Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands.

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportunity to study the pathogenesis of measles immune suppression in unvaccinated children. In peripheral blood mononuclear cells (PBMC) of prodromal measles patients, we detected MV-infected memory CD4+ and CD8+ T cells and naive and memory B cells at similar levels as those observed in NHPs. In paired PBMC collected before and after measles we found reduced frequencies of circulating memory B cells and increased frequencies of regulatory T cells and transitional B cells after measles. These data support our immune amnesia hypothesis and offer an explanation for the previously observed long-term effects of measles on host resistance. This study emphasises the importance of maintaining high measles vaccination coverage.

High avidity HSV-1 antibodies correlate with absence of amnestic Mild Cognitive Impairment conversion to Alzheimer's disease.

Amnestic Mild Cognitive Impairment (aMCI) is an alteration in cognitive abilities that can progress to Alzheimer's disease (AD), a condition in which herpes simplex type 1 (HSV-1) infection might play a pathogenetic role. Prognostic indexes capable of predicting aMCI conversion to AD are only partially understood. The objective of the present work is to verify whether HSV-1 immune responses is involved in conversion of aMCI to AD and correlate with grey matter brain morphometry. Two homogeneous groups of individuals who did or did not convert to AD over a 24-months period were selected after retrospective analysis of a cohort of patients with a diagnosis of aMCI. The selection of subjects was based on: a) clinical follow-up; b) neurocognitive evaluation at baseline and after 24months; c) availability of serum and DNA samples at baseline. 36 aMCI individuals, 21 of whom did (aMCI-converters) and 15 of whom did not (aMCI-non-converters) convert to AD, were included in the study. HSV-1 antibody (Ab) titers, avidity index and APOE genotyping were performed in all the enrolled individuals at baseline. Brain magnetic resonance imaging (MRI) by 1.5T scanner results at baseline were available as well in most (29/36) of these individuals. HSV-1-specific Ab titers were increased at baseline in aMCI-non-converters, and the avidity of these Ab was significantly higher in aMCI-non-converter compared to aMCI-converter (p=0.0018). Receiver operating characteristics analysis showed that HSV-1 avidity had a predictive value in distinguishing between aMCI-non-converters and aMCI-converters (p<0.0001). Notably, a positive correlation was detected as well between HSV-1 antibody titers and MRI-evaluated cortical volumes in the left hippocampus and amigdala (pcorr<0.05). In conclusion, stronger HSV-1-specific humoral responses associate with protection against AD conversion and better-preserved cortical volumes. These results reinforce the hypothesis for a role for HSV-1 in the pathogenesis of AD.

Managing aggression in global amnesia following herpes simplex virus encephalitis: The case of E.B.

AIM: This article describes an integrative approach to the case of EB, a 33 year old male who presented with agitation, delusional ideation and global amnesia after contracting herpes simplex virus encephalitis (HSVE) while in a state prison in 2004. CASE STUDY: Although several prior case studies have described outcome following acute onset of HSVE, this case presents a unique challenge for rehabilitation in several respects. First, EB's pre-morbid history is complicated; in contrast with prior HSVE case studies that have typically involved individuals with a relatively high level of pre-morbid functioning, EB presents with limited educational attainment and a prior history of several incarcerations for violent offenses. Post-injury, his presentation includes significant verbal aggression, threats of harm toward others, physical posturing and occasional physical aggression toward his caretakers. Third, EB presents with a fixed delusion that others are constantly taking advantage of him. These features are present in the context of global amnesia and relatively intact cognitive functioning in other domains. Following a brief review of prior HSVE case studies, this study reviews the outcomes of various pharmacological, cognitive, behavioural and integrative interventions designed for management of EB's aggression and agitation.

Older individuals with HIV infection have greater memory deficits than younger individuals.

The prevalence of HIV-associated neurocognitive disorder (HAND) remains persistently high in the era of combination antiretroviral therapy. We aimed to characterize the pattern of neurocognitive dysfunction in older subjects with HAND in particular amnestic versus non-amnestic impairment. One hundred six subjects from the Johns Hopkins University NIMH Clinical Outcomes cohort underwent standardized neuropsychological (NP) testing between November 2006 and June 2010. We examined performance in seven cognitive domains (memory, attention, speed of processing,visuospatial, language, motor, and executive). Older subjects were defined as age >50 years at the time of NP testing.Subjects were diagnosed with HAND according to established criteria and dichotomized into amnestic cognitive impairment or non-amnestic cognitive impairment with deficit defined as z scores <−1.5 for the verbal and nonverbal memory domains.There were 32 older subjects with a mean age (SD) of 54.2 (2.8) years and 74 younger subjects, 43.7 (4.3) years. Older age was associated with a 4.8-fold higher odds of memory deficits adjusted for potential confounders (p =0.035) identified a priori. With age modeled as a continuous covariate,every 1 year increase in age was associated with a 1.11-fold higher odds of memory deficit (p =0.05). There was a higher proportion of amnestic cognitive impairment among older subjects than younger subjects with HIV infection. Neurodegenerative processes other than those directly due to HIV maybe increasingly important as individuals with chronic HIV infection and HAND survive into older age.

Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease.

After infection with herpes simplex virus type 1 (HSV-1), latent infection persists for life in the trigeminal ganglion and reactivation results in an outbreak of cold sores around the mouth. Many previous studies have reported HSV-1 reactivation to be a risk factor for Alzheimer's disease (AD). This study enrolled subjects with AD (n=85), subjects with amnestic mild cognitive impairment (aMCI; a prodromal stage of AD) (n=34), and healthy controls (n=28). The avidity index of anti-HSV-1 IgG antibodies--a known indicator of HSV-1 reactivation--was measured in order to clarify the relationship between HSV-1 reactivation and symptoms of cognitive function in AD. Cognitive function in AD and aMCI were evaluated using scores from the mini-mental state examination (MMSE) and frontal assessment battery (FAB). The results showed that the subjects with aMCI, for which cerebral function is better preserved than subjects with AD, had a higher anti-HSV-1 IgG antibody avidity index than the AD subjects or healthy controls. Furthermore, the anti-HSV-1 IgG antibody avidity index was even higher in the subjects with high MMSE scores on orientation to time and three-step command subscores. We observed a negative correlation between the anti-HSV-1 IgG antibody avidity index and plasma BDNF concentration, which is an indicator of encephalitis. This suggests that HSV-1 reactivation, as observed through an increase in the anti-HSV-1 IgG avidity index, does not progress to encephalitis. These results suggest that HSV-1 reactivation occurs from the stage of aMCI, which is prodromal to AD, and can affect AD symptoms without an intermediary stage of severe encephalitis. The study demonstrates that the anti-HSV-1 IgG antibody avidity index could be a useful biomarker for the early diagnosis of aMCI as well as AD, and suggests that antiviral medication to treat HSV-1 could play a role in preventing the onset of AD.

Long-term outcome of human herpesvirus-6 encephalitis after allogeneic stem cell transplantation.

Human herpesvirus-6 (HHV-6) encephalitis is recognized as a relatively rare, but sometimes lethal, complication of allogeneic hematopoietic stem cell transplantation (HSCT). Although the development of new diagnostic techniques and antiviral therapy has improved, the prognosis of encephalitis is still unclear. We surveyed 197 patients who underwent allogeneic HSCT between January 2004 and March 2008 at our institution, and 8 (4.0%) were diagnosed as having HHV-6 encephalitis. Five were male and 3 were female, with a median age of 40.5 years. The median onset of HHV-6 encephalitis was 18 days after HSCT, and the median duration of antiviral therapy was 41 days. The median survival time from the onset of encephalitis was 23.1 months (range: 2.7-66.7), and 3 patients died of unrelated causes (sepsis in 2 and gastrointestinal tract bleeding in 1). Cord blood transplantation was identified as the only independent risk factor (relative risk [RR] = 4.98; P = .049) by multivariate analysis. There was no statistical significance of survival after HSCT between the patients with HHV-6 encephalitis and those without HHV-6 encephalitis (the 2-year survival rate was 60% and 52.6%, respectively; P = .617). Four of the 5 surviving patients were unable to return to society because of neuropsychological disorders, including anterograde amnesia and seizures with prominent hippocampal atrophy. Although HHV-6 encephalitis occurring after HSCT is now becoming a curable complication, its sequelae, such as neuropsychological disorders, have a marked influence on the quality of life of long-term survivors. Accordingly, it is necessary to identify risk factors for HHV-6 encephalitis and establish methods for prevention of this complication.

Visual recognition memory: a double anatomo-functional dissociation.

There is an ongoing debate regarding the respective role of anterior subhippocampal structures and the hippocampus in recognition memory. Here, we report a double anatomo-functional dissociation observed in two brain-damaged patients, FRG and JMG. They both suffered from complete destruction of left MTL structures. In the right hemisphere however, FRG sustained extensive lesions to the hippocampus sparing anterior subhippocampal structures, while JMG suffered from the reversed pattern of lesion, i.e., extensive damage to anterior subhippocampal structures but preserved hippocampus. FRG was severely amnesic and failed all recall tasks involving visual material, but exhibited normal performance at a large battery of visual recognition memory tasks. JMG was not amnesic and showed the opposite pattern of performance. These results strongly support the view that right anterior subhippocampal structures are a critical relay for visual recognition memory in the human.

Cognitive rehabilitation of amnesia after virus encephalitis: a case report.

A number of memory rehabilitation techniques have targeted people with various degrees of memory impairments. However, few studies have shown the contribution of preserved non-declarative memory capacity and errorless learning in the treatment of amnesic patients. The current case report describes the memory rehabilitation of a 44-year-old man with amnesia following viral encephalitis. The patient's procedural memory capacity had an important role in the use of a motor imagery strategy to remember people's names. It was further demonstrated that the application of a verbal learning technique was helpful in recalling new verbal information. These different memory rehabilitation techniques are discussed in terms of alternative possibilities in the rehabilitation of amnesic patients.

Relative preservation of 'animate' knowledge in an atypical presentation of herpes simplex virus encephalitis.

A comprehensive battery of neuropsychological tests designed to assess primary cognitive functions, including language and semantic memory, was given to MG, a patient with confirmed herpes simplex virus encephalitis. MG's initial jargon aphasia resolved over time to leave her with a mild phonological impairment. She had a very mild amnesia that was worse for verbal material and a category-specific impairment of semantic memory. This latter impairment resulted in a significant anomia that was worse for manmade/artefact items than for animate kinds. Her naming difficulties were associated with a mild impairment in comprehension that was not specific to category or feature type. MRI revealed a strongly asymmetric and atypical distribution of pathology in MG with the disease affecting the left medial temporal lobe, temporal pole, left frontotemporal and temporoparietal regions.

Topographic amnesia: spatial memory disorder, perceptual dysfunction, or category specific semantic memory impairment?

A 60 year old patient, SE, who presented with a severe difficulty in finding his way around previously familiar environments and a mild prosopagnosia is described. SE had herpes simplex encephalitis resulting in selective right temporal lobe damage. He showed normal spatial learning, but was severely imparied in his ability to recognise pictures of buildings and landmarks. The disorder was not confined to the visual modality, but rather involved a loss of knowledge about famous buildings and landmarks when tested from their spoken name. SE was contrasted with a more severely prosopagnosic patient, PHD, who showed normal ability to recognise buildings and landmarks, indicating that recognition of people dissociates from recognition of buildings/landmarks. It is concluded that SE's failure of place knowledge represents a category specific supramodal semantic memory impairment.

Herpes simplex encephalitis with transient global amnesia as an early sign.

Cerebral ischemia has been proposed as the etiology of transient global amnesia. Recently, however, migranous and epileptic etiologies have attracted attention. A 56-year-old man had transient global amnesia and the next day began to display symptoms of meningoencephalitis. Herpes simplex encephalitis was diagnosed based on the titer of herpes simplex virus antibodies. The transient global amnesia appears to have occurred as an early sign of herpes simplex encephalitis and may have been provoked by an epileptic mechanism.