acyclovir and Leukocytosis

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Encephalitis, Varicella Zoster; Fatal Outcome; Herpesvirus 3, Human; HIV Seropositivity; Humans; Leukocytosis; Male; Middle Aged; Polymerase Chain Reaction; Risk Factors; Unsafe Sex; Young Adult

We describe an immunocompetent 45-year-old woman who had four episodes of neurological disease (meningoencephalitis, multifocal vasculopathy, myelitis and inflammatory brain stem disease) produced by varicella zoster virus (VZV) over an 11-month period, all in the absence of rash. The cerebrospinal fluid (CSF) contained anti-VZV IgG antibody, but not VZV DNA throughout her illness, reaffirming the superiority of detection of anti-VZV IgG in CSF compared to VZV DNA in diagnosing VZV infection of the nervous system. Moreover, 3 of 7 CSF samples examined during the 11 months showed a VZV-induced pleocytosis consisting predominantly of polymorphonuclear cells (PMNs), and 4 of 7 samples also contained increased numbers of red blood cells (RBCs). Because increased PMNs and RBCs in CSF can also occur in patients with central and peripheral nervous system disease produced by cytomegalovirus (CMV), the differential diagnosis of chronic nervous system infection with increased PMNs and RBCs in CSF should include analyses for both VZV and CMV.

Topics: Acyclovir; Antiviral Agents; Cell Count; Central Nervous System Infections; Erythrocytes; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Middle Aged; Neutrophils; Recurrence; Treatment Outcome

To identify the prevalence of herpes simplex encephalitis (HSE), factors influencing the duration of empirical acyclovir and frequency of acute kidney injury (AKI) in children with acute encephalitis syndrome (AES).. Prospective observational study.. Pediatric Emergency Department and PICU of a tertiary hospital in Northern India.. All consecutive, eligible children between 1 month and 12 years old presenting with AES, defined as altered consciousness for greater than 24 hours (including lethargy, irritability, or a change in personality) and two or more of the following signs: 1) fever (temperature ≥ 38°C) during the current illness, 2) seizures or focal neurological signs, 3) cerebrospinal fluid (CSF) pleocytosis, 4) electroencephalogram, and/or 5) neuroimaging suggesting encephalitis, who received at least one dose of acyclovir.. None.. Of the 101 children screened, 83 were enrolled. The median (interquartile range [IQR]) age was 3 years (1-6 yr). Thirty-one children (37.3%) were diagnosed with AES, of which four were labeled as probable HSE (three based on MRI brain, one based on serology). Scrub typhus, dengue, Japanese encephalitis, and mumps were the other infective causes. The median (IQR) duration of acyclovir therapy was 72 hours (24-264 hr); 21 children (25.3%) received acyclovir for less than 24 hours and 11 (13.3%) for greater than or equal to 14 days. New-onset AKI was seen in 18 children (21.7%) but was mostly transient. Death ( n = 8, 9.6%) and discontinuation of care due to futility or other reasons ( n = 15, 18%) were noted in 23 children (28%). Factors associated with duration of acyclovir greater than 7 days, on univariable analysis, were lower modified Glasgow Coma Score at admission, requirement of invasive ventilation, invasive intracranial pressure monitoring, and CSF pleocytosis (5-500 cells). On multivariable analysis, only CSF pleocytosis of 5-500 cells was associated with duration of acyclovir greater than 7 days.. Given the low prevalence of HSE, and the risk of AKI, this study sensitizes the need to review our practice on initiation and stopping of empirical acyclovir in children with acute encephalitis.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Humans; Leukocytosis; Seizures

To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon.. Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR.. Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae.. VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cerebrospinal Fluid; Comorbidity; Electroencephalography; Encephalitis, Viral; Female; Herpesvirus 3, Human; Humans; Lebanon; Leukocytosis; Magnetic Resonance Imaging; Male; Meningitis, Viral; Middle Aged; Neuroimaging; Retrospective Studies; Tertiary Care Centers; Tomography, X-Ray Computed; Treatment Outcome; Valacyclovir; Varicella Zoster Virus Infection; Young Adult

A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/μl, and this later increased to 17/μl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.

Topics: Acyclovir; Aged; Antiviral Agents; Biomarkers; Brain; Clonazepam; DNA, Viral; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Female; Humans; Leukocytosis; Levetiracetam; Magnetic Resonance Imaging; Methylprednisolone; Neuroimaging; Piracetam; Simplexvirus; Stroke

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Topics: Acyclovir; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Substitution; Encephalitis, Herpes Simplex; Female; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Middle Aged; Temporal Lobe

Topics: Acyclovir; Antineoplastic Agents, Alkylating; Antiviral Agents; Brain Stem Neoplasms; Cognitive Dysfunction; Cranial Irradiation; Dacarbazine; Delirium; Dexamethasone; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Glioma; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Seizures; Temozolomide; Young Adult

A 74-year-old man presented with acute right-sided hemiparesis and epilepsia partialis continua in association with fever and confusion. Initial workup revealed possible cerebritis in the left medial frontal lobe without involvement of the temporal lobes. Cerebrospinal fluid (CSF) analysis revealed minimal lymphocytic pleocytosis but negative real-time herpes simplex virus (HSV) PCR. Acyclovir was discontinued on day 5 due to a negative infectious workup and clinical improvement. On day 9 his condition deteriorated and he was transferred to a higher level of acuity for advanced supportive care. Worsening encephalopathy and refractory status epilepticus ensued despite medical care. Repeat CSF analysis showed mild lymphocytic pleocytosis with negative real-time HSV PCR. Brain MRI revealed progression of cortical enhancement. Immunosuppressive therapy and plasma exchange were attempted without clinical response. On day 24, another lumbar puncture showed only mild lymphocytic pleocytosis. Brain MRI showed involvement of the right medial temporal lobe. Subsequently, acyclovir was resumed. The HSV-1 PCR result was positive on day 30. Unfortunately, the patient expired.

Topics: Acyclovir; Aged; Antiviral Agents; Brain; Confusion; DNA, Viral; Encephalitis; Encephalitis, Herpes Simplex; Epilepsia Partialis Continua; False Negative Reactions; Fatal Outcome; Fever; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Male; Real-Time Polymerase Chain Reaction

To analyze the electroclinical features, neuroimaging findings, treatment, and outcome of 12 patients with febrile infection-related epilepsy syndrome (FIRES).. This is a retrospective study of 12 children with FIRES with a mean time of follow-up of 6.5 years carried out at the Garrahan Hospital of Buenos Aires between 1997 and 2012.. Eight males and four females had focal status epilepticus preceded by febrile infection with a mean age at presentation of 8.5 years. In the acute period, the treatment included antiepileptic drugs (AEDs) in all cases, immunotherapy in 10 cases, and burst-suppression coma in eight. The ketogenic diet was tried in two, plasmapheresis in one, and rituximab in one. Two patients treated with IVIG and one patient given steroids had a good response, but in this phase only three patients had a prolonged good response to IVIG and a ketogenic diet. No patients died in this period. In the chronic epilepsy phase, all children had seizures arising from neocortical regions. All patients had refractory epilepsy, and most mental retardation, and behavioral disturbances. All received different AEDs and in this phase a third patient was put on a ketogenic diet. One patient was operated without good results. Only two cases had a good outcome after 2 and 10 years of follow-up.. FIRES is a well-defined severe epileptic syndrome, probably in the group of epileptic encephalopathies, characterized by focal or multifocal seizures arising from the neocortical regions with an unknown etiology. Immunoglobulin and the ketogenic diet may be considered a potentially efficacious treatment.

Topics: Acyclovir; Adolescent; Antiviral Agents; Argentina; Child; Child, Preschool; Electroencephalography; Encephalitis, Viral; Female; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Leukocytosis; Magnetic Resonance Imaging; Male; Retrospective Studies; Seizures, Febrile; Status Epilepticus; Syndrome; Treatment Outcome; Unconsciousness

Topics: Acyclovir; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Behcet Syndrome; Brain Stem; Ceftriaxone; Dexamethasone; Humans; Leukocytosis; Magnetic Resonance Imaging; Male; Meningoencephalitis; Treatment Outcome

Infantile herpes simplex virus encephalitis (HSVE) infection remains a significant cause of morbidity and mortality. Diagnosis is often difficult in this population, where a specific pattern of clinical and laboratory signs are lacking. This often results in unnecessary treatment of infants with empiric acyclovir. This study evaluates the use of empiric acyclovir at the Kentucky Children's Hospital and attempts to correlate any laboratory or clinical findings that may be highly suggestive of HSVE.. Medical records of infants younger than 1 year admitted and treated with acyclovir were evaluated for any consistent pattern of clinical findings suggestive of HSVE. Specifically, serum and cerebrospinal fluid (CSF) white blood cell counts, red blood cell counts, cerebrospinal glucose and protein, and clinical neurological findings upon admission were evaluated.. Two hundred eighteen infants were identified and included in the study. Three infants were identified with polymerase chain reaction-positive HSVE. Only CSF leukocytosis was consistent among HSVE-positive infants. All infants with HSVE exhibited generalized neurological findings. Neither hemorrhagic CSF nor focal neurological findings were indicative of HSVE infection.. Herpes simplex virus encephalitis has a very low prevalence within this population. Clinically significant neurological findings as well as specific risk factors must be present to consider treatment with empiric acyclovir. Apnea and focal seizures are not specific risk factors for herpetic meningitis in infants. Lack of a CSF leukocytosis is a strong negative predictor for HSVE, and hemorrhagic fluid is not specific for HSVE.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Humans; Infant; Leukocytosis; Male; Retrospective Studies; Spinal Puncture

Varicella zoster vasculopathy is a rare complication of chicken pox. Varicella cerebellitis, a post or para-infectious condition, is a common sequelae of chicken pox. Varicella angiopathy presents as acute hemiparesis, aphasia, hemianaesthesia or other focal neurologic or retinal deficits associated with mononuclear pleocytosis and VZV specific antibodies in CSF. Varicella angiopathy affecting the posterior circulation is very rare. We report a 15 yr old boy with progressive neurologic deficits over a month following a chicken pox 3 months prior to the onset of symptoms. On investigation he had infarcts both in the anterior and posterior circulation territories in CT and MRI with mononuclear pleocytosis in CSF elevated IgG and IgM in CSF. He was treated with intravenous acyclovir and corticosteroids.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Brain Infarction; Chickenpox; Herpesvirus 3, Human; Humans; Immunoglobulin G; Immunoglobulin M; Leukocytosis; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed; Treatment Outcome

To assess the etiology, prognosis, and appropriate treatment of hemophagocytic lymphohistiocytosis (HLH) in neonates.. We collected information on neonates in whom HLH was diagnosed between 1997 and 2007 from participating members of the Japanese Society of Pediatric Hematology.. HLH was diagnosed in 20 patients within 4 weeks after birth. Of the diagnostic criteria for HLH-2004, the incidence of fever was quite low in preterm infants, and hypertriglyceridemia and neutropenia were uncommon. Familial HLH (n = 6) or severe combined immunodeficiency-associated HLH (n = 1) was diagnosed in 7 patients, and 2 of them have survived. Herpes simplex virus-associated HLH was diagnosed in 6 patients, and 2 of them have survived. The overall survival rate for the 20 patients was 40%.. HLH is rare in neonates and has a poor prognosis. Early diagnosis and immediate treatment are required when considering the possibility of herpes simplex virus-associated or familial HLH.

Topics: Acyclovir; Adrenal Cortex Hormones; Antineoplastic Agents, Phytogenic; Antiviral Agents; beta 2-Microglobulin; Consciousness Disorders; Cyclosporine; Erythema; Etoposide; Exanthema; Female; Fetal Distress; Fever; gamma-Globulins; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunologic Factors; Immunosuppressive Agents; Infant, Newborn; Infant, Premature; Japan; L-Lactate Dehydrogenase; Leukocytosis; Lymphohistiocytosis, Hemophagocytic; Male; Ocular Motility Disorders; Plasma Exchange; Prognosis; Respiratory Distress Syndrome, Newborn; Seizures; Severe Combined Immunodeficiency

To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days.. Cost-effectiveness analysis.. Decision model.. Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis.. Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures.. Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained.. Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained).. Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

Topics: Acyclovir; Antiviral Agents; Cost-Benefit Analysis; Decision Support Techniques; Disease Progression; Female; Fever; Herpes Simplex; Humans; Infant, Newborn; Leukocytosis; Male; Probability; Quality-Adjusted Life Years; Treatment Outcome

Herpes zoster occurs seldom in infants, especially in the absence of exposure to maternal varicella either intrauterine or postnatal. We report on a case in a 3-month-old infant admitted for herpes zoster in the sciatic nerve territory. No cutaneous eruption was found in the mother or in people who were in contact with the patient. This rare clinical situation is here reviewed, showing that the absence of antenatal or postnatal exposure to herpes viruses does not preclude the occurrence of herpes zoster infection in early infancy.

Topics: Acyclovir; Antiviral Agents; C-Reactive Protein; Female; Fever; Herpes Zoster; Humans; Infant; Leukocytosis

Topics: Acyclovir; Adult; Antiviral Agents; Female; Ganglia, Spinal; Herpes Simplex; Herpesvirus 2, Human; Humans; Hypesthesia; Leukocytosis; Myelitis; Radiculopathy; Sacrum; Syndrome; Urinary Retention

Topics: Acyclovir; Adult; Cerebrospinal Fluid; Diagnosis, Differential; Follow-Up Studies; Humans; Leukocytes, Mononuclear; Leukocytosis; Male; Meningitis, Aseptic; Recurrence; Spinal Puncture; Syndrome; Time Factors