acyclovir and Brain-Damage--Chronic

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.. Actualizacion en infecciones herpeticas congenitas y neonatales: infeccion por citomegalovirus y herpes simple.. Los neonatos son una poblacion especialmente susceptible a las infecciones viricas que frecuentemente afectan al sistema nervioso central. Las infecciones herpeticas pueden transmitirse al feto y al recien nacido, y ocasionar cuadros clinicos graves con deficits sensoriales y cognitivos a largo plazo. Dos terceras partes de los neonatos con encefalitis por virus herpes simple y la mitad de los niños con infeccion congenita sintomatica por citomegalovirus desarrollan secuelas, lo cual supone un alto coste sociosanitario a largo plazo. Afortunadamente, el mejor conocimiento de estas infecciones en los ultimos años y el desarrollo de tratamientos antivirales efectivos han mejorado el pronostico de los pacientes. El valganciclovir (32 mg/kg/dia en dos dosis durante seis meses) previene el desarrollo de hipoacusia y mejora el pronostico neurologico en la infeccion congenita sintomatica por citomegalovirus. El aciclovir (60 mg/kg/dia en tres dosis durante 2-3 semanas) previene el desarrollo de formas graves en la enfermedad herpetica cutanea-ocular-oral, y disminuye la mortalidad y las secuelas en la enfermedad diseminada y localizada en el sistema nervioso central.

Topics: Acyclovir; Antiviral Agents; Brain Damage, Chronic; Cytomegalovirus Infections; Early Diagnosis; Female; Fetal Diseases; Ganciclovir; Hearing Loss, Sensorineural; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Valganciclovir

Viral encephalitis are rare and potentially serious conditions with different etiologist, and not always identifiable. Our aim is to describe the etiological, clinical presentation and neurological outcome of viral encephalitis admitted in Paediatrics Intensive Care Units (PICUs) in Spain.. Observational prospective multicenter study. Children with viral encephalitis admitted to 14 PICUs, for a period of 3 years (2010-2013) were included. Polymerase chain reaction for the etiological diagnosis and neurotropic virus serology in blood and cerebrospinal fluid were used. Personal history, clinical presentation, evolution and neurological status at discharge were recorded.. 80 patients were included with a mean age of 5 years, 70% male. The most relevant clinical symptoms were decreased consciousness (86%), fever (82.4%), seizures (67%), vomiting (42%), headache (27%), agitation (25%) and dis-orientation (23%). The etiologic diagnosis was established in 35%, being more frequent herpes simplex virus and enterovirus. The outcome was discharge without sequelae in 55 patients (69%), mild to moderate sequelae in 19 (23.5%) and severe in 6 (7.5%). Two patients died.. In the Spanish PICU etiological diagnosis was established only in a third of cases of children with suspected acute viral encephalitis. Despite the clinical severity we observed a low mortality and morbidity rate. At discharge from the PICU, most children had no neurological sequelae or were mild.. Etiologia, presentacion clinica y evolucion neurologica de las encefalitis viricas graves en la edad pediatrica (estudio ECOVE).. Introduccion. Las encefalitis viricas son procesos raros y potencialmente graves, con etiologia diversa y no siempre identificable. El objetivo es describir las caracteristicas etiologicas, la presentacion clinica y la evolucion neurologica de las encefalitis viricas que ingresaron en las unidades de cuidados intensivos pediatricos (UCIP) en España. Pacientes y metodos. Estudio prospectivo multicentrico observacional. Se incluyeron los niños ingresados en 14 UCIP con diagnostico de encefalitis virica durante un periodo de tres años (2010-2013). Para el diagnostico etiologico se utilizo reaccion en cadena de la polimerasa y serologia a virus neurotropos en la sangre y el liquido cefalorraquideo. Se registraron los antecedentes personales, la presentacion clinica, la evolucion y la situacion neurologica en el momento del alta. Resultados. Se incluyeron 80 pacientes con edad media de 5 años; el 70%, varones. Los sintomas clinicos mas relevantes fueron disminucion de conciencia (86%), fiebre (82,4%), convulsiones (67%), vomitos (42%), cefalea (27%), agitacion (25%) y desorientacion (23%). Se llego al diagnostico etiologico en un 35%, y los mas frecuentes fueron virus herpes simple y enterovirus. La evolucion fue curacion sin secuelas en 55 pacientes (69%, sobre todo enterovirus, rotavirus y virus respiratorios), secuelas leves-moderadas en 19 (23,5%) y graves en seis (7,5%). Dos pacientes fallecieron. Conclusiones. En las UCIP españolas solo se realizo el diagnostico etiologico en un tercio de los niños con sospecha de encefalitis virica grave. A pesar de la gravedad clinica, hemos observado una tasa de mortalidad y morbilidad baja. La amplia mayoria son dados de alta de la UCIP con ninguna o escasa secuela neurologica.

Topics: Acute Disease; Acyclovir; Adolescent; Antiviral Agents; Brain Damage, Chronic; Child; Child, Preschool; Clarithromycin; Consciousness Disorders; Encephalitis, Viral; Female; Fever; Headache; Humans; Infant; Male; Prospective Studies; Seasons; Seizures; Serologic Tests; Spain; Treatment Outcome; Vomiting

The significance of detecting herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of infants with HSV encephalitis after receipt of prolonged therapy with high-dose (60 mg kg(-1) day(-1)) acyclovir is unknown. We report the clinical and laboratory characteristics, neuroimaging studies and outcomes of four neonates with HSV encephalitis who had persistence of CSF HSV DNA, by polymerase chain reaction (PCR) after 15 to 21 days of high-dose acyclovir therapy.. Retrospective chart review.. All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death.. A persistently positive CSF HSV PCR in neonates may be another risk factor for worse neurodevelopmental outcome. Prospective studies are needed to document how often HSV DNA persists in CSF, elucidate whether it represents an initially high CSF viral load, ongoing viral replication or viral resistance, and determine its possible association with neurodevelopmental impairment.

Topics: Acyclovir; Adult; Antiviral Agents; Atrophy; Brain; Brain Damage, Chronic; DNA, Viral; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Herpes Simplex; Encephalomalacia; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Pregnancy; Prognosis; Retrospective Studies; Simplexvirus; Tomography, X-Ray Computed; Viral Load

Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome.. Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades <=2) and poor outcome (Grades >=3).. Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023-1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794-0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046-1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87-0.967) were independent prognostic factors.. Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Brain Damage, Chronic; Cerebrospinal Fluid; Dexamethasone; Diagnostic Imaging; Encephalitis, Herpes Simplex; Female; Hospital Mortality; Hospitals, University; Humans; Intracranial Hypertension; Male; Middle Aged; Prognosis; Retrospective Studies; Seizures; Spain

Topics: Acyclovir; Antiviral Agents; Brain Damage, Chronic; Cerebrospinal Fluid; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Herpes Simplex; Humans; Infant, Newborn; Neurologic Examination; Polymerase Chain Reaction; Predictive Value of Tests; Treatment Outcome; Viral Load

This study sought to produce a cognitive profile of herpes simplex encephalitis (HSE) survivors from a large group of definitively diagnosed, acyclovir-treated participants. Results from 22 adults who underwent a battery of neuropsychological tests indicated anterograde memory dysfunction to be the most severe and common deficit (although the variation was great), with less severe and less frequent impairments in the areas of retrograde memory, executive functions, and language functioning. Overall, neuropsychological outcome was unimpaired in six participants, mildly impaired in thirteen, moderately impaired in one, severely impaired in two. Older participants and those with a lower level of consciousness before the start of treatment produced poorer scores on certain aspects of cognitive outcome (p < 0.05). A significantly better cognitive outcome was found in participants for whom there was a short delay (fewer than 5 days) between symptom onset and acyclovir treatment compared with those participants for whom there was a longer delay. The two children in the study had disparate results on most tests, the exception being those assessing memory functioning on which both children had scores at population norms. On a naming task designed to explore category-specific knowledge deficits, the adults as a group made more errors on pictures of living things than nonliving things (matched pair-wise for word frequency and visual familiarity), although this difference disappeared on a smaller subset of pictures also matched for visual complexity.

Topics: Acyclovir; Adolescent; Adult; Aged; Amnesia; Anomia; Antiviral Agents; Brain Damage, Chronic; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Viral; Female; Follow-Up Studies; Herpes Simplex; Humans; Male; Middle Aged; Neuropsychological Tests; New Zealand; Paired-Associate Learning; Survivors

Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.

Topics: Acyclovir; Adolescent; Adult; Aged; Anticonvulsants; Athetosis; Basal Ganglia; Brain Damage, Chronic; Cerebral Cortex; Child; Child, Preschool; Chorea; Dominance, Cerebral; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Encephalitis, Viral; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Middle Aged; Neurologic Examination; Recurrence

Using a magnetic resonance imaging-based volumetry, we quantified the volumes of the hippocampal formation (HF), parahippocampal gyrus (PHG), amygdaloid body (AMB), and anterior temporal neocortex (ATN) in 5 post-herpes simplex encephalitic (post-HSE) patients with temporal lobe damage and memory impairment at 12-52 months after the onset, and in 10 age-matched control subjects. In the post-HSE patients, the HF (p < 0.001) and PHG (p < 0.005) were significantly atrophic, while the AMB (p = 0.155) and ATN (p = 0.102) were smaller but not significantly. Performances on the verbal learning memory tests correlated highly with the HF volume, and length of dense retrograde amnesia with the PHG atrophy. Two patients with severe lasting amnesia had a marked atrophy of the HF and PHG, while 3 patients with good recovery from initial amnesia had temporal lobe structures larger than 50% of the control mean volumes. These results suggest that anterograde and retrograde memory functions involve different neural structures; the former is related to the HF and the latter to the PHG. For producing lasting amnesia, either severe HF damage or a combined damage of the HF and PHG might be necessary.

Topics: Acyclovir; Adult; Amygdala; Brain; Brain Damage, Chronic; Encephalitis, Viral; Female; Follow-Up Studies; Herpes Simplex; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Mental Recall; Middle Aged; Neuropsychological Tests; Reference Values; Temporal Lobe; Verbal Learning

A 16-year-old male diabetic patient presented with bilateral salivary gland swellings followed by encephalitis. The EEG did not show the characteristic periodic lateralising epileptic discharges. Neuro-imaging disclosed compromise of temporal and frontal lobes as well as brain stem which correlated well with his clinical deterioration. Serology and frontal brain biopsy were positive for herpes simplex virus while mumps titers were not significant. Despite delayed acyclovir therapy, the patient recovered enough to be discharged home with a permanent pseudobulbar palsy. Herpes simplex encephalitis involving zones other than temporal lobes is exceptional. To our knowledge, there are no reported cases of pseudobulbar palsy as a sequelae of HSV encephalitis.

Topics: Acyclovir; Adolescent; Biopsy; Brain; Brain Damage, Chronic; Diagnosis, Differential; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Inclusion Bodies, Viral; Magnetic Resonance Imaging; Male; Microscopy, Electron; Mumps; Neurologic Examination

Two children, an eight-year-old girl and a seven-month-old boy, recovered from herpes simplex encephalitis with minimal neurological residua following acyclovir treatment. Subsequently, they experienced marked deterioration, interpreted as either recrudescent infection or a post-infectious phenomenon. Features of the deterioration included encephalopathy and hyperkinetic movement disorder. MRI studies showed extensive neocortical damage, without involvement of the basal ganglia, thalamus or subthalamic nuclei. With aggressive supportive care, both children made a slow, steady recovery over several months. This supportive care is best provided in a closely supervised interdisciplinary setting.

Topics: Acyclovir; Brain; Brain Damage, Chronic; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis; Female; Follow-Up Studies; Herpes Simplex; Humans; Infant; Magnetic Resonance Imaging; Male; Neurocognitive Disorders; Neurologic Examination; Neuromuscular Diseases

A severe herpes simplex encephalitis with documented intra-cerebral lesions and brain edema was treated successfully with acyclovir and beta-interferon. The increase in intracranial pressure during the second week was well controlled by ICP monitoring. Life-threatening pressure peaks were avoided through the use of thiopental, osmodiuretics, TRIS, and lidocaine.

Topics: Acyclovir; Adult; Brain Damage, Chronic; Combined Modality Therapy; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Interferon Type I; Intracranial Pressure; Male; Neurologic Examination

Since antiviral chemotherapy is available herpes encephalitis has become of great importance among viral affections of the central nervous system. Five young infants are presented with special problems of this disease and its diagnostic possibilities especially serological and imaging methods (CT scan, nuclear magnetic resonance tomography, ultrasonography of the brain) as well as electroencephalography. Clinical symptoms are very important since all those methods are not sufficient for early diagnosis and prompt onset of antiviral chemotherapy. Herpes encephalitis should be considered after apparent febrile seizures with focal symptoms as well as increasing disturbance of consciousness as manifestation of acute encephalopathy.

Topics: Acyclovir; Brain; Brain Damage, Chronic; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Infant; Magnetic Resonance Imaging; Male