acyclovir and Cognition-Disorders

Viral infections in the fetus or newborn often involve the central nervous system (CNS) and can lead to significant morbidity and mortality. Substantial progress has been made in identifying interventions decreasing adverse neurodevelopmental outcomes in this population. This review highlights progress in treatment of important viruses affecting the CNS in these susceptible hosts, focusing on herpes simplex virus (HSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and enteroviruses. The observation that high-dose acyclovir improves mortality in neonatal HSV disease culminated decades of antiviral research for this disease. More recently, prolonged oral acyclovir was found to improve neurologic morbidity after neonatal HSV encephalitis. Ganciclovir, and more recently its oral prodrug valganciclovir, is effective in improving hearing and neurodevelopment after congenital CMV infection. Increasing evidence suggests early control of perinatal HIV infection has implications for neurocognitive functioning into school age. Lastly, the antiviral pleconaril has been studied for nearly two decades for treating severe enteroviral infections, with newer data supporting a role for this drug in neonates. Identifying common mechanisms for pathogenesis of viral CNS disease during this critical period of brain development is an important research goal, highlighted by the recent emergence of Zika virus as a potential cause of fetal neurodevelopmental abnormalities.

Topics: Acyclovir; Antiviral Agents; Brain; Cognition; Cognition Disorders; Encephalitis, Herpes Simplex; Enterovirus Infections; Female; Ganciclovir; HIV Infections; Humans; Infant, Newborn; Nervous System Diseases; Oxadiazoles; Oxazoles; Pregnancy; Valganciclovir; Virus Diseases

Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint.. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group.. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.. NCT00031486.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cognition Disorders; Encephalitis, Herpes Simplex; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life; Valacyclovir; Valine; Young Adult

To test our hypothesis that valacyclovir, an antiherpes virus-specific medication, added to antipsychotics (APs) would improve cognitive performance and psychopathology among schizophrenia subjects exposed to neurotropic herpes simplex virus, type 1 (HSV1).. Using a double-blind placebo-controlled design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily orally. At each visit, subjects were evaluated for severity of psychopathology and side effects using standardized scales and a study-specific semistructured checklist. A computerized neurocognitive battery validated on both schizophrenia and healthy subjects was administered at baseline and follow-up. Intent-to-treat analysis, using linear regression models that included all randomized subjects, were used to examine differential changes in cognition and psychopathology scores over 18 weeks between valacyclovir and placebo, accounting for placebo response.. Valacyclovir group improved in verbal memory, working memory, and visual object learning compared with placebo group. The effect sizes (Cohen's d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for the visual object learning. Psychotic symptom severity did not improve.. Supplemental valacyclovir may alleviate impairments in cognitive domains that are often observed in schizophrenia but not psychotic symptoms in those exposed to HSV1. If replicated, this approach could provide a novel strategy to treat cognitive impairments in a subgroup of schizophrenia subjects who can be reliably identified using a blood test.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Learning; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Psychotic Disorders; Schizophrenia; Valacyclovir; Valine; Young Adult

Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia - even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable.. In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N=226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5G twice daily for 16weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT).. PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p=0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved in VAL-treated patients (p=0.048, Cohen's d=0.43).. A proportion of age related decline in EMOD is attributable to HSV-1 infection.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Emotions; Female; Follow-Up Studies; Herpes Simplex; Humans; Male; Middle Aged; Neuropsychological Tests; Randomized Controlled Trials as Topic; Severity of Illness Index; Valacyclovir; Valine; Young Adult

Topics: Acyclovir; Aged; Cognition Disorders; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; Humans; Magnetic Resonance Imaging; Male

Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis is a rare syndrome resolving within less than 3 months.. A young 17-year-old woman without previous medical history was admitted to the hospital because of right motor weakness and language disturbances. The symptoms resolved in a few hours and were followed by severe left headaches with important vegetative signs. Several similar episodes were noted in the previous 10 days. Cranial MRI was normal. EEG showed important slowing of the cerebral electrogenesis. More than 250 lymphocytic cells were found at CSF analysis. Outcome was spontaneously favorable, without similar symptoms after 6-month follow-up.. Pseudomigraine with lymphocytic pleocytosis seems to be a particular syndrome of unknown origin. This is an elimination diagnosis, generally with a benign course.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain; Cognition Disorders; Diagnosis, Differential; Electroencephalography; Female; Humans; Lymphocytosis; Magnetic Resonance Imaging; Migraine Disorders

Encephalitis is an uncommon clinical entity compared to traumatic brain injury, and stroke. Many encephalitis survivors have disabling sequelae. There is scant information in the literature addressing outcome following inpatient rehabilitation for encephalitis. Further, it is unclear which of these patients will benefit from acute in-patient rehabilitation.. The purposes of this study are to (1) describe the outcome following in-patient rehabilitation in a cohort of patients with encephalitis, and (2) develop preliminary criteria to guide the selection of patients with encephalitis who may benefit from inpatient rehabilitation.. The demographic, clinical, functional (functional independence measure-FIM) and neuro-psychological data were retrospectively abstracted for eight subjects with a clinical diagnosis of encephalitis aged 5 to 75 years, who were admitted to a brain injury rehabilitation unit between 1990 and 1997.. In the eight subjects, the mean age was 38 years, mean acute hospital stay (ALOS) was 40.3 days, and mean rehabilitation length of stay (RLOS) was 75.9 days. Mean admission FIM (AFIM) was 40.1, mean discharge FIM (DFIM) was 69.9. Mean FIM gain was 29.8 and mean FIM efficiency was 0.39. Adult subjects with an AFIM > 30 at 5 weeks from onset of illness (n = 4) had a FIM LOS efficiency of 0.64 and all four were discharged home. None of the adult subjects with an AFIM < 30 at 5 weeks from onset of illness (n = 3, FIM efficiency = 0.14) were discharged home. A child with an AFIM < 30 (n = 1) had a FIM LOS efficiency of 1.24, made good recovery and was discharged home. FIM LOS efficiency of 0.64 in encephalitis is less, as compared to traumatic brain injury (TBI -1.27) and stroke (1.06).. The results of this study showed that, although subjects with encephalitis make functional gains in rehabilitation, the rate of recovery varies and is generally less than that for TBI and stroke. The study also suggests that FIM scores can be used for screening adult patients after encephalitis for admission to inpatient rehabilitation. Adult patients with an AFIM > 30, 5 weeks post onset of illness are likely to make reasonable progress and be discharged home. If replicated, these results suggest that despite low AFIM scores at 5 weeks from onset of illness (AFIM < 30), children may still make good progress and should be given a trial of in-patient rehabilitation.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Cognition Disorders; Encephalitis, Viral; Female; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Follow up of cognitive sequelae of acute encephalitis and estimation of the frequency of persisting dementia.. Out of a series of 45 consecutive patients with acute encephalitis prospectively studied in 1990-95, 40 were screened for difficulty in everyday life using the Blessed dementia scale (BDS) 3.7 (1.4), mean (SD), years after onset. Eight patients had had herpes simplex encephalitis (HSVE), 16 some other identified aetiology, and in 21 the aetiology was unknown. All, except two patients with a nonherpetic encephalitis, were treated with acyclovir. All patients with disability in BDS (12/40), were invited to a neuropsychological reassessment, and the results of this assessment were compared with those of a similar assessment done after the acute stage. At follow up one patient could not complete the tests due to intractable epilepsy.. In six of 11 cases the symptoms causing disability were mainly psychiatric. Five patients (two with HSVE) had a pronounced memory impairment together with other cognitive deficits, indicating dementia (frequency of 12.8%). In eight of the 11 testable cases cognitive performance had improved over the years, in two cases a decline was found and one patient with severe deficits showed no change. Intractable epilepsy was found in four of 12 cases.. Cognitive decline had taken place already at the acute stage, and further deterioration was uncommon. Considerable improvement occurred in most patients during follow up. Also in patients with HSVE treated with acyclovir the cognitive recovery was substantial and of a magnitude not expected based on previous literature. Intractable epilepsy contributed to the cognitive deterioration in some cases. Affective disorders also had a surprisingly important role for the long term outcome.

Topics: Acute Disease; Acyclovir; Adult; Aged; Antiviral Agents; Cognition Disorders; Depressive Disorder; Encephalitis, Viral; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Prospective Studies; Severity of Illness Index

The long-term neuropsychological and psychiatric sequelae of herpes simplex virus encephalitis (HSVE) and their relationship to the volume of temporal lesions and to amygdala and hippocampus damage remain undefined. We have conducted a prospective study of long-term sequelae in 11 patients with clinically presumed HSVE and detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction. Six months after encephalitis, patients underwent neuropsychological and language assessment. At the same stage, single photon emission computed tomography (SPECT) evaluated the occurrence of hypoperfusion with an index of asymmetry. MRI was used for the measurement of amygdala, hippocampus and cerebral lesions by two blind neurologists. The volume of the amygdala and hippocampus was compared with those of five controls, matched for age and level of education. Long-term memory disorders were seen in 6 patients, associated with the larger lesions and damage of at least two structures. Long-term behavioural changes with emotionalism, irritability, anxiety or depression were prominent in 7. Left prefrontal hypoperfusion appeared in 8 patients, associated with psychiatric disorders in 7 and left amygdala damage in 6. The reduction of amygdala and hippocampus volume was correlated with the overall volume of lesions. Different patterns of mesial temporal lobe damage occurred, involving either amygdala alone, or amygdala and hippocampus, but never hippocampus alone. MRI volumetric measurements in HSVE could be a good indicator of long-term prognosis. Persistant behavioural changes could be related to an amygdala and frontal dysfunction.

Topics: Acyclovir; Adult; Aged; Amygdala; Case-Control Studies; Cerebrovascular Circulation; Cognition Disorders; Encephalitis, Viral; Evaluation Studies as Topic; Female; Herpes Simplex; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Prospective Studies; Tomography, Emission-Computed, Single-Photon

The occurrence of anuria and stupor in a patient treated with acyclovir afforded the opportunity to discuss the renal and neurological toxicity of this drug. Acute renal insufficiency by crystallization of acyclovir and intratubular obstruction is a not infrequent side effect. The risk depends on the dose, the administration mode, the patient's state of hydration and preexisting renal failure. The evolution is typified by a rapid onset (after 24-48 h) and a prompt recovery after ending the treatment. The demonstration in urinalysis of crystals within leukocytes helps to establish the diagnosis. Neurological involvement can vary from confusion to coma. The cerebrospinal fluid is normal and the electroencephalogram shows diffuse slowing. A favorable outcome after ending treatment is the rule. Awareness of the risk factors associated with renal and neurological toxicity should lead to a reduction of its frequency.

Topics: Acute Kidney Injury; Acyclovir; Aged; Aged, 80 and over; Akathisia, Drug-Induced; Cognition Disorders; Herpes Zoster; Humans; Male

Topics: Acyclovir; Cognition Disorders; Confusion; Female; Fever; Herpes Simplex; Humans; Middle Aged