster-associated pain (ZAP), magnetic resonance imaging (MRI) has revealed T2 high-signal intensity zones (MRI T2 HIZ) in the dorsal horn of the spinal cord, associated with postherpetic neuralgia (PHN). We retrospectively analyzed the relationship between PHN and MRI T2 HIZ in patients with refractory ZAP in the subacute phase who underwent temporary spinal cord stimulation therapy (tSCS). METHODS This single-center, case-control study included patients who underwent tSCS for refractory ZAP between 2010 and 2018. MRIs were re-assessed for the presence of T2 HIZ in the dorsal horn of the spinal cord. Patients were divided into T2 HIZ( +) and T2 HIZ(-) groups. Patients with a numerical rating score (NRS) ≥ 3 at the last visit were defined as PHN. The NRS values and the incidence rate of PHN were compared between the two groups. RESULTS Of the 67 cases extracted, 38 were included in the analysis: 22 in T2 HIZ( +) group and 16 in T2 HIZ(-) group. No significant differences were observed in background factors between the two groups. However, the T2 HIZ( +) group had a significantly higher NRS at the final visit (T2 HIZ( +):3.8 ± 2.1, T2 HIZ(-):1.4 ± 1.5; P < 0.05) and had significantly more patients with PHN than the T2 HIZ(-) group (T2 HIZ( +) vs. T2 HIZ(-), 15/22 (68%) vs. 3/16 (19%); odds ratio = 8.67; 95% confidence interval, 1.7-63.3). CONCLUSION T2HIZ is detected in more than half of refractory ZAP, and pain is more likely to remain after tSCS treatment in the T2HIZ( +) group.
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Affiliation(s)
- Kyosuke Arakawa
- Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan.
| | - Masayuki Nakagawa
- Department of Pain Management Clinic, NTT Medical Center Tokyo, Tokyo, Japan
| | - Yoichiro Abe
- Department of Pain Management Clinic, NTT Medical Center Tokyo, Tokyo, Japan
| | - Hiroshi Morimatsu
- Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan
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Yaghmaei E, Najafi A, Daneshvar Kakhki R. Longitudinal Extensive Transverse Myelitis due to Varicella-Zoster Virus Infection in an Undiagnosed HIV-Positive Patient. Case Rep Neurol Med 2024; 2024:9027198. [PMID: 39055723 PMCID: PMC11272404 DOI: 10.1155/2024/9027198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 04/21/2024] [Accepted: 06/13/2024] [Indexed: 07/27/2024] Open
Abstract
Introduction Longitudinal extensive transverse myelitis (LETM) has four main causes: inflammatory, malnutrition, vascular, and infectious causes. Among the commonly described viral causes leading to LETM are the Herpesviridae family, HIV, and HTLV-1. Case Presentation. A 43-year-old man presented with asymmetric weakness of the lower limbs (the left side was weaker), urinary retention, and flank pain. The symptoms began five days after shingle eruption and progressed over twelve days. He was diagnosed with longitudinal extensive transvers myelitis extending from T4 to T6, which corresponded to the same dermatome involved in shingles. The PCR result of cerebrospinal fluid was positive for varicella-zoster virus with a viral load of 500 copies/ml. Additionally, the initial HIV enzyme-linked immunosorbent assay (ELISA) test was positive, and his CD4 count was 72 cells/mm3. Other lab results were normal. Based on the appearance of LETM in the thoracic MRI at T4-T6, VZV myelitis was diagnosed, and treatment was initiated with acyclovir (30 mg/kg divided daily for twenty-one days), methylprednisolone (1 g/day for three days), prophylactic antibiotics (trimethoprim/sulfamethoxazole, rifampin, and isoniazid), and antiretroviral therapy (dolutegravir and Truvada). After 2-month follow-up, he was nearly free of symptoms. Conclusion Infection is one of the critical causes of transverse myelitis. When a patient presents with skin shingles along with myelopathy, varicella-zoster myelitis should be considered, and the patient should be evaluated in terms of immune system dysfunction. Treatment with acyclovir has been shown to be effective in reducing clinical symptoms in such cases.
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Affiliation(s)
- Elahe Yaghmaei
- Department of NeurologyKashan University of Medical Sciences, Kashan, Iran
| | - Ahmad Najafi
- Infectious Diseases Research CenterKashan University of Medical Sciences, Kashan, Iran
| | - Reza Daneshvar Kakhki
- Autoimmune Diseases Research CenterKashan University of Medical Sciences, Kashan, Iran
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Wangaryattawanich P, Condos AM, Rath TJ. Bacterial and Viral Infectious Disease of the Spine. Magn Reson Imaging Clin N Am 2024; 32:313-333. [PMID: 38555143 DOI: 10.1016/j.mric.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
Spinal infections are a diverse group of diseases affecting different compartments of the spine with variable clinical and imaging presentations. Diagnosis of spinal infections is based on a combination of clinical features, laboratory markers, and imaging studies. Imaging plays a pivotal role in the diagnosis and management of spinal infections. The characteristic imaging manifestations of bacterial and viral infections in the spine are discussed with key teaching points emphasized.
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Affiliation(s)
- Pattana Wangaryattawanich
- Department of Radiology, University of Washington School of Medicine, 1959 Northeast Pacific Street, Seattle, WA 98195-7115, USA.
| | - Amy M Condos
- Department of Radiology, University of Washington School of Medicine, 2545 Northeast 85th Street Seattle, WA 98115, USA
| | - Tanya J Rath
- Neuroradiology Section, Department of Radiology, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA
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Mezzetti E, Costantino A, Leoni M, Pieretti R, Di Paolo M, Frati P, Maiese A, Fineschi V. Autoimmune Heart Disease: A Comprehensive Summary for Forensic Practice. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1364. [PMID: 37629654 PMCID: PMC10456745 DOI: 10.3390/medicina59081364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/05/2023] [Accepted: 07/20/2023] [Indexed: 08/27/2023]
Abstract
Autoimmune heart disease is a non-random condition characterised by immune system-mediated aggression against cardiac tissue. Cardiac changes often exhibit nonspecific features and, if unrecognised, can result in fatal outcomes even among seemingly healthy young individuals. In the absence of reliable medical history, the primary challenge lies in differentiating between the various cardiopathies. Numerous immunohistochemical and genetic studies have endeavoured to characterise distinct types of cardiopathies, facilitating their differentiation during autopsy examinations. However, the presence of a standardised protocol that forensic pathologists can employ to guide their investigations would be beneficial. Hence, this summary aims to present the spectrum of autoimmune cardiopathies, including emerging insights such as SARS-CoV-2-induced cardiopathies, and proposes the utilisation of practical tools, such as blood markers, to aid forensic pathologists in their routine practice.
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Affiliation(s)
- Eleonora Mezzetti
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Andrea Costantino
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Matteo Leoni
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Rebecca Pieretti
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Marco Di Paolo
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Paola Frati
- Department of Anatomical, Histological, Forensic and Orthopedical Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy; (P.F.); (V.F.)
| | - Aniello Maiese
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy; (E.M.); (A.C.); (M.L.); (R.P.); (M.D.P.)
| | - Vittorio Fineschi
- Department of Anatomical, Histological, Forensic and Orthopedical Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy; (P.F.); (V.F.)
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Spinal Infections. Neuroimaging Clin N Am 2023; 33:167-183. [DOI: 10.1016/j.nic.2022.07.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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7
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Kannarkat GT. Spinal hematoma from varicella zoster vasculopathy and acquired hyperfibrinolysis. Neurol Sci 2022; 43:5125-5127. [DOI: 10.1007/s10072-022-06098-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 04/26/2022] [Indexed: 11/29/2022]
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8
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Motohashi S, Takahashi J, Umehara T, Komatsu T, Murakami H, Iguchi Y. [A 73-year-old man with polyradiculopathy and multiple cranial neuropathies emerging separate from the originating dermatome of a varicella zoster skin lesion]. Rinsho Shinkeigaku 2022; 62:380-385. [PMID: 35474287 DOI: 10.5692/clinicalneurol.cn-001699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
A 73-year-old man developed delayed-onset multiple cranial neuropathies of cranial nerves V, VII and VIII, and segmental paresis in the ipsilateral upper extremity related to the C4 to Th1 segment, after all skin lesions with varicella zoster (VZV) on the left neck of the C3-4 dermatome had dried and crusted over. On admission, cerebrospinal fluid (CSF) revealed pleocytosis (all mononuclear cells, 12/μl). Treatment was started with intravenous acyclovir (10 mg/kg, every 8 h for 14 days) and methylprednisolone (1,000 mg/day for 3 days). Four days after starting treatment, left segmental paresis was improved, but the multiple cranial neuropathies persisted. Oral prednisolone (0.5 mg/kg/day) was administered for 5 days, then tapered off. All neurological symptoms had disappeared by hospital day 23. Of particular interest was the discrepancy between skin regions affected by VZV (C3-4) and the regions of cranial neuropathy (cranial nerves V, VII, and VIII) and muscle weakness innervated by C4-Th1. Although CSF was negative for VZV DNA according to PCR testing, the antibody index for VZV was elevated. This suggests intrathecal synthesis of VZV antibodies and supports the diagnosis of VZV meningitis. Also, all cranial nerves involved in this case were reported to have the cranial nerve ganglia where VZV could have established latency and been reactivated. This suggests concurrent reactivation on each cranial nerve ganglia without cutaneous lesions, as zoster sine herpete. In addition, anastomoses among the upper cervical nerves, which are found in some patients, may have contributed to this condition. These mechanisms underlie various neurological symptoms associated with VZV infection.
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Affiliation(s)
| | | | - Tadashi Umehara
- Department of Neurology, The Jikei University School of Medicine
| | - Teppei Komatsu
- Department of Neurology, The Jikei University School of Medicine
| | | | - Yasuyuki Iguchi
- Department of Neurology, The Jikei University School of Medicine
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9
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Abstract
Acute myelopathies are spinal cord disorders characterized by a rapidly progressive course reaching nadir within hours to a few weeks that may result in severe disability. The multitude of underlying etiologies, complexities in confirming the diagnosis, and often unforgiving nature of spinal cord damage have always represented a challenge. Moreover, certain slowly progressive myelopathies may present acutely or show abrupt worsening in specific settings and thus further complicate the diagnostic workup. Awareness of the clinical and magnetic resonance imaging characteristics of different myelopathies and the specific settings where they occur is fundamental for a correct diagnosis. Neuroimaging helps distinguish compressive etiologies that may require urgent surgery from intrinsic etiologies that generally require medical treatment. Differentiation between various myelopathies is essential to establish timely and appropriate treatment and avoid harm from unnecessary procedures. This article reviews the contemporary spectrum of acute myelopathy etiologies and provides guidance for diagnosis and management.
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Affiliation(s)
- Elia Sechi
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
| | - Eoin P Flanagan
- Department of Neurology, Mayo Clinic, Rochester, Minnesota.,Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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10
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McEntire CR, Dowd RS, Orru' E, David C, Small JE, Cervantes-Arslanian A, Lerner DP. Acute Myelopathy: Vascular and Infectious Diseases. Neurol Clin 2021; 39:489-512. [PMID: 33896530 DOI: 10.1016/j.ncl.2021.01.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Vascular and infectious causes are rare but important causes of spinal cord injury. High suspicion for these processes is necessary, as symptoms may progress over hours to days, resulting in delayed presentation and diagnosis and worse outcomes. History and clinical examination findings can assist with localization of the affected vascular territory and spinal level, which will assist with focusing spinal imaging. Open and/or endovascular surgical management depends on the associated vascular abnormality. Infectious myelopathy treatment consists of targeted antimicrobial therapy when possible, infectious source control, and again, close monitoring for systemic complications.
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Affiliation(s)
- Caleb R McEntire
- Department of Neurology, Massachusetts General Hospital and Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Richard S Dowd
- Department of Neurosurgery, Tufts University School of Medicine, Boston, MA 02111, USA
| | - Emanuele Orru'
- Department of Radiology, Neurointerventional Radiology Division, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
| | - Carlos David
- Department of Neurosurgery, Tufts University School of Medicine, Boston, MA 02111, USA; Department of Neurosurgery, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
| | - Juan E Small
- Department of Radiology, Neuroradiology Section, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
| | | | - David P Lerner
- Division of Neurology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA; Department of Neurology, Tufts University School of Medicine, Boston, MA 02111, USA.
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11
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Kim HS, Jung JW, Jung YJ, Ro YS, Park SB, Lee KH. Complete recovery of herpes zoster radiculopathy based on electrodiagnostic study: A case report. World J Clin Cases 2021; 9:4303-4309. [PMID: 34141794 PMCID: PMC8173409 DOI: 10.12998/wjcc.v9.i17.4303] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 02/03/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Herpes zoster is a painful infectious disease caused by the varicella zoster virus. Herpes zoster radiculopathy, which is a type of segmental zoster paresis, can complicate the disease and cause motor weakness. This complication should be considered when a patient with a rash complains of acute-onset motor weakness, and the diagnosis can be verified via electrodiagnostic study.
CASE SUMMARY A 64-year-old female with a history of asthma presented to the emergency department with stabbing pain, an itching sensation, and a rash on the right anterior shoulder that had begun 5 d prior. Physical examination revealed multiple erythematous grouped vesicles in the right C4-5 and T1 dermatome regions. Because herpes zoster was suspected, the patient immediately received intravenous acyclovir. On the third hospital day, she complained of motor weakness in the right upper extremity. Magnetic resonance imaging of the cervical spine revealed mild intervertebral disc herniation at C4-C5 without evidence of nerve root compression. On the 12th hospital day, electrodiagnostic study revealed right cervical radiculopathy, mainly in the C5/6 roots. Six months later, monoparesis resolved, and follow-up electrodiagnostic study was normal.
CONCLUSION This case emphasizes that clinicians should consider the possibility of post-herpetic paresis, such as herpes zoster radiculopathy, and that electrodiagnostic study is useful for diagnosis and follow-up.
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Affiliation(s)
- Hyeon Seong Kim
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Ji Won Jung
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - You Jin Jung
- Department of Dermatology, Hanyang University Hospital, Seoul 04763, South Korea
| | - Young Suck Ro
- Department of Dermatology, Hanyang University Hospital, Seoul 04763, South Korea
| | - Si-Bog Park
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Kyu Hoon Lee
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
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12
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Garbi A, Rauer F, Heckmann JG. Herpes zoster and Brown-Séquard syndrome. Wien Klin Wochenschr 2020; 132:545-546. [DOI: 10.1007/s00508-020-01664-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 04/12/2020] [Indexed: 11/29/2022]
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Hagberg L, Price RW, Zetterberg H, Fuchs D, Gisslén M. Herpes zoster in HIV-1 infection: The role of CSF pleocytosis in secondary CSF escape and discordance. PLoS One 2020; 15:e0236162. [PMID: 32697807 PMCID: PMC7375594 DOI: 10.1371/journal.pone.0236162] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 06/30/2020] [Indexed: 12/11/2022] Open
Abstract
HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a ‘model’ of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point.
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Affiliation(s)
- Lars Hagberg
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
- * E-mail:
| | - Richard W. Price
- Department of Neurology, University of California San Francisco, San Francisco, CA, United States of America
| | - Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
- Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
- UK Dementia Research Institute at UCL, London, United Kingdom
- Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
| | - Dietmar Fuchs
- Institute of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria
| | - Magnus Gisslén
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
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14
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Maeda Y, Watanabe M, Maeda N, Ogata H, Shinoda K, Iwaki T, Kira JI. [An autopsied case of severe varicella zoster virus-associated encephalomyelitis under immunosuppressant therapy]. Rinsho Shinkeigaku 2020; 60:351-357. [PMID: 32307398 DOI: 10.5692/clinicalneurol.cn-001413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The patient was a 40-year-old woman who was previously diagnosed with systemic lupus erythematosus and myasthenia gravis and had received prednisolone and tacrolimus for more than 7 years. In February 2017, she noticed pain in her lower back and weakness of the lower limbs, and was referred to our hospital on day 5. She had shingles in the right lower thoracic dermatomes and Brown-Séquard syndrome with right-sided dominant weakness in her lower limbs and left-sided superficial sensory disturbance below the L1 level. Varicella zoster virus (VZV)-associated myelopathy was suspected because of her symptoms and clinical findings. Despite the immediate administration of intravenous acyclovir after hospitalization, she lost consciousness and experienced a seizure related to cerebral hemorrhage in the left temporal lobe on the night of day 5. MRI showed enhanced lesions along the spinal cord and leptomeninges of the brainstem and temporal lobe. VZV-IgG and VZV-DNA were positive in the cerebrospinal fluid. Based on these clinical features and laboratory findings, she was diagnosed as VZV-associated vasculopathy and myelopathy. She subsequently had multiple cerebral infractions and hemorrhage, and developed sudden cardiopulmonary arrest on day 6, culminating in death on day 17. Autopsy showed that inflammatory mononuclear cells had infiltrated the vascular walls of the spinal cord. Immunohistochemistry revealed that some neurons and macrophages in the white matter of the spinal cord were positive for VZV. In addition, atrophic neurons, satellite cells surrounding these neurons, and infiltrating macrophages were immune-positive for VZV at the L2 dorsal root ganglia. These findings were consistent with VZV-associated vasculopathy and myelitis. Under immunosuppressive conditions, VZV can cause shingles and neuronal complications such as vasculopathy and myelitis, which are sometimes fatal despite the immediate administration of intravenous acyclovir. New treatment drugs or drugs to prevent VZV activation are desired.
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Affiliation(s)
- Yasuhiro Maeda
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Mitsuru Watanabe
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Norihisa Maeda
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University.,Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Hidenori Ogata
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Koji Shinoda
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Toru Iwaki
- Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
| | - Jun-Ichi Kira
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University
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Le Guennec L. Manifestazioni neurologiche delle infezioni. Neurologia 2020. [DOI: 10.1016/s1634-7072(20)43298-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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16
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Gailloud P. The contributions of Otto Hebold and Julius Gaupp to the study of spinal vascular malformations: Original documents and historical context. Interv Neuroradiol 2019; 25:604-612. [PMID: 31280634 PMCID: PMC6838847 DOI: 10.1177/1591019919845648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 03/25/2019] [Indexed: 10/20/2023] Open
Abstract
Book chapters and journal articles dealing with spinal cord vascular malformations often reference Otto Hebold and Julius Gaupp, but frequently misrepresent the observations published by the two German authors in the late 19th century. The purpose of this paper is to provide a better appreciation of these important contributions based on abridged translations of original documents set in their historical context, notably regarding the landmark works of Brasch, Raymond and Cestan, and Lindenmann. It is concluded that Gaupp offered the first reliable description of a perimedullary arteriovenous fistula while the lesion reported by Hebold was not a spinal vascular malformation.
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Affiliation(s)
- Philippe Gailloud
- Division of Interventional Neuroradiology, The Johns Hopkins Hospital, Baltimore, USA
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17
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Abstract
Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus that produces varicella then becomes latent in ganglionic neurons. In elderly and immunocompromised individuals, VZV reactivates and typically produces herpes zoster. Studies of patients with VZV vasculopathy have identified key clinical, imaging, and laboratory features to assist in diagnosis and treatment. Complementary studies have further expanded the spectrum of VZV vasculopathy to include the extracranial circulation and identified mechanisms contributing to its pathogenesis. Given our increasing aging population and recognition that VZV reactivation manifesting as zoster is a risk factor for stroke and myocardial infarction, recognition of VZV as a potential cause of vascular disease with or without associated zoster rash is essential to decrease associated morbidity and mortality because VZV vasculopathy can be treated with antiviral therapy.
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Affiliation(s)
- Maria A Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora.,Department of Ophthalmology, University of Colorado School of Medicine, Aurora
| | - Andrew N Bubak
- Department of Neurology, University of Colorado School of Medicine, Aurora
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Abbas SA, El Helou J, Chalah MA, Hilal H, Saliba G, Abboud H, Ayache SS. Longitudinal Extensive Transverse Myelitis in an Immunocompetent Older Individual-A Rare Complication of Varicella-Zoster Virus Reactivation. ACTA ACUST UNITED AC 2019; 55:medicina55050201. [PMID: 31126152 PMCID: PMC6572170 DOI: 10.3390/medicina55050201] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/24/2019] [Accepted: 05/21/2019] [Indexed: 12/29/2022]
Abstract
Varicella-zoster virus (VZV) is a human neurotropic herpes virus that causes chickenpox in children. After becoming latent in dorsal root ganglia, it can reactivate to cause dermatological manifestations, the most common one being shingles or herpes zoster. Severe neurologic dysfunctions can occur in immunocompromised patients such as encephalitis, meningitis, myelitis and neuropathy. Longitudinal extensive transverse myelitis (LETM) is an unusual neurological complication mainly described in immunocompromised patients, with very few cases described in immunocompetent ones. We hereby report a case of VZV-induced LETM in an immunocompetent older adult—a situation rarely described in the literature. LETM is a rare complication of VZV and its pathogenesis; therapeutic interventions and prognosis are far from being fully clarified. However, a prompt diagnosis is needed to allow a rapid initialization of treatment and ensure a better outcome. Although the therapeutic lines are not clear, immunosuppressive agents may have their place in cases of unsuccessful results and/or relapses following acyclovir coupled with a well conducted methylprednisolone therapy. Further studies are highly needed to improve the current understanding of the disease course and mechanisms, and to optimize therapeutic strategies.
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Affiliation(s)
- Samar A Abbas
- Department of Neurology, Hôtel-Dieu de France Hospital, Faculty of Medicine, Saint-Joseph University, Beirut 1104-2020, Lebanon.
| | - Jeanine El Helou
- Department of Neurology, Hôtel-Dieu de France Hospital, Faculty of Medicine, Saint-Joseph University, Beirut 1104-2020, Lebanon.
| | - Moussa A Chalah
- EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France.
| | - Hanine Hilal
- Department of Neurology, Bellevue Medical Center University Hospital, Beirut 1104-2020, Lebanon.
| | - Gaby Saliba
- Department of Infectious diseases, Hôtel-Dieu de France Hospital, Faculty of Medicine, Saint-Joseph University, Beirut 1104-2020, Lebanon.
| | - Halim Abboud
- Department of Neurology, Hôtel-Dieu de France Hospital, Faculty of Medicine, Saint-Joseph University, Beirut 1104-2020, Lebanon.
| | - Samar S Ayache
- EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.
- Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France.
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19
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Thomas AS, Perez JA. Complications of Varicella Zoster Infection of the Central Nervous System. Methodist Debakey Cardiovasc J 2019; 13:76-77. [PMID: 28740587 DOI: 10.14797/mdcj-13-2-76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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20
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Bubak AN, Como CN, Blackmon AM, Jones D, Nagel MA. Varicella zoster virus differentially alters morphology and suppresses proinflammatory cytokines in primary human spinal cord and hippocampal astrocytes. J Neuroinflammation 2018; 15:318. [PMID: 30442152 PMCID: PMC6236967 DOI: 10.1186/s12974-018-1360-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 11/05/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Varicella zoster virus (VZV) is a ubiquitous alphaherpesvirus that produces varicella and zoster. VZV can infect multiple cell types in the spinal cord and brain, including astrocytes, producing myelopathy and encephalopathy. While studies of VZV-astrocyte interactions are sparse, a recent report showed that quiescent primary human spinal cord astrocytes (qHA-sps) did not appear activated morphologically during VZV infection. Since astrocytes play a critical role in host defenses during viral infections of the central nervous system, we examined the cytokine responses of qHA-sps and quiescent primary human hippocampal astrocytes (qHA-hps) to VZV infection in vitro, as well as the ability of conditioned supernatant to recruit immune cells. METHODS At 3 days post-infection, mock- and VZV-infected qHA-sps and qHA-hps were examined for morphological changes by immunofluorescence antibody assay using antibodies directed against glial fibrillary acidic protein and VZV. Conditioned supernatants were analyzed for proinflammatory cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-gamma, and tumor necrosis factor-α] using the Meso Scale Discovery multiplex ELISA platform. Finally, the ability of conditioned supernatants to attract peripheral blood mononuclear cells (PBMCs) was determined using a chemotaxis assay. Quiescent primary human perineurial cells (qHPNCs) served as a control for VZV-induced cytokine production and PBMC migration. To confirm that the astrocytes have the ability to increase cytokine secretion, qHA-sps and qHA-hps were treated with IL-1β and examined for morphological changes and IL-6 secretion. RESULTS VZV-infected qHA-sps displayed extensive cellular processes, whereas VZV-infected qHA-hps became swollen and clustered together. Astrocytes had the capacity to secrete IL-6 in response to IL-1β. Compared to mock-infected cells, VZV-infected qHA-sps showed significantly reduced secretion of IL-2, IL-4, IL-6, IL-12p70, and IL-13, while VZV-infected qHA-hps showed significantly reduced IL-8 secretion. In contrast, levels of all 10 cytokines examined were significantly increased in VZV-infected qHPNCs. Consistent with these results, conditioned supernatant from VZV-infected qHPNCs, but not that from VZV-infected qHA-sps and qHA-hps, recruited PBMCs. CONCLUSIONS VZV-infected qHA-sps and qHA-hps have distinct morphological alterations and patterns of proinflammatory cytokine suppression that could contribute to ineffective viral clearance in VZV myelopathy and encephalopathy, respectively.
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Affiliation(s)
- Andrew N. Bubak
- Department of Neurology, University of Colorado School of Medicine, 4200 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045 USA
| | - Christina N. Como
- Department of Neurology, University of Colorado School of Medicine, 4200 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045 USA
| | - Anna M. Blackmon
- Department of Neurology, University of Colorado School of Medicine, 4200 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045 USA
| | - Dallas Jones
- Department of Neurology, University of Colorado School of Medicine, 4200 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045 USA
| | - Maria A. Nagel
- Department of Neurology, University of Colorado School of Medicine, 4200 E. 19th Avenue, Mail Stop B182, Aurora, CO 80045 USA
- Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 USA
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21
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Bubak AN, Como CN, Blackmon AM, Frietze S, Mescher T, Jones D, Cohrs RJ, Paucek P, Baird NL, Nagel MA. Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes. J Infect Dis 2018; 218:1324-1335. [PMID: 29788447 PMCID: PMC6129113 DOI: 10.1093/infdis/jiy297] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 05/14/2018] [Indexed: 12/11/2022] Open
Abstract
Background Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy. Methods Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes, and viral spread in the presence or absence of the NK-1R antagonists aprepitant and rolapitant. Results VZV infection of HA-sps induced nuclear localization of full-length and truncated NK-1R in the absence of the endogenous ligand, subP, and was associated with extensive lamellipodia formation and viral spread that was inhibited by NK-1R antagonists. Conclusions We have identified a novel, subP-independent, proviral function of nuclear NK-1R associated with lamellipodia formation and viral spread that is distinct from subP-induced NK-1R cell membrane/cytoplasmic localization without lamellipodia formation. These results suggest that binding of a putative viral ligand to NK-1R produces a dramatically different NK-1R downstream effect than binding of subP. Finally, the NK-1R antagonists aprepitant and rolapitant provide promising alternatives to nucleoside analogs in treating VZV infections, including myelopathy.
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Affiliation(s)
- Andrew N Bubak
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Christina N Como
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Anna M Blackmon
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Seth Frietze
- Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington
| | - Teresa Mescher
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Dallas Jones
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Randall J Cohrs
- Department of Neurology, University of Colorado School of Medicine, Aurora
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora
| | - Petr Paucek
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Nicholas L Baird
- Department of Neurology, University of Colorado School of Medicine, Aurora
| | - Maria A Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora
- Department of Ophthalmology, University of Colorado School of Medicine, Aurora
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22
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Abstract
The epidemiology of spinal cord disease in human immunodeficiency virus (HIV) infection is largely unknown due to a paucity of data since combination antiretroviral therapy (cART). HIV mediates spinal cord injury indirectly, by immune modulation, degeneration, or associated infections and neoplasms. The pathologies vary and range from cytotoxic necrosis to demyelination and vasculitis. Control of HIV determines the differential for all neurologic presentations in infected individuals. Primary HIV-associated acute transverse myelitis, an acute inflammatory condition with pathologic similarities to HIV encephalitis, arises in early infection and at seroconversion. In contrast, HIV vacuolar myelopathy and opportunistic infections predominate in uncontrolled disease. There is systemic immune dysregulation as early as primary infection due to initial depletion of gut-associated lymphoid tissue CD4 cells and allowance of microbial translocation across the gut that never fully recovers throughout the course of HIV infection, regardless of how well controlled. The subsequent proinflammatory state may contribute to spinal cord diseases observed even after cART initiation. This chapter will highlight an array of spinal cord pathologies classified by stage of HIV infection and immune status.
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Affiliation(s)
- Seth N Levin
- Department of Neurology, Massachusetts General Hospital, Boston, MA, United States; Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States
| | - Jennifer L Lyons
- Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
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Guillain-Barré syndrome following varicella-zoster virus infection. Eur J Clin Microbiol Infect Dis 2018; 37:511-518. [PMID: 29411189 DOI: 10.1007/s10096-018-3199-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 01/20/2018] [Indexed: 12/19/2022]
Abstract
We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4 weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4 weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40 years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1 year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.
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Pohlen MS, Sunwei Lin J, Wang KY, Ghasemi-Rad M, Lincoln CM. Haemorrhagic conversion of infectious myelitis in an immunocompromised patient. BMJ Case Rep 2017; 2017:bcr2017221866. [PMID: 29197841 PMCID: PMC5720289 DOI: 10.1136/bcr-2017-221866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/22/2017] [Indexed: 11/03/2022] Open
Abstract
A 28-year-old man recently diagnosed with HIV (CD4 19 cells/mm3, viral load 3.6 million copies/mL, not on highly active antiretroviral therapy on initial diagnosis at outside hospital), disseminated histoplasmosis, shingles and syphilis presented with paraplegia developing over 3 days. Spine MRI demonstrated a longitudinally extensive cord lesion extending from C3 to the tip of the conus. Brain MRI was consistent with meningoencephalitis. Cerebrospinal fluid findings were notable for positive varicella zoster virus (VZV) and cytomegalovirus (CMV) PCRs as well as a Venereal Disease Research Laboratory titre of 1:2. Patient was started on treatment for VZV and CMV meningoencephalitis, neurosyphilis and high-dose steroids for infectious myelitis. Repeat spine MRI demonstrated subacute intramedullary haemorrhage of the cervical cord. He was ultimately discharged to a skilled nursing facility for long-term intravenous antiviral therapy and rehabilitation. After 59 days in the hospital, his neurological exam remained grossly unchanged, with flaccid paraplegia and lack of sensation to fine touch in his lower extremities.
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Affiliation(s)
| | | | - Kevin Yuqi Wang
- Department of Radiology, Baylor College of Medicine, Houston, Texas, USA
| | | | - Christie M Lincoln
- Department of Radiology, Baylor College of Medicine, Houston, Texas, USA
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25
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Cui JZ, Zhang XB, Zhu P, Zhao ZB, Geng ZS, Zhang YH, Tian L, Luan HF, Feng JY. Effect of Repetitive Intracutaneous Injections with Local Anesthetics and Steroids for Acute Thoracic Herpes Zoster and Incidence of Postherpetic Neuralgia. PAIN MEDICINE 2017; 18:1566-1572. [PMID: 27492741 DOI: 10.1093/pm/pnw190] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Background Treatment of established postherpetic neuralgia (PHN) is difficult and often disappointing. In this study, we assessed the efficacy of repetitive intracutaneous injections with local anesthetics and steroids in acute thoracic herpes zoster (HZ) pain, herpetic eruption, and incidence of PHN. Methods Ninety-three patients with acute thoracic HZ were randomly assigned to receive a standard treatment of antiviral medication with p.o. analgesics or the standard treatment with the addition of repetitive intracutaneous injections of a local anesthetic and steroid mixture. Patients were permitted to take tramadol when the visual analog scale (VAS) ≥ 4. Pain assessment using VAS was conducted at the initial visit, as well as 1, 2, 4, 12, and 24 weeks after the end of the treatments. Results In comparison with the standard treatment group, the VAS scores of the intracutaneous injection group were significantly lower during the study. The intracutaneous injection group also reported shorter duration of pain and skin eruption than the control group ( P = 0.005 vs P < 0.001, respectively). At 1 month post-therapy, 12.8% patients in the intracutaneous injection group reported zoster-associated pain, compared with 47.8% in the standard treatment group ( P < 0.001). At 3 and 6 months post-therapy, the incidence of PHN was still significantly lower in the intracutaneous injection group than the standard treatment group. EuroQol VAS scores were significantly higher in the intracutaneous injection group vs standard treatment group (P < 0.001). Conclusion Repetitive intracutaneous injections with local anesthetics and steroids along with standard treatment significantly reduce the duration of pain and herpetic eruption and incidence of PHN.
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Affiliation(s)
- Ji-Zheng Cui
- Department of Pain Treatment, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Xiao-Bao Zhang
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Pin Zhu
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Zhi-Bin Zhao
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Zhu-Sheng Geng
- Department of Pain Treatment, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Yun-Hai Zhang
- Department of Pain Treatment, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Liang Tian
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Heng-Fei Luan
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
| | - Ji-Ying Feng
- Department of Anesthesiology, the First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China
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Magnetic Resonance Imaging and Clinical Features in Acute and Subacute Myelopathies. Clin Neuroradiol 2017; 27:417-433. [PMID: 28667382 DOI: 10.1007/s00062-017-0604-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 06/07/2017] [Indexed: 12/22/2022]
Abstract
Differential diagnosis of acute and subacute transverse myelopathy includes inflammatory, infectious, vascular, metabolic and paraneoplastic etiologies. Information on the diagnostic approach to transverse myelopathy with regard to daily clinical practice is provided. The differentiation between five lesion patterns on magnetic resonance imaging (MRI) in myelitis may be helpful: (1) longitudinal extensive transverse myelitis, (2) short segment ovoid or peripherally located, (3) "polio-like", (4) granulomatous and (5) segmental with rash. A correlation with these imaging features is supported if the clinical course and neurological symptoms are known. Although the mean interval from onset to nadir of symptoms in spinal cord infarction is 1 h, an overlap with a fulminant course of myelitis is possible, and impaired diffusion may also occur in acute inflammatory processes. As a result, laboratory testing, including aquaporin-4 antibodies and cerebrospinal fluid analysis, is crucial for the correct interpretation of imaging findings. Moreover, the discrimination of acute complete and acute partial transverse myelitis is advantageous in order to identify diverse entities, the latter often being a precursor to multiple sclerosis. Additional brain imaging is mandatory in suspected demyelinating, infectious, neoplastic and systemic autoimmune disease. A symmetrical lesion pattern restricted to individual tracts or dorsal columns indicates subacute combined degeneration of the spinal cord and, in addition to deficiency syndromes, a paraneoplastic etiology should be considered.
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27
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Ota T, Yamazaki M, Toda Y, Ozawa A, Kimura K. [A case of herpes zoster ophthalmicus preceded one week by diplopia and ophthalmalgia]. Rinsho Shinkeigaku 2017; 57:163-167. [PMID: 28367946 DOI: 10.5692/clinicalneurol.cn-000972] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
A 66-year-old man presented with headache and ophthalmalgia. Diplopia developed, and he was hospitalized. The left eye had abducent paralysis and proptosis. We diagnosed him with Tolosa-Hunt syndrome and administered methylprednisolone at 1 g/day for 3 days. However, the patient did not respond to treatment. No abnormality was found on his MRI or cerebrospinal fluid examination. Tests showed his serum immunoglobulin G4 and antineutrophil cytoplasmic antibody titers were within normal limits. He also had untreated diabetes mellitus (HbA1c 9.2). One week after first presenting with symptoms, herpes zoster appeared on the patient's dorsum nasi, followed by keratitis and a corneal ulcer. Herpes zoster ophthalmicus with ophthalmoplegia was diagnosed. We began treatment with acyclovir (15 mg/kg) and prednisolone (1 mg/kg, decreased gradually). Ophthalmalgia and the eruption improved immediately. The eye movement disorder improved gradually over several months. It is rare that diplopia appears prior to cingulate eruption of herpes zoster ophthalmicus. We speculated that onset of the eruption was inhibited by strong steroid therapy and untreated diabetes mellitus.
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Affiliation(s)
- Tomohiro Ota
- Department of Neurological Science, Chiba Hokusoh Hospital, Nippon Medical School
| | - Mineo Yamazaki
- Department of Neurological Science, Chiba Hokusoh Hospital, Nippon Medical School
| | - Yusuke Toda
- Department of Neurological Science, Chiba Hokusoh Hospital, Nippon Medical School
| | - Akiko Ozawa
- Department of Neurological Science, Chiba Hokusoh Hospital, Nippon Medical School
| | - Kazumi Kimura
- Department of Neurological Science, Nippon Medical School Hospital
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28
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Collongues N, Kremer S, de Sèze J. Mielopatie acute. Neurologia 2017. [DOI: 10.1016/s1634-7072(17)83854-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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29
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Varicella zoster virus vasculopathy: The expanding clinical spectrum and pathogenesis. J Neuroimmunol 2017; 308:112-117. [PMID: 28335992 DOI: 10.1016/j.jneuroim.2017.03.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/16/2017] [Accepted: 03/16/2017] [Indexed: 02/01/2023]
Abstract
Varicella zoster virus (VZV) is a ubiquitous, human alphaherpesvirus that produces varicella on primary infection then becomes latent in ganglionic neurons along the entire neuraxis. In elderly and immunocompromised individuals, VZV reactivates and travels along nerve fibers peripherally resulting in zoster. However, VZV can also spread centrally and infect cerebral and extracranial arteries (VZV vasculopathy) to produce transient ischemic attacks, stroke, aneurysm, sinus thrombosis and giant cell arteritis, as well as granulomatous aortitis. The mechanisms of virus-induced pathological vascular remodeling are not fully elucidated; however, recent studies suggest that inflammation and dysregulation of programmed death ligand-1 play a significant role.
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30
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Hemorrhagic Longitudinally Extensive Transverse Myelitis. Case Rep Neurol Med 2016; 2016:1596864. [PMID: 27847660 PMCID: PMC5099478 DOI: 10.1155/2016/1596864] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 10/03/2016] [Accepted: 10/05/2016] [Indexed: 01/08/2023] Open
Abstract
Longitudinally extensive transverse myelitis (LETM) may be associated with viral triggers, including both infections and vaccinations. We present a case of a healthy immunocompetent 33-year-old woman who developed a hemorrhagic LETM 2 weeks after seasonal influenza vaccination. Hemorrhagic LETM has not to our knowledge been reported after influenza vaccination. It may represent a forme fruste variant of acute hemorrhagic leukoencephalitis.
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31
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McNamara JF, Paterson DL, Allworth A, Presneill J, O'Connell P, Henderson RD. Re-activation of varicella zoster virus associated with anterior spinal cord stroke in pregnancy. Infect Dis (Lond) 2016; 48:705-7. [PMID: 27207607 DOI: 10.1080/23744235.2016.1185535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Affiliation(s)
- John F McNamara
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia.,c Centre for Clinical Research, The University of Queensland, Brisbane , Australia
| | - David L Paterson
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia.,c Centre for Clinical Research, The University of Queensland, Brisbane , Australia
| | - Anthony Allworth
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia
| | - Jeffrey Presneill
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia
| | - Paul O'Connell
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia
| | - Robert D Henderson
- a Royal Brisbane and Women's Hospital, Infectious Diseases , Butterfield Street , Herston , Brisbane , 4006 Australia ;,b Faculty of Medicine and Biomedical Sciences, The University of Queensland , St Lucia , Australia
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Varicella-zoster virus infections of the central nervous system – Prognosis, diagnostics and treatment. J Infect 2015; 71:281-93. [DOI: 10.1016/j.jinf.2015.06.004] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 06/03/2015] [Accepted: 06/06/2015] [Indexed: 11/23/2022]
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Berth S, Carbunar O, Yang NS, Fredericks B, Lipton HL, Valyi-Nagy T. Varicella-zoster virus encephalomyelitis with a prominent demyelinating component. Neuropathology 2015; 35:587-91. [PMID: 26114555 DOI: 10.1111/neup.12224] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 05/02/2015] [Indexed: 11/28/2022]
Abstract
The histopathologic presentation of varicella-zoster virus (VZV) infection of the central nervous system is varied and is not well understood. Here we report a case of VZV encephalomyelitis with prominent demyelinating pathology in a patient with a history of follicular lymphoma treated with allogeneic stem cell transplantation. The patient presented with waxing and waning bilateral limb weakness and mental status changes. MRI showed leptomeningeal, peripheral spinal cord and periventricular cerebral white matter lesions in the brain, and polymerase chain reaction on cerebrospinal fluid detected VZV DNA. The patient expired from developing atrial fibrillation that rapidly progressed to ventricular fibrillation 10 days after admission to our hospital. Autopsy revealed macrophage-rich areas of demyelination in the spinal cord and cerebrum with relative preservation of axons associated with inclusion bodies and positive immunostaining for VZV. This case represents a rare example of VZV encephalomyelitis presenting with a predominantly demyelinating, "multiple sclerosis-like" pathology. The clinical and histopathologic findings and relevant literature are presented and discussed.
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Affiliation(s)
| | | | | | | | - Howard L Lipton
- Neurology.,Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA
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Cobo-Calvo Á, Alentorn A, Mañé Martínez MA, Bau L, Matas E, Bruna J, Romero-Pinel L, Martínez-Yélamos S. Etiologic spectrum and prognosis of longitudinally extensive transverse myelopathies. Eur Neurol 2014; 72:86-94. [PMID: 24942967 DOI: 10.1159/000358512] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Accepted: 01/08/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND Patients with a first episode of longitudinal extensive transverse myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical spectrum of LETM and to analyze the related clinical and laboratory variables that can be used as functional prognostic markers. METHODS A retrospective review was conducted of clinical, radiologic and biochemical data of patients admitted for LETM between 1993 and 2011. RESULTS Our cohort included 72 patients [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34 months (IQR 17.2-63). The modified Rankin Scale (mRS) score was ≥2 at the end of follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients, multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9, spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related LETM in 2 patients each. Unfavorable outcome was associated with mRS ≥2 at admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and older age (OR 1.06, 95% CI 1.01-1.11). CONCLUSION Idiopathic LETM was the most frequent diagnosis at the end of follow-up. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery.
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Affiliation(s)
- Álvaro Cobo-Calvo
- Multiple Sclerosis Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain
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Abstract
Primary infection of humans with varicella zoster virus (VZV) causes varicella (chickenpox), after which the virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates from one or more ganglia and typically causes herpes zoster (shingles). Zoster may also be complicated by VZV vasculopathy due to productive virus infection of the cerebral arteries. In recent decades, the clinical spectrum of VZV vasculopathy has expanded to include not only transient ischemic attacks and ischemic and hemorrhagic stroke, but also multifocal VZV vasculopathy, with temporal artery infection mimicking giant cell arteritis, extracranial vasculopathy, aneurysm with and without subarachnoid hemorrhage, arterial dissection and dolichoectasia, ischemic cranial neuropathies, cerebral venous sinus thrombosis, spinal cord infarction and peripheral thrombotic disease.
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Affiliation(s)
- Maria A. Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045
| | - Don Gilden
- Department of Neurology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, Tel: 303-724-7326, Fax: 303-724-4329
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Yamaguchi M, Chiba A, Yanagawa T, Mato T, Hirai K, Inoue T, Oya Y, Kusunoki S, Ito K, Yamamoto K. Guillain-Barré syndrome following herpes zoster in a patient with systemic sclerosis. Mod Rheumatol 2014; 11:251-4. [PMID: 24383736 DOI: 10.3109/s101650170014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Abstract We report the case of a patient with systemic sclerosis (SSc) who developed Guillain-Barré syndrome (GBS) 6 weeks after herpes zoster. Muscle weakness developed first, and thereafter severely in the muscles in the same segment as the zoster. Serum anti-GM1 and -GD1b IgM autoantibodies were detected in the acute phase. The clinical course and the findings of nerve conduction studies and a sural nerve biopsy were compatible with GBS accompanied by underlying chronic polyneuropathy. SSc might have affected the neurological manifestation via the development of underlying neuropathy and a possible contribution to the autoimmune basis in GBS.
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Affiliation(s)
- M Yamaguchi
- Department of Medicine and Physical Therapy, University of Tokyo School of Medicine , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 , Japan
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Cho TA, Mckendall RR. Clinical approach to the syndromes of viral encephalitis, myelitis, and meningitis. HANDBOOK OF CLINICAL NEUROLOGY 2014; 123:89-121. [PMID: 25015482 DOI: 10.1016/b978-0-444-53488-0.00004-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Tracey A Cho
- Department of Neurology, Harvard Medical School and Neuro-ID Program, Massachusetts General Hospital, Boston, MA, USA
| | - Robert R Mckendall
- Departments of Neurology and Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA.
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Abstract
A large number of causal agents produce spinal cord lesions in the tropics. Most etiologies found in temperate regions also occur in the tropics including trauma, herniated discs, tumors, epidural abscess, and congenital malformations. However, infectious and nutritional disorders occur with higher prevalence in tropical regions. Among the most common infectious etiologies are tuberculous Pott's disease, brucellosis, and neuroborreliosis. Parasitic diseases such as schistosomiasis, neurocysticercosis, and eosinophilic meningitis are frequent causes of nontraumatic paraplegia. The retrovirus HTLV-1 is a cause of tropical spastic paraparesis. Nutritional causes of paraparesis include deficiencies of vitamin B12 and folate; endemic clusters of konzo and tropical ataxic myeloneuropathy are associated in Africa with malnutrition and excessive consumption of cyanide-containing bitter cassava. Other toxic etiologies of tropical paraplegia include lathyrism and fluorosis. Nutritional forms of myelopathy are associated often with optic and sensory neuropathy, hence the name tropical myeloneuropathies. Acute transverse myelopathy is seen in association with vaccination, infections, and fibrocartilaginous embolism of the nucleus pulposus. Multiple sclerosis and optic myelopathy occur in the tropics but with lesser prevalence than in temperate regions. The advent of modern imaging in the tropics, including computed tomography and magnetic resonance imaging, has allowed better diagnosis and treatment of these conditions that are a frequent cause of death and disability.
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Affiliation(s)
- Don Gilden
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
| | - Maria A Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Randall J Cohrs
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
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Booss J, Tselis AC. A history of viral infections of the central nervous system: foundations, milestones, and patterns. HANDBOOK OF CLINICAL NEUROLOGY 2014; 123:3-44. [PMID: 25015479 DOI: 10.1016/b978-0-444-53488-0.00001-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- John Booss
- Departments of Neurology and Laboratory Medicine, Yale University School of Medicine, New Haven, CT and Department of Veterans Affairs Medical Center, VA Connecticut, West Haven, CT, USA
| | - Alex C Tselis
- Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, USA.
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Abstract
STUDY DESIGN Case report. OBJECTIVE To report this rare varicella-zoster virus (VZV) complication in a patient with multiple sclerosis. SUMMARY OF BACKGROUND DATA Longitudinally extensive transverse myelitis is a spinal cord lesion that extends over 3 or more vertebral segments. A common feature in neuromyelitis optica, longitudinally extensive transverse myelitis can also occur in several other diseases. METHODS A 15-year-old boy with relapsing-remitting multiple sclerosis, who has been treated with immunomodulators for 6 months, developed a subacute left brachiocrural hemiparesis with ipsilateral decreased sensation in the trunk and limbs. This was interpreted as a new relapse and was treated consequently. During the evolution, the patient developed a cutaneous rash in the left C8 metameres, followed by asymmetric tetraparesis. RESULTS Magnetic resonance imaging demonstrated an extensive cervical-thoracic myelopathy. Cerebrospinal fluid analysis revealed 17 leukocytes per microliter (95% mononuclear), protein 41 mg/dL, and negative VZV-DNA by polymerase chain reaction, but elevated anti-VZV immunoglobulin G cerebrospinal fluid/serum index, with a normal albumin cerebrospinal fluid/serum index, all of which were consistent with intrathecal synthesis of anti-VZV antibody. We were able to rule out all other causes included in the differential diagnosis, namely, vascular disease, tumor, and autoimmune conditions, especially those associated with neuromyelitis optica spectrum disorders. CONCLUSION Awareness of the potentially varied presentation of VZV myelitis can enable earlier recognition and specific treatment.
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Takahashi T, Tamura M, Takasu T. Diagnostic value of a "wide-range" quantitative nested real-time PCR assay for varicella zoster virus myelitis. J Med Virol 2013; 85:2042-55. [PMID: 23934732 DOI: 10.1002/jmv.23690] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2013] [Indexed: 12/29/2022]
Abstract
Myelitis is one of the rarest neurological complications of varicella zoster virus (VZV) infection. In this study, the authors remodeled the "wide-range" quantitative nested real-time (QNRT) polymerase chain reaction (PCR) assay to quantitatively detect a small amount of VZV-DNA in cerebrospinal fluid (CSF). For use as a specific internal control "calibrator," an original mutation-VZV (MZ) plasmid was developed. The initial copy number of VZV-DNA in CSF specimens was measured by the amplification rate of the MZ-plasmid. For 17 consecutive CSF specimens collected from three elderly patients with VZV myelitis, the diagnostic value of the wide-range QNRT-PCR assay was evaluated and compared with other conventional PCR assays and enzyme immunoassay (EIA). The MZ-plasmid demonstrated statistically uniform amplifications (F=1.016) against a wide range (1-100,000) of copy numbers of mimic VZV-DNA. The wide-range QNRT-PCR assay quantitatively and rapidly (within 48 hr) detected 5,863, 3,052, 958, and 6,721 copies/ml of VZV-DNA in the CSF specimens collected from all patients in the acute phase. Additionally, there was a significant difference (*P=0.023) in the copy number of VZV-DNA between before and after acyclovir treatment. Other conventional single PCR assays all revealed negative results, but were nevertheless time-consuming (7 days). The IgG EIA-value for VZV was continually elevated throughout the clinical course of all patients. The MZ-plasmid was thus regarded as an appropriate "calibrator" in the wide-range QNRT-PCR assay. This assay is a novel, rapid, accurate, quantitative, and highly sensitive technique, and will contribute as a reliable and useful clinical examination for the rapid diagnosis of VZV infection to central nervous system.
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Nagel MA. Varicella zoster virus vasculopathy: clinical features and pathogenesis. J Neurovirol 2013; 20:157-63. [PMID: 23918503 DOI: 10.1007/s13365-013-0183-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Revised: 06/04/2013] [Accepted: 06/21/2013] [Indexed: 11/30/2022]
Abstract
Varicella zoster virus (VZV) vasculopathy is caused by productive virus infection of cerebral arteries, leading to inflammation, pathological vascular remodeling, and ischemic or hemorrhagic stroke. VZV vasculopathy occurs in immunocompetent and immunocompromised individuals and involves both large and small vessels. MRI abnormalities include more deep-seated than superficial lesions, particularly at gray-white matter junctions, and lesions may enhance. Diagnosis is challenging, since stroke can occur months after zoster rash and in the absence of rash or CSF pleocytosis. The best virological test for diagnosis is detection of anti-VZV IgG antibody in the CSF. Pathological studies of VZV-infected arteries from patients with VZV vasculopathy reveal that the arterial adventitia is the initial site of infection, after which virus spreads transmuraly towards the lumen. Histological and immunohistochemical studies of VZV-infected arteries show a thickened intima, disrupted internal elastic lamina, and loss of smooth muscle cells, that likely contribute to weakening of the vessel wall and occlusion. Early in disease, VZV-infected arteries contain CD4+ and CD8+ T cells, macrophages, and rare B cells, in addition to abundant neutrophils in early disease. Importantly, perivascular inflammatory cells underlie the areas of thickened intima, raising the possibility that soluble factors secreted by these cells contribute to arterial remodeling. This review discusses the clinical features of VZV vasculopathy and potential mechanisms of VZV-induced cerebrovascular remodeling and stroke.
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Affiliation(s)
- Maria A Nagel
- Department of Neurology, University of Colorado School of Medicine, 12700 E. 19th Avenue, Mail Stop B182, Aurora, CO, 80045, USA,
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Abstract
OPINION STATEMENT Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of cerebrospinal fluid (CSF), serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IgM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants, gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir.
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Affiliation(s)
- Maria A. Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Don Gilden
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
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Fleming J, Fogo A, Haider S, Diaz-Cano S, Hay R, Bashir S. Varicella zoster virus brachioplexitis associated with granulomatous vasculopathy. Clin Exp Dermatol 2013; 38:378-81; quiz 382. [DOI: 10.1111/ced.12096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2012] [Indexed: 11/29/2022]
Affiliation(s)
- J. Fleming
- Department of Dermatology; King's College Hospital; London; UK
| | - A. Fogo
- Department of Dermatology; King's College Hospital; London; UK
| | - S. Haider
- Department of Haematology; King's College Hospital; London; UK
| | - S. Diaz-Cano
- Department of Dermatology; King's College Hospital; London; UK
| | - R. Hay
- Department of Dermatology; King's College Hospital; London; UK
| | - S. Bashir
- Department of Dermatology; King's College Hospital; London; UK
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Falcone EL, Adegbulugbe AA, Sheikh V, Imamichi H, Dewar RL, Hammoud DA, Sereti I, Lane HC. Cerebrospinal fluid HIV-1 compartmentalization in a patient with AIDS and acute varicella-zoster virus meningomyeloradiculitis. Clin Infect Dis 2013; 57:e135-42. [PMID: 23728149 DOI: 10.1093/cid/cit356] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We report a case of AIDS presenting as varicella-zoster virus (VZV) meningomyeloradiculitis associated with human immunodeficiency virus (HIV) quasispecies compartmentalization within the cerebrospinal fluid (CSF), and a CSF viral load that was 1 log higher than in peripheral blood. Prolonged antiviral therapy for both VZV and HIV type 1 was associated with partial resolution.
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Affiliation(s)
- E Liana Falcone
- Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1684, USA.
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Grahn A, Hagberg L, Nilsson S, Blennow K, Zetterberg H, Studahl M. Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections. J Neurol 2013; 260:1813-21. [PMID: 23471614 DOI: 10.1007/s00415-013-6883-5] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Revised: 02/21/2013] [Accepted: 02/23/2013] [Indexed: 11/28/2022]
Abstract
Varicella-zoster virus (VZV) is one of our most common viruses causing central nervous system (CNS) infection with sometimes severe neurological complications. Glial fibrillary acidic protein (GFAp), light subunit of neurofilament protein (NFL) and S-100β protein are cerebrospinal fluid (CSF) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases. So far, these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections. In this prospective study, we measured CSF GFAp, NFL and S-100β as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group (n = 14). Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls (p = 0.002 and p = 0.03) while levels of S-100β were reduced. In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes. No correlations between the levels of biomarkers and viral load, neurological sequels or clinical outcome were found in this limited number of patients. These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus.
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Affiliation(s)
- Anna Grahn
- Department of Infectious Diseases, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Östra, SE-416 85 Göteborg, Sweden.
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Nagel MA, Traktinskiy I, Stenmark KR, Frid MG, Choe A, Gilden D. Varicella-zoster virus vasculopathy: immune characteristics of virus-infected arteries. Neurology 2012; 80:62-8. [PMID: 23243076 DOI: 10.1212/wnl.0b013e31827b1ab9] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVE Pathologic changes in varicella-zoster virus (VZV)-infected arteries include inflammation, thickened intima, and paucity of smooth muscle cells. Since no criteria have been established for early vs late VZV vasculopathy, we examined inflammatory cells and their distribution in 6 normal arteries, and 2 VZV-infected arteries 3 days after onset of disease (early) and 10 months after protracted neurologic disease (late). METHODS VZV-infected temporal artery obtained 3 days after onset of ischemic optic neuropathy from an 80-year-old man, VZV-infected middle cerebral artery (MCA) obtained 10 months after protracted disease from a 73-year-old man, and 5 MCAs and 1 temporal artery from normal subjects, age 22-60 years, were examined histologically and immunohistochemically using antibodies against VZV and inflammatory cell subsets. RESULTS In both early and late VZV vasculopathy, T cells, activated macrophages, and rare B cells were found in adventitia and intima. In adventitia of early VZV vasculopathy, neutrophils and VZV antigen were abundant and a thickened intima was associated with inflammatory cells in vaso vasorum vessels. In media of late VZV vasculopathy, viral antigen, but not leukocytes, was found. VZV was not seen in inflammatory cells. Inflammatory cells were absent in control arteries. CONCLUSIONS Both VZV and neutrophils exclusively in adventitia in early VZV vasculopathy indicate that disease begins there. Late VZV vasculopathy is distinguished by viral antigen without inflammation in media, revealing a human virus in an immunoprivileged arterial media. Association of thickened intima and inflammation in vaso vasorum vessels in early VZV vasculopathy support the role of virus-induced inflammation in vessel wall remodeling.
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Affiliation(s)
- Maria A Nagel
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
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