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Richard J Whitley - One of the best experts on this subject based on the ideXlab platform.
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Herpes Simplex virus
Handbook of Clinical Neurology, 2014Co-Authors: Rebecca W Widener, Richard J WhitleyAbstract:Abstract Herpes Simplex virus (HSV) infections of the central nervous system (CNS) have varied presentations. Some, such as encephalitis, can have devastating outcomes. In only a few short decades a vast amount of knowledge has been uncovered about the pathogenicity of this virus, its diagnosis, and treatment. Non-invasive diagnostics with polymerase chain reaction have replaced brain biopsy as the mainstay of diagnosis and antiviral therapy with acyclovir has largely improved mortality. However, despite these scientific advancements, morbidity remains high. The clinician must maintain a high index of suspicion with neonates, children, and adults, as HSV can often mimic other CNS diseases and prompt initiation of treatment is integral.
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adenine arabinoside therapy of biopsy proved Herpes Simplex encephalitis
Journal of the Medical Association of the State of Alabama, 2010Co-Authors: Richard J Whitley, Lawrence T Chien, Raphael Dolin, George J. Galasso, Seng Jaw Soong, Charles A. AlfordAbstract:Abstract We evaluated adenine arabinoside (vidarabine) for treatment of Herpes Simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 Herpes Simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic Herpes Simplex. (N Engl J Med 297:289–294, 1977)
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Herpes Simplex encephalitis adolescents and adults
Antiviral Research, 2006Co-Authors: Richard J WhitleyAbstract:Herpes Simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system despite available antiviral therapy. Children and adolescents account for approximately one third of all cases of HSE. Clinical diagnosis is suggested in the encephalopathic, febrile patient with focal neurologic signs. However, these clinical findings are not pathognomonic because numerous other diseases in the central nervous system can mimic HSE. Neurodiagnostic evaluation can provide support for the diagnosis by the demonstration of temporal lobe edema/hemorrhage by magnetic resonance image scan and spike and slow-wave activity on electroencephalogram. In the current era, the diagnostic gold standard is the detection of Herpes Simplex virus (HSV) DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Although PCR is an excellent test and preferable to brain biopsy, false negatives can occur early after disease onset. Acyclovir is the treatment of choice and is administered at 10 mg/kg every 8 h for 21 days. Even with early administration of therapy after the disease onset, nearly two thirds of survivors have significant residual neurologic deficits. Current investigative efforts are assessing the prognostic value of quantitative PCR detection of viral DNA at the onset of therapy as well as at the completion of therapy and the contribution of prolonged antiviral therapy to improved neurologic outcome.
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Herpes Simplex encephalitis children and adolescents
Seminars in Pediatric Infectious Diseases, 2005Co-Authors: Richard J Whitley, David W. KimberlinAbstract:Herpes Simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system despite available antiviral therapy. Children and adolescents account for approximately one third of all cases of HSE. Clinical diagnosis is suggested in the encephalopathic, febrile patient with focal neurologic signs. However, these clinical findings are not pathognomonic because numerous other infections in the central nervous system can mimic HSE. Support for the diagnosis from a neurodiagnostic perspective is aided by the demonstration of disease of the temporal lobe by magnetic resonance image scan and spike and slow-wave activity on electroencephalogram. In the current era, the gold standard for establishing diagnosis is the detection of Herpes Simplex virus DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Although PCR is an excellent test and far more desirable than brain biopsy, false negatives can occur early after disease onset. Current therapeutic management calls for the administration of acyclovir at 10 mg/kg every 8 hours for 21 days. Even with early administration of therapy after the onset of disease, nearly two thirds of survivors will have significant residual neurologic deficits. Recent investigative efforts are assessing the value of PCR detection of viral DNA at the completion of therapy and the value of prolonged antiviral therapy.
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neonatal Herpes Simplex virus infection
Current Opinion in Infectious Diseases, 2004Co-Authors: Richard J WhitleyAbstract:Purpose of reviewIn spite of the availability of antiviral therapy for the treatment of neonatal Herpes Simplex virus infections, the outcome remains poor, particularly for babies with disseminated multi-organ infection or central nervous system disease. This review considers recent advances that im
David W. Kimberlin - One of the best experts on this subject based on the ideXlab platform.
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neonatal Herpes Simplex virus infections
Seminars in Perinatology, 2018Co-Authors: Swetha G. Pinninti, David W. KimberlinAbstract:Neonatal Herpes Simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.
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neonatal Herpes Simplex virus infection
Infectious Disease Clinics of North America, 2015Co-Authors: Scott H James, David W. KimberlinAbstract:Herpes Simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement.
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Neonatal Herpes Simplex virus infections.
Pediatric clinics of North America, 2013Co-Authors: Swetha G. Pinninti, David W. KimberlinAbstract:Neonatal Herpes Simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal Herpes Simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal Herpes disease.
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Herpes Simplex encephalitis children and adolescents
Seminars in Pediatric Infectious Diseases, 2005Co-Authors: Richard J Whitley, David W. KimberlinAbstract:Herpes Simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system despite available antiviral therapy. Children and adolescents account for approximately one third of all cases of HSE. Clinical diagnosis is suggested in the encephalopathic, febrile patient with focal neurologic signs. However, these clinical findings are not pathognomonic because numerous other infections in the central nervous system can mimic HSE. Support for the diagnosis from a neurodiagnostic perspective is aided by the demonstration of disease of the temporal lobe by magnetic resonance image scan and spike and slow-wave activity on electroencephalogram. In the current era, the gold standard for establishing diagnosis is the detection of Herpes Simplex virus DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Although PCR is an excellent test and far more desirable than brain biopsy, false negatives can occur early after disease onset. Current therapeutic management calls for the administration of acyclovir at 10 mg/kg every 8 hours for 21 days. Even with early administration of therapy after the onset of disease, nearly two thirds of survivors will have significant residual neurologic deficits. Recent investigative efforts are assessing the value of PCR detection of viral DNA at the completion of therapy and the value of prolonged antiviral therapy.
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Herpes Simplex viruses
Clinical Infectious Diseases, 1998Co-Authors: Richard J Whitley, David W. Kimberlin, Bernard RoizmanAbstract:Herpes Simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, Herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with Herpes Simplex encephalitis. The use of HSV for gene therapy heralds a new era of Herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.
Richard P Morse - One of the best experts on this subject based on the ideXlab platform.
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choreoathetosis after Herpes Simplex encephalitis with basal ganglia involvement on mri
Pediatrics, 2008Co-Authors: Megan Wills Kullnat, Richard P MorseAbstract:Children with Herpes Simplex virus encephalitis have a relapse in ∼25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for Herpes Simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after Herpes Simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-Herpes Simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and Herpes Simplex virus encephalitis. Current understanding of the pathophysiology of post-Herpes Simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.
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choreoathetosis after Herpes Simplex encephalitis with basal ganglia involvement on mri
Pediatrics, 2008Co-Authors: Megan Wills Kullnat, Richard P MorseAbstract:: Children with Herpes Simplex virus encephalitis have a relapse in approximately 25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for Herpes Simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after Herpes Simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-Herpes Simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and Herpes Simplex virus encephalitis. Current understanding of the pathophysiology of post-Herpes Simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.
Birgit Sköldenberg - One of the best experts on this subject based on the ideXlab platform.
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Herpes Simplex encephalitis in sweden 1990 2001 incidence morbidity and mortality
Clinical Infectious Diseases, 2007Co-Authors: Anders Hjalmarsson, Paul Blomqvist, Birgit SköldenbergAbstract:Background. Herpes Simplex encephalitis (HSE) is a devastating disease. Methods. In Sweden, a nationwide retrospective study of the incidence, morbidity, and mortality associated with HSE during the 12-year period 1990-2001 was conducted. The national inpatient register data were used, and diagnostic data from the virus laboratories were validated. Results. In the study period, 638 patients hospitalized in Sweden received a primary diagnosis of HSE. Of these, 236 patients had a confirmed infection of the central nervous system due to Herpes Simplex virus type 1. This corresponds to an incidence of confirmed HSE due to Herpes Simplex virus type 1 of 2.2 cases per million population per year. Of the survivors, 87% were readmitted to the hospital. The most frequent diagnosis at readmission was epilepsy, which was found in 49 patients (21% of the 236 total patients; 24% of 203 survivors), with a median onset 9.3 months after the diagnosis of HSE. This corresponds to a 60- to 90-fold increase in risk, compared with that for the general population. Neuropsychiatric sequelae were evident in 45 (22%) of 203 surviving patients. The incidence of venous thromboembolism, including pulmonary embolism, was 5-14 times higher than that in the general population. Among patients with HSE due to Herpes Simplex virus type 1, the 1-year mortality was 14% (33 of 236 patients died), which was 8 times higher than expected. Conclusions. This is, to our knowledge, the first study to report long-term, nationwide follow-up data for patients with virologically confirmed HSE. There is considerable morbidity after HSE, with epilepsy being the most common diagnosis. This demonstrates the need for expanding our knowledge of the pathogenesis of HSE to direct more effective antiviral and antiinflammatory treatments.
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rapid diagnosis of Herpes Simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid
The Lancet, 1991Co-Authors: E Aurelius, A Staland, Marianne Forsgren, B. Johansson, Birgit SköldenbergAbstract:Abstract With the aim of improving early diagnosis of Herpes Simplex encephalitis a polymerase chain reaction (PCR) assay with two "nested" primer pairs was developed for the amplification of Herpes Simplex virus DNA in cerebrospinal fluid (CSF). Southern blotting was used to confirm the specificity of the amplification. The assay was applied to 151 CSF samples from 43 consecutive patients with Herpes Simplex encephalitis verified by the finding of Herpes Simplex virus/viral antigen in a brain biopsy sample or at necropsy (13) and/or intrathecal production of IgG antibody to the virus (40). As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be Herpes Simplex encephalitis but excluded by the absence of intrathecal antibody synthesis) were tested. PCR detected Herpes Simplex virus DNA in 42 of the 43 patients with proven Herpes Simplex encephalitis; all but 1 were positive in the first CSF sample taken. The 1 PCR-negative patient had been treated with acyclovir from 20 h after the onset of symptoms. All the control subjects were PCR negative, as were 270 internal contamination controls. The PCR result remained positive in samples drawn up to 27 days after the onset of neurological symptoms. This method is a rapid and non-invasive means to diagnose Herpes Simplex encephalitis; it is highly sensitive and specific.
Megan Wills Kullnat - One of the best experts on this subject based on the ideXlab platform.
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choreoathetosis after Herpes Simplex encephalitis with basal ganglia involvement on mri
Pediatrics, 2008Co-Authors: Megan Wills Kullnat, Richard P MorseAbstract:Children with Herpes Simplex virus encephalitis have a relapse in ∼25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for Herpes Simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after Herpes Simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-Herpes Simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and Herpes Simplex virus encephalitis. Current understanding of the pathophysiology of post-Herpes Simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.
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choreoathetosis after Herpes Simplex encephalitis with basal ganglia involvement on mri
Pediatrics, 2008Co-Authors: Megan Wills Kullnat, Richard P MorseAbstract:: Children with Herpes Simplex virus encephalitis have a relapse in approximately 25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for Herpes Simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after Herpes Simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-Herpes Simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and Herpes Simplex virus encephalitis. Current understanding of the pathophysiology of post-Herpes Simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.